ICSM Y2 LCRS 1

Define 'term', 'pre-term' and 'post-term' in relation to pregnancy

'term' covers gestational ages from 37 - 41 weeks of gestation, with deliveries either side of these limits being 'preterm' or 'post-term' respectively.

List the developmental domains

(1) gross motor and posture - the ways that the limbs move (2) fine motor and vision - the ways that the hands move (also dependent on eyesight) (3) language/speech and hearing (4) social skills - emotional and behaviour

State the 4 classes of antiretroviral drugs (anti-HIV drugs)

(HIV) Entry inhibitors (HIV) Reverse transcriptase (RT) inhibitors (HIV) Integration inhibitors (HIV) Protease inhibitors

State the equation to calculate height velocity of a child.

(Height now - Height at last visit)/(Age now - Age at last visit), measured around 60months to 1 year apart

What are the two components that bone is made of?

(OSTEOID) ORGANIC COMPONENTS - type 1 collagen INORGANIC COMPONENTS - hydroxyapatite

What is the difference between high and low molecular weight heparins?

(high weight) heparin = antithrombin activator/stimulator low weight heparin = antithrombin activator/stimulator AND direct factor Xa inhibitor

What is the mechanism of action of Enfuvirtide

(inhibits G41, penetrates host cell membrane and enables viral capsid to enter)

What is the next most likely cause for a peptic ulcer if the patient is H. Pylori negative?

(prolonged) NSAID use (i.e. aspirin)

Summarise how ultrasounds are used to assess and track foetal growth

- Bi-parietal diameter (BPD): distance between the two sides of the head - Head circumference (HC) - Abdominal circumference (AC) - Femur length (FL) This is then combined to create and estimated foetal weight (EFW)

What are the physiological effects of salbutamol

- Bronchial smooth muscle relaxation - Decreased PI hydrolysis - Increased Na/Ca exchange - Opens potassium channels

List the side effects of ACE inhibitors (6)

- Cough - Angioedema - Renal failure - Hypotension

How does the age of diagnosis of diabetes affect life expectancy?

- Diabetics are expected to die earlier when age of diagnosis is earlier i.e. the earlier you are diagnosed, the more years are shaved off of your life expectancy

State the measurements that are recorded when tracking an infant's growth (6)

- Head circumference - Weight - Height/length - Leg length - BMI - needs to be plotted on a growth chart - Growth velocity - measured in cm/year

List 4 causes for tall stature

- If the parents are tall, the child is likely to be tall - Early puberty - makes a child tall at first - syndromes - e.g. Marfan's syndrome = really long arm span and really tall - Growth hormone excess

Summarise the basic metabolism/pharmacokinetics of Mesalazine and Olsalazine and their uses in the treatment of IBD

- Olsalazine (the linked form of the 5-ASA drug) has to be ACTIVATED by the gut flora - It is metabolised by colonic flora - so olsalazine only works in the colon - Mesalazine will be absorbed all the way through the gut so is better in circumstances where more of the gut is affected

Summarise the 2 step process of alcohol metabolism

- STEP 1: ALCOHOL DEHYDROGENASE & MIXED FUNCTION OXIDASES convert ALCOHOL -->ACETALDEHYDE - Acetaldehyde is a VERY TOXIC PRODUCT, so we don't want it building up in the blood - STEP 2: ALDEHYDE DEHYDROGENASE converts acetaldehyde --> ACETIC ACID (inert) - This reaction occurs BOTH in the liver and the stomach to produce an inactive product

What is the major metabolite of nicotine? What does the metabolising

- The major metabolite is cotinine - it is an inactive and inert metabolite - Carried out by hepatic CYP2A6

Give 2 examples of adjuncts (dopa decarboxylase inhibitors)

- carbidopa - benserazide

Which receptor (MR or GR) does Prednisolone mainly act on

- glucocorticoid with weak mineralocorticoid activity

Which suffix do ACE inhibitors tend to end with?

-pril e.g. ramipril, elanapril

Between what weeks is the first trimester of pregnancy?

0-13 weeks

What percentage of cocaine is found within the Erythroxylum coca plant?

0.6-1.8% cocaine

What is required for the activation of Tenofovir

1 or two phosphorylation steps

Structure of type 2 receptors

1 subunit with 7 transmembrane domains

What fraction of spermatazoa reach the ovum?

1%

Name 2 voltage gated Na+ channel blockers

1) Carbamazepine 2) Lamotrigine

Name 3 treatments of parkinsons

1) Dopamine replacement 2) Dopamine receptor agonists 3) Monoamine oxidase B (MAOb) inhibitors

Where is the GABA-A receptor located and what does its activation do

1) GABA-A receptor: post-synaptic • Type 1 ionotrophic receptor --> causes Cl- influx into post-synaptic cell • causes hyperpolarisation = more difficult to excite the cell

What are the 6 general pathways by which the GABA-A receptor can be activated?

1) Linkage of GABA Receptor PRotein, GABA-Modulin and BDZ-RP and opening of chloride channel 2) Initiation pathway 1 due to Benzodiazepine entry 3) Increased affinity of reversible GABA/BDZ binding 4) Linkage of Barbiturate Receptor PRotein and BDZ-Receptor Protein 5) Increased affinity of GABA - Barb binding 6) Direct activation of chloride channel

What are the goals/guides of treatment in diabetics to prevent macrovascular disease?

1) Treat lipids with statins more aggressively in diabetics compared to non-diabetics 2) Treat blood presssure more aggressively in diabetics compared to non-diabetics 3) Treat/control hyperglycaemia in diabetics

What is the half life of nicotine?

1-4 hours

What are the 3 steps of bacterial wall synthesis

1. Peptidoglycan synthesis 2. Peptidoglycan transportation 3. Pepptidoglycan incorporation

How many known prostanoid receptors are there?

10

What percent of 60yr olds have T2DM?

10%

What percentage of alcohol consumed is breathed off unchanged? What does this allow for?

10% allows for simple breath test to get an estimate of total alcohol in the body

Between which weeks does the placenta undergo rapid growth to prepare for foetal growth?

10-12 weeks

What is the half life of TCAs?

10-20 hours - ONE DOSE DAILY

What is the approximate ratio for the amount of cannabis stored in the adipose tissue compared to the blood in chronic cannabis users?

10^4 : 1 fatty tissue:plasma

Between what weeks is the second trimester of pregnancy?

14-26

What is the limit age for walking independently?

18 months

What is the plasma half life of SSRIs?

18-24 hours

Give the subunit composition of ganglion nicotinic receptors

2 alpha + 3 beta

Give the subunit composition of muscle nicotinic receptors

2 alpha + beta + delta + epsilon

State two important targets of immune checkpoint blockade therapy.

2 important molecules targeted in immune checkpoint blockade: CTLA4 PD-1 These molecules deliver inhibitory signals to T cells. So if they are blocked, the T cell response is enhanced

Where is the GABA-B receptor located and what does its activation do

2) GABA-B receptor: pre-synaptic • 'Auto-receptor' --> exactly like the alpha-2 receptors found in noradrenergic synapses • negative feedback on GABA release

How long does the onset of clinical effects of SSRIs usually take?

2-4 weeks

State the ranges of thickness of the endometrium during the mestrual and proliferative phases of the endometrial cycle

2-4mm during menstrual 7-16mm during proliferative

What proportions of alcohol are usually absorbed from the stomach and small intestines respectively?

20% from stomach, 80% from small intestines

What is the half life of cocaine?

20-90mins

What is the most common direct cause of congenital adrenal hyperplasia

21-hydroxylase deficiency due to inherited gene

Between what weeks is the third trimester of pregnancy?

27-39

Which polymorphism leads to people not responding well to codeine?

2D6 polymorphism If this results in good faster metabolism of codeine then you'll get more morphine and the effect will be too pronounced If this causes poor metabolism then you'll get reduction in effect

How should folic acid supplementation be given to the mother

3 MONTHS prior to conception (12 weeks running up to pregnancy) • The egg does most of its development before it is selected as the main follicle within these 3 months

Half life of pilocarpine and bethanechoL

3-4 hours

Which enzyme can convert pregnenolone to progesterone

3-Beta

How long after smoking a cannabis cigarette will the effects persist in the body?

30 days

What is the half life of physostigimine

30mins

What percentage of all pregnancies are spontaneously lost in the first trimester of pregnancy?

33%

Which type of cranial nerve palsy is most common?

3rd nerve palsy

Structure of type 1 receptors

4 or 5 subunits with transmembrane alpha helices

At what age does Paget's disease usually start to become apparent?

40-50+ years

Give duration of action of tubocurarine

40-60mins

How many cases of Parkinson's are due to genetic causes

5%

What percentage of deaths from NSAIDs are due to GI and CVS problems respectively?

50% from GI and 50% from CVS

Average age of menopause

51 years (can range between 45-55)

By what point are limbs fully formed and patterned

56 days

What does 5alpha reductase convert testosterone into? What does this act on

5a-reductase action turns testosterone à DHT. o Acts on AR - androgen receptor

How often do replacement hormone therapies dosage need to be checked?

6-12 months

What is impaired fasting glucose level?

6.0-7.0 mmol/l

What is the risk of amputation in diabetics compared to non-diabetics?

60x greater than non-diabetics also has a poor subsequent prognosis

What percentage of sodium is reabsorbed via the proximal convoluted tubule?

65-70%

What is impaired glucose tolerance range?

7.8-11.1 mmol/l

What percentage of cocaine is metabolised down into ecogonine methyl ester and benzoylecgonine?

75-90%

What percentage of alcohol consumed is metabolised?

90% (10% is excreted off unchanged by breathing)

What proportion of circulating testosterone is protein bound

98%

What radioisotope is administered when the aim is to trace not treat

99- Tc pertechnetate Low tracer dose of radioiodine

What is normal fasting glucose level?

<6mmol/L

What is diabetic glucose tolerance level?

>11.1 mmol/l

What fasting blood glucose level indicates diabetes?

>7mmol/L

Define drug

A chemical substance that causes a physiological response in the body

What is achondroplasia? Explain its pathogenesis

A form of dwarfism where cartilage is converted into bone and a lack of bone growth

What is macrosomia?

A high-birthweight infant

What is an 'XX' male? How does this occur?

A male with two XX chromosomes but one will carry the SRY region of the Y chromosome

What is hyperemesis gravidarum?

A rare severe form of morning sickness that can be so powerful it can cause weight loss

What is the mesolimbic pathway?

A reward pathway that is a collection of dopaminergic neurones that originate in the ventral tegmental area (this is where the cell bodies are), and project to the ventral striatum (in particular, an are called the nucleus accumbens). Dopamine release in nucleus accumbens causes the feeling of reward. It is an endogenous system.

What happens after the oxygen molecule has picked up its first electron from the ferrous ion in the catalytic site of the Cyt P450

A second electron will be donated from the NADPH to the ferric ion and then to the oxygen molecule so it becomes increasingly unstable

Describe what happens in Viral (de Quervain's) thyroiditis and give the progression of the disease

A virus attacks the thyroid gland, consequently the thyroid stops making thyroxine and makes viruses instead. Thus there is zero iodine uptake Since there is zero radioiodine uptake, the stored thyroxine is released (hyperthyroidism). Four weeks later the stored thyroxine is exhausted and this results in hypothyroidism. After a further month, resolution occurs (like in all viral diseases) and the patient then becomes euthyroid (normally functioning thyroid gland) again

What is a virion?

A virus that is active outside of the host cell (complete infective form of a virus)

Which apoproteins identify LDLs and HDLs respectively?

A1 - HDL B - LDL

What class of drugs tend to end with the suffix '-pril'

ACE inhibitor

What is the first step hypertension treatment for patients below 55

ACE inhibitor or angiotensin receptor blocker

What is the first line treatment for patients with diabetic nephropathy?

ACE inhibitors reduces rate of decline of kidney function as well as assisting in reducing blood pressure

What is the third step hypertension treatment for patients

ACEi/ARB with CCB + thiazide-like diuretic

Why should special care be taken when administering ACEi/ARBs to patients taking K+ supplements or are on K+ sparing diuretics?

ACEi/ARBs prevent the action of AngII. One of the main actions of AngII is to stimulate aldosterone secretion Aldosterone promotes K+ excretion/loss So ACEi/ARBs are basically aldosterone production inhibitors so lead to a hyperkalaemic effect. Therefore, patients who are already actively regulating K+ need to be monitored to make sure they don't become hyperkalaemic

Explain the peripheral mechanisms by which opioids mediate their anti-tussive effects

ACh and neurokinin (NK) are the two NTs involved in coughing. C-fibres (neurones) send information up to the cough centre, via the vagus nerve Opioids decrease the firing rate of C-fibres ACh and NK (Neurokinin) release inhibited by opioids

What is the greater determinant of force of contraction of the heart out of preload and afterload?

AFTERLOAD an ↑ preload = small ↑ in F.O.C. (100% ↑ ventricular volume would only ↑ F.O.C. by 25%)

What is pseudohypoparathyroidism also known as?

ALLBRIGHT HEREDITARY OSTEODYSTROPHY

What is the pharmacological treatment for an acute/uncomplicated H. Pylori positive peptic ulcer?

ANTIBIOTICS - Amoxicillin (penicillin-like) and Clarithromycin (bacterial protein synthesis disrupted) + PROTON PUMP INHIBITORS - Reduces acid secretion

Summarise the traditional glutamergic neurotransmission

AP causes voltage gated sodium channels to open and then voltage gated calcium channels to open Calcium influx leads to vesicle attachment to the presynaptic membrane Vesicle and glutamate exocytosis

Out of ACEi and ARBs which is preferred for afrocarribbeans in stage 2

ARBs

Which class of drugs end with the suffix -sartan?

ARBs e.g. losartan

State the antiplatelet drug that prevents platelet aggregation

Abciximab

What is an arrhythmia?

Abnormal or irregular heartbeat

What cytology is Paget's disease characterised by?

Abnormal, large and numerous osteoclasts

What is the main problem with anti-TNFa therapy as treatment for IBD

About 50% of patients lose response to the drugs in 3 years

What are Ethosuximides used against

Absence seizures

Give an example of an Alpha glucosidase inhibitor

Acarbose

Give the main effect of growth hormone therapy in children

Accelerates linear growth and reduces body fat as protein synthesis stimulated and fat storage decreased

Acetyl choline synthesis

Acetyl coA and choline are combined using choline acetyltransferase

Describe how acetylcholine is synthesised and how it is broken down into its two constituent parts

Acetyl coA and choline are combined using the enzyme acetyltransferase Acetylcholine is broken back down with acetylcholinesterase

Conjugating agent in acetylation and product of reaction?

Acetylcholine Product is the acetylated derivative of the drug and coA

What are the two types of cholinesterase

Acetylcholinesterase Butyrylcholinesterase

Which enzyme breaks down ACh at a neuromuscular junction? What are the products

Acetylcholinesterase Acetate and choline are produced

What is required for the activation of Zidovudine

Activated by a 3-step phosphorylation process

Explain the mechanism/pathway by which stimulation of cannabinoid receptors leads to feelings of euphoria

Activation of CB1R on GABA neurones projected towards VTA means that release of GABA (which is inhibitory) on the VTA is reduced. This means there is an increased rate of firing of the VTA dopaminergic neurones onto the nucleus accumbens agonising the D1 receptors

Summarise the mechanism of action of fibrates and the effect they have on blood lipids

Activation of PPAR nuclear receptors Lower plasma fatty acids and lipids Increases HDLs effectively but doesn't change LDLs much

What are the characteristic signs of the fatty streak formation phase

Activation of T cells Adherence and activation of platelets Formation of foam cells derived from macrophages and T lymphocytes

How do most drugs enter urine to be excreted

Active secretion

What are the indications of use for anti-platelet drugs?

Acute coronary symptoms (used to prevent MI) Atrial fibrillations (used to prevent strokes)

Explain how and why diuretics are used in heart failure

Acute reduction in congestion with use as more volume is being lost in urination

What is the treatment used for HSV

Acyclovir - nucleoside analogue

What is the antidote for paracetamol poisoning?

Add compounds with -SH groups (e.g. methionine) so that this gets oxidised instead of the key hepatic enzymes

What is the test for Addison's

Addison's can be tested for if 9am cortisol is low and ACTH is high. A short synACTHen test is done (synthetic ACTH), whereby synACTHen is given intramuscularly, and the cortisol response is measured.

Give the presentation of complete 21-hydroxylase deficiency in neonates

Addisonian crisis (cortisol and aldosterone completely gone) Sex steroids will be in excess Girls may have ambiguous genitalia (due to virilisation by excess adrenal testosterone)

What is given to patients alongide Dopamine replacements

Adjuncts - supplementary to L-DOPA - Dopa decarboxylase inhibitors eg: carbidopa, benserazide - COMT inhibitors eg: entacapone, tolcapone

What are the 3 underlying principles that customised foetal growth charts are adjusted in accordance to?

Adjusted to reflect maternal constitutional variation (maternal height, weight, ethnicity, parity) • Optimised by presenting a standard free from pathological factors such as diabetes and smoking

How can you minimise the unwanted effects of glucocorticoid therapy

Administer locally where possible Use minimum effective dose Use a GR-selective steroid Use ACTH in children to reduce growth suppression

What are the five stages of a drug's journey in the body

Administration Absorption Distribution Metabolism Excretion

Define obesity for adults and children

Adults - BMI of >25kg/m2 is overweight, >30kg/m2 is obese. Will change for children with age

Distinguish between affinity and efficacy

Affinity is the ability to bind to a receptor - both agonist and antagonist. Efficacy is the ability to induce a biological response - agonist only.

What is Sodium Valproate used against

Against all forms of epilepsy

What are the 2 risk factors for Alzheimer's disease?

Age (main risk factor) - risk increasing exponentially by 65 Genetic mutations - 3 known proteins (APP, PSEN and ApoE)

List the non-modifiable risk factors for macrovascular disease (4)

Age, sex, birth weight, genes

Agonist vs antagonist

Agonist will generate a response after binding to a receptor whereas antagonist will not generate any response

What is the mechanism and effect of GLP-1 agonists

Agonists of GLP-1 receptor Decrease glucagon Decrease glucose Decrease weight

What does Dexamethasone bind to for its distribution phase in pharmacokinetics

Albumin (weakly even then)

State a drug that can potentiate the CNS depressant activity of TCAs

Alcohol

Give an example of a drug that would decrease vasopressin secretion

Alcohol Glucocorticoids

Give the oxygenation path of alcohol to the product it is excreted as

Alcohol -> Acetaldehyde -> Acetic acid

Explain the mechanism by which alcohol can bring about its euphoric effects acutely

Alcohol binds to the mu receptor on GABA neurones to inhibit GABA release Less GABA means less inhibition on DA release

Summarise the endocrine effects seen from CHRONIC alcohol consumption and the reasons for them

Alcohol increases ACTH leading to Cushing's Negative effect on testosterone secretion

Briefly outline the mechanism of action of aldosterone

Aldosterone diffuses into cell and binds to intracellular receptors bound to chaperone proteins The chaperone proteins detach The aldosterone-receptor complex enters nucleus and transcribes genes

Describe the features of the distal convoluted tubule

Aldosterone inducable sodium channels in apical membrane and Na/K antiporters in basal ADH inducable AQA2 sythesis

What are the two ways in which K+ sparing diuretics can work? i.e. what are the two types/subclasses of K+ sparing diuretics?

Aldosterone receptor antagonists Inhibitors of aldosterone sensitive sodium channels Less sodium reabsorption means less osmotic gradient for water to move out of collecting tubule

Explain why combination treatment for peptic ulcers is the current best practice

All causes for peptic ulcers have the proton pump as the end point in increasing acid production Some causes, e.g. H pylori, also decrease mucus and which makes the gastric lining even more vulnerable so good to treat the ROOT cause

Where is acetylcholinesterase found? Describe its properties.

All cholinergic synapses It has very RAPID action and it is HIGHLY SELECTIVE for acetylcholine

What are the potential unwanted side-effects of potassium iodide treatment

Allergic reactions

Which drug can cause toxicity in the XO pathway

Allopurinol (drug taken for gout) as it inhibits xanathine oxidase

Noradrenaline tend to be more selective to which classes of adrenoceptors, respectively?

Alpha 1 and 2 instead of beta 1 and 2

Which sympathetic effects are regulated by alpha-1 receptors

Alpha 1: Pupil dilation Piloerection (goosebumps) Vasoconstriction Constriction of bladder and constriction of urinary sphincter

Which sympathetic effects are regulated by alpha-2 receptors

Alpha 2: Salivary secretion GI sphincter contraction

How are patients prepped for surgical treatment of a phaechromocytoma

Alpha blockade is the first therapeutic step. Patients may need IV fluids as this commences Beta blockade is then added to prevent tachycardia

Which adrenoreceptor does is targeted by clonidine

Alpha-2 selective

Which adrenergic receptors are responsible for sympathetic responses in vasculature

Alpha1 - constriction Beta2 - dilation

Summarise the different types of pharmacokinetic drug-drug interactions that can occur

Alteration in absorption (e.g. irreversible binding in the GI tract) Protein-binding interactions (releasing protein bound drugs leads to potency increase) Drug metabolism and excretion

Which maternal changes would you see from the first trimester

Altered emotions Altered immune function Altered hormones Altered brain function

State 4 drugs/classes of antibiotics that target protein synthesis. Which is most commonly adopted

Aminoglycosides Chloramphenicol Macrolides - most used Tetracycline

State an example of a frequently used tricyclic antidepressant

Amitriptyline

What is a main barbiturate used?

Amobarbital

How can HBa1C be used to measure blood glucose over time

Amount of HbA1C is measured - HbA1C red blood cells react with glucose irreversibly. As RBCs have a lifespan of 3months+ it is a good measure of long term glycaemic control

Give an example of a polyene

Amphortericin

Give the genetic mutations that lead to early onset Alzheimer's (before 65)

Amyloid precursor protein --> Early onset Alzheimers (symptoms onset before 65yrs old)

What is the difference between opiates and opioids

An opiate is a natural substance derived from poppies Opioids are any substance that has opiate-like effects

What are the two major effects of cocaine?

Anaesthetic effect due to sodium channel blockage Reuptake inhibition of dopamine

List the positive physiological effects of opioids

Analgesia Euphoria Depression of cough centre

What are the 3 main clinically useful properties of NSAIDs?

Analgesic Antipyretic Anti-inflammatory

State 3 types of chromosomal problems that can occur during development

Aneuploidy (too many or too few) Translocations

List some mediators that cause contraction of vascular smooth muscle and the receptors that they act on

Angiotensin 2 on the Angiotensin 1 receptor PGG2 and PGH2 on the T prostanoid receptor Endothelin 1 on the ETa/b receptor

What is the overall physiological difference between anticoagulant drugs, antiplatelet drugs, and thrombolytic drugs in relation to how they affect haemostasis?

Anicoagulants and antiplatelets are drugs involved in slowing down and reducing formations of clots Thrombolytics are necessary to breaking down clots that have already formed

What are the common side effects of dihydropyridines

Ankle oedema (vasodilation) Headache (vasodilation) Palpitations (baroreceptor reflex from vasodilation)

Give the pharmacodynamics of Ethosuximides (how it affects the bdy)

Antagonises T-type calcium channels and thus reduces activity in relay thalamic neurones

Male fertility hormones: where is Luteinising hormone produced?

Anterior pituitary gland

Summarise the mechanisms by which anti-TNF alpha therapy (Infliximab) carry out their therapeutic effect

Anti-TNF alpha reduces activation of TNFa receptors in the gut by mopping up any free floating TNFa befor it can bind Anti-TNFa also binds to membrane associated TNFa, inducing cytolysis in the cells expressing TNFa Activated T cells apoptose

What is the major pleiotropic effect of statins?

Anti-inflammatory effects

In which circumstance are patients going to be more susceptible to the side effects/risks of NSAIDs?

Anti-inflammatory usage (more risk) Analgesic usage (low risk)

State the unwanted/side effects of TCAs at therapeutic doses

AntiPNS effects like dry mouth and constipation Postural hypotenion Sedation

Which type of antibiotics would not be effective against gram -ve enzymes

Antibiotics that target cell walls since gram -ves have thin layers of peptidoglycan anyway

List the drugs used in the treatment of peptic ulcers and summarise their mechanisms of action

Antibiotics: removal of H pylori infection Proton pump inhibitors: e.g. omeprazole - reduce acid production from parietal cells Histamine H2 antagonists: reduce acid production from parietal cells

State which type of anti-haemostatic therapy is targeted towards the initiation stage

Anticoagulants

Give the main effect and effect mechanism of vasopressin

Antidiuretic effect - acts on v2 receptors of renal and cortical and medullary collecting ducts where stimulation and insertion of aquaporin2s occur

What is the major clinical use of diuretics?

Antihypertensive

List the four types of drugs that cause the most serious adverse drug reactions

Antineoplastic (cytotoxic) drugs Cardiovascular drugs NSAIDs/Analgesics CNS drugs

State which type of anti-haemostatic therapy is targeted towards the amplification stage

Antiplatelets

What types of drugs are used to target/prevent the amplification/activation of platelet phase of haemostasis?

Antiplatelets

When do hypos usually occur in T1DM patients?

Anytime but often a clear pattern (e.g. pre-lunch hypos). Nocturnal which are common but not often recognised by the patient

Summarise the 4 features that should be assessed when examining a foot of a diabetic patient

Appearance Feel Pulse Neuropathies

What percentage of bacteria have developed some form of antibiotic resistance?

Approx 70%

What does aromatase convert testosterone into? What does this act on

Aromatase action turns testosterone à 17b-oestradiol. o Acts on ER - oestrogen receptor.

What is the normal daily intake of calcium and how is this removed from the body daily to maintain equilibrium

Around 1000mg of calcium enters the body through the gut every 24 hrs 850mg is lost as faeces and 150mg is excreted through kidneys every 24 hrs Hydroxyapatite crystals in bone can be broken down to increase calcium levels

How does blood pressure affect incidence microvascular complications?

As blood pressure increases, the incidence of microvascular disease increases

How does maternal body temp change throughout pregnancy

As foetus increases in size it contributes to the maternal body temperature leading to its increase

Why is head circumference one of the measurements used to track an infant's growth?

As the brain grows, the fontanelles (unfused skull) allow expansion of the head. If the head isn't growing well, we can infer that the brain isn't growing well. We also want to measure head circumference, to see if there is increased fluid in the head.

Why do we get hyponatraemia and hyperkalaemia in adrenocortical failure

As the lack of cortisol causes hypotension and this stimulates secretion of ADH Cortisol also suppresses ADH so when its levels are low ADH's are high The excess ADH causes increased water uptake and salt wasting Aldosterone levels are lowered so its function of increasing potassium secretion into urine is reduced

Explain countercurrent effect of kidneys

Ascending is imperm to water but perm to ions Descending is perm to water but imperm to ions When interstitium's osmolarity increased from ascending limb pumping, the descending limb increases as its water is pulled out More fluid filling into the tubule pushes readjusts the osmolarity in the descending limb while the ascending limb continues to pump out sodium into the interstitium The new water is again pulled into the interstitium This way water is reabsorbed into the blood

State the antiplatelet drug that inhibits production of thromboxane

Aspirin

What are the antiplatelet therapies given in NSTEMIs

Aspirin and Clopidogrel

State two drugs that can displace TCAs from the plasma proteins most of them are bound to

Aspirin and phenytoin

What is the most likely reason/mechanism that mediates the side effects of aspirin?

Aspirin inhibits COX covalently, not because it is selective for COX-1

Why would use of aspirin not really help against DVT?

Aspirin is an antiplatelet drug Would be effective in arterial thrombi but in venous thrombi you see few platelets

Effects of bethanechol

Assist bladder emptyingEnhanced gastric motility

What is polycystic ovarian syndrome associated with

Associated with increased CVS risk and insulin resistance (diabetes

Summarise the screening and detection used to identify intra-uterine growth restriction (IUGR)

At 24 weeks gestation Blood flow through uterine arteries measured to identify high resistance flow

Identify the key developmental milestones for the social skills domain

At 6 weeks - smiles responsively 12 months - can drink from cup with two hands 18 months - can eat by themselves 2 years - potty trained

Identify the key developmental milestones for the fine motor and vision domain

At 6 weeks - will turn head to follow object At 10 months - has mature pincer grip At 2-5 years - ability to draw without directly copying

How can use of beta-blockers lead to some degree of 'exercise intolerance'?

At low doses b1 selective antagonists will reduced hr and contractility so oxygen demand harder to be met

When does growth stop?

At the end of puberty when the epiphyses fuse

Identify the key developmental milestones for the gross motor skills domain

At time of birth: Limbs flexed in symmetrical posture, head lag on pulling up At 12 months - walks unsteadily At 15 months - walks steadily

State a selective beta adrenoceptor antagonist (and state which beta class)

Atenolol and Nebivolol - selective for beta 1

Explain the advantages of using atenolol over propranolol as an anti-hypertensive

Atenolol is selective for b1 while propanolol has equal b affinities so Has less effect on airways and liver than non-selective drugs

Which non-depolarising NM blocker is given to patients with hepatic or renal impairment and why?

Atracurium (not affected by liver or kidney excretory function, will get hydrolysed by plasma)

What can be given to abolish muscarinic effects

Atropine (competitive muscarinic antagonist)

Which muscarinic receptor antagonists have effects on the CNS?

Atropine and Hyoscine

What type of poisoning is physostigimine used to treat

Atropine poisoning because it increases the synaptic concentration of acetylcholine so it can outcompete the atropine

Give examples of muscarinic receptor antagonists

Atropine. Hyoscine.

What effects do Atropine and Hyoscine have on the CNS in normal and toxic does respectively

Atropine: § Normal dose - little effect. § Toxic dose - mild restlessness à agitation. Hyoscine: § Normal dose - sedation, amnesia. § Toxic dose - CNS depression or paradoxical CNS excitation (associated with pain)

Briefly summarise the HIV life cycle

Attachment and entry (viral capsid endocytosis) Replication and integration (RNA -> DNA) Assembly and release (of viral RNA and essential proteins)

What are the two phases implantation is split up into

Attachment phase - outer trophoblast cells make contact with the uterine surface epithelium Decidualisation phase - changes of the underlying uterine stromal tissue into thick layer of modified mucous membrane

What are the positive symptoms of schizophrenia

Auditory and visual hallucinations Paranoia delusions Denil of thought of oneself

What happens in Graves' disease and what is produced as a result

Autoimmune disease where antibodies bind to and stimulate TSH receptors in the thyroid Results in excess Thyroxine production and a smooth goitre (symmetrically enlarged thyroid gland)

State the two classes of antifungals typically used

Azoles - (inhibits cyp450 involved in membrane ergosterol synthesis) Polyenes - (binds to ergosterol and creates pores)

What would be expected upon examination of a neuro-ischaemic foot? (5)

BASICALLY A COMBO OF ISCHAEMIC AND NEUROPATHIC FOOT numb - due to neuropathy, patient usually can't feel the ulcer dry - indicates autonomic neuropathy (dysfunctional oil/sweat secretion) cold - indicates poor blood supply pulseless - again due to poor blood supply ulcers at points of high pressure loading e.g. ball of foot, AND at the foot margins e.g. at ends of toes

Explain why opioid use (especially chronic) leads to constipation

BASICALLY THERE ARE BARE OPIOID RECEPTORS WITHIN THE MYENTERIC PLEXUS, SO DEPRESSION OF THESE LEADS TO OVERALL LOWER GI MOTILITY --> CONSTIPATION

Briefly describe the mechanism/pathway of tissue damage by glucose

BASICALLY, HIGH GLUCOSE LEADS TO OXIDATION/INFLAMMATION OF TISSUES

How do the different types of insulin treatments for T1DM change their insulin profile throughout the day?

