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