BASICALLY, SHORT ACTING INSULIN FOR MEAL TIMES, AND THEN THERE ARE DIFFERENT TYPES OF INTERMEDIATE (LONG ACTING) INSULINS THAT HAVE BEEN MODIFIED FOR ALTERED METABOLISM TO INCREASE THEIR TIME IN CIRCULATION THESE LONG ACTING ONES HELP TO KEEP A BASAL LEVEL OF INSULIN AND KEEP THE PATIENT GOING BETWEEN MEALS. THE SHOT TYPES AND DOSES CAN BE ADJUSTED TO SUIT MEAL SIZES AND TIMINGS

Why do smokers tend to put on weight after smoking cessation ?

BECAUSE NICOTINE IS A STIMULANT, IT INCREASES METABOLIC RATE (but appetite stays the same). THIS IS ASSOCIATED WITH WEIGHT GAIN.

Give the type of antibiotics that would disrupt peptidoglycan transportation

Bacitracin - inhibits bactoprenol regenration

Summarise the progression of diabetic retinopathy

Background diabetic retinopathy Pre-proliferative diabetic retinopathy Proliferative retinopathy Maculopathy

State the 5 overall mechanisms by which bacteria can develop antibiotic resistance

Bacteria produces another target for drug to affect Bacteria increases enzyme levels to compensate Enzyme alteration so functions despite drug Increased efflex systems to prevent AB entry Production of anti-AB enzymes

What class of drugs are used as sedatives/hypnotics?

Barbituates and Benzodiazepines Sedatives - lower dose Hypnotics - higher dose

What class of drugs are used as sedatives/hypnotics ? Give three examples

Barbiturates and BDZs Temazepam (BDZ) Oxazepam (BDZ) Amobarbital (Barb)

Compare the Method Of Actions of BDZs vs Barbs:

Barbs increase the DURATION of Cl channel opening BZDs increase the FREQUENCY of opening

Compare the selectivity of BDZs vs Barbs: What does this mean clinically?

Barbs less selective so barbs are more dangerous

What are the different types of insulin that are administered to T1DM patients?

Basically short acting for meals, and long acting for a balanced insulin profile throughout the day and inbetween meals

Why do ACE inhibitors have cough as a common side effect (~25% of patients)?

Because ACE also breaks down bradykinin, inhibiting ACE means there is an increased amount/accumulation of bradykinin bradykinin is known to initiate coughs

Why is there poor correlation between plasma cannabinoid concentration, particularly delta9-THC, and the degree of intoxication?

Because cannabinoids are so lipid soluble, they accumulate in fatty tissue, particularly the adipose and brain. They are then released slowly and gradually

Why do diuretics that work later on in the nephron have weaker diuretic effects?

Because diuretics mostly revolve around inhibiting sodium reabsorption which in turn leads to less water reabsorption by reducing the interstitial osmolarity The later on you go into the nephron/tubule, the more sodium has already been reabsorbed so the impact of the drug is less

Briefly describe how polydactylyl occurs

Because infants are still growing/developing/cells dividing a lot so very little, if any, scar tissue persists

Why is adrenaline classed as a physiological antagonist when used as a treatment for anaphylaxis

Because it has physiologically opposing effects to anaphylaxis but doesn't bind the actual histamine receptors

Why does it appear that diabetic patients have reduced incidence of malignancy as a cause of death?

Because most diabetic patients die younger due to other reasons (usually macrovascular disease) before they even have time to develop cancerous malignancies

Alcohol is extremely water soluble, however it can still diffuse across plasma membranes with relative ease. Why is this?

Because the alcohol molecule is so small, that lipid/water solubility doesn't really matter

How come metyrapone has a hypertensive side effect

Because the deoxycortisone that is prevented from being converted accummulates in the zona glomerulosa where it has aldosterone-lik activity (salt retention -> hypertension)

Why is a proton pump inhibitor used in all cases of peptic ulcers?

Because the end point of all 4 receptors/mechanisms involved in gastric acid regulation is the proton pump therefore, PPIs will help treat the ulcer regardless of the underlying cause

Give an example of a Thiazide

Bendrofluazide

What class of drugs are used as anxiolytics?

Benzodiazepenes only

What class of drugs are used as anxiolytics? Give two examples

Benzodiazepenes only Diazepam and Oxazepam

Adrenaline tend to be more selective to which classes of adrenoceptors, respectively?

Beta 1 and 2 instead of alpha 1 and 2

Which sympathetic effects are regulated by beta-1 receptors

Beta 1: Lipolysis Increased renin secretion Increased heart rate and contractability (receptors on san and avn)

Why might isoprenaline not be the ideal treatment for cardiogenic shock

Beta 2 receptor stimulation alongside B1's inotropic effects mean vasodilation, pooling and decreased venous return which can cause arrhytmias (where refractory period of av node is prolonged) combined with tachycardic effects

State two drug classes that decrease contractility of the heart

Beta blockers (reduced phosphorylation and cross bridge formation) Calcium antagonists (stops further entry of calcium into myofibrils)

List 3 drugs/drug types that can decrease heart rate How do they do this

Beta blockers - decrease If and ICa Calcium antagonists - decrease ICa Ivabradine - decrease If All prolong depolarisation duration

Which class of anti-arrhythmic drug (vaughn-williams classification) acts on the part just before the dip of the ventricular membrane potential

Beta blocking class 2s

Give an example of AB resistance where we see production of AB destructive enzymes from bacteria

Beta lactamases hydrolyse C-N bonds in the Beta Lactam rings

What is the 'honeymoon phase' relating to T1DM? What is its clinical significance?

Beta-cell function gradually gets worse in phases. At one point the beta-cell function will decrease to the point of hyperglycaemia and the presentation of symptoms. The patient usually goes to A&E, is diagnosed then given insulin. However it is common for the beta-cell function to rebound slightly. This is important to note as the patient may have to come off the insulin or lower their dose for a few months after their initial diagnosis, after which they will be on insulin permanently. It is important to be aware of the honeymoon phase as wrong dosage of insulin could induce a hypoglycaemic attack

Give the type of antibiotics that would disrupt peptidoglycan incorporation

Beta-lactams (e.g. penicillins) - bind covalently to transpeptidase to inhibit its action

List a GABA-Receptor protein antagonist, and a BDZ-receptor protein antagonist: What is each of their clinical uses?

Bicuculline (pronounced bye-kuk-you-leen) Clinical use = none Flumazenil Clinical use: counteract BDZ overdose

Describe the structure of non-depolarising NM blocking drugs

Big, bulky and have restricted movement around the bonds

What class of drug is Metformin and when is it used?

Biguanide class - oral antihyperglycaemic insulin sensitiser Used in overweight T2DM patients when diet alone doesn't succeed (nearly always) Insulin resistance decreased and therefore peripheral glucose disposal increased

What does RANKL do? What is it inhibited by?

Binds to RANK on osteoclasts and stimulates activation and differentiation Inhibited by Osteoprotegerin - acts as a competitive inhibitor for RANK-L

What is adenosine's mechanism of action

Binds to a2s on vsmc leading to relaxation of smooth muscles Binds to a1s on nodal tissue in heart and normalises tachyarrhythmia to normal sinus rhythm

Give the pharmacodynamics of Levetiracetam (how it affects the bdy)

Binds to synaptic vesicle associated protein (SV2A) - prevents glutamate release

Which of the two major types of depression is typically onset first

Bipolar - normally early adults age onset Unipolar tends to onset later

What are the two treatment options for Paget's disease?

Bisphophonates Simple analgesia

What is the first line treatment for osteoporosis?

Bisphosphonates

Explain why alpha adrenergic receptor blockers can be used as antihypertensive agents

Block a1 mediated vasoconstriction

What is the molecular basis of anti-inflammatory effects of glucocorticoids

Blockade of eicosanoids - arachidonic acid derivatives which act as pro-inflammatory signalling molecules involved in inflammation, immunity and in the CNS

Summarise the mechanisms/physiological effects of ACE inhibitors that allow it to retain sodium

Blocked angII effect on the Kidneys and less aldosterone secretion in adrenal medulla

What can cannabinoid receptor agonists be used for?

Blocking hunger (off market as also caused depression and suicide)

Side effects of ecothiopate

Blurred vision Sweating Respiratory difficulty Hypotension GI disturbance and pain Bradycardia

Side effects of pilocarpine

Blurred visionHypotensionSweatingRespiratory difficultyGI disturbance and pain

How is osteoporosis measured and graded?

Bone mineral density measured by DEXA Osteoporosis = BMD <2.5 SDs or more (i.e. T-score <-2.5).

Are most low birthweight infants as a result of growth restriction or as a result of being born early?

Born early

In which state can albumin bind to drugs? Ionised or unionised?

Both

Which receptor (MR or GR) does cortisol/hydrocortisone mainly act on

Both

How can osteomyelitis and Charcot's foot be distinguished from one another?

Both come across in similar fashions on investigation, but major difference is that osteomyelitis will have infection and/or ulcer and Charcot's foot will not

How is the incidence of autism and ADHD changing?

Both increasing in incidence

Why is botulinum toxic

Botulinum binds to the ACh vesicles and stops them docking with the inner membrane. o Forms SNARE complexes.

What are the common side effects of veramapil

Bradycardia and AV block (calcium channels blocked) Constipation (gut calcium channel blocked)

Where is cannabinoid receptor 1 located?

Brain

What is the mesolimbic pathway responsible for

Brain reward pathway

What conditions does HRT increase the relative risk of? In which women will the risk be higher?

Breast cancer Venous Thromboembolism Stroke Gallstones Risk higher in older postmenopausal women

Summarise the pathogenesis of paraneoblastic cerebellar degeneration (PCD)

Breast tumour recognised by immune system via CDR2 protein - antibodies produced against tumour cells The antibodies end up crossing the blood brain barrier causing an autoimmune immunological disease

Give examples of dopamine receptor agonists

Bromocriptine and Cabergoline

List 5 possible side effects due to usage of beta adrenoceptor antagonists

Bronchoconstriction - life-threatening of airway disease Cardiac failure - problem for ps with heart disease Hypoglycaemia - masking of symptoms, non-selective will also block hepatic glycogenolysis Fatigue - reduced co Coldness of extremities (loss of beta mediated vasodilation)

List the 4 major desirable physiological action of PGE2 and other prostanoids in general

Bronchodilation Renal salt and water homeostasis Gastroprotection Vasoregulation

What is the effect of beta 2 adrenoceptors

Bronchodilation Vasodilation

How does adrenaline treat anaphylaxis

Bronchodilation via Beta-2 Tachycardia via Beta-1 Vasoconstriction via Alpha-1

What are the two main ways that drug molecules move around the body

Bulk flow transfer - is in bloodstream so will move in bulk to the tissues Diffusion transfer - molecule by molecule over short distances

Where is butyrylcholinesterase found? Describe its properties.

Butyrylcholinesterase is found in plasma and most tissues but NOT in cholinergic synapses It has a broad substrate specificity - it hydrolyses other esters e.g. suxamethonium It shows genetic variation

How can you diagnose epilepsy?

By looking at brain activity through: Electroencephalography Magnetic resonance imaging

How do replacement methods of nicotine try to ween people off of cigarettes?

By maintaining a low level of nicotine in the blood - limited effectiveness as the main thing smokers are trying to replicate is the spike in nicotine that they get when they have a puff of a cigarette

How is calcium concentration sensed in the parathyroid glands (and throughout other various organs/parts of the body)?

By the calcium sensing receptor

What is the second step hypertension treatment for patients

CCB or thiaide-like diuretics WITH ACE inhibitor or Angiotensin receptor blocker

Which type of cells are involved in cell-mediated reactions

CD8+ T-cells

State the unwanted/side effects of TCAs at toxic (high) dose

CNS excitement, seizures CVS cardia dysrhythmias

Why does the COX2 selective family to have worse CVS risk compared to non-selective NSAIDs

COX 2 responsible for more CVS regulation

Summarise how aspirin brings about an anti-platelet effect and reduces platelet aggregation

COX1 inhibition reduced TXA2 synthesis Covalent bonding eans permanent inhibition Reduces PGI2 synthesis

Summarise the mechanism that should allow caffeine to theoretically mediate euphoric effects

Caffeine is an adenosine receptor antagonist (adenosine decreased domapine release and tissue response to dopamine) Dopamine and dopamine response therfore increased

State two proteins that some strains of H. Pylori can produce which makes it more virulent

CagA - antigenic VacA - more intense inflammation

What is the main hormone involved in decreasing serum calcium concentration?

Calcitonin - but note that this doesn't have a very significant role

How does calcitonin induce signalling pathways within its target cells?

Calcitonin receptor = transmembrane G-protein linked receptor Activation of adenyl cyclase or phospholipase C as second messenger systems

Why do mechanisms that regulate calcium also tend to regulate phosphate too?

Calcium and phosphate metabolism are linked This is because the calcium stored in your bones is complexed with phosphates to form hydroxyapatite crystals - Ca5(PO4)3(OH) - so they are effectively in an equilibrium - and calcium in your bone is the larget store of calcium

Which drugs are class 4 according to Vaughan Williams classification

Calcium channel blockade

Which class of anti-arrhythmic drug (vaughn-williams classification) acts on the plateau part of the ventricular membrane potential

Calcium channel blockading Class 4s

What is the first step hypertension treatment for patients over 55

Calcium channel blocker or thiazide like diuretic

Why might dating a pregnancy by last-menstrual period be inaccurate?

Can be inaccurate due to irregular periods, abnormal bleeding, oral contraceptives, breastfeeding

What are the benefits of using methyldopa

Can be used as antihypertensive - renal and cns flow are well maintained

Explain why b-blockers would not be the best option for an antihypertensive in patients with Asthma/COPD, diabetes and cardiac failure respectively

Can cause bronchoconstriction in asthmatics Lack of sympathetic drive may remove ability to maintain adequate cardiac output - degree of cardiac failure In hyperglycaemics it masks their symptoms (sweating, palpitations, tremors) and prevents b2 stimulated glycogenolysis

What type of fungal infections do azoles treat

Candidiasis and systemic infections

What are the two major cannabinoids involved in the effects of using marijuana?

Cannabidiol Δ9-THC

What is the most abundant G-protein coupled receptor in the brain?

Cannabinoid receptor 1

What is capacitation of sperm?

Capacitation is where sperm reaches its full activity and fertilising capability following their entry to the female reproductive tract (oviduct)

What happens to the sperm as it enters the uterus and the fallopian tubes

Capacitation where the sperm functionally matures upon entering environment

What are the 3 ways glucose can be directly monitored in diabetic patients?

Capillary glucose levels (dependent on tissue perfusion) Blood testing Using a continuous glucose monitor - measures glucose over 24hr period to fine tune glucose profile

Give examples of thiourylenes and explain what they are used for

Carbimazole and Propylthiouracil - used in the daily treatment of hyperthyroid conditions and work by inhibiting enzymes thyroperoxidase and peroxidise transaminase. Also inhibit the production of antibodies in Grave's disease and reduce the conversion of T4 to T3 in peripheral tissues

H. Pylori can cause peptic ulcers. Which investigations take place, and what would their result be, in an H. Pylori positive peptic ulcer?

Carbon-urea breath test - patient given urea and then their breath is tested for nitrogen that H. Pylori would metabolise the urea to Stool antigen test - testing for H.Pylori antigens in patient's stool

State the unwanted side effects of beta blockers and why that particular side effect might be mediated (5)

Cardiac failure or worsening (b1) Bradycardia (b1) Bronchoconstriction (b2) Hypoglycaemia (b2)

What is the effect of beta 1 adrenoceptors

Cardiac stimulation, renin release

What is dobutamine used to treat

Cardiogenic shock - but you still must be very careful - it is still capable of causing arrhythmias

What is isoprenaline used to treat

Cardiogenic shock Acute heart failure Myocardial infarction

State a drug that is a non-selective antagonist for alpha/beta adrenoceptors

Carvedilol - non selective for both alpha1, beta1 and beta 2

What are COMT and MAO

Catecholamine degrading enzymes

What happens in pituitary apoplexy

Caused by presence of a pituitary adenoma - leads to infarct of the pituitary gland like in Sheehan's syndrome

Why does giving a muscarinic agonist to someone with angle closure glaucoma help

Causes constriction of the sphincter pupillae and opens up the angle to increase drainage of intraocular fluid

Why should haemorrhagic strokes not be treated with thrombolytics

Causes further bleeding

What physiological effects does Phentolamine have

Causes vasodilation and fall in blood pressure due to a1 blockade. However, simultaneous blockade of a2 receptors tends to increase NE release which enhances the reflex tachycardia that occurs. Increases GIT motility and diarrhoea is a common occurrence - no longer clinically used.

What features of the cell in the descending limb make it permeable to water

Cells have loose tight junctions Not many mitochondria Don't pump ions

State and describe the 3 phases by which normal foetal growth is characterised by

Cellular hyperplasia - increased cell division (happens rapidly in the first 4-20 weeks) Hyperplasia and hypertrophy - cell division slows down and we see an increase in cell size Hypertrophy alone (28-40 weeks)

What are the two type of diabetes Insipidus and differentiate between them

Central (cranial) diabetes insipidus is due to the absence/lack of circulating vasopression, caused by a problem in the production/release of vasopressin from the neurohypophysis. Nephrogenic diabetes insipidus results from end-organ resistance to vasopressin, either through a lack of V2 receptors, or mutated receptors, or problems with the post-receptor intracellular mechanisms

What will be the result of a fluid deprivation test in a patient with diabetes

Central diabetes there is a lack of central production of vasopressin

Give the aetiology of central/cranial diabetes insipidus

Central/Cranial is caused by anything that leads to damage of the neurohypophysis. This can be due to injury, surgery, central thrombosis, tumours (intrasellar and suprasellar), and also granulomatous infiltrations of the median eminence

Explain the central mechanisms by which opioids mediate their anti-tussive effects

Central: 5HT1A-receptor antagonist: 5HT1A-receptor is a negative feedback receptor for serotonin Seratonin in the cough centre inhibits coughing By reducing firing of 5HT1Ar we see increased seratonin release and thus less coughing

Give the two subclasses of beta lactams

Cephalosporins Carbapenems

What are the main parts of the brain that are affected by Mu opioid receptors?

Cerebellum Nucleus Accumbens Important to pain and sensation

What are the main parts of the brain that are affected by Delta opioid receptors?

Cerebral cortex Nucleus Accumbens Motor and cognitive function

How do genetic and environmental factors affect the onset of T1DM?

Certain genetic abnormalities can be detected in patients that make them more susceptible to T1DM Higher prevalence of T1DM in winter months and certain places in the world suggesting there may be an influence from a viral pathogen

What physiological product bars sperm from entering the cervix

Cervical mucous - usually hostile to sperm and will form a physical barrier This changes at midcycle to permit sperm to enter uterus

State 3 drug interactions to be aware of with MAOIs

Cheese reaction (Tyramine + MAOIs) ->hypertensive crisis MAOIs + TCAs -> hypertensive episodes MAOIs + Pethidine -> hyperpyrexia (high fever)

What are the three main categories of tertogens

Chemical, physical, infectious

Summarise the mechanisms of chemotherapy induced nausea and vomiting (CINV)

Chemotherapeutic agents like cisplatin are toxic to the lining of the stomach Enterochromaffin cells are destroyed leading to the release of free radicals and therefore excessive 5HT (seratonin) release The excessive seratonin causes increased activity of the solitary tract --> increased activity of the VC --> NAUSEA AND VOMITING.

Which enzyme converts HDL to LDL?

Cholesteryl ester transfer protein

State two types of muscarinic receptor agonists and give an example of each.

Choline esters Alkaloids

Where is choline acetyltransferase exclusively found

Cholinergic nerve terminal

Summarise the mechanism of the effects on the liver leading to fatty liver as a result of chronic alcohol consumption

Chronic abuse of alcohol leads to depletion of NAD+ Causes pyruvate conversion to lactate and acetyl coA conversion to ketones Fat and lipid metabolism impaired Build up of fats in the liver

How does chronic alcohol use lead to hepatitis?

Chronic alcohol leads to permanent disruption of Krebs cycle Acidosis, ketosis and generation of oxygen free radicals occur leading to the creation of a proinflammatory environment. Hepatitis describes these changes

Which form of nicotine administration has the lowest bioavailability?

Cigarettes

Which class of anti-arrhythmic drugs are beta-blockers?

Class 2 anti-arrhythmic

How does vaginal mucus production change throughout pregnancy?

Clear mucus is produced throughout the pregnancy

For what process is the HIV protease necessary

Cleaves Gag precursor to active Gag which enables normal assembly and release since it is an essential structural protein

What are the clinical features of a phaechromocytoma and why is it classed as a medical emergency

Clinical features include hypertension in young people and episodic severe hypertension. This can cause myocardial infarction or stroke, and high adrenaline can cause ventricular fibrillation and death making it a medical emergency

Give symptoms of polycystic ovarian syndrome

Clinical features include: Hirsutism. Menstrual cycle disturbance. Increased BMI.

Describe how clomiphene treats polycystic ovarian syndrome

Clomiphene binds to the oestrogen receptors in the hypothalamus and blocks normal negative feedback resulting in an increase in GnRH and gonadotrophin secretion.

State the antiplatelet drug that prevents platelet activation

Clopidogrel

Describe the similarities/differences in structure between codeine and morphine and how this affects its activity

Codeine has a methyl group at position 3 instead of a hydroxyl group A hydroxyl group needs to be present at position 3 for binding to occur Codeine must therefore undergo some metabolism in order to be lipophilic and enter the brain having action there

/what is the mechanism of action of tubocurarine

Competitive nAChR antagonist -70-80% block will prevent reaching of threshold

What type of NM blocking drug is tubocurarine

Competitive/non-depolarising

Which type of extra chromosomal aneuploidy tend to have more severe syndromes: Partial/mosaic or complete trisomy?

Complete trisomies

Summarise the development of the conceptus into the blastocyst

Conceptus = fertilised ovum Conceptus divides as it travels down the fallopian tubes (3-4 days), receiving nutrients from uterine secretions The conceptus compacts to a morula and then forms a blastocyst of 2 separate cell populations: the inner mass becomes the embryo while the outer trophoblast becomes the placenta

What are the general side-effects of BDZ?

Confusion, amnesia, ataxia Potentiate other CNS depressants

Define zero-order kinetics in the context of drug excretion

Constant amount of a drug is removed from the body per unit time regardless of how much of the drug is still in the body

Define binge drinking

Consuming more than 8 units of alcohol in one sitting

Effect of muscarinic stimulation of the eye

Contraction of ciliary muscle to accommodate for near vision Constriction of sphincter pupillae (circular muscle of the eye) - this constricts the pupil and increases drainage of intraocular fluid Lacrimation - flow of tears

Give the non-major actions of vasopressin

Contraction of non-vascular smooth muscle (e.g. gut motility) via V1a receptors Increased ACTH secretion via V1b receptors Increased Factor VIII and von Willebrand factor production (possible haemophilia treatment) via V2 receptors

What are the implications of renal artery stenosis?

Contributes to hypertension and renal failure Can permanently damage renal function

How do men produce almost all of their oestrogen?

Conversion of testosterone to oestrogen by aromatase

Which regions of the brain does alcohol affect

Corpus callosum (passes infrom from left to right brain) Hypothalamus Reticular activating system Hippocampus Cerebellum Basal Ganglia

List the 3 types of bone and their respective properties

Cortical bone - found around outside and is hard Trabecular - found on the inside where it is spongy Cortical and trabecular are both formed in a strong lamellar pattern where fibrils laid at alternate orientations Woven bone - weaker where fibrils laid randomly

Explain how a 24 hour urine collection test can help determine whether a patient has Cushing's

Cortisol is usually highest at 9am and lowest at midnight if asleep in normal patients, but in Cushing's syndrome the cortisol levels are constantly high

What is the retinal feature of pre-proliferative diabetic retinopathy?

Cotton wool spots (soft exudates i.e. soft edges) - indicates general retinal ischaemia

What are the two forms of inhalational cocaine?

Crack (alkaline solvent) Freebase (non-polar solvent)

Region of the gut affected in Crohn's vs Ulcerative colitis

Crohn's = Any part UC = Rectum spreading proximally

Presence of abcesses and fissures in Crohn's vs Ulcerative colitis

Crohn's = common UC = uncommon

Describe the inflammation in Crohn's vs Ulcerative colitis

Crohn's = patchy UC = continuous

Which gut layers are affected in Crohn's vs Ulcerative colitis

Crohn's: All layers UC: Mucosa and submucosa

Summarise the effectiveness of aminosalicylates in ulcerative colitis and Crohn's disease respectively

Crohn's: Ineffective in inducing remission but help maintain surgically induced remission UC: Effective at induction and maintenance of remission

How is azathioprine used in ulcerative colitis and crohn's disease respectively?

Crohn's: Only maintain remission UC: Some success but no real reason to use over mesalazine

State the autoimmune mediators and cytokines involved in ulcerative colitis and Crohn's disease respectively

Crohn's: Th1-mediated, TNF-alpha UC: Th2-mediated, IL5 and IL13

Explain the difference between cumulative height and height velocity

Cumulative - height which denotes the total of all the growth they've done so far Height velocity - how fast a child is growing in cm per year

What are the potential causes of cushing's

Cushing's can be caused by taking too many steroids a pituitary tumour (which causes Cushing's disease) an ectopic tumour (e.g. in the lung) secreting ACTH an adrenal adenoma secreting cortisol.

Give the condition associated with excess corticotrophin (ACTH)

Cushing's disease

List 3 syndromes associated with obesity

Cushings syndrome Prader Willi syndrome Lawrence-Moon-Beidl syndrome

Summarise and explain the ACUTE effects of alcohol on the CVS and vasculature

Cutaneous vasodilation (calcium entry impaired, prostaglandins promoted) Increased heart rate (diminished control of arterial baroreceptors, SNS dominance)

HRT can be administered in a cyclical fashion or a combined continuous fashion. What does this mean?

Cyclical - oestrogen given every day while progesterone given in the last 12-14 days of the month Continuous combined - oestrogens and progestogens given continuously all the time.

What enzyme system is extremely important to drug metabolism and where are these enzymes found?

Cytochrome P450 - a family of 57 enzymes that are mainly found in the liver and are capable of metabolising a lot of xenobiotics

Describe Dopamine metabolism

DA removed from synaptic cleft by dopamine transporter and noradrenaline transporter Can be metabolised by Monoamine Oxidase A and B and Catechol-O-methyl transferase

State two molecules important in the synthesis of nucleic acids in bacteria and state the enzymes involved

DHOp synthase converts PABA to produce DHOp (this is sequentially converted to DHF) DHF reductase converts DHF to produce THF molecules = DHOp and THF enzymes = DHOp synthase and DHF reductase

Explain the mechanism by which Disulfiram can be used as alcohol aversion therapy

DISULFIRAM is a drug that BLOCKS aldehyde dehydrogenase - it is used in alcohol aversion therapy - If this is given to alcoholics, whenever they drink alcohol, acetaldehyde builds up --> toxic/nausea effects --> PUTS THEM OFF (sometimes/hopefully)

Which enzyme is used in the DOPA -> Dopamine reaction

DOPA decarboxylase

Which enzyme breaks down GLP-1?

DPP4

Give an anticoagulant that works by inhibiting factor 2a

Dabigatran

State a low molecular weight heparin

Dalteparin

What causes the redness seen in inflammation

Damaged cells release histamine which lead to vasodilation of blood vessels > increased blood > heat + erythema (redness)

Indicate how parasympathetic stimulation promotes repolarisation

Decrease in cAMP, increase in potassium channels

What are the main muscarinic effects on cardiovascular system

Decrease in heart rate Decrease in cardiac output (due to decreased atrial contraction) Decrease in total peripheral resistance (due to vasodilation) Decrease in blood pressure

Summarise the mechanism of action of aminosalicylates used for IBD therapy

Decrease of antibody secretion Non-specific cytokine inhibition Reduced cell migration

How should T2DM patients change their diet to improve outcomes and prevent progression of the disease?

Decrease total number of calories Reduce refined carbohydrate Increase the amount of complex carbohydrate Reduce fat Increase unsaturated:saturated fat content Increase soluble fibre

How come thiazide use has a vasodilatory effect with chronic use?

Decreased Total Peripheral Resistance by activation of eNOS and calcium channel antagonism

What signalling pathway does stimulation of a2 adrenoreceptors induce?

Decreased cAMP (inhibitory g protein coupled receptor) so phosphorylase kinase can't phosphorylate

What effect does muscarinic stimulation have on the heart and what is the mechanism for this

Decreased cardiac output Binding of AC to M2 (Gi protein linked receptor) -> decrease in cAMP production -> decrease in Ca2+ influx, which leads to a decrease in cardiac outpu and increase in K+ efflux, which leads to a decrease in heart rate

How does bone mass change with age?

Decreases after 30 years old for both men and women, but exacerbated post-menopause due to loss of oestrogen

Effect of drug metabolism on: Half-life Exposure duration Drug accummulation in body

Decreases half life and exposure duration Prevents drug accummulation

How does drinking alcohol on a full stomach affect the speed of onset of intoxication?

Decreases it as the rate of gastric emptying will decrease

What are the cognitive defects of shizophrenia?

Defecits in memory, planning, decision making

Describe the impact of the microbiome in the pathology of IBD

Defective interaction between mucosal immune system and gut flora - infection Disrupted innate immunity and impaired clearance - more pathogenic bacteria and less commensal/anti-inflammatory Pro-inflammatory compensatory responses which lead to physical damage and chronic inflammation

What are the leading congenital causes of GH deficiency in children

Deficiency of hypothalamic GHRH Mutations of the GH gene (very rare) Developmental abnormalities (e.g. aplasia or hypoplasia of the pituitary)

What is meant by delay and disorder of childhood development respectively?

Delay - slow acquisition of skills. Disorder - mal-development of a skill.

Summarise the mechanisms and pathways involved in the pathophysiology of gastroparesis causing nausea and vomiting

Delay in emptying means reduced stomach contraction which means reduced seratonin release

What is gastroparesis?

Delayed emptying of the stomach

What type of NM blocking drug is suxamethonium

Depolarising

Explain the mechanism by which opioids cause euphoria

Depress firing rate of GABA interneurons More dopaminergic neurone activity Increased dopamine leads to increased feelings of reward

List the negative physiological effects of opioids

Depression of respiration Simulation of chemoreceptor trigger zone (nausea/vomiting) Pupillary constriction GI Effects

Define what is meant by psychosis and psychotic disorders

Derangement of personality and loss of normal social functioning

Summarise the transport that occurs in the descending limb of the loop of henle

Descending limb - only H2O reabsorption via AQA molecules.

What is desmopressin (DDAVP) and what is it used to treat

Desmopressin is a V2 analogue agonist (longer lasting V2 equivalent of vasopressin) It is used to treat: Cranial diabetes insipidus Nocturnal enuresis (involuntary urination) Haemophilia

Give the role of the Subtantia Gelatinosa in the modulation of pain tolerance and perception

Determines the level of inhibition necessary on the sensory neurones from the nrm

Which glucocorticoid analogue has the longest duraction of action and which has the shortest

Dexamethasone has the longest Hydrocortisone has the shortest

Explain how a low dose dexamethasone suppression test can help determine whether a patient has Cushing's

Dexamethosone is an artificial steroid - normal patients will respond by suppressing cortisol levels so zero, but Cushing's patients will fail to supress their cortisol levels

How does varying degrees of glycaemic control affect microvascular complications?

Diabetes damages your blood vessels mainly in eyes, kidneys and feet. The worse your glucose control the higher the risk of microvascular complications

What is the main condition associated with a lack of vasopressin

Diabetes insipidus

What is diabetic amyotrophy?

Diabetic amyotrophy is a disabling illness that is distinct from other forms of diabetic neuropathy. It is characterized by weakness followed by wasting of pelvifemoral muscles, either unilaterally or bilaterally, with associated pain.

What is the main cause of visual loss in people in people of working age?

Diabetic retinopathy

What is the relation between having diabetes and MI

Diabetics are at higher risk of ischaemic heart disease than normal people are

What are the two main sources of vitamin D (cholecalciferol)?

Diet Sunlight (UV converts 7-dehydrocholesterol to cholecalciferol)

How can a drug move through a cell's lipid membrane

Diffusion through lipid membrane or aqueous pore Carrier molecules Pinocytosis

Give examples of non rate-slowing calcium antagonists

Dihydropiridines

What is the most commonly used non rate-limiting calcium channel blocker

Dihydropyridines

What are the two types of CCBs? Which one is used to treat hypertension and why?

Dihydropyridines and nonDihydropyridines DHPs used to treat hypertension as have a selective effect on vasculature to decrease TPR

Example of a chemical antagonism:

Dimercaprol is a chelating agent that enables formation of heavy complexes that are excreted more easily by the kidneys

Two types of cholinomimetic drug

Directly Acting - muscarinic agonists Indirectly Acting - acetylcholinesterase inhibitors -> increase the synaptic concentration of acetylcholine

Summarise how NSAIDs cause peptic ulcers

Directly cytotoxic so reduces mucus production and inhibit COX for prostaglandins necessary for mucus production Increases acidity -> Peptic ulcer

Explain the mechanism by which opioids cause miosis (pupil constriction)

Disinhibitory effect on mu-opioid receptors More stimulation of pupillary constriction in the Edinger-Westphal nucleus

What classifies as a secondary endocrine gland disease

Disorder at the anterior pituitary

What classifies as a primary endocrine gland disease

Disorder at the endocrine gland itself

What classifies as a tertiary endocrine gland disease

Disorder at the hypothalamus

Summarise and explain the acute endocrine effects of alcohol

Diuresis (alcohol dehydrogenase suppresses vasopressin release, less water reabsorption, increased urine)

Explain why diuretics commonly lead to hyperuricaemia

Diuretic drugs use the organic anion transporter to enter the tubule and compete for this transporter with uric acid in the blood A greater concentration of uric acid results in the blood

State the 4 different types of childhood developmental delay that can occur

Domain-specific or global Consonant (domains affected equally) or dissonant (domains affected unequally)

Anticholinesterases used to treat Alzheimer's

Donepezil Tacrine

Summarise the 4 drugs used to treat Alzheimers:

Donepezil - reversible cholinesterase inhibitor Rivastigimine - pseudoreversible cholinesterase inhibitor Galantamine - reversible cholinesterase inhibitor Memantine - noncompetitive NMDA receptor (glutamate receptor) blocker

What can Monoamine Oxidase B metabolise

Dopamine

Which receptors can dopamine act on?

Dopamine (DA) can act on D1,5(Gs linked) or D2-4 (Gi-linked) receptors

What can cause hyperprolactinaemia?

Dopamine antagonist drugs § Prolactinoma. § Stalk compression due to pituitary adenoma. PCOS. § Hypothyroidism - primary. § Oestrogens, pregnancy and lactation

Which enzyme is used in the Dopamine -> Noradrenaline reaction Where does this last reaction occur

Dopamine beta-hydoxylase Vesicle

How can hyperprolactinaemia be treated

Dopamine receptor agonists that decrease prolactin and GH release as well as reduce pituitary tumour sizes

Which enzyme causes the reuptake of dopamine?

Dopamine transporter

Summarise the mechanism by which cocaine mediates its euphoric effects

Dopamine transporters on the receiving neuron will flip the dopamine molecules back into the pre-synaptic cell Cocaine will block the dopamine transporters on the presynaptic cell so dopamine stays in synapse Euphoric feeling prolonged

What can Monoamine Oxidase A metabolise

Dopamine, Noradrenaline and Seratonin

What is used to assess uterine blood flow

Doppler ultrasound techniques

State the major targets for opioids in relation to pain modulation

Dorsal horn and periphery - increase inhibition. (targets the substantia gelatinosa specifically) PAG - enhance firing. NRPG - activates.

Summarise the virology/structure of Herpes Simplex Virus

Double stranded DNA virus Surrounded by a tegumet and enclosed in a lipid bilayer

Summarise the effects of PGE2 on the stomach and how the use of NSAIDs affects this

Downregulates HCl secretion Stimulates bicarbonate and mucus secretion NSAIDs therefore increase risk of stomach and gut ulceration

Give the side effects of prazosin

Dramatic hypotensive effect

What happens in the first step of the oxidation cycle of cytochrome 450?

Drug binds to the iron in the catalytic site of the Cyt P450. An electron is then fed in from NADPH which turns the ferric ion into a ferrous ion (Fe3+ to Fe2+)

What forms may a pharmacokinetic antagonism reduce drug concentration by

Drug concentration is reduced by reducing absorption, increasing metabolism or increasing excretion e.g. Amobarbital

Where do most drug elimination interactions occur?

Drug elimination interactions almost always occur in the renal tubules

What are the long term treatment methods that are used to follow immediate intervention for SIADH

Drugs which prevent vasopressin action in the Kidneys (e.g. lithium, di-methyl-chlor-tetracycline, and also V2 receptor antagonists)

Explain the advantages and disadvantages of using carvedilol over atenolol/propranolol as anti-hypertensives

Dual acting b1 and a1 agonist so will affect the tpr as well as heart More effect antihypertensive despite more side effects

What could be the causes of hypopituitary dwarfism?

Due to a lack of somatotrophin. Result of: Genetic determination; Malnutrition; Emotional deprivation; Endocrine disorders

Why is there increased pigmentation when there is adrenocortical deficiency

Due to cortisol deficiency there is high ACTH production ACTH is produced following modification of the precursor POMC POMC also gives rise to MSH so when there is high ACTH we also get high MSH

Why do opioids that are administered orally have quite a low bioavailability?

Due to extensive first pass liver metabolism

Why might usage of beta-blockers cause fatigue in the patient?

Due to reduced cardiac output and reduced skeletal muscle perfusion (due to beta-2 blockade on vasculature).

Which period of pregnancy is maternal blood pressure usually the lowest? What is the implication of this?

During second trimester - high risk of maternal fainting so pregnant women should not be standing for prolonged periods of time

What can the metabolic complications of T2DM lead to

Dyslipidaemia (abnormal handling of cholesterol) which then leads to macrovascular complications

List the modifiable risk factors for macrovascular disease (4)

Dyslipidaemia, high BP, smoking, diabetes

List the symptoms and signs of autonomic neuropathy

Dysphagia (problems swallowing), constipation, bladder dysfunction, postural hypotension

List the 4 receptors that PGE2 can activate

EP1 to EP4

What type of IUGR is highly correlated to pre-eclampsia

Early IUGR

What are the major two metabolites of cocaine?

Ecogonine methyl ester Benzoyl ecgonine

Define pharmacodynamics

Effect and mechanisms of action of drugs on the body

What does N-demethylation do to a drug

Effectively removes the pharmacological activity

Describe how the effect of growth hormone replacement therapy will change over time

Effects are most prominent in first year and then this decreases due to increasing resistance in the body to the replacement hormone (antibody formation)

What are the two ways that the start of a pregnancy are determined/defined as? Explain the clinicial implications of these different definitions

Either from the last menstrual period (conventional) OR From the point of fertilisation The advice given will largely depend on the gestational age - for this to be effective the right time frame will need to be used

Summarise the metabolism of codeine

Either metabolised by CYP2D6 - slow CYP3A4 - fast

How does cocaine influence sweat production and cutaneous vasodilation?

Elevates threshold for sweating and cutaneous vasodilation threefold

Why is leg length one of the measurements used to track an infant's growth?

Enables detection of proportional growth

What is the body's natural form of THC?

Endogenous anandamide - binds to cannabinoid receptors and downregulates adenylate cyclases (depressant activity)

State the key phases and their durations of the endometrial cycle within the menstrual cycle

Endometrial cycle: • menstrual phase (5 days), • repair and proliferative phase (9 days), • secretory phase (13 days).

Where in a cell do you find Cytochrome P450 enzymes and flavin(w/monooxy)

Endoplasmic reticulum

List 3 endogenous agonists of opioid receptors

Endorphins Enkephalins Dynorphins/neoendorphins

What are the three stages of atherosclerosis development

Endothelial dysfunction Fatty acid streak formation Complicated plaque formation

State the two HIV entry inhibitor drugs

Enfuvirtide Maraviroc

Explain why maternal appetite tends to alter throughout pregnancy

Enlarged uterus will push on the GI tract including stomach and reduce its distensibility - will lead to preference of numerous smaller meals rather tha one big one Cravings might occur for foods that contain required nutrients

How do COMT inhibitors work?

Entacapone and Tolcapone Increased amounts of levodopa

What is enteral and parenteral administration

Enteral = using the GI tract Parenteral = using anything except the GI tract

What is apotential problem of biliary excretion of drugs?

Enterohepatic recycling - the drug may return to the liver so there is drug persistence

How do thyroid hormones interact with cells

Enters the cell and has a specific intracellular receptor that it binds to that then affects DNA production to regulate cell activities

What are the three ways that drugs can interact with enzymes

Enzyme inhibitors False substrate - chemical compound which closely imitates the action (e.g.methyldopa used to replace norepinepherine) Prodrugs - precursor to active drug version that is formed after metabolisation by interaction with enzyme

Give the aetiology in cases of congenital adrenal hyperplasia

Enzymes in the steroid synthesis pathway fail to work

Where is sperm stored prior to ejaculation?

Epididymis

What happens with chronic/complicated chronic peptic ulcers as opposed to uncomplicated

Epigastric pain and burning session instead of just after meals

What component of the fungal cell wall/membrane is usually targeted?

Ergosterol which is found in cell membranes

Describe the 2 types of dopamine receptor agonists and give examples for each type

Ergot derivatives (Bromocriptine and Pergolide) Non-ergot derivatives (Ropinirole and Rotigotine)

Give the two main types of hydrolysis enzymes

Esterases and amidases

How does ethnicity play a role in CHD prediction? Which ethnicity is affected most?

Ethnicity may increase risk despite having the same BP and cholesterol South Asians are affected most

How often does each ovary release a secondary follicle

Every 56 days (the two ovaries alternate)

Give two causes of vitD toxicosis

Excessive vitD deficiency treatment Granulamatous disease like sarcoidosis - macrophages produces excessive 1-alpha hydroxylase

What is the mesocortical pathway responsible for

Executive functions and complex behavioural patterns

Briefly summarise and describe the exogenous pathway of lipid metabolism

Exogenous pathway - Lipids enter blood following ft absorption from diet Chylomicrons broken down by lipases into chylomicron remnants

What are the autoimmune symptoms of graves disease

Exopthalmos (antibodies bind to muscles behind eyes to cause swelling) Pretibial myxoedema (hypertrophy) - leads to non-pitting swellings in the shin area

Denosumab is a more effective drug than bisphosphonates at treating osteoporosis, but why is denosumab the second line treatment to bisphosphonates?

Expense

Why are patients that are given radioiodine treatments advised to avoid pregnant women and children

Exposure can have teratogenic effects (disruption of growth + development of fetus)

Give the mechanism of action of suxamethonium

Extended end plate depolarisation results as suxamethonium isn't metabolised as rapidly as ACh so there is a depolarisation block of the NMJ that is called a phase 1 block

Summarise the principle side effect profile of dopamine receptor antagonists

Extra pyramidal side effects

What are the possible side effects of Metformin

Extremely safe - possible risk of GI problems. Could exacerbate renal, cardiac and liver failure.

In what order does flaccid paralysis from tubocurarine affect the muscles

Extrinsic eye muscles -> small muscles of face, limbs and pharynx -> respiratory muscles

What causes the swelling seen in inflammation

Exudation of plasma + leukocytes > swelling (local oedema)

How is phenylepherine normally administered

Eye drops, IV, Intranasal administration

Which factors does antithrombin deactivate

F10a and F2a

Where does fertilisation normally occur

Fallopian tube

Which patients are most in need of PCSK9 inhibitors

Familial hypercholesterolaemia

Give the aetiology of nephrogenic diabetes insipidus

Familial or caused by drugs like lithium and DMCT

Why is cocaine so addictive?

Fast onset so powerful behavioural stimulus Fast breakdown so desire to binge consume

What is the biological half life of isoprenaline

Fast plasma half-life of 2 hours

What does Raloxifene increase the risk of?

Fatal stroke and venous thromboembolism

What is Felypressin and what is used for

Felypressin is a V1 analogue agonist Used to prolong the action of local anaesthetics (anaesthetic effect concentrated as blood flow out of the area is decreased)

Why can methadone be used to ween someone off of heroin and fentanyl cannot?

Fentanyl cleared really fast as metabolism only needs one enzyme Methadone meabolised by several enzymes so clearing takes longer time Methadone persists in body for longer so prevents need for constantly readministering

Summarise the metabolism of fentanyl

Fentanyl is predominantly converted by CYP3A4-mediated N-dealkylation to norfentanyl, a nontoxic and inactive metabolite

What is the timescale of onset of effects from cocaine?

Few seconds

Summarise the benefits and drawbacks of using budesonide over prednisolone in Crohn's disease?

Fewer side effects Less effective at inducing remission in active Crohn's.

Summarise the unwanted effects and negative drug-drug interactions of SSRIs

Fewer than MAOIs and TCAs Nausea and diarrhoea, (10% of patients) insomnia, loss of libido (30% of patients)

What is FGF-23 and what does it do?

Fibroblast growth factor 23 It is a molecule/hormone released by osteocytes, in response to calcitriol.

What is the pattern of insulin secretion in response to a meal?

First phase response - stored insulin that is ready to be released when stimulated. Second phase response - produced and secreted insulin over time to maintain levels and store away

What is the order of channels opening during the upstroke of the action potential

First the hyperpolarisation-activated channels (If) open to allow sodium in This initial positive turn is then propagated by T calcium channels The major arm of the upstroke is facilitated by the L type calcium channels Once AP reaches above 0 the potassium channels open and repolarisation begins

When is the fastest growth phase in a child's life

First two years of life

Describe what happens when you have a Flavin deficiecy

Fish odour syndrome - Trimethylamine produced in the GI tract as a product of protein metabolism - smells horrible Flavin with monooxygenases is required to to convert trimethylamine into trimethylamine N-oxide which is odourless and excreted in urine

What is the physiological effect of tubocurarine

Flaccid paralysis

What are the side effects of alpha glucosidase inhibitors?

Flatulence

Which enzyme catalyses the N-oxidation reaction

Flavin containing monooxygenases

Describe the structure of depolarising NM blockers (suxamethonium)

Flexible and rotatable pair of ACh molecules that can each bond to one of the alpha subunits on the nAChR and stimulate th receptor

Give an example of an azole

Fluconazole

What are the unwanted effects of desmopressin

Fluid retention and hyponatraemia

What is used to antagonise he BDZ effect

Flumazenil

What is the most commonly prescribe anti-depressant?

Fluoxatene (aka prozac)

State a common SSRI

Fluoxetine

Which class of antibiotics target bacterial DNA replication?

Fluroquinolones - inhibit DNA gyrase and topoisomerase which are needed for DNA to release its tension and become open to replication

Summarise the need for an altered maternal immune system during pregnancy.

Foetus is a non-self entity and so needs to suppress antibodies that might attack this

What happens to the production of progesterone in late stage pregnancy when it is time for parturition

Foetus reaches a certain size, the production of steroids is switched from production of progesterone to production of oestrogen

How can anencephaly be prevented

Folate supplementation similar to what is used to prevent spina bifida

List some stimuli that induce the mesolimbic pathway

Food, exercise, sex

How does the yellow card scheme (ADR detection system) apply for established and newly licensed drugs respectively?

For established drugs only serious ADRs reported For newly licensed drugs any ADRs reported

Where is parathyroid hormone secreted from?

From parathyroid glands

List the 4 major routes of administration for drugs of abuse with speeds of absorption of each

From slowest to fastest: Eat or drink (oral) - very slow absorption Snort (intranasal) - slowed by mucous membranes Inject (intravenous) - rapid (seconds) Smoke (inhalational) - rapid (seconds)

What is a full agonist? Partial agonist?

Full = max response Partial = less than max

What is meant by an orally active drug

Function retained post-stomach acid digestion

Give an example of a loop diuretic

Furosemide

What type of receptors are adrenergic receptors

G-protein coupled receptors

What type of receptor is the parathyroid hormone receptor?

G-protein linked receptor

Explain the mechanism by which opioids lead to sensations of nausea and vomiting

GABA keeps the Chemoreceptor Trigger Zone suppressed - Mu opioid receptor activation in the CTZ switches this inhibition off. The CTZ then sends more signals to the medullary vomiting centre, and you feel nauseous.

Describe the full metabolism of GABA:

GABA to Succinic Semialdehyde via GABA-Transaminase Succinic Semialdehyde to Succinic Acid via Succinic Semialdehyde Dehydrogenase

What are the two enzymes involved in GABA metabolism, and where are they each located?

GABA-T & SSDH are mitochondrial

Summarise the mechanism of action of GH-IGF1 axis

GH from anterior pituitary binds to GH receptor on liver (to produce IGF1) or directly on other tissues to bring about direct effects (most bind to liver though) IGF1 has paracrine and autocrine effect - stimulate osteoblasts to divide and grow making bones longer and stronger

What have NSAIDs been shown to increase the risk of?

GI and CVS related morbidity and Mortality

Where do reduction reactions occur in the body and why there?

GI tract - low oxygen environment and residence of bacterial enzymes that act as reductases

What is the enzyme that adds the fatty octanol group to ghrelin? Why is this done?

GOAT - Ghrelin O-acyltransferase is responsible for adding the fatty acid group to ghrelin - this enables it to cross the blood brain barrier

Distinguish between the mineralocorticoid receptor and the glucocorticoid receptors in terms of their affinity for cortisol

GR - low affinity MR - High affinity (but generally not activated, as most cortisol present in the circulation near MR receptors has been converted to inactive cortisone by 11β-hydroxysteroid dehydrogenase)

Distinguish between the mineralocorticoid receptor and the glucocorticoid receptors in terms of their steroid specificity

GRs - Selective for glucocorticoids MRs - Do not distinguish between cortisol + aldosterone

Give the symptoms of hyperprolactinaemia in women

Galactorrhoea (milk production) Secondary amenorrhoea or oligomenorrhoea Loss of libido Infertility

Give the symptoms of hyperprolactinaemia in men

Galactorrhoea (uncommon since appropriate steroid background usually inadequate) Loss of libido Impotence Infertility

What are the clinical features of hyperprolactinaemia

Galactorrhoea. § Hypogonadism - reduced (GnRH secretion) LH action. § Prolactinoma - headache and visual field defects.

What are the side effects of tubocurarine

Ganglion blockade and histamine release leading to Hypotension Tachycardia (reflext to hypotension) Bronchospasm Apnoea

What are the two main types of nicotinic cholinoceptors?

Ganglionic Muscular

What does PTH excess lead to in the GI tract?

Gastric acid Duodenal ulcers

List the 4 major side effects of aspirin seen at therapeutic dose

Gastric irritation Nephrotoxicity Prolonged bleeding time Bronchospasm in sensitive asthmatics

What happens as a result of H Pylori's increased acid production and how does this contribute to peptic ulcers

Gastric metaplasia due to increased acid exposure and decreased somatostatin Downregulation of defense factors

What is the difference in presentation of a gastric and duodenal ulcer?

Gastric ulcers cause pain on intake of food Duodenal ulcers relieved in pain with meal as this causes pyloric sphincter to close

Which drug groups have target sites other than the typical four target sites

General anaesthetics - reduce synaptic transmission without interacting with transport systems or receptors Antacids - basic chemical compound so simply neutralise stomach acid Osmotic purgatives - draw water into the bowel due to its physiochemical properties

In general, how does lipid solubility affect potency of opoiods?

General rule of thumb - the more lipid soluble, the more potent as it can enter the CNS more easily/quickly

List 7 causes of short stature

Genetic Pubertal growth and delay IUGR/SGA Dysmorphic syndromes Endocrine disorders Chronic paediatric disease Psychosocial deprivation

Give the general aetiology of type 1 diabetes

Genetic disposition + Environmental influence leads to autoimmune destruction of beta islet cells in pancreas so there is a deficiency of insulin. Hyperglycaemia results.

Give the general aetiology of type 2 diabetes

Genetic influence has major effect leading to obesity and insulin resistance. The beta-islet cells overwork themselves and eventually fail

Why do asian populations tend to drink less alcohol compared to Western societies?

Genetic polymorphism more prevalent in these populations where the aldehyde dehydrogenase enzyme is less effective Aldehyde builds up leading to more pornounced nausea and toxicity (asian flush)

What does the mode of delivery of a IUGR/FGR foetus depend on? (5)

Gestation of pregnancy Condition of pregnancy State of cervix

Summarise the physiological effect and second messenger mechanism used to bring out these effects in alpha-2 adrenoceptors

Gi-linked Presynaptic autoreceptors inhibiting NA release

Give the condition associated with excess somatotrophin (GH)

Gigantism and acromegaly

What is the clinical use of methylodopa

Given to pregnant women as antihypertensive; it has no adverse effects on the foetus despite crossing the blood-placenta barrier.

What is parturition?

Giving birth

What is ecothipate used to treat

Glaucoma

What is physostigimine used to treat

Glaucoma

What is GABA reuptaken by

Glial cells Presynaptic cells GABA transaminase breaks down GABA into SSA

Give an example of a sulphonylurea

Gliclazide or Glibenclamide

Define child development

Global improvement of characteristics such as growth understanding skill acquisition sophisticated responses and behaviour

What type of hormones are produced in the zona fasciculata? What is the principle hormone

Glucocorticoids (principle steroid = cortisol)

Which sympathetic effects are regulated by beta-2 receptors

Gluconeogenesis and Glycogenolysis Bronchodilation Vasodilation

Give examples of transport systems that drugs can target

Glucose transporters in hepatocytes Neurotransmitter transport Sodium-Potassium pump

Most common phase 2 reaction

Glucuronidation

Six types of phase 2 reactions and the enzymes that enable them

Glucuronidation Acetylation Sulphation Methylation Amino Acid Conjugation Glutathione Conjugation Glucuronyl Transferase Acetyl Transferase Sulphotransferase Methyl Transferase Acyl Transferase Glutathione S-Transferase

Describe the synthesis of GABA:

Glutamate -> GABA via Glutamate Decarboxylase (GAD)

Why is glutathione conjugation important

Glutathione is conjugated using electrophiles so they can be excreted Electrophiles are damaging species often generated during metabolism - can cause protein and dna damage so must be removed

Give the type of antibiotics that would disrupt peptidoglycan synthesis

Glycopeptides (binds to pentapeptides) and prevent PtG synthesis

Describe the GnRH-LH/FSH negative feedback loop in females

GnRH from hypothalamus stimulates LH and FSH release from pituitary LH and FSH act on the ovaries causing them to produce oestradiol+progesterone+inhibin in the follicular phase

Describe the GnRH-LH/FSH negative feedback loop in males

GnRH from hypothalamus stimulates LH and FSH release from pituitary LH and FSH acts on Sertoli and Leydig cells in the testis to produce testosterone and inhibin (which then negatively acts in the pituitary and hypothalamus).

Why are thiazide diuretics used over other classes of diuretics when used to treat hypertension?

Good iitial response (diuretic effect lost after 4-6 weeks)

Summarise the physiological effect and second messenger mechanism used to bring out these effects in alpha-1 adrenoceptors

Gq-linked Post synaptic on vascular smooth muscle

At what point of pregnancy is the increased tendency for blood clotting in the mother the greatest? Why might this be?

Greatest at term - prevents massive blood loss during delivery

What is growth mainly dependent on after the first year of life

Growth hormone

Summarise the factors involved in growth during puberty and the differences between males and females

Growth hormones playing a role but ALSO sex hormones Sex steroid increase the pace of growth and fuse growth plates to define that to be the final height

Describe the growth rate of boys and girls during childhood (i.e. from post-infancy to puberty)

Growth rate of boys and girls is similar (5-6cm/year)

What effect does parasympathetic dominance have on the gut and the bladder

Gut - increased motility Bladder - increased frequency of urine release

What are incretin hormones

Gut hormones that enhance insulin secretion in response to food after eating

Explain how bicarbonate is reabsorbed in the proximal convoluted tubule

H+ is pushed out of the cell via Na/H antiporter Bcarbonate from the tubular fluid reacts with this to make carbonic acid Carbonic anhidrase on the apical membrane will concert this to water and carbon dioxide The water and carbon dioxide pass into the cell and recombine to form carbonic acid then H+ and HCO3- The carbonate will be absorbed and the H+ antiported back out

List some factors that affect the combination and duration of drugs used to treat hepatitis C infections

HCV genotype viral load past treatment experience liver health

Which HLA haplotypes can significantly increase the susceptibility of acquiring T1DM?

HLA-DR3 and HLA-DR4

Which enzyme do statins inhibit?

HMG-CoA Reductase

What are the treatments for male hypogonadism

HRT - replace testosterone for ALL patients. For fertility - testosterone isn't enough, need SC gonadotrophins (LH&FSH). Hyperprolactinaemia - dopamine agonist to inhibit prolactin.

What do HSV1 and HSV2 cause respectively?

HSV1 -> Cold sores HSV2 -> Genital herpes

Why do you have to be wary about using HbA1c to monitor glucose control in patients with haemoglobinopathies or blood loss?

Haemoglobinopathy changes the red cell half life so HbA1c will not be as accurate an indication of long term glycaemic control

What is maculopathy? Describe its features. What do they implicate for the patient?

Hard exudates near the macula Same disease as background retinopathy but occurs near the macula (central colour and acuity area of the retina so threatens direct vision )

What are the 3 retinal features of background diabetic retinopathy?

Hard exudates. (cheese/yellow coloured deposition of lipid with harsh edges) Microaneurysms - small blood vessels bulge. Blot haemorrhages - blots of blood.

What is the leading cause of hypothyroidism

Hashimoto's disease where there is immune damage to the thyroid Can also occur due to therapy of thyroid tumours, iatrogenic

Why are dopamine replacement drugs not ideal

Have long term side effects including dyskinesias and on-off effects

Why are barbiturates not a 1st line drug

Have unwanted effects Depress respiration Reduce REM sleep Potentiate effects of CNS Depressants (e.g. alcohol)

Summarise the principle side effect profile of seratonin receptor antagonists

Headaches and constipation

List 5 target tissues for antihypertensive drugs

Heart - determines CO Sympathetic nerves for vasoconstriction Kidney - deals with blood volume Arterioles - determines tpr CNS - regulates bp control

What kind of symptoms would you expect with a stable plaque

Heart pain due to thick cap obstructing blood flow to th e heart

What do height centiles signify?

Height centiles express how many people in the population are at a particular height at any age. It is essentially a normal distribution at each age/time point

Which type of drug would affect the release of ACh during neuromuscular transmission

Hemicholinium (blocks reuptake of choline), calcium entry blockers, neurotoxins

Give an anticoagulant that works by increasing the activity of antithrombin

Heparin

What are the side effects of thiazolidinediones?

Hepatitis and heart failure

Why does codeine less potent/have slower effects than heroin?

Heroin more lipid soluble so can get in the brain and undergo conversion there

Give examples of Ganglion Blocking Drugs and how they work

Hexamethonium - the first anti-hypertensive drug used but LOTS of side effects as very general. Primarily an ion-channel blocker (so not a lot of affinity). Trimetaphan - used for when you want hypotension during surgery, IV-administered, short acting. o Primarily a receptor antagonist (so has affinity). a-bungarotoxin is an example of a GBD that is irreversible (used by snakes). o This drug binds mainly to somatic nicotinic receptors (NRs) whereas the GBDs above bind to autonomic NRs

Give the effects of high dose anticholinesterase drugs on CNS activity

High - Unconsciousness, respiratory depression and death

What are the consequences of cannabinoids being extremely lipid soluble?

High accumulation in fatty tissue despite poor circulation Due to laws of equilibrium the cannabinoids in the fatty tissue will seep back into the blood slowly so the effects persist and will be pronounced in chronic users Poor correlation between cannabinoid conc and degree of intoxication

Explain how promethazine is used in the treatment of motionsickness

Histamine H1 receptor blocker Pathway to ctz disrupted

Give the vascular mechanisms of inflammation

Histamine release > vasodilation + increased blood flow Increased capillary permeability > plasma exudate Activation of enzyme cascades > release of inflammatory mediators eg complement, bradykinin.

What is the tuberoinfundibular pathway responsible for

Hormonal control

What are the potential unwanted side effects of MRAs

Hot as hell - decrease in sweating and thermoregulation defects. § Dry as a bone - decreased secretions. § Blind as a bat - cyclopegia (paralysis of eye muscles so no accommodation). § Mad as a hatter - CNS disturbance (i.e. tremors etc.).

Common symptoms of menopause

Hot flushes Sleep disturbance Depression Urogenital atrophy Decreased Libido Joint pain (lowered oestradiol means less of an antiinflammatory effect)

What is potency and what implications does it have

How much of the drug is needed to act as an inhibitor - the lower the number, the more powerful an inhibitor

Summarise some of the possible drug interactions to be aware of with TCAs

Huge increase in potency if coadministered with drug that releases it from bound plasma proteins Increased duration of effects if drugs that compete with hepatic metabolism coadministered Drugs that potentiate effects on CNS e.g. alcohol Antihypertensives

Summarise the maternal hormonal changes throughout pregnancy for HCG

Human chorionic gonadotrophin (HCG) is the key hormone produced in early human pregnancy. • hCG shows peak levels in maternal plasma in the first trimester (~8th week gestation), and declines thereafter

Summarise the three-way interaction between mother, fetus and placenta in oestrogen production

Human placenta - does not express the enzymes needed to convert pregnenolone to androgens so this occurs in foetal adrenals. DHEA from the foetal adrenals converted to 17b oestradiol in the placenta Foetal liver also site for DHEA-S hydroxylation The hydroxylated DHEA-S is then converted to oestriol in the placenta

What type of enzymes are all the ones that are involved in the synthesis of adrenocortical steroids classed as

Hydroxylase enzymes

Which MRA is used to prevent motion sickness and how does it do this

Hyoscine patch: § Inhibits the muscarinic receptors in the vomiting centre so the sensory mismatch (from a mismatch from what the eyes see and what the labyrinth reports in balance) cannot induce vomiting when suffering from motion sickness.

What can excess vitamin D lead to? (vit d toxicosis effects)

Hypercalcaemia and hypercalciuria

What is Cushing's syndrome?

Hypercortisolism and all of its effects, regardless of the original cause

What happens in diabetic induced neuropathy

Hyperglycaemia causes the vasa nervorum vessels to get inflamed and blocked resulting in neuropathy

What is the major side effect of K+ sparing diuretics?

Hyperkalaemia

State and explain the effects of Leptin deficiency

Hyperphagia - excessive eating as there is no leptin to suppress your appetite making the brain think that the body is starving Lowered energy expenditure, sterility and immunocompromisation - evolutionarily based mechanisms to conserve energy in the starving state

Give the condition associated with excess prolactin

Hyperprolactinaemia

List the potential uses of ACE inhibitors (6)

Hypertension Heart failure Post MI Diabetic Nephropathy Progressive Renal insufficiency High CVS-disease-risk patients

List the negative cardiovascular effects of NSAIDs

Hypertension MI Stroke

Define hypertension

Hypertension = blood pressure consistently >140/90mmHg (normal + 20/10).

What symptoms does clonidine treat

Hypertension and migraines

What are the 4 overall features seen in diabetic nephropathy?

Hypertension, progressive kidney deterioration, proteinuria and classic histological features

What are the different gonadotrophin-related conditions that could lead to amenorrhoea

Hypo/pit disease. Kallmann's syndrome (anosmia with low GnRH). Low BMI - low leptin will shut off the reproductive system. Post-pill amenorrhoea.

Describe the effect of cannabis on the anterior cingulate cortex

Hypoactivity - will lead to inability to adjust behaviour appropriately (sign of psychosis)

What is a risk of treating complications of T2DM

Hypoglycaemia

What are the possible side effects of sulphonylureas

Hypoglycaemia and weight gain

List 3 endocrine causes of hypocalcaemia

Hypoparathyroidism (insufficient PTH) Pseudohypoparathyroidism (target cell resistance to PTH) Vitamin D Deficiency

Distinguish between hypopituitarism and panhypopituitarism

Hypopituitarism is the decreased production of all or specific anterior pituitary hormones while panhypopituitarism is the decreased production of all anterior pituitary hormones

List the side effects of ARBs (4)

Hypotension Hyperkalaemia Renal failure

What are the potential causes of male hypogonadism :

Hypothalamic-pituitary disease (Hypopituitarism, Kallmans syndrome (anosmia & low GnRH), Illness/underweight (low BMI)) Primary gonadal disease (Congenital: Klienfelter's syndrome (XXY), Acquired: Testicular torsion, chemotherapy) Hyperprolactinaemia. Androgen receptor deficiency

Male fertility hormones: where is Gonadotrophin releasing hormone produced?

Hypothalamus

What are the main parts of the brain that are affected by kappa opioid receptors?

Hypothalamus Neuroendocrine role

Explain how the hypothalamus is involved in pain perception/tolerance

Hypothalamus increases sensitivity to pain when body is sick - this deincentivises sick person doing activities that may put body under further strain

What does the hypothalamo-adenohypophysial axis comprise of

Hypothalamus, anterior pituitary, various endocrine glands

State 3 endocrine problems that can cause the short stature

Hypothyroidism (also, thyroxine is so important for brain development) Growth hormone deficiency Steroid excess

Name what is measured in diagnosis and the one used to replace the hormone when there is a deficiency of GH

IGF 1 and height against growth chart GH

Which IGF is important in antenatal growth?

IGF-2 also controls growth (hormone that is paternally imprinted)

Give the changes seen in the first and second phase responses in patients with impaired glucose tolerance

IGT patients have lowered first and second phase response - will make insulin eventually but this takes time

What helps to stimulate the decidualisation process

IL-11, histamin, prostaglandins, and TGF-beta

Explain how PTH indirectly stimulates osteoclasts to increase bone reabsorption

INDIRECT STIMULATION OF OSTEOCLASTS to increase bone resorption - BECUASE OSTEOCLASTS DO NOT HAVE PTH RECEPTOR -- Instead, PTH directly binds to osteoblasts, inhibits them, and stimulates them to produce osteoclast stimulating factors (by upregulating RANKL activity (a type of TNF) and allows for osteoclastogenesis) - simplified but that's all you really need to know for now

What is implicated in patients with macrovascular disease but no diabetes? How/why?

INSULIN RESISTANCE The first 4 stages of athersclerosis are heavily exacerbated by insulin resistance. This is due to excess activation of the mitogenic pathway by chronically higher levels of insulin

How is dobutamine usually administered

IV administration

What is the treatment of organophosphate poisoning

IV atropine - blocks muscarinic receptors so the effect of the raised synaptic acetylcholine concentration is negated Put on respiratory because of respiratory depression from the excess ACh which causes a depolarising block If found within the first few hours, the patient should be given IV PRALIDOXIME, which can unblock the enzymes

Describe how corticosteroid therapy is used to treat Acute (Addisonian Crisis) adrenocortical failure

IV/IM infusion of hydrocortisone or dexamethasone every 6hrs Saline infusion Glucose infusion

Define biological sex

Identifies gender as a result of chromosome conformations that produce different gamete

List 3 potential causes of hypoparathyroidism

Idiopathic Hypomagnesaemia Suppression by raised plasma calcium concentration (ie. feedback system is working properly)

Explain the timing of exposure to thalidomide and the defects that it brings about

If exposure to thalidomide occurs v early on (and for longer) i.e. around day 27, then the limb ridges are only just being formed and can lead to complete lack of limbs. If taken a bit later, e.g. day 40, some upper limb development may be present, but will be severely halted

Hypoglycaemia can be treated by intramuscular glucagon injections. In what circumstance that is relevant to a hospital setting might this method of emergency treatment not be effective?

If the patient has been hypoglycaemic for days and the glycogen stores in the liver have been depleted

Summarise the sequence of events in IUGR/FGR

If the placenta fails, there is higher resistance within the umbilical artery The baby begins to stop growing, so there is a reduction in foetal movements. The baby will try to compensate, by diverting all their blood to the vital organs (i.e. brain) It shuts down supply to the kidneys, resulting in less amniotic fluid. Suddenly, there will be decompensation. We need to get the baby out NOW to prevent intrauterine death

Where is cannabinoid receptor 2 located?

Immune cells

List the peripheral effects of cannabis

Immunosuppresant Tachycardia/vasodilation

How does cannabis affect the immune system?

Immunosuppresant that works by agonising cannabinoid 2 receptors on lymphocytes and phagocytes

What is the overall goal of tumour immunotherapy?

Immunotherapy tries to enhance immune responses to cancer/tumours mostly trying to enhance the ADAPTIVE immune response (i.e. T-cell and B-cell mediated)

What are the effects of different levels of hypoglycaemic attacks?

Impairment of mental processes at <3mmol/L Impaired consciousness at <2mmol/L Recurrent hypos man warning system in body is lost

Why can MRA drugs be used to treat Parkinson's

In Parkinson's disease, the substantia nigra neurones are lost which usually produce dopamine for the striatum. The lack of dopamine gives the Parkinson's disease symptoms. However, a muscarinic receptor antagonist drug decreases the negative inhibition on release of dopamine into the striatum from another source meaning dopamine can continue to be released into the striatum.

What is Ezetimibe given in addition to and why

In addition to statins as allows LDL to be reduced further than 6% per dose doubled

Where do lipophilic drugs tend to localise?

In fatty tissues - brain and testes

Why would aspirin (pKa of 3.4) be more readily absorbed in the stomach than in the intestine

In stomach the pH is lower than pKa so more are unionised and easily absorbed

Describe the Amyloid hypothesis of Alzheimers disease:

In the cell membrane there is beta secretase instead of alpha secretase When beta secretase cleaves Amyloid Precursor Protein instead of alpha (which is present in nonpathological cases) then it produces a larger C99 fragment This C99 releases beta-amyloid after getting digested by gamme secretase Beta-amyloid forms toxic aggregates

Describe how vomiting and feelings of nausea change throughout pregnancy

In the first trimester these feelings will be most prominent in parallel with high levels of hcG but will fall significantly once hitting the second trimester, again parallel with hcG

What is the difference in the pathogenesis between pupil-sparing and non-pupil sparing 3rd nerve paulsy from mononeuropathy?

In the non-pupil sparing 3rd nerve palsy you will see the aneurysm pressing on the PNS fibres causing a fixed dilated pupil

Give the pharmacodynamics of Lamotrigine (how it affects the bdy)

Inactivates sodium channel and therefore reduces neuronal activity

Define the characteristics of attention deficit hyperactivity disorder (ADHD)

Inattention Hyperactivity Impulsivity Lasting more than 6 months

How do conjoined twins occur?

Incomplete inner cell mass separation - this is usually because the conceptus tries to separate later in development to what you would expect with normal twins

How do beta receptors have a positive impact on myocyte contractility

Increase cAMP -> increased PKA -> promotion of contractile machinery + reduction of calcium entry back into the sarcoplasmic reticulum

How does maternal joint flexibility change throughout pregnancy and why?

Increase in flexibility in pelvic joints, needed for delivery

What is the effect of synthetic progestins on oestrogen related CVS complications

Increase risk as synthetic progestins negate the beneficial effects of oestrogens in young females

What is the mechanism and effect of Gliptins

Increase the half-life of exogenous GLP-1 agonists and increase GLP-1 leading to reduced levels of glucagon and glucose

Summarise the physiological changes that occur to allow erection of the penis and clitoris

Increased PNS activity to pudendal artery -> increased activity of NOS and vasodilation Blood flow increased to corpus cavernosum Clitoris enlarges in a similar way

Which maternal changes would you see from the second trimester

Increased blood volume Increased blood clotting Decreased blood pressure Altered fluid balance

What signalling pathway does stimulation of b1 adrenoreceptors induce?

Increased cAMP (g coupled receptor) so protein kinase can phosphorylate

What signalling pathway does stimulation of b2 adrenoreceptors induce?

Increased cAMP (g coupled receptor) so protein kinase can phosphorylate

Indicate how sympathetic stimulation promotes depolarisation

Increased cAMP which increases hyperpolarisation-activated cyclic nucleotide gated channels, aka funny channels (If), and calcium channels

How is acid secretion increased

Increased calcium and/or cAMP concentration Translocation of secretory vesicles to apical parietal cell

What are the characteristic signs of endothelial dysfunction phase

Increased endothelial permeability Upregulation of adhesion molecules Leucocyte adhesion and migration into artery wall

Summarise the changes in kidney function during pregnancy

Increased fluid retention and higher plasma volume as pregnancy goes on so blood volume is increased significantly as foetus grows

When does increased impedance/resistance in the umbilical arteries become apparent? What does this lead to?

Increased impedance in the umbilical arteries becomes evident only when at least 60% of the placental vascular bed is obliterated. As the baby becomes more hypoxic, there is high resistance to virtually no end diastolic flow. Reversible flow results as the baby becomes more acidotic.

List the adverse/side effects of anti-TNFa therapy (infliximab)

Increased incidence of TB and other infections Worsening of heart failure

Summarise the use of nutrition based therapies to manipulate the microbiome as a treatment for IBD

Increased intake of probiotic foods (which come with their own good bacteria that will compete for space with the pathogenic bacteria in the gut)

Summarise the cardiovascular effects associated with cocaine use and the mechanisms mediating them

Increased oxygen demand on heart (increased sympathetic drive from increased catecholamines) Decreased oxygen delivery (due to vasoconstriction) Overall result -> Ischaemia

What other conditions are people with type 1 diabetes likely to present with

Increased prevalence of other autoimmune disorders

Describe the Inflammation hypothesis of Alzheimers disease:

Increased release of inflammatory mediators from microglial cells Phagocytosis -> decreased neuroprotective proteins Neuronal death results

How can you tell if there are unwanted side effects of hyperthyroidism from replacement therapy

Increased temperature, sweating, sensitivity to heat and increased appetite but loss of weight Tremors, cardiac dysrhythmias and cardiac failure

Which maternal changes would you see from the third trimester

Increased weight Altered joints

What are the side effects of Phentolamine

Increases GIT motility and diarrhoea is a common occurrence Postural hypotension

How does sodium bicarbonate increase aspirin excretion

Increases blood pH causing aspirin to ionise making it less lipid soluble and less likely to be reabsorbed in the nephron

Summarise and explain the changes in urinary frequency throughout the trimesters of pregnancy

Increases in the first trimester, normalises in second then increases again in the third trimester First trimester due to maternal hormones affecting kidney function Third trimester is due to uterus exerting pressure on the bladder

Define small for gestational age (SGA)

Infant has birthweight less than 10 percentile

Summarise the effects of cocaine overdose on the CNS and explain why

Infarctions from vasoconstriction effect occurring in the brain Stimulation of hyperpyrexia (very high fever) Combinations lead to sezures and inductions of epilepsy

What form of administration is the worst in terms of bioavailability

Inhalation

Which form of administration of cocaine gives the quickest onset of effects?

Inhalation and IV administration fastest and virtually the same in terms of onset time Snorting (intranasal) Oral

Which route of administration will lead to the fastest drug effect in the brain?

Inhalation as drugs are right next to the heart

What is Liddle's syndrome?

Inherited disease where aldoserone actiated sodium channel always open leading to hypertension

Summarise the mechanism of action and impact of glucocorticoids in IBD

Inhibit production of IL1 and TNFalpha by dendritic cells Antiinflammatory and immunosppressive effect

What effect do loop diuretics have

Inhibit the sodium-chloride-potassium cotransporter in the ascending limb of the loop of henle Lower interstitial osmolarity means a weaker osmotic gradient between tubule and interstitium, therefore less water reabsorption

What is the mechanism of action of potassium iodide

Inhibiting iodination of thyroglobulin Inhibiting thyroid peroxidase generation

What are the two ways in which diuretics work in general?

Inhibiting reabsorption of sodium and chloride (get excreted insteas of pulling water into superstitium) Increasing osmolarity of tubular fluid (osmotic gradient reduced)

How fast are cyp450 enzymes induced as compared to how they are inhibited

Inhibition is very rapid while induction can take hours to days This is because inhibition is the deactivation of enzymes that are already present while induction requires new enzymes to synthesise before we see the effect

What is the effect of alpha 2 adrenoceptors

Inhibition of NA release

Explain the mechanism by which cannabis affects eating behaviours

Inhibition of pre-synaptic GABA which increases Melanin Concentrating Hormone activity Increased production of orexin Both work to INCREASE HUNGER

Explain what PCSK9 is and its relation to statin use.

Inhibitor of the LDL receptor so prevent LDLs being removed from circulation Statins coinduce the expression of LDL receptors and PCSK9 Where PCSK9 inhibitor antibodies are given with statins we see a big decline in cholesterol

Give the pharmacodynamics of Sodium Valproate (how it affects the bdy)

Inhibits GABA transaminase which leads to an increase in GABA mediated inhibition

Summarise the mechanism of action of Ezetimibe and the effects of it on blood lipids

Inhibits cholesterol absorption and lowers LDL considerable amount Activated in intestines as a glucuronide

What would be the general pharmacological treatment plan for a patient with a DVT?

Initial treatment with dalteparin Upon confirming DVT, oral warfarin should be given

What is the nigrostriatal pathway responsible for

Initiating and fine tuning of movement - inhibition will lead to disorders

State the 3 overall stages in the formation of a thrombus.

Initiation = small-scale production of thrombin, on surface of tissue factor bearing cells Amplification = large-scale production of thrombin occurring on surface of platelets Propogation = Thrombin mediated fibrin generation (enough thrombin to convert the fibrinogen to fibrin)

Summarise the preventative management and education for diabetic foot (8)

Inspect feet daily Don't walk bare foot Inspect shoes Control diabetes

Give the physiological mechanism that leads to hyperglycaemia from insulin deficiency

Insulin is important in reducing hepatic glucose output and driving the uptake of glucose by the muscles Insulin ensures fatty acids do not leave adipose tissue and prevents protein destruction in muscle Insulin deficiency means there is hepatic glucose output and little muscle uptake leading to hyperglycaemia Insulin deficiency causes fatty acid release which are used to orm ketones by the liver leading to ketone acidosis

What is the relationship between body fat mass and insulin levels?

Insulin levels are proportional to body fat however when patients are obese they develop insulin resistance

How does insulin production/secretion and insulin resistance change with age? What are the implication of this?

Insulin production decreases with age Resistance increases with age When resistance exceeds insulin production we cannot mke enough insulin to compensate for resistance

If a person cannot control their T1DM with insulin injections, how can they be treated instead?

Insulin pump - device administers continuous insulin with preprogrammed rates Islet cell transplants where beta cells from a dead donor's liver are injected. They migrate around through hepatic portal veins and produce insulin. Immunosuppressive agents needed.

What class of drug is sulphonuryleas and how do they work

Insulin secretagogues - block ATP sensitive potassium channel to increase beta cell insulin secretion

What are the therapeutic mechanism and effect of thiazolidinediones?

Insulin sensitizer peripherally and modifies adipocyte differentiation to shift weight gain peripherally Overall improvement in glycaemia and dyslipidaemia

How is tubocurarine administered

Intravenously

How can you avoid hepatic first pass metabolism

Introducing drug intravenously

Which target site do local anaesthetics work at

Ion channels - block VGSCs to block pain transmission via nociceptor neurons

Which MRA is used for asthma and COPD and how does it treat them

Ipratropium Bromide: § Used for Asthma and COPD as it causes bronchodilation.

Summarise the mechanism of action and hence physiological effects of monoamine oxidase inhibitors

Irreversible inhibition of monoamine oxidases which breakdown monoamines This leads to prolonged duration of action

What does paracetamol overdose lead to and how?

Irreversible liver failure

What are the two major CVS related issues of cocaine use?

Ischaemia and infarction Anaesthetic effect that leads to problems in rhythm and left ventricular function

What is the major cause of mortality in patients with diabetes?

Ischaemic heart disease

Describe the adrenoreceptor selectivity of isoprenaline

Isoprenaline is beta selective, but not particularly selective in terms of which beta receptor it prefers

Which types of hormones' production is blocked by ketoconazole and how does this happen

It blocks the production of glucocorticoids, mineralocorticoids and sex steroids It inhibits steroidogenesis due to non-specific inhibition of cytochrome P450 enzymes

What are the muscarinic effects on non-vascular smooth muscle

It causes CONTRACTION of non-vascular smooth muscle Lungs - bronchoconstriction GI tract - increased motility Bladder - increased bladder emptying

What is Tolvaptan and what is it used for

It is a Vaptan - a V2 receptor antagonist It is used in the treatment of hyponatraemia associated with SIADH

What type of drug is Spironolactone and what is it used for

It is an aldosterone receptor antagonist Used in treatment of primary hyperaldosteronism as well as other conditions affected by aldosterone like oedema, congestive heart failure, nephritic syndrome and cirrhosis of the liver

When is Metyrapone used?

It is used to treat some cases of Cushing's syndrome, for example bronchial tumours that are inaccessible to surgery. Control of Cushing's symptoms prior to surgery

How is noradrenaline broken down in the synapse

It isn't.

What is the role of GABA transaminase?

It metabolises GABA

How long does adenosine act for

Its actions are short-lived (20-30s) and it is consequently safer than verapamil.

How does ivabradine affect myocardial oxygen demand

Ivabradine increases the heart rate which causes myocardial muscle's oxygen demand to incrrease

Give examples of tertiary (dealing with the hypothalamus) hypopituitarism defects

Kallmann's Syndrome - caused by deficiency of GnRH - causes decreased function of glands producing gonadotrophins Prader-Willi Syndrome - a rare genetic disorder in which seven genes on chromosome 15 are deleted/unexpressed on the paternal chromosome; one symptom manifests as hypogonadism.

Explain the basis of the mechanism of CETP inhibitors in improving blood lipids. Why was the drug not ideal though?

Keeps LDL levels low and HDL high as HDLs not allowed to convert into LDLs Drug not ideal as it proved fatal from its pleiotropic effects

Why is diabetic ketoacidosis more common in T1DM and in what instances will it be seen in T2DM

Ketoacidosis occurs in T1DM as there is insulin deficiency so fatty acids from adipose tissues are released and made ketone bodies out of In T2DM since insulin is still being pumped ketone bodies are not produced Ketoacidosis can occur in T2DM also if pancreas stops working for a period.

Where are V2 receptors for vasopressin found

Kidney Endothelial cells

List some genotypes of sex linked extra chromosome aneuploidies and briefly describe their syndrome/presentation

Kleinfelter's Syndrome (extra X chromosomes) -> Decreased fertility

Which cells in the small intestines secrete PYY and GLP-1?

L cells

Describe how dopamine is synthesised

L-Tyrosine --> L-Dopa via tyrosine hydroxylase L-Dopa --> dopamine via DOPA decarboxylase

What percentage of calcium influx required for myocyte contraction comes via the L-type calcium channel and sarcoplasmic reticulum respectively?

L-ype channels contribute about 25% while ryanodine receptors contribute 75% of calcium necessary for contraction

What are the investigations to undertake when there is suspected male hypogonadism

LH, FSH, testosterone levels - if all LOW, MRI pituitary. Prolactin. Sperm count. Chromosomal analysis - i.e. Klienfelter's syndrome

State the effects of low, moderate and high doses of cholinesterase inhibitors

LOW - enhances muscarinic effects MODERATE - further enhances muscarinic effects + increases transmission at ALL autonomic ganglia (nicotinic receptors) HIGH - depolarising block at autonomic ganglia and NMJ (the nicotinic receptors get overstimulated so they shut down)

What are the negative symptoms of schizophrenia

Lack of emotion, speech and motivation

Why do you get hypoglycaemia in adrenocortical failure

Lack of glucocorticoids to stimulate gluconeogenesis and inhibit glucose uptake into tissues

What is Charcot's foot?

Lack of sensation in foot leads to abnormal pressures on it whilst walking. After extended periods of this, it leads to re-arrangement of the bones within the ankle and feet

Give features of conjugating agents

Large Polar Endogenous

Describe and explain the relationship between alcohol dosing and frequency of administration in relation to its pharmacokinetics

Large doses in one go will lead to high blood ethanol for a longer period than is does were smaller for the same amount and spread across multiple administrations This is because liver enzymes become saturated and a lot of alcohol gets into the blood

What is a key property of the conjugates formed from glucuronidation and explain how this affects its excretion

Large molecular weight products so can't pass through glomerulus and excreted in bile instead

Summarise the propogation phase of haemostasis

Large scale production of thrombin from activated platelets Thrombin used to generate fibrin strands from fibrinogen

Give non-endocrine hormone production cases of short stature

Laron dwarfism - caused by GH receptor defect in the intracellular mechanism complex of the hepatocytes (leads to problem with IGF1 production) PYGMY - caused by an IGF1 receptor defect on the target tissues

When does most foetal weight gain occur and what can happen if this period is disturbed or interrupted?

Last 20 weeks of gestation If disturbed can suffer from Intrauterine growth restriction (IUGR) refers to a condition in which an unborn baby is smaller than it should be

List some reasons as to why the symphysis-fundal height might be overestimated

Last menstrual period date gestation is measured from might be wrong Multiple children Maternal obesity Complications

List some reasons as to why the symphysis-fundal height might be underestimated

Last menstrual period date gestation is measured from might be wrong Transverse baby position Complications

Describe which cases diabetes can present atypically in patients

Latent autoimmune diabetes in adults presents in older patients but has type 1 presentation Patients with t2dm can present with ketoacidosis at the initial stage when this is actually a t1dm Monogenic diabetes can present as type 1/2

What impact do loop diuretics have on potassium cycling and why is it significant

Leads to reduction of potassium cycling since less basolateral Na/K ATPase activity Positive luminal potential reduced Less paracellular movement of cations includiong sodium More sodium in the tubule means more K will be lost Overall, this leads to HYPOKALAEMIA and - Loss of K+ recycling earlier on in tubule means that there is decreased reabsorption of Ca2+ and Mg2+

What does testosterone help develop in adulthood

Lean body mass. Muscle size and strength. Bone formation and mass (in young adults). Libido and potency.

What is the crown-rump length?

Length of foetus from top to bottom

Summarise the mechanisms/physiological effects of ACE inhibitors that allow it to induce thirst effect

Less SNS activation of thirst in brain via AT1R

Define extremely low birthweight (ELBW)

Less than 1000g

Define very low birthweight (VLBW)

Less than 1500g

Define low birth weight (LBW)

Less than 2500g

Give clinical features of hypothyroidism

Lethargy, depression Deepening voice Cold intolerance Hypertension Weight gain Constipation

What helps to stimulate attachmentof the blastocysts to the endometrium

Leukemia inhibitory factor and IL-11

Name a drug involved in preventing glutamate exocytosis

Levetiracetam

Name the dopamine replacement drug used to treat Parkinson's

Levodopa (converted to dopamine by DOPA decarboxylase

Within what time period can levonorgestrel and ulipristal be taken, respectively?

Levonorgestrel = 72hrs Ulipristal = 120hrs

Indicate how replacement therapy is done for thyroid hormones

Levothyroxine sodium is used - it works by acting as a T4 analogue. The alternative is Levothyronin sodium which is a T3 analogue and much more fast acting however this is used in rare cases such as a myxoedema comas

What are the consequences to exposure to the teratogen thalidomide

Limbs primarily affected. In addition, deformed eyes and hearts, deformed alimentary and urinary tracts, blindness and deafness.

What are the characteristic signs of the complicated plaque formation phase

Lipid rich necrotic core formed from death and rupture of foam cells in the fatty streak Formation of fibrous collagen cap over lipid core

What is the effect of beta 3 adrenoceptors

Lipolysis

Give the type of antibiotics that would disrupt gram +ve membrane

Lipopeptides (e.g. daptomycin)

What is normally used to treat bipolar depression

Lithium - stabilises mood swings between mania and depression

How do phase 1 reactions affect the polarity of a drug

Little effect on the polarity of a drug

Where does metabolism of glucorticoids occur

Liver

Where is thyroxine binding globulin synthesised -

Liver

Where is most of IGF-1 synthesised?

Liver - 70% of IGF-1 produced here

Two main routes of drug excretion

Liver and kidneys Mainly kidneys

Summarise the metabolism and excretion of cannabis and its metabolites.

Liver converts the delta9-THC to 11-hydroxy-THC 65% of this 11-hydroxy-THC will be secreted into the gut where it can be reabsorbed due to high lipid solubility Over time all the drug gets cleared

Which type of molecules tend to get excreted via the biliary route

Liver will concentrate molecules with large molecular weights that are very lipophilic

Which type of drug would affect the conduction of nerve APs in motor neurones during neuromuscular transmission

Local anaesthetics

Explain how the locus coeruleus is involved in pain perception/tolerance

Locus coeruleus activated by stress pathway leading to automatic signal to dampen down pain in the short term (when stress is high)

List some long-acting and short-acting benzodiazepines: How does this affect their use?

Long acting = Anxiolytics (e.g. Diazepam) Short acting = Sedative/Hypnotics (e.g. Temazepam, Oxazepam)

Give the pharmacokinetics of Ethosuximides (how it affects the bdy)

Long half-life (50+ hours)

Why is Cabergoline the dopamine receptor antagonist of choice over Bromocriptine

Longer lasting and administered less regularly Unwanted side effects the same as bromocriptine but are less pronounced

State the 3 classes of diuretics used clinically

Loop diuretics Thiazides Potassium sparing diuretics

Which diuretic would have the most powerful effect on renin secretion?

Loop diuretics would have the greatest effect as the target that allows Na and Cl to enter the MACULA DENSA CELL is the SAME target that aldosterone act on (the triple transporter). influence renin secretion indirectly (through hyponatraemia) and directly (blocking the triple transporters that are on the macula densa cells).

What happens in tonic-clonic seizures

Loss of consciousness -> Muscle stiffness, jerking -> Wakes up

List the biological (somatic) symptoms of depression (3)

Loss of libido Slowing of thought and action Loss of appetite, sleep disturbance

Give the clinical features of male hypogonadism (lack of testosterone)

Loss of libido. Impotence. Small testes. Decreased muscle bulk. Osteoporosis.

What are the five main mechanisms of drug tolerance

Loss of receptors - over-stimulation causes receptor endocytosis Change in receptor shape - conformation no longer effective Pharmacokinetic factors - metabolism of drug increased after repeated use Physiological adaption - aims to maintain stable internal environment Exhaustion of mediator stores

Why do some patients taking beta-blockers complain of cold extremeties?

Loss of β-receptor mediated vasodilatation in cutaneous vessels

Give the effects of low dose anticholinesterase drugs on CNS activity

Low - CNS excitation with the possibility of convulsions

How are low weight heparins administered compared to normal weight

Low = subcutaneous injections High = subcutaneous and IV

Why is it very difficult to die from cannabis as compared to heroin or alcohol

Low CB1 receptor expression in medulla Medulla contains cardio-respiratory centre Cannabis therefore can't have an effect on this vital region

hat is the difference in physiological effects between high and low-dose aspirin treatment?

Low dose inhibition of COX1 means reduced platelet aggregation but this is less pronounced as the endothelial cells are able to replenish their COX enzymes since they have a nucleus so only platelet-led production really affected In high dose the endothelial cell nucleus will be permanently inhibited

What is the fourth step hypertension treatment for patients

Low dose spironolactone Beta blocker or alpha blocker

Why does alcohol require a much larger dose to bring out an effect compared to other drugs such as nicotine or cocaine?

Low pharmacological potency

Describe the potency of alcohol. Why is this so?

Low potency Will influence lots of different receptors due to uncomplicated shape but won't fit most of these very well so not a lot of efficacy

What factors are associated with increased occurence of hypos in T1DM patients?

Low quality glycaemic control patients. More common in patients with low HbA1C.

Give 3 factors that stimulate the renin-angiotensin system

Low renal sodium reabsorption Low renal perfusion pressure High SNS activation

List the emotional (psychological) symptoms of depression (4)

Low self-esteem Low motivation Misery, apathy, pessimism Anhedonia (inability to derive pleasure from activities)

What are the theoretical uses of nicotinic acid? Why is it not used in clinical practice?

Lowers LDL, increases HDL, stimulates fibrinolysis Not well tolerated by patients

Which two areas are usually assessed/scanned in DEXA for osteoporosis?

Lumbar spine Hip (pelvis/neck of femur)

Which type of muscarinic receptor would you find in the salivary glands, CNS and stomach

M1

What are the three types of muscarinic receptor and where are they found

M1 - neural tissue M2 - heart M3 - exocrine and smooth muscle

What is the main difference in the GPCR function of M1, M3 and M5 receptors compared to M2 and M4?

M1, M3 and M5 = Gq protein linked receptors - they stimulate PLC which increases IP3 and DAGM2 and M4 = Gi protein linked receptors (inhibitory) - they decrease the production of cAMP

Which type of muscarinic receptor would you find in the heart

M2

Which muscarinic receptors are not excitatory

M2 - the ones on the heart

Which type of muscarinic receptor would you find in the salivary glands, bronchial/visceral smooth muscle, eyes, and sweat glands

M3

Describe the selectivity of bethanechol.

M3 selective agonist

Which type of muscarinic receptor would you find in the CNS alone

M4 and M5

Explain how opioids bring about their analgesic effects

MAIN EFFECT: act on substantia gelatinosa to prevent information relay to the spinothalamic tract Will also switch off GABA i central regions that sed inhibitory signals (PAG, NRPG)

State which monoamines Monoamine oxidase (MAO)-A and -B preferentially breakdown respectively

MAO-A: NA & 5-HT MAO-B: DA

Why is an influx of macrophages associated with a plaque rupture

Macrophages release matrix metalloproteinases that are involved in collagen breakdown

How is macrovascular disease present around the body?

Macrovascular Disease is a systemic disease and is commonly present in multiple arterial beds.

Give the main actions of testosterone

Main actions of testosterone: Development of male genital tract. Secondary sexual characteristics. Maintenance of adult fertility. Anabolic effects (muscle and bone growth).

What indication of use is most common for anticoagulant prescription

Mainly venous thrombosis

Major and minor abnormalities occur in what percentage of pregnancies?

Major abnormalities ~3% of pregnancies (cause 25% of infant deaths. ) Minor abnormalities ~15% (little health impact)

What is the function of phase 2 reactions

Make drug more water soluble and polar so they are excreted in urine easily

When is aminoglutethamide used as a treatment

Malignant adrenocortical carcinoma Malignant of prostatic cancer (NB: corticosteroids must be replaced)

What are the 4 main categories/factors associated with causing FGR/IUGR?

Maternal medical factors (hypertension, infection) Maternal behavioural factors (smoking, alcohol) Foetal factors (abnormalities, infection) Placental factors (cysts, infarctions)

What is the key difference between full agonists with high and low affinities

Max response will be generated by both but low affinity will require higher dose

What is the effect on bioavailability if the first pass metabolism is extensive

Means there will be low bioavailability

What is the intended purpose of active secretory mechanisms that lead into the bile

Meant for active transport systems of glucuronides and bileacids but drugs can hitch a ride onto this mechanism

What is the function of phase 1 metabolism

Meant to release or unmask functional groups that are necessary to phase 2 reactions

How can autonomic neuropathy be assessed?

Measure changes to the heart rate in response to the valsalva manoeuvre - should have a change in heart rate if used properly Look at ECG and compare the R-R intervals

How are pituitary deficiencies dagnosed

Measurement of circulating hormones before and after a provocation test

How is hypopituitarism diagnosed

Measuring of basal plasma values of pituitary or target hormones, especially after provocation

How do the mechanisms of IHD change in patients with diabetes?

Mechanisms the same but occurs earlier due to insulin resistance

What is meant by median age and limit age in terms of childhood development?

Median age - age when half of the standard population of children achieve that level. Limit age - age by which they should have achieved the level and is equal to 2 S.Ds from the mean age.

Describe the features of the proximal convoluted tubule

Mediated by the sodium/chloride cotransporter (draws ions into the cell to give to interstitium) Impermeable to free water reabsorption

When does meiosis I and II occur and complete during human oogenesis?

Meiosis I starts during embryonic development, but halts at the diplotene stage of prophase I (primary follicle); this persists until puberty when meiosis resumes as secondary follicles develop. Secondary follicles undergo meiosis II as they are released from ovaries but only progress past metaphase II if fertilisation

What happens following successful fusion of the sperm and the oocyte

Meiosis of maternal chromosomes resumes, forming female pro-nucleus (23 chromatids), and 2nd polar body Sperm chromosomes de-condense and sperm head expands to form male pro-nucleus (23 chromatids) NOTE: both pro-nuclei are haploid at this point (1n) Chromatids then duplicat and mitosis occurs

Briefly summarise the mechanism of vascular smooth muscle contraction

Membrane depolaristion opens the voltage gated calcium channel Through the voltage gated calcium channel calcium enters and binds calmodulin The calcium-calmodulin complex activates myosin light chain kinase VSM contracts

What is premature ovarian failure/insufficiency (POF)? Give possible causes?

Menopause occurring before 40 POF may be autoimmune or secondary to surgery, chemotherapy or radiation

State the two aminosalicylates used in treatment for IBD

Mesalazine/5-amino-salicylic acid Olsalazine (2 linked mesalazine molecules)

Summarise the histological changes seen in diabetic nephropathy

Mesangial expansion Basement membrane thickening Glomerulosclerosis

Summarise the metabolism of TCAs

Metabolised hepatically to active metabolites but these are less potent and will be excreted in the urine

Where are thiourylenes metabolised and where are they excreted

Metabolised in liver and excreted via urine

What can Catechol-O-methyl transferase metabolise

Metabolises all catecholamines

Why is the half life of cocaine very short?

Metabolism by plasma and liver cholinesterases

What treatments are used for polycystic ovarian syndrome

Metformin. Clomiphene. Gonadotrophin therapy (as part of IVF treatment)

Describe the structures of methadone and fentanyl in relation to morphine

Methadone conforms to the 'Morphine Rule' - tertiary nitrogen, quarternary carbon, phenyl group. Fentanyl - has a tertiary carbon NOT a quarternary carbon. still possesses the tertiary nitrogen (incredibly important for receptor binding).

List the 5 major opioids in order of lipid solubility

Methadone/Fentanyl > Heroin > Morphine

Explain how nausea and vomiting due to gastroparesis is treated

Metoclopramide stimulates gastric emptying by acting on the stomach itself and stimulating contractility Inhibits dopamine receptors in vomiting centre Antagonist for seratonin receptor so inhibits activation of ctz

Give the mechanism of action of Metyrapone

Metyrapone inhibits the enzyme 11β-hydroxylase, and in doing so cuts off the production of corticosterone and cortisol. Steroid synthesis in the zona fasciculata and reticularis is arrested at the 11-deoxycortisol stage. 11-deoxycortisol has no negative feedback effect on the hypothalamus and pituitary gland therefore ACTH secretion thus increases and plasma deoxycortisol levels are increased.

How does incidence of micro and macrovascular disease change with HbA1c levels?

Micro - at low HbA1c there is no incidence. At high HbA1c incidence high Macro - at high HbA1c there is some incidence. Steadily increases with HbA1c levels

What happens in paracetamol overdosing

Microsomal enzymes in liver are saturated so the paracetamol broken down by different set of enzymes which releases toxic metabolites

How do micro- and macrovascular disease affect morbidity and mortality respectively?

Microvascular disease causes morbidity; macrovascular disease causes morbidity (diseased state) AND mortality (death)

What type of hormones are produced in the zona glomerulosa? What is the principle hormone

Mineralocorticoids (principle steroid = aldosterone)

Explain the mechanism that increases tolerance to alcohol

Mixed Function Oxidase becomes very upregulated in chronic drinkers. This means that alcohol is metabolised more effectively/quicker in chronic drinkers

State a reversible monoamine oxidase A inhibitor and a beneficial and negative consequence of it compared to regular MAOIs

Moclobemide is a reversible MAO-A inhibitor (RIMA) - it is SELECTIVE and REVERSIBLE • It has fewer drug interactions, but a shorter duration of action (taken 2-3 times a day)

What gives beta-lactamase resistant antibiotics their resistant property?

Moleculr shields around their beta lactam rings to stop betalactamases breaking them apart

Which enzyme metabolises dopamine?

Monoamine Oxidase A and B

Summarise the mechanism of action of TCAs

Monoamine reuptake inhibitors Causes delayed down-regulation of beta-adrenoceptors and 5HT2 receptors (timecourse matches well with clinical onset of symptom relief)

How can peripheral neuropathy be investigated for

Monofilament examination which tracks loss of sensation in different parts of the foot

Summarise the mechanisms/physiological effects of ACE inhibitors that allow it to reduce TPR

More bradykinin (so more vasodilation) and less AngII (so less vasoconstriction)

In which people is peripheral neuropathy more likely to occur

More common in tall people and people with poor glucose control

What happens in status epilepticus seizures

More than 5 mins of continuous seizure activity

State 4 opiates

Morphine Codeine (Heroin) Papaverine Thebaine

Why are the effects of morphine mediated for a prolonged period of time compared to what would otherwise be expected?

Morphine is active directly Some metabolites of morphine are also active and potent in the smae way that morphine is do the effects are prolonged

What is the most active and potent metabolite of morphine

Morphine-6-glucoronide

For drugs that are metabolised by the CYP450 system: are most metabolised by predominantly a single isoenzyme, or by multiple isoenzymes? Explain the implications

Most drugs undergo metabolism by multiple isozymes Being metabolised by more than one enzyme is useful because if one of the isozymes is inhibited (e.g. by another drug having higher affinity for that isoenzyme), the other isozymes could increase their activity to compensate for the inhibited isozymes.

Describe the clinical presentation of parkinsons' motor symptoms

Motor symptoms - resting tremor, bradykinesia (slowed movements), rigidity, postural instability

What is the nigrostriatal pathway responsible for?

Movement

Summarise and explain the distribution of cannabis throughout the body

Moves from lung to bloodstream to well perfused tissues Most of the sole

Which opioid receptor influence the analgesic affect the most?

Mu

List the types of opioid receptors and their endogenous ligands

Mu receptors - Endorphins only Delta receptors - Endorphins AND Enkephalins Kappa receptors - Dynorphins

What is meant by preeclampsia

Multisystem disease normally manifesting as hypertension and proteinuria Will arise in women after the 20th week of gestation

State 4 receptors that are involved in the regulation of gastric acid secretion and their respective ligands + sources

Muscarinic Receptor - Acetylcholine Prostaglandin Receptor - Prostaglandins Histamine receptor - Histamine from enterochromaffin cells Cholecystokinin B receptors - Gastrin

What are the two main types of nicotinic receptor

Muscle and Ganglion

What is Levetiracetam used against

Myoclonic seizures

What is topiramate used against

Myoclonic seizures

What is the primary determinant of myocardial oxygen demand?

Myocyte contraction

Example of a physiological antagonism:

NA binds to alpha1 receptors causing vasoconstriction while histamine will bind to histamine receptors and cause vasodilation

Which two channels mediate the removal of calcium from the myocyte?

NCX (sodium-potassium exchanger) PMCA ATPase Calcium channel mediate removal of calcium from cells

How does cocaine affect the affinity/efficacy of dopamine?

NO DIRECT EFFECT ON RECEPTOR INTERACTION SO DOESN'T AFFECT AFFINITY OR EFFICACY

Summarise the mechanism of action of NSAIDs

NSAIDs inhibit prostanoid (e.g. prostacyclin, prostaglandins) synthesis by blocking COX

What is the difference in the underlying cause between a STEMI and NSTEMI?

NSTEMI = partial occlusion --> no elevation of ST segment on ECG STEMI = full occlusion --> ST elevation on ECG

What is the treatment for opioid overdose?

Naloxone - has a long side chain of carbons and therefore antagonistic properties once bound to opioid receptors

Summarise the classifications of drugs of abuse

Narcotics Depressants Stimulants Miscellaneous (effects from multiple classes)

What is the main V2 mediated action of vasopressin

Naturesis (the process of excretion of sodium in the urine via action of the kidneys ) Note: It is also only evident with high doses of vasopressin, and may contribute to hyponatraemia

List some of the unwanted side effects as a result of the oestrogen from combined oral contraceptives (6)

Nausea Headache Increased weight CVS problems Endometrial hyperplasia Breast Cancers

List the symptoms commonly seen in a hangover

Nausea (as alcohol irritant) Headache (vasodilation) Fatigue (sleep deprivation) Restlessness and muscle tremors Polyuria and Polydipsia (decreased VP)

What side effects might be caused by taking levenorgestrel?

Nausea and vomiting

Give the unwanted potential side effects of bromocriptine and cabergoline

Nausea, vomiting, abdominal cramps Dyskinesias Psychomotor excitation Postural hypotension Vasospasm in fingers and toes (caution Raynaud's disease)

What are the potential unwanted actions of of ketoconazole

Nausea, vomiting, abdominal pain • Alopecia (loss of hair) • Gynaecomastia (breasts on men) • Oligospermia (low concentration of sperm in semen) • Ventricular tachycardias • Liver damage (this is possibly fatal, therefore liver function needs to be monitored clinically + biochemically) • Reduced androgen production

What are the unwanted actions of trilostane

Nausea, vomiting, diarrhoea Flushing

What are the potential unwanted side effects of metyrapone

Nausea, vomiting, dizziness, sedation • Hypoadrenalism + hypertension on long-term administration • Sedatory effects poses a caution against the impaired performance of skilled tasks e.g. driving • Hypertension

How do combined oral contraceptives supress ovulation?

Negative feedback effect on pituitary and hypothalamus Cervical mucus thickened by progestogens and progestogen receptors upregulated by oestrogen Oestrogen counteracts the androgenic effects of synthetic progestogens

Summarise the mechanisms and pathways involved in the pathophysiology of motion sickness induced nausea and vomiting

Neural mismatch between auditory labyrinth and vestibular system This causes increased histamine release from hypothalamus activating histamine receptors in the chemoceptor trigger zone Vomiiting centre activated as well via cholinergic system

Which types of pathways regulate fertility and parenting

Neuroendocrine pathways

Define epilepsy

Neurological condition that causes many seizures

What is Wernicke's encephalopathy?

Neuropsychiatric condition caused by overwhelming metabolic demands (e.g. FROM THIAMINE DEPRIVATION)

What process doesn't occur fully to result in spinda bifida?

Neurulation

Identify the key developmental milestones for the language/speech and hearing domain

New born - startles 12 months - two to three words other than dada or mama 1.5-3 years - talks consistently in 3-4 word sentences

Give an example of a drug that would increase vasopressin secretion

Nicotine

Give the mechanism of action of nicotine

Nicotine binds to the nicotinic ACh receptor which leads to sodium influx and increased nerve activity Neurone heavily stimulated to secrete increased levels of dopamine in the nucleus accunbens (increased feelings of reward)

Summarise the cardiovascular pharmacodynamics of long term nicotine use

Nicotine is proatherogenic - has negative effect on the lipid profile Nicotine increases thromboxane (promotes plaelet aggregation) Decreases NO

What is the pKa of nicotine? What are the implications of this on its absorption from cigarette smoke?

Nicotine pKa = 7.9 Cigarette smoke is quite acidic which is why nicotine is poorly absorbed if it is within smoke No buccal absorption but absorption will occur in the alveoli as this is INDEPENDENT of pH

List the 4 main methods of administering nicotine

Nicotine spray Nicotine gum Cigarettes Nicotine patch

Is transmission through nicotinic receptors faster than through muscarinic?

Nicotinic as they are ionotropic receptors and ionotropic transmission faster than GPCR

What type of drugs are all ganglion blocking drugs

Nicotinic receptor antagonist

Which type of receptors are present at all autonomic ganglia

Nicotinic receptors are present at ALL autonomic ganglia.

Give the structure of nicotinic receptors

Nicotinic receptors consist of 5 subunits (alpha, beta, gamma, delta or epsilon)

List some mediators that cause relaxation of vascular smooth muscle

Nitric oxide C-type natrurietic peptide PGI2 Endothelial hypopolarising factor

How could NSAIDs be developed to reduce GI and CVS side effects/risks?

Nitric oxide or hydrogen sulphide releasing NSAIDs - protective to GI and CVS

Why is paracetamol not considered an NSAID

No antiinflammatory action

What is the effect of NM blocking drugs on consciousness?

No effect

What is the effect of NM blocking drugs on pain sensation?

No effect

What is required for the activation of Efavirenz

No phosphorylation required as does not incorporate into viral DNA Binds to and changes Reverse transcriptase shape instead

How come when giving HRT to a patient with a hysterectomy you can just give oestrogen on its own

No uterus so risk of endometrial carcinoma is nil

Explain how hyoscine is used in the treatment of motionsickness

Non specific muscarinic receptor antagonist Cholinergic system that induces the vomiting centre is blocked

What type of anticholinesterases can cross the blood brain barrier

Non-polar ones

Describe the selectivity of pilocarpine.

Non-selective muscarinic receptor agonistIt stimulates ALL muscarinic receptors

Which autosomal loss-based aneuploidies are viable?

None

Briefly summarise noradrenaline synthesis

Noradrenaline is derived from tyrosine in the diet Tyrosine converted to DOPA via tyrosine decarboxylase DOPA converted to Dopamine via DOPA decarboxylase Dopamine converted to Noradrenaline via dopamine beta hydroxylase

What does a bone mineral density DEXA T-score of >-1.0 indicate?

Normal bone density

Explain a possible mechanism as to how PGE2 lowers pain threshold

Normal pain threshold pathway is mediated by activation of P2X3 nociceptors More PGE2 might activate another pathway that further sensitises more nociceptors

Where does influenza mainly act

Nose, throat and bronchi

How is tubocurarine metabolised

Not metabolised only excreted

Which oestrogens are produced by the placenta after day 40 of pregnancy and what are their respective sources?

OESTRADIOL AND OESTRONE = FROM MOTHER AND FOETUS VIA PLACENTA OESTRIOL = FROM FOETUS

At what point during tumour pathogenesis and growth does an immune response begin to mount against it

ONLY WHEN THE TUMOUR REACHES A RELATIVELY LARGE SIZE DOES IT SEND OUT INFLAMMATORY SIGNALS. (these signals are basically DAMPs) At this stage, there is recruitment of cells involved in innate immunity - macrophages, NK cells and dendritic cells.

How are progesterone-only contraceptives administered?

ORAL Progesterone Only Pill HAS V SHORT HALF LIFE, SO TAKEN AT THE SAME TIME EVERY DAY AS IT HAS A SHORT DURATION OF ACTION

What does a bone mineral density DEXA T-score of -1.0 to -2.5 indicate?

OSTEOPAENIA (low bone mineral density)

Describe how corticosteroid therapy is used to treat Congenital adrenal hyperplasia

Objectives of therapy = replace cortisol, supress ACTH production + replace aldosterone o Therapy is also optimised by measuring adrenal androgens

What is octreotide an example of in the context of treatment

Octreotide is an example of chemotherapy that can be used - it is a somatostatin analogue and thus inhibits GH release. Somatostatin would also inhibit insulin glucagon and gastrin

What is tubular fluid reabsorption controlled/induced by in the efferent ducts of the testes/seminiferous tubules?

Oestrogen

Why does osteoporosis occur as a complication of menopause

Oestrogen = anabolic hormone Deficient oestrogen leads to loss of bone matrix and increased risk of fracture

Why does capacitation have to happen in the female

Oestrogen and calcium dependent - right ionic and proteolytic environment is only found in the female

What is the hormone and mechanism responsible for labour and myometrial contractions

Oestrogen as it increases the number of oxytocin receptors and Phospholipase A2 Oxytocin as its binding leads to increased calcium influx and therefore contraction and enables cervical dilation

Which hormone is responsible for the concentration of epididymal fluid?

Oestrogen as they control tubular reabsorption

Name what is measured in diagnosis and the one used to replace the hormone when there is a deficiency of LH and FSH in women

Oestrogen deficiency and libido Ethinyloestradiol/Medroxyprogesterone

Why does CVD occur as a complication of menopause

Oestrogen has beneficial effects on lipid profile and endothelial function Loss increases risk factors

Oestrogen in younger women reduces the risk for CVS complications, but increases it in older women. Why is this?

Oestrogen has beneficial effects on lipid profiles and endothelial function. However, it also has a prothrombotic and proinflammatory response too In older women, who are more likely to have atherosclerosis, the proinflammatory and thrombotic response exacerbates the already existing atherosclerosis, so the beneficial effects on lipid profiles etc, is nullified

How does aromatase deficiency present in males?

Oestrogen is required in men for tubular fluid reabsorption and for bones. In aromatase deficiency, men are infertile and have osteoporosis. They will also be tall (oestrogen required to close growth plates).

Explain why HRT for menopause involve administration of progestogens alongside oestrogens?

Oestrogens cause endometrial proliferation - the progestogens will work to prevent endometrial hyperplasia and subsequent endometrial carcinomas

What causes Paget's disease of bone?

Often positive family history (possible genetic cause) • There is evidence for viral origin (e.g. measles virus)

Describe the clinical presentation of parkinsons' autonomic NS symptoms

Olfactory deficits Orthostatic hypotension Constipation

Where do hepatitis viruses act

On liver hepatocytes

How does the effect of acetylcholine binding differ between nicotinic and muscarinic receptors

On nicotinic they are relatively weak compared to muscarinic

Give the mechanism of acyclovir function

Once acyclovir triphosphate is incorporated into the strand in viral DNA replication then no further bases can be added to it

What is 11-hydroxy-THC?

One of the major metabolites of delta9-THC is 11-hydroxy-THC - it is actually MORE POTENT than Δ9-THC

Which drugs are class 1 according to Vaughan Williams classification

Ones that cause sodium channel blockade

What percentage of opoids in the circulation are available for absorption into tissue?

Only 20% as the pH of blood is 7.4 and therefore most opioids are ionised and less lipophilic

Which type of hepatitis virus infections require treatment?

Only chronic infections

Which subunits of the nicotinic cholinoceptor does acetylcholine bind to?

Only the alpha subunits (there are two of them)

Give the pharmacokinetics of carbamazepine (how it is dealt with by the body)

Onset after 1 hour Has a 16-30 hour half life

Give the pharmacokinetics of Lamotrigine (how it is dealt with by the body)

Onset of activity within 1 hour Has a 24-34 hour half life

Briefly describe how polydactylyl occurs

Opening or split in the upper lip resulting from asymmetrical growth of the palate's two halves

Explain the tolerance mechanism towards opioids

Opioid upregulate arrestin in tissues Arrestin causes receptor internalisation Over-internalisation of receptors means tissue resistant to opioids

Which opioids can cause urticaria and how?

Opioids that have a hydroxyl group on position 6 (e.g. morphine and codeine) This causes non-IgE mast cell degranulation Leads to histamine release

Explain the mechanism that leads to the dependence and withdrawal symptoms seen when opioid administration is stopped

Opioids' suppression of adenylate cyclase means the body upregulates it When opioid have been taken away there is overcompensation of AC Overactivation will lead to withdrawal symptoms like shakes and diarrhea

What are the two main routes of administration of cannabis? What is the bioavailability of THC after each route of admin?

Oral - 5-15% Inhalation - 25%

Summarise the treatment options for hypoglycaemia

Oral - if patient is conscious feed patient with quick acting glucogels and complex ketones that will be able to maintain blood glucose after treatment Parenteral - Intravenous dextrose, 1mg glucagon

How are SSRIs administered?

Orally

How are MAOIs administered? Describe the rate of absorption

Orally Rapid absorption

Summarise the key pharmacokinetics of bisphosphonates

Orally active but poorly absorbed so needs to be eaten on an empty stomach

How are opiods/opiates usually administered?

Orally for therapeutic IV for abusive

How are TCAs administrated

Orally, fast absorption

State two drug classes that increase myocardial oxygen supply

Organic nitrates Potassium channel openers

What type of compound are irreversible anticholinesterases

Organophosphates

Which drug is used to treat influenza? State its mechanism of action

Oseltamivir - neuraminidase inhibitor

State the two main cell types involved in bone remodelling and explain their respective roles

Osteoblasts - synthesise bone via mineralisation and calcification Osteoclasts - release lysozymal enzymes which cause bone resorption

What are the two main complications of menopause

Osteoporosis Cardiovascular complications

Why do non-K+ sparing diuretics lead to potassium loss, whereas K+ sparing diuretics don't?

Other diuretics increase the amount of sodium reaching the latter parts of the dct This leads to an inccrease sodium-potassium exchange in this area to reabsorb sodium and lose potassium in urine Potassium sparing diuretics act on the latter most dct channels so this exchange doesn't get to take place

State the key phases and their durations of the ovarian cycle within the menstrual cycle

Ovarian cycle: • follicular phase (14 days), • luteal phase (14 days)

What are the general causes of amenorrhoea

Ovarian failure Gonadotrophin failure Hyperprolactinaemia Androgen excess (gonadal tumour)

Which two CYP450 isoenzymes account for over 50% of all drug metabolism?

Over half of drug metabolism is done by 2D6 and 3A4

What are the three types of reaction that fall under phase 1 metabolism

Oxidation Reduction Hydrolysis

What is N-demethylation and what does this reaction produce

Oxidation of a methyl group attached to a nitrogen Produces formaldehyde (HCHO)

What is N-oxidation? Describe the N bond formed and what is formed

Oxidation of the nitrogen group itself Nitrogen has two free electrons that can form a dative bond with oxygen generating an amino oxide

What is O-demethylation?

Oxidative attack of P450 on a methyl group attached to oxygen Converts oxygen to hydroxyl group and releases formaldehyde (HCHO)

Conjugating agent used in sulphation

PAPS

Explain how PGE2, and hence NSAIDs, affect salt/water homeostasis and renal function

PGE2 increases renal blood flow NSAIDs therefore responsible in reduction of renal artery flow and reduced glomerular filtration rate

How do PGE2 and NSAIDs influence body temperature?

PGE2 stimulates hypothalamic neurones which stimulates a rise in body temperature NSAIDs inhibit PGE2 production and therefore reduce raised temperatures

Why part of the autonomic NS would a muscarinic receptor antagonist mainly antagonise

PNS

How come cranial nerve palsy is pupil sparing

PNS fibres on the outside so do not easily lose their blood supply

Which drug is prescribed to treat peptic ulcers regardless of aetiology?

PPIs (omepprazole, lanzoprazole)

Which part of the nephron are exogenous agents (i.e. drugs) secreted into the tubule?

PROXIMAL CONVOLUTED TUBULE the metabolites of most drugs have big/polar groups added to them, these are recognised on the basolateral side of the PCT cell and then absorbed and secreted onto the other side (transcellular movement)

Explain the mechanism by which PTH stimulates bone resorption

PTH binds to osteoblast, inhibits its activities and stimulates it to produce osteoclast activating factors (OAFs)

Explain the pathophysiology of osteitis fibrosa cystica

PTH is released in high amounts in renal failure because of lack of 1-alpha hydroxylase activity to form calcitriol - this means reduced gut calcium absorption, so PTH is released to resorb bone to prevent hypocalcaemia

Through which dermatome is Angina pain usually perceived?

Pain spreads down dermatome T1 in the chest, arm and neck and is bought on by exertion or excitement

List the unwanted/side effects of use of azathioprine in IBD

Pancreatitis Bone marrow suppression Hepatotoxicity

Which type of thyroid cancers are stimulated to grow by TSH and uptake radioiodine?

Papillary and follicular thyroid carcinomas

What does paracetamol overdose lead to and how?

Paracetamol normally metabolised by CytP450 Toxic metabolite produced - if the enzyme mopping it up becomes saturated it will go on to oxidise key hepatic enzymes and cause cell death

Where is calcitonin produced and released from?

Parafollicular cells within the thyroid

Which limb of the ANS (Parasym or sym) dominates in the lungs and eyes at rest and what effect does this have?

Parasympathetic - this enables a partial level of constriction

Summarise the treatments for osteitis fibrosa cystica

Parathyroidectomy, calcitriol analogues and low phosphate diet

Aripiprazole: MOA + side effects

Partial agonist of dopamine and seratonin receptors

Are the arterioles relaxed or constricted at rest

Partially constricted

The first stage treatment for hypertension for patients below 55 years old are ACE inhibitors or ARBs. Why are these drugs not the first step for patients above 55 or of Afro-Caribbean origin?

Past the age of 55 you tend to have low renin/renin sensitivity so you are less responsive to ACE inhibitors or angiotensin receptor blockers

What are the two forms of oral/iv/intranasal cocaine?

Paste Cocaine HCl

List the different forms of cocaine from lowest to highest purity.

Paste Cocaine HCl (acidic solvent) Crack (alkaline solvent) Freebase (non-polar solvent)

Why is Crohn's not cured by surgery whereas ulcerative colitis can be?

Patchy inflammation so hard to get rid of completely

What is the general Method Of Action of BDZs?

Pathway 2 - initiate GABA linkage and opening of chloride channels Pathway 3 - increased affinity of binding for GABA

What is the survival time for a newborn with complete 21-hydroxylase deficiency

Patient will survive for 24 hours or less as their sodium will be lost in urine

What is the main danger of peripheral neuropathy?

People can't sense damage to their feet leading to undetected injury and infection

Why is leptin ineffective as a weight control drug?

People who are obese and have high amounts of white adipose tissue have high levels of circulating leptin but it their weight problem occurs because they are RESISTANT

Summarise the third step of bacterial wall synthesis

Peptidoglycan incorporated into the cell wall Pepptidoglycan pentapeptides cross-linked together by transpeptidase enzymes

Summarise the first step of bacterial wall synthesis

Peptidoglycan synthesis A pentapeptide is created on N-acetyl muramic acid (NAM) N-acetyl glucosamine (NAG) - associates with NAM to form peptidoglycan

Summarise the second step of bacterial wall synthesis

Peptidoglycan transportation Bactoprenol moves peptidoglycan across the cell membrane

What is the bioavailability of a drug?

Percentage of drug absorbed into systemic circulation

List the two complications of diabetes that lead to (diabetic) foot disease

Peripheral neuropathy Peripheral vascular disease

What are phaeochromocytomas?

Phaeochromocytomas are tumours of the adrenal medulla which secrete catecholamines (adrenaline + noradrenaline).

List the 3 overall types of drug-drug interactions

Pharmacodynamic interactions (drugs' effects within the body) Pharmacokinetic interactions (body's effects on drugs - absorption, distribution etc) Pharmaceutical interactions (drug interactions outside the body)

Give an example of a classic monoamine oxidase inhibitor

Phenelzine

State a drug that is non selective for alpha receptors

Phentolamine - nonselective for alpha 1 and alpha 2

Give examples of rate-slowing calcium antagonists

Phenylalkylamines Benzothiazepines

What signalling pathway does stimulation of a1 adrenoreceptors induce?

PhosphoLipace C-> IP3 -> DAG (via G-protein coupled receptors)

Summarise the mechanism of action of viagra

Phosphodiesterase (which deactivates cyclic GMP) is inhibited by viagra ensuring the vasodilatory mechanism of NOS activation goes ahead

Give the four types of drug antagonism

Physiological antagonism - two drugs act on two different receptors and so have opposing effects in the same tissue Receptor blockade Chemical antagonism - where drug reacts in solution Pharmacokinetic antagonism - where one drug reduces the concentration of another at site of action

Explain two major mechanisms that are involved in the regulation/alteration of the immune system during pregnancy

Placenta expresses unusual Human Leukocyte Antigens on the surface that signals that the tissue is human. Will suppress leukocytes Factors are produced at the utero-placental interface which decrease Th1 responses and increase Th2 system

What effect does methylation have on polarity

Polarity decreased by methylation

How is polycystic ovarian syndrome diagnosed

Polycystic ovaries on ultrasound scan. Oligo-/anovulation - irregular or no ovulation. Androgen excess - can be assessed by clinical evaluation (i.e. hirsutism).

Give the type of antibiotics that would disrupt gram -ve membrane

Polymyxin

List the symptoms that a patient may present with for T1DM (6)

Polyuria Polydipsia Vision blurring Weight loss Fatigue Thrush (vaginal yeast infection)

Symptoms of diabetes insipidus

Polyuria Polydipsia Hypoosmolar urine

What do P450 enzymes have in their catalytic site

Porphyrin ring and Ferric (Fe3+) group

Give the pharmacodynamics of Diazepam (how it affects the bdy)

Positive allosteric modulator of GABA receptor - increases GABA-mediated inhibition

Summarise the pharmacodynamics by which alcohol is seen to have positive CVS effects

Positive cvs profile (increased HDLs, decreased platelet aggregation

Describe the influence of nicotine on Alzheimer's disease development?

Positive impact - associated with decreased beta amyloid toxicity and decreased amyloid precursor protein

Describe the influence of nicotine on Parkinson's disease development?

Positive impact - use increases number of cytochrome proteins that will metabolise neurotoxins

What are the central effects of cocaine from acute use?

Positively reinforcing effects like mood amplification and heightened energy

List 5 pre-disposing factors for osteoporosis

Post menopausal oestrogen deficiency Age related bone homeostasis deficiency e.g. osteoblast senescence Hypogonadism Endocrine conditions Iatrogenic (problem result of medical treatment)

Give side effects of suxamethonium

Post-operative muscle pains Bradycardia (due to direct muscarinic action on heart) Hyperkalaemia Raised intraocular pressure

Which synapses does pilocarpine (directly acting cholinergic) primarily act on

Postganglionic parasympathetic synapses

What is Raloxifene used to treat?

Postmenopausal osteoporosis

Which drugs are class 3 according to Vaughan Williams classification

Potassium channel blockade (depolarisation prolongation)

Which class of anti-arrhythmic drug (vaughn-williams classification) acts on the downstroke part of the ventricular membrane potential

Potassium channel blocking class 3s

What is potassium cycling and what does it lead to

Potassium is being reabsorbed and lost from and to the lumen through transporters This means there is an overall positive luminal potential (since positive ions number replenished everytime potassium moves into the lumen) This leads to the paracellular movement of other cations like Mg, Ca and Na as this positive luminal potential leads to their repulsion

What is potency? What determines this?

Potency = power of the drug Dependent on affinity of drug to receptor and efficacy (ability to generate response after binding)

How has the potency of cannabis changed over the last few decades? What are the implications of this?

Potency has increased over the years Meaning both the harmful and beneficial effects have gotten more pronounced Cannabidiol: believed to have a protective effect from the negative effects by THC

What is the general method of action of barbs

Potentiate the effects of GABA by: Pathway 4 - linkage and oopening of chloride channels Pathway 5 - increased binding of GABA Pathway 6 - direct opening of chloride channels

Give maternal factors that contribute to foetal growth

Poverty Maternal age Drugs Disease

State the effects of angiotensin II

Powerful vasoconstrictor Directly promotes kidney to increase water and salt retention Indirectly stimulates aldosterone production

State a selective alpha adrenoceptor antagonist (and state which alpha class)

Prazosin - selective for alpha 1

State and describe 4 factors that influence childhood growth

Pre-birth events (poor foetal growth, low birth weight) Medical issues in childhood Genetic factors Randomness

Give the condition associated with excess gonadotrophins (LH and FSH)

Precocious puberty in children

What is a natural cause of amenorrhoea

Pregnancy and lactation

What are the investigations that could be used to determine suspected amenorrhoea

Pregnancy test. § LH, FSH, oestradiol and androgen blood test. § Day 21 progesterone - can tell you if the woman ovulated in the previous cycle. § Prolactin, thyroid function tests. § Chromosomal analysis - i.e. Turner's syndrome. § Ultrasound scan ovaries/uterus

Give the synthesis pathway of DHEA starting from Pregnenolone

Pregnenolone --(17-Alpha Hydroxylase)--> 17-hydroxypregnenolone --(17,20-Hydroxylase)--> DHEA

What are the different ovarian conditions that could lead to amenorrhoea

Premature ovarian failure. Ovariectomy/chemotherapy. Ovarian dysgenesis - Turner's syndrome (45X).

Give the genetic mutations that lead to late onset Alzheimer's (before 65)

Presenilin-1 --> Late onset Alzheimers (symptoms onset after 65 years old) Apolipoprotein E --> Late onset Alzheimers (symptoms onset after 65 years old)

List 3 endocrine causes of hypercalcaemia

Primary Hyperparathyroidism Tertiary Hyperparathyroidism Vitamin D Toxicosis

Differentiate between primary amenorrhoea, secondary amenorrhoea and oligomenorrhoea

Primary amenorrhoea - failure to begin spontaneous menstruation by age 16. Secondary amenorrhoea - absence of menstruation for 3 months in a woman that has previously had cycles. Oligomenorrhoea - irregular long cycles.

What are the most common endocrine abnormalities that will lead to infertility

Primary gonadal failure - gonads fail so HIGH GnRH and LH/FSH but no inhibin/testosterone etc. Hypo/pituitary disease - hypothalamus/pituitary fail so low FSH/LH and low/no inhibin/testosterone etc.

Explain the differences between primary, secondary and tertiary hyperparathyroidism

Primary hyperparathyroidism is where there is an adenoma on the parathyroid gland causing unregulated excessive secretion of PTH Secondary is where there is a chronically low calcium concentration so the negative feedback loop is constantly stimulating PPTH secretion Tertiary is where the parathyroid gland becomes autonomous because of long term chronic stimulation so even when alcium levels return to normal, secretions remain high

What types of drugs are heroin and codeine?

Prodrugs - need conversion to morphine to have an effect

Define sexual reproduction

Production of offspring that differ genetically from both parents

How do non-rate slowing calcium antagonists affect the heart

Profound vasodilation in vasculature will lead to reflex tachycardia

Give the synthesis pathway of Androstenedione from Progesterone

Progesterone --(17-Alpha Hydroxylase)--> 17-hydroxyprogesterone --(17,20-Hydroxylase)--> Androstenedione

What hormonal composition is required during the implantation phase

Progesterone domination in the presence of oestrogen

What occurs if a pregnant women is given progesterone antagonists?

Progesterone is key to maintaining the pregnancy - progesterone antagonists leads to loss of pregnancy at ALL gestational ages.

List the 3 main clinical features of diabetic nephropathy

Progressive proteinuria Increased BP Deranged renal function

What is the therapeutic/physiological effect of alpha glucosidase inhibitors?

Prolongs the absorption of oligosaccharides This allows insulin secretion to cope following defective first phase insulin

What are the downsides to tibolone administration?

Promotes increased risk of stroke and increased risk of breast cancer

State a drug that is non selective for beta receptors

Propanolol and sotalol - non selective for beta 1 and beta 2

Why does the inhibition of prostanoid production (even a single one) lead to multiple, complex consequences?

Prostanoids have wide ranging effects and cross over in terms of functionality

What is the influence of nicotine on Alzheimer's disease development?

Protective effect - decreases beta amyloid toxicity AND decreases Amyloid Precursor Protein

What is the role of primitive reflexes and when should they disappear by?

Protective, serving to promote support, balance and orientation Disappears after 4-6 months

Why do patients with nephropathy start to have peripheral oedema?

Protein loss in urea so oncotic pressure in vessels reduced so less fluid reaborbed from ECF

Give the common clinical manifestations of acromegaly

Protrusion of lower jaw Kyphosis - barrel chest and general curvature of spine Hypertension Galactorrhoea (women + rarely in men), menstrual abnormalities, decreased libido + impotence Hypertension Abnormal glucose tolerance + symptoms of diabetes mellitus

How do organic nitrates increase myocardial oxygen supply

Provide direct NO which increases cGMP which stimulates potassium channel opening and relaxing directly

Why is the aqueous humour important

Provides oxygen and nutrients to the cornea and lens as they don't have a blood supply

Where does active secretion of acids and bases occur in the nephron

Proximal convoluted tubule

List the central effects of cannabis

Psychosis -> schizophrenia Memory loss (effect on limbic regions) Psychomotor performance

Briefly summarise the control and pattern of release and mechanism of growth hormone

Pulsatile release of GHRH occurs, mainly in the night time Growth hormone stimulates secretion of IGF-1 from liver which then directly influences growth (promotes metabolism and division, prevents cell death, stimulates osteoblasts and chondrocytes). IGF1 and somatotropin have negative feedback effect on pituitary and hypothal

Which type of 3rd nerve paulsy does diabetes cause?

Pupil-sparing

How does egg quantity and quality change with increasing age?

Quality decreases, stored quantity decreases

How does sperm quantity and quality change with increasing age?

Quantity and quality decreases

How can respiratory distress syndrome (RDS) be prevented/reduced in terms of severity?

RDS is brought on when there are low levels of surfactant Can be treated by glucocorticoids which increase surfactant production

What is radiculopathy and how does it present

Radiculopathy - dermatomes affected. Pain over spinal nerves, usually dermatomes on the abdomen or chest wall.

Why is it particularly important that we avoid suxamethonium in patients with glaucoma

Raised intraocular pressure is a side effect

Signs of SIADH

Raised urine osmolarity Decreased initial urine volume Hyponatraemia due to increased water reabsorption

What is mononeuritis multiplex?

Random combination of peripheral nerve lesions

Summarise the rapid and delayed effects of monoamine oxidase inhibitors

Rapid - Increased cytoplasmic NA and 5HT2 Delayed - delayed clinical response due to downregulation of beta adrenoceptors and 5HT2s

State two acute complications of T1DM

Rapid decompensation - KETOACIDOSIS Hypoglycaemia

Describe the mechanism of action of irreversible anticholinesterases

Rapid reaction with active site leaving a blocking group that is stable and resists hydrolysis

Give the main advantage of intravenous exposure of a drug

Rapid systemic exposure and high bioavailability

Summarise the aspects of Virchow's triad

Rate of blood flow - slow will mean blood factors not replenished Consistency of blood - imbalance between pro and anticoagulation factors will cause hypercoagulability Blood vessel wall integrity - damage leads to collagen exposure

What are the two classes of calcium antagonists?

Rate-slowing (act on cardiac and smooth muscle) Non-rate slowing (act on smooth muscle)

Summarise the transport that occurs in the ascending limb of the loop of henle

Reabsorption of sodium, chloride and potassium ions through triple ion transporter in the apical membrane

Distinguish between the two types of unipolar depression

Reactive depression - onset following stressful life events, non-familial inheritance Endogenous depression - unrelated o external events, familial pattern of inheritance

What is the rebound effect? What might help reduce/cure the symptoms of a hangover?

Rebound overexcitation effect is where hangover symptoms peak as blood alcohol concentrations near zero Going back to sleep and sleeping through the rebound effect will avoid symptoms

Which two types of ion channels are there

Receptor linked Voltage gated

Main target sites for drugs in biological system

Receptors Ion channels Transport systems (carrier molecules that transport substances against their concentration gradient) Enzymes

How is Diazepam administrated

Rectal gel - fast onset

Summarise the differences between red and white thrombus morphology

Red thrombi have high fibrin and form within blood vessel's lumen as part of thrombosis White thrombi have high platelets and form within atherosclerotic plaques as part of atherosclerosis

What are the diet changes a T1DM patient should undertake?

Reduce fats and refined carbohydrates Increase complex carbs and soluble fibre Distribute food evenly throughout the day with regular meals and snacks `

Explain the mechanism and effects of SGLT-2 inhibitors and why they are therapeutic in treating diabetes

Reduce glucose absorption and enable glycosuria so glucose levels are reduced Reduce mortality and reduce risk of heart failure

Why are DOPA decarboxylase inhibitors used

Reduce required levodopa dosage

What is the ultimate goal of hypertension treatment?

Reduce risk of death from cardiovascular and renal events

List 3 possible unwanted side effects of exogenous adrenaline when used clinically

Reduced and thickened secretions CVS tachycardic abnormalities Skeletal muscle tremors

Explain the mechanisms by which alcohol brings about its depressant effects on the CNS acutely

Reduced excitation (reducing stim at NMDA) Increased inhibition via allopregnenolone

Why is aripiprazole preferred to other antipsychotics

Reduced instances of hyperprolactinaemia and weight gain compared to other antipsychotics Otherwise equal in efficacy

What symptoms does someone with a GH deficiency present with

Reduced lean mass, increased adiposity + increased waist to hip ratio • Reduced muscle strength + bulk, reduced exercise performance • Decreased plasma HDL-cholesterol + raised LDL-cholesterol • Impaired psychological well-being + quality of life

Summarise the mechanisms/physiological effects of ACE inhibitors that allow it to treat heart failure

Reduced preload - venodilation means less preload due to less venous return Reduced afterload - reduced TPR means reduced afterload

Define sedative

Reducer of mental and physical activity without inducing unconsciousness

Summarise the use of antibiotic treatment with rifaximin to manipulate the microbiome as a treatment for IBD

Reduces bacterial transcription of inflammatory mediator mRNA Induces and sustains remission in Crohn's

What does Raloxifene reduce the risk of? Why?

Reduces risk of vertebral fractures and breast cancer Has tissue-selective effects - oestrogenic in bone and anti-oestrogenic in breast and uterus

How do glucocorticoids affect cellular events in inflammation control

Reducing influx/activity of PMNs Inhibiting recruitment/activity of monocytes Inhibiting angiogenesis Blocking clonal proliferation of T cells Inhibiting fibroblast function inhibit the production of pro-inflammatory mediators enhancing production of anti-inflammatory proteins

Explain how beta-adrenoceptor antagonists are used to treat angina

Reducing myocardial demand by decreasing inotropic and chronotropic effects

Summarise the 3 mechanisms that allow beta blockers to be antihypertensives

Reduction in hr and force of contraction so CO decreased Heart doesn't have to work as hard so reduced BP Decreased renin and angiotensin 2 so decreased vasoconstriction and decreased aldosterone Blockade of presynaptic beta adrenoreceptors so reduced NE effects

What are the side effects of salbutamol

Reflex tachycardia, tremor, blood sugar dysregulation

Give the four factors that affect drug distribution

Regional blood flow Capillary permeability Extracellular binding (plasma protein binding) Localisation in tissue

Summarise the cancer-immunity cycle

Release of cancer cell antigens Uptake of antigens by APCs Priming and activation of T cells in lymph nodes Trafficking of T cells to tumours T cells infiltrate tumours and kill the cancer cells The dead cancer cells release antigens

Describe neurotransmission in the GABAergic synapse

Released tonically AND by neuronal stimulation GABA activates inhibitory post-synaptic GABAa receptors GABA opens chlorinechannels on postsynaptic membranes so it harder to create action potential GABA taken up by GAT and metabolised by GABA transaminase

How is foot ulceration directly managed/treated?

Relief of pressure via bed rest and total contact cast Long term antibiotics Debridement Revascularisation Amputation

What are the actions of paracetamol?

Relieve mild pain Antipyretic

Explain two major reasons/factors for this increased risk during labour/delivery

Remodelling of uterine spinal arteries means vessels can lose large volumes of blood following delivery Placental tissue is relatively inflexible and so any left in can prevent uterine contraction

What is the treatment plan for peptic ulcers caused by NSAID use?

Removal of NSAIDs Proton pump inhibitor or Histamine antagonist Histamine receptor increases acid secretion

Define anxiolytics

Remove anxiety without impairing mental or physical activity

How does one treat pituitary deficiency

Replacement therapy - the hormones that the pituitary hormones stimulate the production of are replaced instead of the pituitary hormones themselves since they are easier to administer

List the features of opioid overdose

Respiratory depression Pinpoint pupils (miosis)

List the short term problematic outcomes of intrauterine growth restriction (IUGR) (7)

Respiratory distress Intraventricular haemorrhage Sepsis Hypoglycaemia Necrotising enterocolitis Jaundice Electrolyte imbalance

List the medium-term problematic outcomes of intrauterine growth restriction (IUGR) (3)

Respiratory problems Development Delay Special Needs

Why do patients with T2DM have initially increased fasting plasma glucose levels

Result of cori cycling from previous night's meal where an excessive amount of glucose will have been converted to lactate which will later return as glucose from hepatic output

List the 3 sites of microvascular complications

Retinal arteries Glomerular arterioles in kidneys Vasa nervorum (tiny blood vessels supplying nerves)

What is likely to have occurred already if there is nephropathy

Retinopathy

List some of the microvascular complications of T2DM

Retinopathy Nephropathy Neuropathy

Summarise the mechanism and use of the anti-depressant drug Venlafaxine

Reuptake inhibition of 5HT and NA (increased dose leads to increased inhibition of NA)

What are the two types of anticholinesterase? Give examples of each.

Reversible - physostigmine, neostigmine, donepezil Irreversible - ecothiopate, dyflos, sarin

Mechanism of reversible anticholinesterases

Reversible anticholinesterases donate a CARBAMYL group, which blocks the active site of the acetylcholinesterase Carbamyl groups are removed by slow hydrolysis (takes mins rather than miliseconds)

What is the mesolimbic dopamine pathway responsible for?

Reward and pleasure

State the drugs used to treat hepatitis C infection Summarise its mechanism of action

Ribavirin - purine analogue Boceprevir - protease inhibitor

State some of the clinical features of IBDs

Right iliac fossa pain Diarrhoea Skin rash

Give an anticoagulant that works by inhibiting factor 10a

Rivaroxaban

State some infectious teratogens

Rubella HIV Syphillis

How does the effect of statins change as you increase the dose?

Rule of 6 - doesn't matter which statin you use, if you double the dose you will get a 6% reduction in LDL

Through what channels do calcium ions in the sarcoplasmic reticulum exit

Ryanodine receptors

What is the conjugating agent/high energy intermediate for methylation?

S-adenosyl methionine

What type of drug is raloxifene?

SERM - Selective Oestrogen Receptor Modulator

State the types of drugs administered for STEMIs and NSTEMIs respectively

ST-elevated myocardial infarcts - antiplatelets&thrombolytics (fully occluded artery) Non ST-elevated myocardial infarcts - antiplatelets (partiall occluded artery)

What type of condition do all chromosomal developmental problems lead to?

SYNDROMES (i.e. people with the same chromosomal abnormality don't always present the same way, or have all of the same features, however there is usually some overarching themes to their presentation)

Which SNS agonists have resistance to COMT and MAO

Salbutamol Isoprenaline (resistant to MAO) Phenylepherine (resistant to COMT)

Muscarinic effects on exocrine glands

Salivation Increased bronchial secretions Increased GI secretions (including gastric HCl production) Increased sweating (sympathetic-mediated)

State some side-effects of bethanechol (directly acting cholinergic9.1

Same as pilocarpine + bradycardia, nause

State the unwanted side effects of potassium channel openers and organic nitrates?

Same as side effects of dihydropyridines

State two protease inhibitor drugs

Saquinavir Ritonavir (reduces metabolism of protease inhibitor)

Summarise the classification of psychoses

Schizophrenia Affective disorders Affective disorders can be further split into Mania and Depression

During which stages of pregnancy does most weight gain occur?

Second and particularly third

When does intrauterine growth restriction (IUGR) usually develop/become apparent and why?

Second and third trimesters Almost all weight gain occurs in the later stage of pregnancy

Where are proton pumps (H+-K+ ATPase) expressed

Secretory vesicles within parietal cells

Iodothyronine Synthesis and secetion

See Y1 Endo 4 Flashcards

What are partial/focal seizures?

Seizures that start in a particular region of the brain and then spread outward

Summarise the mechanism of action of SSRIs

Selective monoamine (5HT) reuptake inhibition Propose less troublesome side effects, safer in overdose cases Less effective against severe depression

What is the selectivity ratio and what implications does it have

Selectivity ratio is how selective the statin is about which cells it will affect - if highly selective it is more likely to be concentrated in the liver

Give an example of a monoamine oxidase B inhibitor and how it works

Selegiline - reduces dosage of L-Dopa or will increase wait time before levodopa required

How does thyroxine increase sympathetic potency in the body

Sensitises Beta-adrenoreceptors to ambient levels of adrenaline and noradrenaline

Give the role of the thalamus in the modulation of pain tolerance and perception

Sensory -> thalamus via spinothalamic tract Thalamus directs signals to PAG + Cortex PAG activates the NRM (the effector arm) NRM sends inhibitory descending signals to the dorsal horn thus increasing pain tolerance

Name the hormone measured in diagnosis and the one used to replace the hormone when there is a deficiency of TSH

Serum T3 Thyroxine

Name the hormone measured in diagnosis and the one used to replace the hormone when there is a deficiency of ACTH

Serum cortisol Hydrocortisone

Name what is measured in diagnosis and the one used to replace the hormone when there is a deficiency of LH and FSH in men

Serum testosterone and libido Testosterone undecanoate

Describe the causes of parkinsons

Severe loss of dopaminergic projection cells in the SNc Lewy bodies and neurites found in neuronal cell bodies (consist of abnormally phosphorylated neurofilaments, and lewy bodies filled with toxic proteins ubiquitin and alpha-synuclein)

What enables penile erection

Sexy thoughts in the brain or tactile stimulation to penis (activated by limbic system in the brain) Tactile stimulus can also activate a reflex arc via the pudendal nerve

What type of hypopituitarism is specific to women? How does it occur?

Sheehan's syndrome - occurs when there is a post partum haemorrhage whereby blood loss causes spasm of the hypophysial arteries causing ischaemia and necrosis of the pituitary gland

Describe the relative periods of the plasma half life and duration of action of MAOIs

Short half life but long duration of action due to irreversible inhibition

Why is nicotine from cigarettes addictive?

Short lasting action of drug and fast breakdown means there will be more incentive for binge consumption

What are the clinical symptoms of Alzheimers? (5)

Short term memory loss Disorientation/confusion Language problems Personality changes

What are less common causes of hypothyroid conditions

Side effect of radioiodine therapy (where thyroid tumours are attacked) Side effect of drug treatment (glucocorticoids, thiourylenes, lithium.)

Why is Ipratropium bromide more suited to treating lung conditions as an MRA instead of atropine

Similar molecular shape to atropine but has an extra nitrogen-containing polar group attached that allows it to linger more in the lungs as it cannot cross the mucosa as easily as atropine would.

When is ketoconazole used?

Similar to metyrapone; used in the treatment + control of symptoms of Cushing's

State the pros and cons of using symphysis-fundal height for detection of stunted growth

Simple and inexpensive But low detection rate (50%+)

What are the two different types of partial/focal seizures

Simple: Retained awareness/consciousness Complex: impaired awareness consciousness

How does treatment using radioiodine work

Single dose given orally - the radioiodine is processed in the same way as stable iodide. Once it is concentrated in the colloid, the iodine will emit short range beta particles which have cytotoxic effects on the follicular cells. This leads to fewer cells being able to produce thyroxine

Structure of type 3 receptors

Single protein with 1 transmembrane domain and 1 intracellular domain

Summarise the virology/structure of influenza

Single stranded RNA virus Envelope proteins (Neuraminidase and Hemmagglutinin)

Which areas are most affected in Paget's disease? (5)

Skull, spine, tibia, femur and pelvis

Describe the clinical presentation of parkinsons' neuropsychiatric symptoms

Sleep disorders Memory deficits Depression Irritability

Define hypnotics

Sleep inducers

How is calcium release from the sarcoplasmic reticulum initiated

Small increase in calcium ions in cytoplasm from outside the membrane Process called calcium induced calcium release

Where are V1 receptors for vasopressin found

Smooth muscle (vascular + smooth muscle) Anterior pituitary gland Liver Platelets CNS

Name a GABA transaminase inhibitor

Sodium Valproate

Name two inhibitors of GABA metabolism, their method of action and their clinical use:

Sodium Valproate Vigabatrin Enable more GABA and more inhibition in the brain by inhibiting GABA Transaminase

Which class of anti-arrhythmic drug (vaughn-williams classification) acts on the upstroke part of the ventricular membrane potential

Sodium blockading class 1s

List 5 foetal hormones that are involved in and influence the growth of the foetus

Somatotrophin Prolactin FSH/LH Insulin Androgens Iodothyronines

What is the most important hormone in (childhood) growth?

Somatotrophin. Increases insulin resistance to raise blood glucose so is diabetogenic

What causes the pain seen in inflammation

Some inflammatory mediators activate sensory afferents > pain

Which type of drug would affect the central processes in the nervous system during neuromuscular transmission

Spasmolytics (diazepam, baclofen)

Propogation for AP along muscle fibre

Spasmolytics (e.g. Dantrolene)

What is the speed of onset of intoxication from alcohol proportional to and why?

Speed of intoxication onset is proportional to gastric emptying - this is because most of the absorption is done in the small intestines so intoxication will be delayed in a similar manner

Describe the acrosome action when the sperm reaches the ovum

Sperm's acrosome binds to the ovum zona pellucida's ZP3 glycoprotein receptor Calcium ion influx to sperm stimulated by progesterone leads to hyaluronidase and proteolytic enzyme release allowing penetration of the zon pellucida

Give the three forms of spina bifida

Spina bifida occulta (CNS ok but spine hasn't formed correctly) Meningocele (swelling through spinal cord, filled with the CSF) Myelomeningocele (swelling/herniaion that also includes nervous tissue - very severe)

The epiphyses of which bones are usually the last to fuse?

Spinal growth last, bones in pelvis last to fuse

Give an example of a Potassium sparing diuretic

Spironolactone Amiloride

Walkthrough spironolactone's mechanism of action

Spironolactone is a prodrug which is rapidly converted to canrenone; a competitive antagonist of the mineralocorticoid receptor. This blocks Na+ reabsorption and K+ excretion in the kidney tubules (potassium sparing diuretic).

Give the pharmacodynamics of carbamazepine (how it affects the bdy)

Stabilises inactive state of the sodiu channel and therefore reduces neuronal ctivity

Describe the 3 types of angina

Stable - pain on exertion due to fixed narrowing of to not play coronary Unstable - pain with less excretion - thrombus but without complete occlusion Variable - occurs at rest, caused by coronary artery spasm

What are the differences between stable and unstable atherosclerotic plaques and what are the potential consequences of each?

Stable plaques will have a thick fibrous cap Unstable plaques will have thinner fibrous caps and richer cores of lipids and macrophages

Describe stage 3 of parkinsons progression

Stage 3 = Synuclein deposition in the SN

Describe stages 1 and 2 of parkinsons progression

Stages 1 and 2 = Synuclein deposition in areas that aren't the Substantia Nigra - pre-symptomatic

How does breast size change throughout pregnancy

Starts enlarging from the first trimester and this continues right up til delivery

What is the first line pharmacological treatment for dyslipidaemia?

Statins

Summarise the mechanism of action of statins

Statins act on the mevalonate pathway (cholesterol synthesis) by inhibiting HMG-CoA Reductase Two main products within this pathway are Geranyl pyrophosphate and farnesyl pyrophosphate GPP and FPP necessary to activation of proteins that enable growth Blocking cholesterol synthesis causes liver cells to respond by synthesising more LDL receptors LDL binds to these LDL receptors and so circulating levels are lowered

What is Diazepam used against

Status epilepticus seizures

Summarise the pharmacokinetics of infliximab (anti-TNF alpha) therapy and hence the administration plan in treatment for IBD

Stays in the body for very long so repeat infusion every 8 weeks

How do potassium channel openers increase myocardial oxygen supply

Stimulates hyperpolarisation - ability of coronary arteries to contract is impaired

What are the effects of chronic alcohol consumption on the GIT?

Stomach tissue exposure to acetaldehyde can lead to damage of the gastric mucosa Ulceration common Increased stomach cancer risk

How does thalidomide carry out its effects

Stops blood vessel development leading to cell death results

How do calcium antagonists decrease contractility

Stops further entry of calcium into myofibrils leading to decreased contractility

What effect does a ganglion blocker have on the gut and why?

Stops motility leading to constipation At rest parasympathetic dominance is enabling gut motility. When ganglions get knocked out this effect ceases

Pharmacokinetics definition

Study of how drugs are handled by the body

Define Pharmacokinetics What sort of things does this study normally focus on

Study of how drugs are handled within the body Mainly concerned with: -how drug conc changes over time -how drugs pass across cell membranes -how often drugs should be given, long term effects and how they interact

What is the principle area affected in parkinsons?

Substantia nigra - accounts for the motor symptoms seen

What are the substrates and products of the P450 mediated oxidation reaction

Substrates: Drug, NADPH, oxygen, protons Products: Hydroxylated drug, water, NADP+

List the main benefits of anti-TNFa therapy

Successful in treating Crohn's Great for maintaining fistula closure

What happens in myoclonic seizures

Sudden brief muscle contractions

Define seizure

Sudden changes in behaviour due to electrical hypersynchronisation of neuronal networks in the cerebral cortex

What happens in tonic/atonic seizures

Sudden muscle stiffening/sudden loss of muscle control

How do patients with mononeuropathy usually present?

Sudden wrist drop or foot drop as a result of sudden loss of motor control Cranial nerve palsy leading to double vision

How does the adaptive drifty gene hypothesis explain the obesity epidemic we see today

Suggests fat people would die because of predation while thin people would starve in the cold As humans learned to defend against predators, those with genes that made them fat weren't selected against Genetic drift lead to more of the population having these genes

How does the thrifty gene hypothesis explain the obesity epidemic we see today

Suggests genes that coded for metabolic effciency and fat storage were selected for in the past as people who were able to store more fat were able to survive famines and pass on their genes

If zero-order kinetics are observed what does this suggest about the involvement of enzymes

Suggests that the enzymes are saturated and that the rate of removal has therefore peaked

Summarise the 4 classifications of fungal infections

Superficial - outermost layer of skin Dermatophyte - skin, hair or nails Subcutaneous - innermost skin layers Systemic - primarily the respiratory tract

What technique is used to definitively diagnose hyperpituitary secretion

Suppression test measurements where circulating hormone levels are tested for before and after giving a suppression agent (e.g. glucoe for GH)

Give the different classes of arrhythmias

Supraventricular Ventricular Complex (supraventric and ventric)

How can surgery help spina bifida?

Surgery can remove the anatomical lesions but won't be able to counteract the functional problems that may result from damage to nervous tissue

What happens in glaucoma

Sustained raised intraocular pressure - causes damage to the optic nerve and retina leading to blindness

Which NMJ blocking drugs are the depolarising nicotinic receptor agonistic kinds

Suxamethonium

How come the side effect of bradycardia is normally prevented

Suxamethonium is used post operatively after general anaesthesia by which point the patient would have already been given a competitive muscarinic antagonist atropine

Where in the SNS can you find muscarinic receptors

Sweat glands only

Which limb of the ANS (Parasym or sym) dominates in the liver

Sympathetic - for fight and flight glycogenolysis and gluconeogenesis

Which features about sympathetic and parasympathetic responses differ?

Sympathetic = coordinated and divergent Parasympathetic = discrete and localised

List the symptomatic therapies for IBDs

Symptomatic treatments: Glucocorticoids Aminosalicylates Immunosuppressives

What is meant by negative symptoms of schizophrenia

Symptoms that occur as a result of decreased mesocortical dopaminergic activity

What is meant by positive symptoms of schizophrenia

Symptoms that occur as a result of increased mesolimbic dopaminergic activity

What enables vesicle attachment to the presynaptic membrane

Synaptic vesicle associated protein (SV2A)

Summarise and explain the different types of pharmacodynamic drug-drug interactions that can occur

Synergistic action (combined effect means amplification) Overlapping toxicity Antagonistic effects

Briefly summarise the synthesis of calcitonin

Synthesised as pre-procalcitonin Gradually cleaved down to Calcitonin - a 32 amino acid polypeptide (basically how all polypeptide hormones are synthesised)

What is tibolone and what is it used for

Synthetic prohormone with oestrogenic, progestogenic and weak androgenic actions Reduces fracture risk

Describe stages 4, 5 and 6 of Parkinson's

Synuclein deposition in the amygdala and cortical areas

What type of fungal infections do polyenes treat

Systemic infection

State the equation for half-life in first-order kinetics reactions.

T1/2 = Vd x log(2)/ClVd = volume of distributionCl = clearance

List some of the complications and associated features of obesity (7)

T2 Diabetes Orthopaedic problems CVD problems Psychological problems Cancer risk Respiratory difficulties Polycystic ovaries

Give the changes seen in the first and second phase responses in patients with T2DM

T2DM patients basically have no first or second phase response but will have a higher baseline for insulin production

Which of T3 and T4 binds more readily to the intracellular receptor

T3

When do T4 and T3 hav their peak effects

T3 - 2 days T4 - 9 days

Which of T4 and T3 is a prohormone

T4

Summarise initiation of haemostasis

TF bearing cells activate F5 and F10 F5 and F10 make up the pro-thrombinase complex The prothrombinase complex activates F2 into thrombin

Why does THC slowly accumulate in fatty tissues?

THC is extremely lipid soluble

What is primarily responsible for oestrogen production after day 40

THE PLACENTA TAKES OVER OESTROGEN PRODUCTION VIA DHEAS DHEAS is a precursor produced in the foetal and maternal adrenals

Briefly summarise the routes of metabolism/effector mechanisms of azathioprine and the consequences of such

TPMT Pathway - produces metabolite which is hepatotoxic HPRT Pathway - metabolite is beneficial but may cause myelosuppression XO Pathway - leads to inert metabolites

Describe the Tau hypothesis of Alzheimers disease:

Tau is a soluble protein present in axons important in assemble and stability of microtubules Hyperphophorylated tau self aggregates as becomes insoluble Neurofibrillary tangles formed from this are neurotoxic

What effect does metabolism generally tend to have on a drug

Tends to reduce the pharmacological or toxicological effect of the drug by making it more polar, soluble and easy to excrete

State the drug used to treat hepatitis B infection Summarise its mechanism of action

Tenofovir - nucleotide analogue Inhibits reverse transcriptase

What is Terlipressin and what is it used for

Terlipressin is a V1 analogue agonist It is used to treat haemorrhages in oesophageal varices

Summarise the structure of morphine and how its features relate to its activity

Tertiary Nitrogen - permits receptor anchoring and responsible for analgesic effect Methyl group attached to N is important to agonistic effects Hydroxyl group at position 3 is required for binding Hydroxyl group at position 6 increases the lipophilicity of the drug by ten-fold

What are the relative contributions of the testes and accessory sex glands to the volume of seminal fluid ejaculated

Testes = small contributor Accessory Sex Glands = major contributor

Male fertility hormones: where is testosterone produced?

Testis (Leydig cells)

Male fertility hormones: where is inhibin produced?

Testis (sertoli cells)

Give sites of testosterone production

Testosterone/androgens are produced in: Leydig cells of the testis. Adrenal cortex. Ovaries. Placenta. Tumours.

Which cytokines will be produced by Th1 cells and what action do they carry out

Th1 cells produce IL-2 and IFN-γ > proliferation + differentiation into CD8+ T-cells

Which cytokines will be produced by Th2 cells and what action do they carry out

Th2 cells produce IL-4 which acts on B cells > B cell proliferation + antibody production

State some chemical teratogens

Thalidomide Lithium Cocaine

What is the function of the anterior cingulate cortex?

The ACC is heavily involved with performance monitoring with behavioural adjustment in order to avoid losses. E.g. Driving a car whilst talking to a friend and then it starts raining so you stop talking to focus on the road.

How is a combined oral contraceptive cycled?

The COC is taken for 21 days (or 12 weeks) and is then stopped for 7 days

For what effects are muscarinic receptor antagonists used in anaesthetic premedication

The MRAs block the PNS and so block; bronchoconstriction (so bronchodilates), watery secretions (more thick secretions decreases chance of aspirations), decreased HR and contractility (protect the heart from slowing effects of other drugs) and also sedates the patient.

How come we can produce drugs that specifically target the somatic nervous system

The NMJ nAChR is different in structure to the ganglionic nAChR

Give the role of the NRPG in the modulation of pain tolerance and perception

The NRPG is independent of the thalamus and will automatically suppress pain before it has a chance to process it

How does alpha-2 adrenoceptor feedback work in modulating noradrenaline release

The a2 receptor is a prejunctional receptor found on the neurone that releases noradrenaline and acts on negative feedback - will trigger reduction of NA exocytosis on binding of NA to it

Biological half-life

The amount of tie for the concentration of a drug to reach half its original value

What happens in angle closure glaucoma

The angle between the cornea and the iris is narrowed which decreases the drainage of intraocular fluid through the canals of Schlemm

Why does brain function alter during pregnancy?

The brain is exposed to particularly high levels of steroids like progesterone which alter brain function

Where is aqueous humour produced? Describe its passage through the eye.

The capillaries in the ciliary body produce aqueous humour Aqueous humour passes anteriorly into the anterior chamber and is then drained through the canals of Schlemm into the venous system

What determines a nicotinic receptor's ligand-binding properties

The combination of the subunits

Why is the urethra not compressed during penile erection?

The corpus spongiosum protects it

Why are foetal weight graphs (and old crown-rump length graphs) likely to be inaccurate, hence limiting its use as comparison to track the growth of a mother's pregnancy?

The data used to make these graphs are from miscarriages But cause of miscarriage is often foetal growth restriction - hence inaccuracies likely as it probably does not depict normal growth in the first place

What happens once the oxygen molecule has picked up two electrons from the Cyt P450's catalytic site

The drug that is bound in the site is converted to its hydroxylated derivative and the unstable oxygen is reacted with two protons to give water. The drug is released and the P450 with its ferric group is ready to undergo another cycle

Hepatic first pass metabolism

The effect/change to drug that occurs upon the first pass through the liver

Why are people that metabolise morphine less well more likely to experience negative side effects

The effects of the metabolites of Morphine will be similar to that of the morphine itself without the negative side effects - where it is not metabolised as well the effects will remain but with the negative side effects in tow

Why does oestrogen and progesterone increase beyond what negative feedback would normally allow at the beginning of the prgnancy

The hCG produced by the trophoblasts do not factor into the axis and will act as LH on the corpus luteum stimulating further oestrogen and progesterone production

By which enzymes are most opioids metabolised by?

The majority of opioids are metabolised in the liver by either CYP3A4 and/or CYP2D6

What happens once the drug has bound to the iron in the Cyt P450's catalytic site and the Fe3+ has picked up an electron from the NADPH

The molecular oxygen binds to the catalytic site and the ferrous ion loses its electron to the oxygen, becoming ferric once again

Why may it be dangerous to administer suxamethonium (depolarising NM blocker) to a burns/soft tissue injury patient?

The nerves remaining in that tissue become hypersensitive and so when we administer suxamethonium you get an exaggerated response which can lead to ventricular arrhytmias

To what does ACh bind to in the nmj

The nicotinic acetylcholine receptors on the end plate

What is the main difference between the Hypothalamus-Pituitary-Gonadal axis (HPG axis) between normal and postmenopausal women

The oestradiol production from the follicles is low in women with menopause while in normal women it is high matching the response of GnRH and LH+FSH

What factors will affect the ration of ionised to non-ionised ratio of the drug

The pKa of the drug The pH of the environment

Give key details of the presentation of Plummer's that makes it distinct from Graves'

The patient does not present with pretibial myxoedema, and does not present with exophthalmos either as there are no antibodies involved. The tumour results in an asymmetric enlargement of the thyroid, which can be seen on a scintogram

What is menopause

The permanent cessation of menstruation

What CNS structure is important to generating a respiratory rhythm

The pre-Bötzinger complex is a small area in the ventrolateral medulla that can generate a 'respiratory' rhythm.

Summarise the mechanism by which opioids cause repiratory depression

The pre-Bötzinger complex is active during inspiration and is inhibited by opioids. Central chemoreceptors provide tonic drive to the respiratory motor output by sensing changes in pH and are inhibited by opioids (via Mu2 receptors)

Give the properties of the derivatives formed in sulphation

The product is the sulphuric acid derivative of the drugThis is very polar and water-soluble

How does previous intrauterine growth restriction and/or intrauterine death affect subsequent pregnancies?

The risk of IUGR and still-birth is increased in subsequent pregnancies

What is a clearance

The volume of plasma that is cleared of a drug per unit time

What is the general location of action for NM blocking drugs?

Their location of action is post-synaptic - they act on the nicotinic receptors on the motor end plate

Which mechanism prevents multiple sperm binding to the same ovum

There is a cortical reaction following sperm binding to the ZP3 receptor which degrades other ZP3s on the zona pellucida meaning there are no more places for further sperm to bind

What is a common/major problem with the use of alpha adrenoceptor antagonists?

There is a fall in arterial pressure causing problems of postural hypotension Fall in tpr causes reflex tachycardia

What happens in Plummer's disease

There is a toxic nodular goitre. This is not an autoimmune condition, but is a benign adenoma that is overactive at making thyroxine.

Which parts of the world have the highest alcohol consumption?

There is heavy alcohol use in Western Europe/Europe in general. The worst place in the world in terms of the amount of alcohol drunk per capita is Ireland.

What effect would diuretics have on renin secretion?

There would be hyponatraemia over time due to the excretion of sodium low Na concentration in the kidney stimulates renin secretion RENIN INCREASES ALDOSTERONE, WHICH PROMOTES REABSORPTION OF SODIUM • Often, diuretics are given WITH ACE inhibitors, to reduce the effect

What can happen to lipid soluble molecules in the pct and dct

They can be reabsorbed

Why don't pre-diabetics have increased rate of microvascular complications?

They don't yet have the chronically high (fasting/resting) blood glucose, but they do have the macrovascular risks/properties)

What are the 3 main stages in the capacitation of sperm?

They lose their glycoprotein coat Their surface membrane characteristics change They develop whiplash movements of their tail

What is the use of thiamine in the CNS?

Thiamine acts as an essential coenzyme to the TCA cycle and the pentose phosphate shunt. Thiamine deprivation ultimately leads to cell death

What is used to treat nephrogenic diabetes insipidus? Give the mechanism

Thiazides such as bendroflumethiazides Possible mechanism: Blocking sodium/chloride transport in dct which leads to diuretic effect -> volume decrease leads to compensatory increase in sodium reabsorption from pct -> pct water reabsorption also increases -> less fluid reaches collecting duct and urine

Why might thiazides lead to magnesium loss, but increased calcium reabsorption?

Thiazides work early in the DCT and cause Kidney to try and upregulate Sodium reabsorption later on. Potassium is linked to magnesium reabsorption - increased potassium loss from Na/K pumping leads to reduced magnesium reabsorption - mechanism unclear As Na reabsorption is attempted to be upregulated by the kidney, this increases calcium reabsorption as the reabsorption of sodium and calcium seem to be linked together

What can be given in preparation for a thyroidectomy?

Thiourylenes - will reduce symptoms while waiting for radioactive iodine to act Potassium iodide

What is meant by use dependency in the context of receptor blockade

This is where the blockade effect becomes more pronounced when the tissue it is acting on is more active E.g. Nociceptor neurons fire much more rapidly and so their ion channels are open ore regularly making it easier for blockade drugs to get in and stop passage of ions

Summarise the platelet activation and amplification phase of haemostasis

Thrombin activates platelets on a positive feedback basis The activated platelets change shape and begin to attach to other platelets

What is the pharmacological treatment for ischaemic stroke and STEMI?

Thrombolytic drug - Alteplase Serine protease which helps convert plasminogen to plasmin and degrades fibrin to dissolve the clot

State which type of anti-haemostatic therapy is targeted towards the propogation stage

Thrombolytics

What kind of smptoms would you expect with an unstable plaque

Thrombosis as the fibrous cap is thin making rupture from a BP surge likely and causing collagen exposure

What is the entrance route for surgeries that aim to treat pituitary hypersecretion

Through the nose (transphenoidal)

Give the condition associated with excess thyrotrophin (TSH)

Thyrotoxicosis

What are characteristic signs of chronic inflammation (when a pathogen persists)

Tissue damage (cell death or ulceration) Impaired tissue function (eg restricted joint movement, bronchospasm) Local repair processes (proliferation of local cells, becoming fibrous connective tissue) Scarring

List two selective oestrogen receptor modulators (SERMs)

Tissue selective oestrogen receptor agonist Raloxifene - oestrogenic activity in bone. Antioestrogenic activity in breast and uterus Tissue-selective oestrogen receptor antagonist Tamoxifen - oestrogenic effect in bone and uterus but antagonistic effect on oestrogen receptors in breast

List some reasons explaining the importance of dating a pregnancy accurately

To prevent SGA or LGA confusion To prevent Inappropriate inductions To be able to give steroids in preterm delivery appropriately

Why does chronic use of cocaine lead to cocaine binging and more negative central effects?

Tolerance increases so some of the euphoric effect is lost Dopamine metabolised without being reuptaken Fewer dopamine vesicles available to replenish synapse

What is carbamazepine used against

Tonic clonic seizures and partial seizures

What is Lamotrigin used against

Tonic-clonic seizures Absence seizures

Why don't drug-protein complexes enter the filtrate when they reach the glomerulus

Too large

Why is the Vaughn-Williams classification for anti-arrythmics of limited clinical significance?

Too much cross over in the effects of new drugs for them to be classified

Summarise some available strategies to be able to minimise the unwanted side effects of glucocorticoid (and general drug) use in treatment for IBD

Topical admin Low dose if combined with another drug Use variant with high hepatic first pass metabolism

How can the GI side effects of NSAIDs be limited without resorting to COX2 selective agents which increase CVD risk?

Topical application (less systemic access) Limit use in people with GI ulceration history Coadminister omeprazole (reduces stomach acid)

Name a drug involving action on glutamate receptors (NMDA and kainate) by inhibiting them

Topiramate

Summarise the forms calcium takes within the blood and which one the bioactive component is

Total = 2.5mM Half is unbound ionised calcium in the blood. This is BIOLOGICALLY ACTIVE. 45% of calcium is bound to plasma proteins in the blood 5% of calcium exists as diffusible salts

What are the central effects of cocaine from chronic use?

Total insomnia Decreased libido

How are thyroid carcinomas treated

Total thyroidectomies followed by a large dose of radioiodine and thyroxine to suppress TSH

What are the different types of calcium channel?

Transient t-type or long lasting l-type

What are the ways to treat amenorrhoea

Treat the cause - i.e. low BMI. § Primary ovarian failure - infertile so HRT. § Hypo/pit disease - HRT for oestrogen replacement and gonadotrophins for fertility treatment.

What is used to treat hyperprolactinaemia

Treat the cause - stop the drugs. § Dopamine agonists - cabergoline and bromocriptine. § Prolactinoma - DA agonists or pituitary surgery

Describe how corticosteroid therapy is used to treat Primary (failure of the adrenal cortex) adrenocortical failure

Treat with titrated doses of oral hydrocortisone + fludrocortisone, with electrolyte level + BP monitoring

Describe how corticosteroid therapy is used to treat Secondary (ACTH deficiency) adrenocortical failure

Treat with titrated hydrocortisone

What can cannabinoid receptor agonists be used for?

Treating MS pain Anti-emitics (against vomiting and nausea) in cancer

Exogenous adrenaline is frequently used for anaphylaxis. List 3 other clinical uses for adrenaline

Treating asthma (bronchodilatory effects via Beta-2) Treating cardiogenic shock (intotropic effects via Beta-1) Aiding anaesthesia (via Alpha-1 vasoconstrictory effects)

What are the clinical uses of salbutamol

Treatment of asthma Treatment of premature labour (relaxes uterine smooth muscle)

What symptoms from hyperthyroidism occur due to increased sympathetic activation

Tremors Heart palpitations/tachycardia Lid lag

Give examples of drugs that acts on transport systems

Tricyclic antidepressants - slow down postsynaptic reuptake into nerve terminals Cardiac glycosides which slow down the sodium potassium pump and therefore increase intracellular calcium ion concentration leading to increased forces of contraction

Mechanism of muscarinic effects on vasculature

Triggers the production of nitric oxide (NO) from the endothelial cells, which causes vasodilation and a decrease in Total peripheral resistance

What constitutes glutathione?

Tripeptide made up of Glycine, glutamine, cysteine

Give the structure of BDZs

Triple-ring structure All BDZs act on GABAa receptors

Which muscarinic receptor antagonists have opthalmic effects? What is the effect?

Tropicamide: § Used in examination of the retina - causes dilation/miosis.

What are the two major causes of adrenocortical failure

Tuberculosis Addison's Disease (most common worldwide where a bacterial infection causes damage to your adrenals) Autoimmune Addison's disease (most common in he UK)

Which NMJ blocking drugs are the non-depolarising competitive nicotinic receptor antagonistic kinds

Tubocurarine Atracurium

Which type of drug would affect the depolarisation of the motor end plate during neuromuscular transmission

Tubocurarine Suxamethonium

Give the causes of SIADH

Tumours (ectopic secretion) • Neurohypophysial malfunction (e.g. meningitis, cerebrovascular disease) • Thoracic disease (e.g. pneumonia) • Endocrine disease (e.g. Addison's disease) • Physiological i.e. non-osmotic stimuli (e.g. hypovolaemia, pain, surgery) • Drugs (e.g. chlorpropamide) • Idiopathic

What are the leading causes of acquired GH deficiency

Tumours of the hypothalamus or pituitary • Other intracranial tumours nearby (e.g. optic nerve glioma) • Secondary to cranial irradiation (radiotherapy) • Head injury • Infection or inflammation • Severe psychological deprivation

List some potential reasons for abnormal/short growth despite having normal hormones during childhood (4)

Turner's syndrome Down's syndrome Skeletal dysplasia Significant illnesses

What is the difference between chimerism and mosaicism?

Two genotypes present in person In chimerism this is because two fertilised zygotes have fused so there is double the normal amount of genetic material going on In mosaicism there are two genotypes present but this is because there is an additional population of cells with a distinct genotype

How many ACh molecules are required to activate a nAChR? Explain why

Two molecules of ACh because there are two alpha subunits and both need to be activated

Which type of diabetes is likely to occur in young and lean patients

Type 1

What are the four types of receptors and how does their speed of transmission vary

Type 1 - ionotropic Type 2 - G protein coupled Type 3 - tyrosine kinase linked Type 4 - intracellular steroid type Speed of transmission decreases 1 to 4

What sort of receptors are nicotinic receptors

Type 1- ionotropic receptors

Which type of diabetes are people who are older and more obese likely to suffer from

Type 2

Give the pathogenesis of type 2 diabetes

Type 2 behaves as a genetic disorder which contributes to insulin resistance Intrauterine growth restriction greatly increases the chances of developing T2DM (poor growth of a fetus while in the mother's womb)

What is the largest cause for blindness and renal disease in the UK for people of working age?

Type 2 diabetes

What sort of receptors are muscarinic receptors

Type 2- GPCRs

Explain the relationship and interactions between tyramine, cheese and MAOIs

Tyramine = trace amine derivative of tyrosine (SNS activator) Tyramine-containing foods + MAOI leads to a hypertensive crisis PATIENTS TAKING MAOIs MUST AVOID FOODS THAT ARE HIGH IN TYRAMINE (e.g. mature cheese, red wine).

Give the reaction steps for Noradrenaline synthesis from Tyrosine

Tyrosine -> DOPA DOPA -> Dopamine Dopamine -> Noradrenaline

What is the rate limiting enzyme in dopamine synthesis?

Tyrosine hydroxylase

Which enzyme is used in the Tyrosine -> DOPA reaction

Tyrosine hydroxylase

Give a conjugating agent used for glucuridination

UDPGA

How/when are glucocorticoids used in ulcerative colitis and Crohn's disease respectively?

Ulcerative colitis - use is in decline Crohn's disease - drug of choice for inducing remission

In what state are drugs like aspirin easily absorbed - ionised or unionised?

Unionised

What are the major two types/classes of depression?

Unipolar depression Bipolar depression

List the causes of antibiotic resistance (4)

Unnecessary prescription Livestock farming (use in populated farming to stop infections between animals) Lack of development of more antibiotics Lack of regulation

What negative CVS issues does COX 2 inhibition lead to

Unrestrained platelet acivation Decreased protection against arrhythmias Increased blood pressure

Which limbs begin development first?

Upper

How can cannabinoid receptor expression change in different disease states such as multiple sclerosis/chronic pain and fertility/obesity?

Upregulation in disease states Can be positive (e.g. in multiple sclerosis it is regulatory and compensates for pain perception) Can be directly contributing to pathology (e.g. fertility and obesity)

What are the two main uptake+breakdown mechanisms of noradrenaline

Uptake 1 transport protein (found in neuronal tissue) followed by breakdown by Monoamine Oxidase Uptake 2 transport protein (found in extraneuronal tissue) followed by Catechol-O-Methyl Transferase

How does the source of progesterone during pregnancy change (luteo-placental shift)?

Upto 8 weeks of gestation it is the corpeus luteum (driven by hcG) that sources progesterone but after this point it is the placenta

Summarise the virulence factors of H. Pylori that contributes to peptic ulcer formation

Urease present - will metabolise urea into NH4Cl and monochloramine -> epithelial cell damage Enzyme will also evoke immune response

What would the treatment for a complicated peptic ulcer caused by H. pylori be?

Use more antibiotics for a longer period Omeprazole used to help control the acidity

How is it determined as to whether it would be appropriate to class a foetus at IUGR/FGR?

Use of serial observations so growth is being tracked over time Allows us to see if size of foetus is significantly low on the centile biometry

Give key properties of ganglion blocking drugs

Use-dependant blocks - the drug works best when the channel is open so the more the receptor is used, the more it is blocked. Incomplete blocking - Ion-channel blockade is only partial (as some ions still pass through) Some GBDs do NOT have affinity as some types DON'T bind to the receptor, just block the ion-channel itself.

When is trilostane used

Used in cushing's syndrome, particularly in primary hyperaldosteronism Circulating corticosteroids and plasma electrolytes are monitored and replaced with glucocorticoids and mineralocorticoids when necessary. also used in the reduction of sex steroid hormone production, e.g. in post-menopausal breast cancer

List 4 uses of SNS antagonists and false transmitters

Used to treat Arrhythmias Angina Glaucoma Hypertension

For which patient cases is the therapeutic administration of leptin useful?

Useful for people who are leptin deficient E.g. helps to restore LH pulsatility in women with low body fat that has led to amenorrhoea

Explain how chemotherapy induced nausea and vomiting is treated

Using 5HT (seratonin) receptor antagonists like ondansteron WITH Glucocorticcoids that will reduce free radicals Aprepitant: neurokinin 1 receptor antagonist (nk1 receptors connect solitary tract and vomiting center)

Give the duration of action of suxamethonium

V short lived, approx 5 mins

What are the non-major effects of vasopressin

V1a receptors are responsible for the potent vasoconstrictor actions • V1b receptors are found specifically on corticotrophs in the APG, and mediate the release of corticotrophin (ACTH) • V2 receptors are involved in the production of Factor VIII + von Willebrand factor, therefor has an important role in blood clotting

What are the small vessels supplying nerves called?

Vasa nervorum

What is the effect of alpha 1 adrenoceptors

Vasoconstriction and relaxation of GI tract

Why is phenylephrine used as a nasal decongestant?

Vasoconstriction of vessels in the nose

What is the main V1 mediated action of vasopressin

Vasoconstriction that increases blood pressure

What causes a decrease to afterload with Organic nitrate and potassium channel opener use

Vasodilation - decreased afterload Venodilation - decrease preload

What is the most commonly used rate-limiting calcium channel blocker

Verapamil

What might indicate to a T1DM patient that they had a nocturnal hypoglycaemic episode?

Very high glucose when waking up might indicate they had a hypoglycaemic episode during their sleep This is because their autonomic (catecholamine, cortisol, SNS drive) would have compensated and overly increased their glucose levels

What features of the cell in the ascending limb make it impermeable to water

Very tight junctions MAny mitochondria for active transport Very high metabolic activity

Summarise the cellular mechanism of action of opioid receptors

Via depressant actions Increased K+ efflux (hyperpolarisation) Reduced Calcium influx (Less neurotransmitter exocytosis) Reduced adenylate cyclase activity (reduced general cell activity)

State the class of drugs used to prevent HIV DNA integration into host DNA and its mechanism of action Give an example

Viral integrase inhibitors E.g. Raltegravir

What is the retinal feature of proliferative diabetic retinopathy?

Visible new vessels - on disc or elsewhere in retina

Why is the epididymal fluid important to spermatazoa?

Vital for maturation process, provides energy for the journey and coats the sperm in protective layer

Which clotting factors does warfarin inhibit the production of?

Vitamin K dependent factors Factors 2, 7, 9, and 10

What is apparent volume of distribution

Volume of water in which drug would have to be distributed to give its plasma concentration

Summarise the CNS areas involved in control of nausea/vomiting and identify the main mechanistic triggers

Vomiting centre Chemoceptor triggering zone, which communicates with the vomiting centre Mechanistic triggers = GI problems,motion sickness, cytotoxic drugs

Give an anticoagulant that works by reducing levels of other factors

Warfarin

If taken orally, what part of the GI tract are opioids best absorbed and why?

Weak bases so will be absorbed best in the slightly alkaline conditions of the small intestines (where it is less ionised) pKa <8

What sort of pH do most drugs have

Weakly acidic or weakly basic

What is a common side effect of T2DM medication? What are the clinical implications of this?

Weight gain, metformin only drug that doesn't cause this problem

Describe the inheritability of obesity

Weight is highly heritable and mainly polygenic There are some very rare monogenic obesity syndromes

Summarise some of the biological evidence that does not fully support the monoamine theory of depression.

When antidepressant drugs are given the change in monoamine levels is rapid but there is a significant delay before any clinical effect is observed

Summarise the delivery mechanism of nicotine from cigarettes

When cigarette is heated, tar droplets form which nicotine dissolves into

What is peripheral neuropathy?

When nerve damage is developed in the hands and feet. Symptoms include: loss of sensation in the hands and feet, they get a pins and needles feeling, muscle weakness, erectile dysfunction in men, and trouble walking.

When should spironolactones not be used

When patient has renal or hepatic disease

When is the equilibrium of a drug shifted towards the unionised state of the drug

When the pH of the environment is lower than the pKa

When do plasma binding proteins increase in the body

When the patient is pregnant or they are being given prolonged treatment with oestrogens and phenothiazines

At what point is a patient classed as having 'resistant' hypertension?

When the patient's blood pressure is not being properly controlled after 3 drugs are being administered together

How does chimerism occur?

When two genetically distinct conceptuses combine to form one individual with two complete genomes in their body

What is ion trapping

Where a drug enters the blood stream in ionised form and thus is retained in the aqueous medium and unable to move back into the tissues

What is the end-stage effect on the liver from chronic alcohol use?

Where inflammatory environment is so bad that active liver tissue is replaced with connective tissue (Acetaldehyde, the first metabolite of ethanol, can upregulate transcription of collagen I directly)

What is mononeuropathy?

Where only one nerve is affected

Define first-order kinetics in the context of drug excretion

Where the rate of drug excretion is proportional to the conc of drug remaining in the body (when there is a higher conc in the body, the excretion rate is higher)

What is drug tolerance

Where the responsiveness to a drug is decreased as the administration of the drug is done repeatedly

What is anencephaly? What is it a result of?

Where the top part of the head doesn't develop properly Caused by incompete anterior neuropore closure

What is autonomic neuropathy?

Where there is a loss in sympathetic and parasympathetic function to the GI tract, bladder and CVS

What is piebaldism and what is it caused by?

Where there is a pale triangle on the abdomen and streak on forehead caused by mild mutation of C-KIT receptor

What happens in conn's syndrome

Where there is primary hyperaldosteronism (typically due to a benign adrenal cortical tumour in the zona glomerulosa)

What happens in absence seizures

Where you blank out and stare into space

What are the advantages of using BDZs over Barbs

Wide therapeutic window Mild effect on REM sleep Does not induce liver enzymes

Explain the consequences of diabetes on adipocyte breakdown

Without insulin, lipolysis occurs releasing non-esterified fatty acids and glycerol. The NEFAs contribute to dyslipidaemia and the glycerol moves into the liver increasing hepatic glucose output

A man and a woman of similar height and weight share a bottle of wine equally. Explain why the blood alcohol levels in the woman are likely to be higher.

Women have less alcohol dehydrogenase in their stomachs Men have more body water as well so the alcohol in their blood will be more diluted

Explain how the log dose curve showing the response of skeletal muscle to increasing concentrations of Ach would be altered in the presence of tubocurarine

Would be shifted to the right as more ACh would be required to bring out a response in the prescence of tubocurarine This is because ACh has to surmount/outcompete tubocurarine

What is the only XY linked loss-based aneuploidy that is viable? Which syndrome is it characterised by?

X - Turner's Syndrome. Female, short stature, infertile

State some physical teratogens

X rays and ionising radiation

Does bipolar depression have strong inheritance

Yes

Summarise the sequence of steps in the progression of atherosclerosis

You get the initial lesion which leads to macrophage infiltration and isolated foam cells A fatty streak forms after intracellular lipid accumulation This leads to an intermediate lesion characterised by small extracellular lipid pools and intracellular lipid accumulation Atheroma then comes together as the extracellular lipid pools merge to form a core of extracellular lipid Fibroatheroma is developed following the addition of fibrotic+calcific layers Complicated lesion then forms causing thrombosis and haematomas/haemorrhages

What effects would you look for in a drug that you wanted to treat an atropine overdose with

You would want to give a drug that either enhanced ACh activity (anticholinesterase) or inhibits atropine.

State 3 classes of drugs used to prevent replication of HIV

Zidovudine (Nucleoside reverse transcriptase inhibitor) Tenofovir (Nucleotide reverse transcriptase inhibitor) Efavirenz (Non-nucleotide reverse transcriptase inhibitor)

Name of the DNA binding domain of the steroid-receptor complex

Zinc fingers

What happens in psychogenic polydipsia

a central disturbance combined creates the sensation of thirst and leads to increased drinking (polydipsia), leading to the expansion of extracellular fluid volume and a decrease in plasma osmolality.

What type of hormone is parathormone?

a polypeptide hormone

What is Holt-Oram syndrome and what is it caused by?

a range of heart and hand defects Caused by the mutation of TBX5 gene - a TF involved in development of the heart and hands

Describe the reaction that happens when the sperm and oocyte meet

a. Acrosome reaction - penetration of zona pellucida (& Coronal cells). b. Calcium flux. c. the cortical reaction is initiated, leading to hardening of the zona pellucida and the exclusion of other sperm

Which adrenoceptor does Prazosin selectively antagonise What are the physiological effects of this

a1 Causes vasodilation and a fall in BP (CO decreases due to fall in venous pressure as a result of dilation of capacitance vessels). Less reflex tachycardia as they do not block the a2 receptors to increase NE release prazosin also causes a modest decrease in LDL and an increase in HDL

Why is a selective alpha-1 receptor blocker preferred over a non-selective alpha receptor blocker in treatment for hypertension?

a2 antagonism can increase HR

Why do alpha 2 receptors and baroreceptors reduce the effectiveness of phentolamine?

a2 blockade means negative feedback effects are lost so NA release increases. Increased baroreceptor firing from lowered arterial pressure will have the same effect (NA increases) NA competes with phentolamine for the receptor

How long does the progression of a primary follicle to ovulation usually take?

about 3 months

What is dobutamine's biological half life

about two minutes

What is amenorrhea?

absence of menstruation

What is thyroid storm? Why is it a medical emergency?

acute, life-threatening form of thyrotoxicosis that may present w/ Afib, fever, and delirium emergency as there is a 50% chance of mortality if it is untreated.

What is the difference in pharmacological treatment between a DVT comapared to PE?

add heparin as well as dalteparin because heparin has a slightly faster mechanism of action and PE is more dangerous

What is the mid-parental centile and what is it used for?

adjusts the normal distribution up or down for the parents' height. i.e. the line will stay parallel to the other centiles, but just shifted up/down in order to estimate the maximum potential height of the child.

Where does Noradrenaline synthesis occur?

adrenal medulla and postganglionic neurons of the sympathetic nervous system

After which trimester is the likelihood of a pregnancy to reach term 95%+?

after first trimester (13 weeks) so pregnancies that pass the first trimester are most likely to be successfull

State the two major enzymes that metabolise alcohol. State the percentage of metabolism done by each enzyme

alcohol dehydrogenase (75%) and mixed function oxidase (25%)

Which receptor (MR or GR) does Fludrocortisone mainly act on

aldosterone analogue used as an aldosterone substitute (both)

Summarise the mechanism and use of the anti-depressant drug Mirtazapine

alpha2 receptor antagonist Increases NA and 5HT release in the brain Useful in SSRI intolerant patients

Define teratogen

an agent or factor that causes malformation of an embryo.

Nutrient and glycoprotein secretion into the epididymal fluid is controlled by which hormone?

androgens (ie testosterone)

What type of hormones are produced in the zona reticularis? What is the principle hormone

androgens and oestrogens (principle steroid = DHEA)

Male fertility hormones: where is Follicle stimulating hormone produced?

anterior pituitary gland

What are acquired immune responses initiated by

antigenic products of invading microorganisms which reach the lymph nodes hypersensitivity (inappropriate) reactions to exogenous substances; hypersensitivity reactions to endogenous proteins that are normally innocuous (i.e. autoimmunity).

Define severe hypoglycaemia

any hypoglycaemic episode that requires the help of another person to treat it

Why is PYY a difficult target for drug manipulation?

as it has a narrow therapeutic window People also react differently to the levels in their system.

What is the part of the nephron that is impermeable to water?

ascending limb of loop of henle

Why might beta-blockers make patients more susceptible to hypoglycaemia?

b-blockers may mask hypoglycaemic symptoms (tremors etc.) and non-selective b-blockers will also block hepatic glycogenolysis (b2).

Explain the mechanism by which beta-blockers are able to be used as effective agents to treat glaucoma

b1 receptors on ciliary body linked to carbonic anhydrase Carbonic anhydrase action leads to aqueous humour production in blood vessels If blood flow and bp is reduced then carbonic anhydrase effectiveness decreases and less aqueous humour produced

Which type of sympathetic stimulation to the liver stimulates hepatic glycogenolysis?

b2

Why can tubocurarine be used as the neuromuscular blocker for pregnant women?

because it does not cross the placenta (and BBB)

Why does hepatitis A not require antiviral treatment?

because it only produces an acute infection where the patient gets better by themselves for a month or so

Why does orally administered oestradiol require a much larger dose than other methods of administration?

because it undergoes a significant amount of first-pass metabolism

Why are thrombolytics not generally used?

because they are v dangerous drugs and can lead to excessive bleeding That's why they're only used in emergencies

All drugs ending in -olol are what type of drug?

beta blockers

Which drugs are class 2 according to Vaughan Williams classification

beta blockers

Why is Aspirin unique amongst the NSAIDs?

binds IRREVERSIBLY to COX enzymes

What is the method of action of maraviroc

blocks CCR5 chemokine receptor which HIV GP120 binds to

What is the mechanism of action of verapamil

blocks VGCC and thus depresses SA firing and subsequent AV node conduction. Verapamil is a rate-limiting calcium channel blocker. They get into the nodal tissue, block calcium channels and therefore decrease depolarisation. This is an attempt to normalise the rhythm.

Describe and explain the changes in relative risk for cardiovascular events for diabetic men and women

both diabetic men and women are at greater risk of CV events compared to normal. The risk is greater for diabetic women. Oestrogen in women generally has protective effects on the CVS, but after menopause and if diabetic then the risks for them catch up to those of men and even surpass

Where is acetylcholinesterase located in the NMJ?

bound to the basement membrane of the postsynaptic terminal

How do copper IUDs (intrauterine contraceptive devices) work?

by affecting sperm viability and function

How can the effects of non-depolarising NM blockers be reversed?

by using anticholinesterases (e.g. neostigmine) (allows ACh to surmount/out-compete the NM blocker)

Beta blockers can worsen heart failure due to overly decreased CO and blockade of dilatory beta2 adrenergic receptors in the musculature increasing the load on the heart. How can this be prevented?

by using beta blockers with ISA to give some dilatory effects at rest via b2 and by using mixed adrenergic blockers such as carvedilol as a1 blockade leads to additional dilatory effects

Summarise the intracellular mechanisms by which PGE2 can mediate its effect by activation of various receptors

cAMP generation (EP2 and EP4) or calcium ion mobilisation (EP1 and EP3)

What does a high dose dexamethasone suppression test help to determine

can be used to distinguish pituitary Cushing's disease from other types Only pituitary Cushing's will supress cortisol to 50%, whereas ectopic ACTH and adrenal tumours will not suppress at all

Why is it important to avoid concentrated glucose solutions when treating hypoglycaemia

can cause severe skin reactions

Due to what kind of complications does acromegaly normally increase the morbidity risk

cardiovascular and/or respiratory complications

Give the clinical features of cushing's syndrome

centripetal obesity moon face buffalo hump hypertension hypokalaemia osteoporosis diabetes

List 3 potentially viable trisomy disorders and state the name of their respective syndrome

ch21 - Down's Syndrome ch18 - Edward's Syndrome ch13 - Patau's syndrome

How does Wernicke's encephalopathy present?

characterised by the triad ophthalmoplegia, ataxia, and confusion.

State the class of antibiotics that target bacterial RNA synthesis (transcription). State a specific example

class = rifamycins. Do so by inhibiting rna Polymerase example = rifampicin (important example to know because it is a CYP450 inducer)

What are needed to increase the binding affinity between the CD4+ T-Helpers and the antigens on the APCs

co-stimulatory factors

What would be expected upon examination of an ischaemic foot? (3)

cold - indicates poor blood supply pulseless - again due to poor blood supply ulcers at the foot margins e.g. at ends of toes

State what a combined oral contraceptive

combination of an oestrogen (ethinyl oestradiol) and a progestogen (levonorgestrel or norethisterone).

What are the two types of NM blocking drugs?

competitive (non-depolarising) depolarisingcompetitive (non-depolarising) depolarising

Summarise the principle side effect profile of muscarinic receptor antagonists

constipation, drowsiness and dry mouth

What are the principal actions of oxytocin

constriction of myometrium at parturition, and also the milk ejection reflex.

What is the major determining factor of blood pressure?

constriction/radius of arterioles (BP = CO x TPR

How does treatment and control of hyperglycaemia affect incidence of macrovascular disease and mortality from macrovascular events in patients with T2DM?

control and treatment of hyperglycaemia DOES NOT significantly change the mortality and occurence of macrovascular disease Instead, multiple risk factors need to be solved with first. Namely, insulin resistance

What does Prednisolone bind to for its distribution phase in pharmacokinetics

corticosteroid binding globulin

What does hydrocortisone bind to for its distribution phase in pharmacokinetics

corticosteroid binding globulin

Which channels/currents do calcium antagonists affect in order to decrease heart rate?

decrease ICa

Which channels/currents does ivabradine affect to decrease heart rate?

decrease If

Which channels/currents do beta blockers affect in order to decrease heart rate?

decrease If and ICa

How is infertility defined?

defined as inability to conceive after 12 months of normal, regular, unprotected sexual activity

What is the graded end-plate potential proportional/dependant on?

depends on how much ACh released and how many receptors stimulated/receptor density

What is the physiological effect of Suxamethonium

depolarising neuromuscular block (phase 1 block) basically leads to flaccid paralysis of the skeletal muscles

What is the most common cause of neuropathy and therefore lower limb amputation?

diabetes

What are the 2 main chemical groups of TCAs?

dibenzazepines and dibenzcycloheptenes

What is the main reason/cause for pre-eclampsia?

diminished remodelling of the spiral arteries by cytotrophoblast, which causes decreased blood flow and hence decreased nutrient supply to the placenta and fetus. Also can lead to IUGR

What is the symphysis-fundal height?

distance over the abdominal wall from the symphysis to the top of the uterus

Why is Dobutamine used preferentially over isoprenaline?

dobutamine does not have that b2 effect which is optimal

Summarise the principle side effect profile of histamine receptor antagonists

drowsiness

What are the side effects to using methyldopa

dry mouth, sedation, orthostatic hypotension, and male sexual dysfunction - so rarely used

Cases of hypopituitarism: Simmond's disease - symptoms What are the symptoms mainly caused by?

due mainly to decreased thyroidal, adrenal and gonadal function. The result is secondary amenorrhoea or Oligomenorrhoea (women), impotence (men), loss of libido, tiredness, waxy skin, loss of body hair, hypotension

Why does menopause occur?

due to progressive oocyte depletion that begins before birth and is completed between the 4th and 5th decade of life

Why is respiration always assisted when giving NM blocking drugs?

due to the muscular relaxation effects, it can lead to respiratory depression if not assisted

At what point during the pregnancy can the baby survive if delivered prematurely?

end of second trimester i.e. 26 weeks, without medical care however, with modern/intensive care, can be pushed back to 22 weeks

Which two cycles does the menstrual cycle consist of?

endometrial cycle ovarian cycle

Which channel does aldosterone effect when it binds to the kidney

epithelial sodium channel Increased entry of sodium into the kidney tubule

Define intra-uterine growth restriction (IUGR)

failure of the infant to achieve its predetermined (genetic) potential for a variety of reasons

Which out of the 3 liver disease progression are reversible: fatty liver hepatitis cirrhosis

fatty liver is very reversible hepatitis is still reversible cirrhosis not reversible

How does GIT metabolism of alcohol differ between men and women?

females tend to have ~50% LESS alcohol dehydrogenase in the stomach so this route of metabolism is less effective in women and hence more of the alcohol is metabolised in the liver in women

State 2 beta lactams that are resistant to destruction by beta lactamases

flucloxacillin = resistant amoxicillin = not resistant by itself, but clavulanic acid confers beta lactam resistance so is co-administered

What is the function of hCG?

functional homologue of LH, driving the production of oestrogens and progesterones from the ovaries (drives the corpus luteum).

State a beta lactam that primarily targets gram positive and gram negative bacteria respectively

g +ve = penicillins (G and V) g -ve = amoxicillin

What is pilocarpine used to treat

glaucoma (miosis), dry mouth (med name here is Salagen)

What is glomerulosclerosis and how does it affect blood pressure?

glomerulosclerosis = hardening of the capillaries in the glomerulus this hardening contributes to high blood pressure. As more glomerular capillaries get harder, the blood pressure is likely to increase

Which types of hormones' production is blocked by Aminoglutethamide and how does this happen

glucocorticoids, mineralocorticoids and sex steroid hormones. works by inhibiting the conversion of cholesterol to pregnenolone

What needs to be given with testosterone in order to restore fertility

gonadotrophins

What is measured in a pregnancy test and when?

hCG is produced in the placenta and can be measured after two weeks of conception in urine or earlier in the blood

Why are beta-blockers not used in patients with congestive heart failure?

heart failure patients already have a lacking cardiac output so slowing it down and decreasing it's contractility/output further with beta blockers will just exacerbate their problem

Explain how FGR/IUGR and the health of the foetus can be monitored

heart range changes seen on the CTG (Cardiotocography) foetal movement monitored by checking number of kicks compared to cardiff kick chart measure changes in foetal circulation by foetal doppler

Which hepatitis viruses are associated with chronic infections?

hep B and C

How does the GnRH-LH/FSH loop change in females when in the ovulation phase

high levels of oestradiol trigger a switch to positive feedback on the hypothalamus triggering a large GnRH and LH release

Why are there no cyclical ovarian or uterine functions during pregnancy?

high levels of steroids suppress the HPG axis, leading to very low levels of LH and FSH throughout pregnancy, and hence no cyclic ovarian or uterine functions.

What is produced by trophoblasts that stimulates oestogen and progesterone production from the corpus luteum

human chorionic gonadotrophin (hCG) - works by acting on LH receptors

What crystal type is embedded within the bone matrix that act as a calcium resevoir?

hydroxyapatite crystals

Give signs of adrenocortical failure

hyperpigmentation (of mucous membranes, skin hair) autoimmune vitiligo weight loss muscle weakness hypotension

What condition causes about 50% of all ischaemic strokes?

hypertension

What is the single most important risk factor for stroke?

hypertension - causing about 50% of ischaemic strokes

What are the main two consequences of Conn's

hypertension and hypokalaemia

What are the typical adverse/unwanted effects of glucocorticoid therapy

iatrogenic Cushing's syndrome. The typical symptoms will include potassium loss, sodium and water retention, hypertension, muscle wasting, centripetal obesity, moon face, buffalo hump, hyperglycaemia (leading to steroid diabetes), increased appetite, osteoporosis, increased risk of infection, poor wound healing, easy bruising, impaired growth, disorders of menstruation, mood changes.

Define the characteristics of autism

impairments of social interactions and communication restricted, repetitive, and/or stereotyped patterns of behaviour, interests and activities.

What are the potential benefits of GH replacement therapy in adults

improved body composition, improved muscle strength + exercise capacity, normalisation of HDL-cholesterol, increased bone mineral content, improved psychological well-being and improved quality of life

Where is the highest density of nAChR usually located on skeletal muscle?

in the middle of the muscle/fibres

What are the unwanted potential side effects of octreotide

include GI tract disturbances, transient hyperglycaemia (caused by an initial reduction in insulin secretion), and in rare cases gallstones

Describe the rate of change of the symphysis-fundal height between weeks 14-32

increase in about ~1cm per week

Breifly summarise the pathophysiology as to how H. Pylori causes peptic ulcers

increased acidity, decreased mucus --> vulnerability of epithelia and damage to it)

What physiological effects are normally associated with acromegaly

increased growth of periosteal bone, cartilage, fibrous tissue, connective tissue, and internal organs (cardiomegaly, splenomegaly, hepatomegaly etc)

What metabolic effects are normally associated with acromegaly

increased plasma insulin response to oral glucose load, which leads to increased insulin resistance, which results in an impaired glucose tolerance test in 50% of patients and diabetes mellitus in 10%

What are the possible adverse effects of growth hormone replacement therapy in adults

increased risk of cardiovascular accidents, increased soft tissue growth (leading to e.g. cardiomegaly) and increased susceptibility to cancer

What do DPP4 inhibitors do that helps tread t2dm

increases half-life of endogenous GLP (as normal half life v short (1min) due to rapid breakdown by DPP4)

What are the roles/functions of GLP-1?

incretin role in augmenting glucose-stimulated insulin release also reduces food intake by suppressing appetite

Cases of hypopituitarism: Simmond's disease - causes

infiltrative processes (e.g. lymphocytic), pituitary adenomas, craniopharyngiomas, cranial injury and following surgery

How do glucocorticoids affect vascular events in inflammation control

inhibit the vasodilator response and reduce fluid exudation

What effect do thiazides have

inhibiting the sodium/chloride cotransporter located in the distal convoluted tubule

What type of receptors are corticosteroid receptors

intracellular receptors that when bound, translocate to the nucleus and alter DNA transcription.

What is mosaicism and how does it occur?

involves the presence of two or more populations of cells with different genotypes in one individual who has developed from a SINGLE fertilized egg can result from many different mechanisms including chromosome nondisjunction, anaphase lag, and endoreplication.

Why can significant illnesses and chronic paediatric diseases lead to short stature

inflammation, poor nutrition and the effects of drugs such as steroids blocks the intracellular signalling processes of GH - so IGF-1 will be much lower

What is Korsakoff's psychosis?

irreversible memory loss, confabulation, personality change (development of Wernicke's encephalopathy after significant cell death has taken place)

What is type 2 diabetes?

is a state of chronic hyperglycaemia, sufficient to cause long-term damage to specific tissues, notably retina, kidney, nerves and arteries

What is hyperpituitarism normally caused by

isolated pituitary tumours but can also be ectopic (i.e. from nonendocrine tissue) in origin

How does alcohol tend to affect cellular activity

it's generally a DEPRESSANT so decreases cellular activity

How is the prevalence of T2DM changing?

it's increasing • Seen with increasing age, but now seen in children and teenagers The global prevalence is estimated to double over the next 35 years. The greatest prevalence will be in South Asia, in the India subcontinent

Why is it generally advised for asthmatic patients to not take NSAIDs?

it's v difficult to identify those who are sensitive to NSAIDs without actually trying/experimenting with them. COX inhibition favours production of leukotrienes which are potent bronchoconstrictors Safer for asthmatics to stay away

What is meant by the protective actions (taken during stressful times) seen from cortisol

keeps the body's response to stress in check, ie prevents an overshoot. For example suppression of production of inflammatory mediators to prevent shock (hypotension, oedema and tissue damage)

Which stages of pregnancy have the greatest maternal risk?

labour and delivery that poses the dominant risk and is the commonest cause of maternal death linked to pregnancy.

State the key advantage and disadvantage of SSRIs

less severe side effect profile however, it is less effective

How do the levels of oestrogens, progesterone and placental lactogens change throughout pregnancy?

levels increase as the size of the placenta increases

What are most autosomal translocations associated with?

linked with development of tumours/malignancy: lymphoma, leukaemia, sarcoma • Mutations of genes can stop them from functioning (TSGs) or can accelerate their function (oncogenes)

What are the possible adverse effects of growth hormone replacement therapy in children

lipoatrophy at injection side, intracranial hypertension, headaches, increased incidence of leukaemia

What is the major route of metabolism of alcohol?

liver alcohol --> acetaldehyde by alcohol dehydrogenase and mixed function oxidase (acetaldehyde is toxic so it is converted to carboxylic acids by aldehyde dehydrogenase)

What are the two main sites of metabolism of alcohol? Which enzymes are involved at each site?

liver (does 85% of the metabolism) - by alcohol dehydrogenase and mixed function oxidase Stomach (does 15% of the metabolism) - by alcohol dehydrogenase

What is lower HbA1c associated with?

lower rate/risk of complications, particular microvascular complications

How does PGE2 affect pain threshold?

lowers the pain threshold --> hyperalgesia

Which phase of the ovarian cycle of the menstrual cycle tends to be the phase that changes in length when there are periods of stress and other factors?

luteal phase (follicular phase tends to stay the same at 14 days)

In diabetes, what factors cause the macrovascular and microvascular damages respectively?

macro = increased mitogenic pathway and dyslipidaemia (i.e. insulin resistance) micro = oxidative damage from chronic hyperglycaemia

What is meant by the permissive actions (taken during non-stressful times) seen from cortisol

maintain body systems in a state to be able to respond to stress, eg up-regulation of cytokine receptors in preparation for combating infection

What are the unwanted potential side effects of spironolactone

menstrual irregularities, gynaecomastia (androgen receptor binding), and also GI tract irritation

Why does morphine have more negative side effects than its equally potent metabolites

morphine has greater affinity than M6G for the μ2-opioid receptor thought to be responsible for many of the adverse effects of μ-receptor agonists

Describe the basis of the Cardiff kick chart

mothers can count foetal movements/kicking using the Cardiff kick chart - Mothers record the time taken each day to feel ten foetal movements

Which cells are responsible for detecting/binding to the antigen being presented on the surface of APCs

naïve CD4+ T-helper cells

Why is the neuraminidase envelope protein on influenza viruses of special importance?

neuraminidase allows the virus to be released by the currently infected cell, and then infect other cells

State two classes of drugs that can compete with the hepatic microsomal enzymes and hence interfere with TCA metabolism

neuroleptics and oral contraceptives

What type of a drug is aspirin and what is it used to treat

non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin

What is normal cortisol level and what can this reach when the patient is under stress

normal cortisol=20md/day, with an increase to 200-300mg during stress

Give the methyldopa's pharmacokinetics

not broken down within the neuron by MAO Therefore, tends to accumulate in larger quantities than NA and displaces NA from vesicles

What would be expected upon examination of a neuropathic foot? (6)

numb - due to neuropathy, patient usually can't feel the ulcer warm - indicates good/normal blood supply dry - indicates autonomic neuropathy (dysfunctional oil/sweat secretion) palpable foot pulses Absent (ankle) reflexes - due to neuropathy ulcers at points of high pressure loading. (e.g. ball of foot)

List 4 factors that affect the pulsatility of GnRH and hence GH

nutrition, sleep, exercise, stress

Differentiate between Azoospermia and Oligospermia

o Azoospermia - absence of sperm in ejaculate. o Oligospermia - reduced sperm in ejaculate.

What is bitemporal hemianopia normally caused by

occurs when growth of a suprasellar tumour presses onto the optic chiasm, causing a lesion which damages the optic nerves

What is the main oestrogen variant in pregnancy

oestriol

What percentage of codeine is metabolised into an active component?

only 10% of the codeine is metabolised to produce morphine - this is what is responsible for codeine's analgesic property.

What is the half life of GLP-1 and why?

only about 1 minute due to rapid breakdown by DPP4

How many follicles are usually released during the woman's reproductive lifetime?

only about 400 of them will be released at ovulation during a reproductive lifetime; 12 per year for 30-35 years on average.

What are the 3 possible routes of administration for HRT?

oral, transdermal, transvaginal

What are the fundamental differences between osteomalacia and osteoporosis?

osteomalacia = vit d deficiency with ABNORMAL blood biochemistry osteoporosis = decreased bone mass with NORMAL blood biochemistry

What does a bone mineral density DEXA T-score of <-2.5 indicate?

osteoporosis

Where does the majority of the blood pressure drop throughout the vasculature?

over the lengths of arterioles

What are the two main secretions of the neurohypophysis

oxytocin and vasopressin

What is the pKa of cocaine? What are the implications of this when consuming cocaine orally?

pKa = 8.7 so if in the acidic environment of the gastrointestinal tract it will ionised and be absorbed slower

What is angina?

pain that occurs when the O2 supply to the myocardium is insufficient for its needs

What symptoms will someone who has recently contracted Viral (de Quervain's) thyroiditis present with

painful dysphagia, hyperthyroidism, pyrexia and raised erythrocyte sedimentation rate (ESR). The patient will have tender pretracheal lymph nodes and a tender and palpable thyroid, which will be enlarged more on one side

What are symptoms of graves disease that result due to hyperthyroidism

patient feels sweaty and hot they lose weight with increased appetite muscle wasting shortness of breath tremor palpitations and tachycardia sympathetic effects such as lid lag

In which types of patients is suxamethonium not administered?

patients who have a known defect which leaves them with v low levels of butyrylcholinesterase (aka pseudocholinesterase) as that is how suxamethonium is metabolised - this defect is about 1 in 3000 burns/soft tissue injury patients to prevent hyperkalaemia Patients with eye injuries or glaucoma as this drug can increase intraocular pressure

What is the relationship between peripheral vascular disease and peripheral neuropathy in relation to diabetic foot?

peripheral neuropathy is the main cause for diabetic foot however peripheral vascular disease worsens diabetic foot a lot

Define hypoglycaemia

plasma glucose of <3.6 mmol/L

What is meant by the pleiotropic effect of drugs?

pleiotropy includes all of a drug's actions other than those for which the agent was specifically developed. It may include adverse effects which are detrimental ones, but is often used to denote additional beneficial effects.

What are the three different types of cells that migrate into tissue when inflammation occurs

polymorphonuclear leukocytes (which kill pathogens via toxic oxygen) monocytes (which are transformed into macrophages) platelets (which contribute to tissue repair)

What is meant by hyperglycaemic memory?

poor diabetes control, even for a brief period, will give an increased risk of microvascular complications compared to someone that has had good control since the beginning of their diagnosis

Summarise the differences between treatment for H. Pylori positive and H. Pylori negative peptic ulcers

positive = combination of antibiotics and PPIs negative = combination of H2 receptor antagonist and PPI

Why is prazosin a better antihypertensive agent compared to phentolamine?

prazosin = a1 selective antagonist phentolamine = non-selective alpha antagonist therefore, prazosin still allows the a2 negative feedback on noradrenaline release, which leads to less noradrenaline release, leading to less vasoconstriction and prevents tachycardia

Which hormone's production does trilostane cut off and how

prevents the production of glucocorticoids, mineralocorticoids and sex steroids. So aldosterone, corticosterone, cortisol and androstenedione production are all cut off. Trilostane blocks the activity of 3β-hydroxysteroid dehydrogenase

State at what stages of the cancer-immunity cycle the CTLA4 and PD-1 targets are involved

priming/activation of (T-) lymphocytes and the killing of tumour/cancer cells

What are the granulosa cells of ovarian follicles are responsible for?

produce oestrogens/progesterone during the second half of the ovarian cycle

What are the four families of eicosanoids

prostaglandins, prostacyclins, thromboxans and leukotrienes.

Give unwanted side effects of thiourylenes

rashes, headaches, nausea, jaundice + joint pain.

What are the aims of treatment for cardiac rhythm disturbances?

reduce sudden death, alleviate symptoms, prevent stroke

What is the physiological effect of clonidine

reduces effect of SNS as stimulation of pre-junctional a2 receptors is a negative feedback to reduce noradrenaline exocytosis Less vasoconstriction - ↓ TPR and BP

What is released by the CD4+ T helper cells upon activation? What does this do?

release of IL-2 (autocrine) and expression of IL-2 receptors IL-2 causes proliferation of the CD4+ T-helper cell into a clone of activated T cells (Th0) which then differentiate into either Th1 or Th types

Give the cellular mechanisms of inflammation

release of pro-inflammatory mediators from mast cells involvement of tissue macrophages release of vasodilators + other mediators from endothelial cells angiogenesis and fibrous tissue development from fibroblasts

Give the different applications for which glucocorticoids (cortisol or synthetic cortisol) can be used

replacement therapy differential diagnosis of Cushing's syndrome control inflammation immunosuppression in hypersensitivity, autoimmune disease and transplant patients (prevention of rejection) mature the foetal lung prior to pre-term birth

How does basal body temperature change at the time of ovualtion and by how much?

rises slightly, by about 0.5 degrees celcius

Summarise the synthesis of parathyroid hormone

same synthesis pathway as other polypeptide hormones - initially synthesised as pre-proPTH - eventually cleaved down to 84aa polypeptide which is PTH

Describe the adrenoceptor selectivity for Phenylephrine

selective a1 (and some a2) v v v little effect on beta receptors

Which two hormones are required to sustain the function of sertoli cells?

sertoli cells are where spermatogenesis occurs FSH and testosterone are required

How important is genetics to ibd

significant

Why are beta-blockers no longer the first line treatment for hypertension and instead other drugs such as CCBs, ATII receptor blockers etc are used?

similar effects of lowering blood pressure like b-blockers, however they do not have the same large side effect profile as b-blockers

State the 3 most important environmental factors contributing to the risk of IBD

smoking, diet and microbiome.

What is the physiological effect of adenosine

smooth muscle relaxation decreased chronotropy decreased dromotropy

Structure of type 4 receptors

steroid receptors found in the nucleus

Which 3 SNS mechanims can be hypothetically be used to treat glaucoma?

stimulation of a1 (e.g. phenylephrine) --- reduces blood flow to ciliary body so therefore less aqueous humour production, therefore reduced intraocular pressure stimulation of a2 (e.g. clonidine) --- negative feedback of a2 reduces capability of ciliary body to produce aqueous humour antagonist of b1 --- b1 would upregulate aqueous humour production, so blocking it with a beta blocker would prevent this. However this isn't really used

How is teriparatide administered?

subcutaneously daily- do not exceed 2 years

What determines the substrate supply to the foetus, ultimately affecting the way the foetus grows?

substrate supply is dependent on the placenta This is in turn dependent on the placental and uterine vascularity and interaction

What does leptin do?

suppresses appetite, released from white adipose tissue Purpose is to signal to the hypothalamus when one has sufficient fat reserves for normal functioning

What are the three types of treatments that can be given for acromegaly

surgery; radiotherapy; and chemotherapy

Which receptor (MR or GR) does Dexamethasone mainly act on

synthetic glucocorticoid with no mineralocorticoid activity

What do GLP1 receptor agonists do that helps tread t2dm

synthetic, longer acting version of GLP (e.g. saxenda) so can enhance insulin secretion for longer

Why do people abuse drugs?

take advantage of the mesolimbic reward pathway to create feelings of euphoria

Summarise the mechanism that causes pseudohypoparathyroidism

target organ resistance to PTH (multiple underlying causes). Believed to be due to defective Gs protein (needed to increase cAMP intracellularly in response to PTH receptor activation)

What is the body's largest endocrine organ?

the GI tract

What is selectivity

the capacity to have a preference for binding to some objects but not others

How many ovarian primordial follicles are present during development and at birth?

the human ovaries contain ~6m primordial follicles at ~20w development about 1-2 million primordial follicles at the time of birth,

Which gene codes for GLP-1? Explain its synthesis

the preproglucagon gene This is the same gene that glucagon is derived from, however cleavage of the initial transcript is different in L-cells compared to alpha-cells of the pancreas, leading to the different products

What is the problem with using Oseltamivir for treating influenza? What is the best treatment option instead?

the problem is that it must be inhaled as soon as you are infected with the influenza virus. However, by the time symptoms become apparent, it is too late - the drug would need to be taken earlier. The BEST way to stop influenza is by vaccination (

What are the thecal cells of the developing follicles are responsible for?

the production of estrogens

Why does the timing for folliculogenesis and the ovarian cycle not line up?

the time taken for a primordial follicle to develop into a secondary (mature) oocyte is more than one month (actually ~3 months) so does not reflect ovarian funtion/cycle Ovaries contain multiple follicles at all stages of development at any time, with one dominant follicle entering the later stages to form a secondary (Graafian) follicle.

How are men and women differentially affected by Paget's disease?

they're both affected equally

When are non-selective alpha adrenoceptor antagonists (e.g. phentolamine) usually used as antihypertensives?

to treat phaechromocytoma-induced hypertension (has GI side effects)

What is the climacteric phase?

transitional phase during which ovarian function and hormone production decline - occurs at start of menopause

What type of surgeries are used to treat Cushing's

transphenoidal hypophysectomy (specific for pituitary Cushing's disease) bilateral adrenalectomy unilateral adrenalectomy

Which type of diabetes mellitus has more of a genetic basis behind its cause?

type 2

State the major forms of IBD

ulcerative colitis crohn's disease • Distinction between UC and CD is incomplete in around 10% patients (Indeterminate Colitis)

Which enzyme metabolises morphine?

uridine 5 diphosphate glucuronosyltransferase. aka UDPGT - so it is basically glucuronidated (which produces ACTIVE metabolites)

When are progesterone-only contraceptives used?

used when oestrogens are not a good idea - i.e. CVS problems, history of thrombosis

What are the uses and mechanisms of ARBs?

uses = hypertension and heart failure mechanisms = basically same as ACE inhibitors - reducing preload by inhibiting sodium and thus water retention and reducing afterload by inhibiting angII mediated vasoconstriction

How does aromatase deficiency present in females?

virilisation - hirsutism, deepening voice, and amenorrhoea.

What does Ethosuximides block

voltage gated calcium channels

How does Warfarin reduce the levels of vitK dependent factors

warfarin inhibits vitamin k epoxide reductase which reduces vitamin k This means there is less reduced vitamin k available Therefore reduced production of the factors that require reduced vitamin K

How is the problem of weight/obesity treated in patients with T2DM?

we can use orlistat (GI lipase inhibitor), but morbidly obese patients should consider surgery

When is aldosterone secreted?

when blood Na+ concentration falls or K+ concentration rises directly causing production of angiotensin II which stimulates the adrenal gland

Why are analogues with high degrees of sensitivities (like prednisolone and dexamethasone) used in preference to hydrocortisone

when given systemically in doses sufficient to produce a beneficial clinical effect, hydrocortisone binds to mineralocorticoid receptors (MR) and produces unwanted aldosterone-like effects.

Within what time frame does an ovulated egg have to be fertilised and why?

within 24 hours of ovulation because it starts to degenerate after that

What effect do potassium-sparing diuretics have

work by interfering with the sodium-potassium exchange in the distal convoluted tubule of the kidneys or as an antagonist at the aldosterone receptor.

What is the average range of weight gain of the mother over the course of her pregnancy? What factors account for this?

~10-15kg This will include the weight of the foetus amniotic fluid and placenta increased fluid retention increased nutritional stores (to feed the baby after delivery).

When is the vast majority of organogenesis complete by?

~week 12

Give the Ganglion Blocking Drugs' effects on the body at rest

§ CVS effects; hypotension - blood vessel vasoconstriction inhibited and kidney renin secretion inhibited (so no AngII). § Smooth muscle effects; pupil dilation, decreased GI-tone, bladder dysfunction, bronchodilation. § Exocrine secretions; decreased secretions.

What is the most potent and harmful cannabinoid from the cannabis plant?

Δ9-tetrahydrocannabinol (Δ9-THC)

Give the physiological effect of phenylepherine

α1-mediated vasoconstriction Mydriasis (pupil dilation)

Describe the adrenoceptor selectivity of salbutamol (ventolin)

β2 >> β1 >>> α2/α1 • Much more beta 2 selective than the other drugs -> relaxation of bronchial smooth muscle

Where are the mu receptors found in the periphery that interaction with will lead to antitussive effects

μ-opioid receptors also located in the airway vagal sensory neurons

List the main classes of anti-emetic drugs (4)

• 5-HT3A receptor antagonists • Histamine H1 receptor antagonists • Muscarinic receptor antagonists • Dopamine D2 receptor antagonists

Outline the principle clinical uses and mechanism of action of the 4 main classes of anti-emetics

• 5-HT3A receptor antagonists: chemotherapy induced N&V • Histamine H1 receptor antagonists: motion sickness • Muscarinic receptor antagonists: motion sickness • Dopamine D2 receptor antagonists: gastroparesis induced N&V

Summarise the mechanism of action of azathioprine

• Azathioprine is a pro-drug that has to be activated by the gut flora to 6-mercaptopurine • 6MP a purine antagonist, thus interferes with DNA synthesis and cell replication and is therefore immunosuppressive, § Impairs cell/Ab mediated immune response § Impairs mononuclear cell infiltration § Impairs leukocyte proliferation § Impairs antibody synthesis § Enhances T cell apoptosis

Summarise the monoamine theory of depression

• Depression = a functional deficit of central monoamine transmission • Mania = a functional excess of central monoamine transmission • Noradrenaline & 5-HT are the two monoamines involved in this hypothesis

List 5 types of disease that is included within macrovascular disease

• Early widespread atherosclerosis • Ischaemic heart disease (e.g. myocardial infarction) • Cerebrovascular disease (e.g. stroke) • Renal artery stenosis (causes hypertension and renal failure) • Peripheral vascular disease

By how much does folic acid supplementation decrease the incidence of spina bifida?

• Folic acid in the diet decreases incidence by approx. 70% • The potential for benefit is large with folic acid

Describe what happens in the menstrual phase of the endometrial cycle

• Menstrual phase- shed blood and endometrial lining; remaining basal endometrium is very thin.

How much do most newborns grow (height) in the first year of life? What is this mainly dependant on?

• Rapid initial growth ~23-25 cm in first year • The baby's growth is nutritionally dependant for the first year (first 9-12 months) - nutrition controls growth in the first year of life

Describe what happens in the proliferative phase of the endometrial cycle

• Repair and proliferative phase- stimulation of endometrial cell proliferation; increase in thickness, number and length of glands/ arteries.

Describe what happens in the secretory phase of the endometrial cycle

• Secretory phase- production of nutrients and other factors. Epithelial glands widen, endometrium thicken, increased coiling of arteries.

What is reverse cholesterol transport and what molecule is responsible for it?

• This is a process where cholesterol is taken OUT of blood vessels (tunica intima) and foam cells HDLs are the mediator for this

What is interesting about the drugs for Alzheimers disease?

• none of them target any of the pathways we've just looked at LOL • they're just completely random that no1 knows why they even work