MIDTERM QUESTIONS for FINAL Exam

What is the difference between desensitization and tolerance?

"Desensitization" is often used interchangeably with the term tachyphylaxis, and it describes the phenomenon in which the effect of a drug is lessened upon maintained administration. This effect occurs over a timeframe of minutes, which is what makes it unique from the term "tolerance." Tolerance is a slower and more gradual decrease in the effect of a drug, and occurs over a timeframe of days or weeks.

An individual containing one poor metabolizing allele and one extensive metabolizing allele will have a total functional activity score of: between 0 and 1 1 between 1 and 2 2 0

1

In order to be considered a polymorphism a variant of an allele must be present in what percent of the population? 1 5 10 15

1

In the somatic nervous system, how many motor neuron(s) connect the central nervous system to the skeletal muscle?

1

Two NMDA antagonists

1) Ketamine is an anesthetic and analgesic and blocks glutamate 2) Memantine licensed for the treatment of moderate to severe Alzheimer's disease

The four main classes of antihypertensive agents include:

1) Sympatholytic agents 2) Direct vasodilators 3) Diuretics 4) Renin-Angiotensin-Aldosterone system Inhibitors

Factors affecting absorption following oral administration

1) gi motility (diabetes and migranes can slow motility:( ) 2) splanchnic blood flow (increases with presence of food, so take a drug with food to help absorb) 3) particle size 4) physiochemical factors (ionization, water solubility)

4 therapeutic goals for myocardial infarction:

1)Maintain oxygenation 2) Reduce cardiac oxygen demand by reducing cardiac workβ-adrenergic receptor antagonistsACE inhibitorsAngiotensin receptor antagonists 3) Treat painOpioids 4) Prevent further thrombosis Aspirin Clopidogrel Heparin

Polymorphisms of interest to pharmacogenomics occur in four areas..... = ? ? ? ?

1. phase I metabolizing enzymesExample: CYP2D6 and Tamoxifen 2.Phase II metabolizing enzymesExample: Thiopurine-S-methyltransferase and Thiopurine 3.TransportersExample: Organic anion transporter and Simvastatin 4.Drug TargetsExample: Vitamin K epoxide reductase and Warfarin

For an intravenous route of administration, what is the bioavailability assumed to be? 100% 75% 0% 50%

100

To achieve a loading dose of a drug where the volume of distribution of the drug is 35 L and the clearance rate is 70 ml/min, and the desired dose is 3 mg/L, one should administer how many mg of drug initially? 105 mg 350 mg 70 mg 210 mg

105mg -- The loading dose of a drug is defined as the [volume of distribution] X the [desired therapeutic plasma concentration].

An extensive metabolizer that has two copies of an allele which encodes for an enzyme with normal activity will have a total functional activity score of 0 1 2 Greater than 2

2

In the autonomic nervous system, how many motor neuron(s) connect the central nervous system to the skeletal muscle?

2

How much of a 10mg dose of morphine reaches the systemic circulation if morphine has a bioavailability of F = .24? 2.4 mg 4.1mg 0.24 mg 24 mg

2.4mg

What is the half-life of a drug that has a volume of distribution at steady state equal to 462 liters and a clearance rate of 40 ml/min? 2 hours 4 hours 8 hours 16 hours

8 hrs

What does Selegiline do?

= Monoamine oxidase inhibitor decreased dopamine caatabolism for PD.

The plateau phase (phase 2) of an action potential observed in non-pacemaker cardiac cells is a result of which of the following? A delayed efflux of Ca2+, which balances a slowly decreasing efflux of K+ A delayed influx of Ca2+, which balances a slowly increasing efflux of K+ A delayed influx of Ca2+, which balances a slowly increasing influx of K+ A delayed influx of both Na+ and Ca2+, which balances a slowly increasing efflux of K+

A delayed influx of Ca2+, which balances a slowly increasing efflux of K+

Which of the following can produce a therapeutic response? A drug concentrated in the urine A drug concentrated in the bile A drug unbound to plasma proteins A drug not absorbed from the GI tract

A drug unbound to plasma proteins Only free drug is able to diffuse into the tissues to produce a therapeutic response. A drug bound to a plasma protein such as albumin is too large to transverse a membrane by simple diffusion or even to enter a channel via a transporter. Drug bound to bile will be excreted into the intestine to be eliminated in the feces.

Indicate which of the following statements concerning Phase I metabolic drug reactions are correct. A major source of Phase I reactions is the cytochrome P450 enzyme system locate in the liver endoplasmic reticulum The products of Phase I reactions are usually more lipid soluble than the parent drug Addition of a glucuronyl group is an example of a Phase I reaction and a major source of Phase I reactions is the cytochrome P450 enzyme system locate in the liver endoplasmic reticulum A major source of Phase I reactions is the cytochrome P450 enzyme system locate in the liver endoplasmic reticulum and the products of Phase I reactions are usually more lipid soluble than the parent drug Addition of a glucuronyl group is an example of a Phase I reaction

A major source of Phase I reactions is the cytochrome P450 enzyme system locate in the liver endoplasmic reticulum

Which of the following forms covalent bonds with their receptors? A partial agonist An inverse agonist An inverse antagonist A competitive antagonist A non-competitive antagonist

A non-competitive antagonist Note that an irreversible antagonist is also referred to as a non-competitive antagonist. An irreversible antagonist binds to a receptor in such a way that it cannot be easily removed from the receptor. Typically, irreversible antagonists contain reactive groups that form strong covalent bonds with the receptor. Therefore, an excess amount of agonist will not be able to displace or surmount an irreversible antagonist from the receptor.

Irinotecan is a topoisomerase inhibitor found to be very active against lung and colon cancers. Which of the following statements is NOT true about Irinotecan? The active metabolite of Irinotecan (SN-38) causes severe toxicity The toxic effects of Irinotecan are eliminated by glucuronidation A polymorphism in the population effects the pharmacodynamics of irinotecan A polymorphism is found in UDP-glucuronyltransferase that effects the toxicity of irinotecan

A polymorphism in the population effects the pharmacodynamics of irinotecan

Intrinsic activity refers to a pharmacological compound's ability to elicit Strong receptor binding Weak receptor binding A response Blockade of a response

A response

The nucleus basalis of Meynert degenerates as a hallmark of what disease? Parkinson's disease Huntington's disease Creutzfeld-Jacob disease Alzheimer's disease

AD

The presence of amyloid plaques is a feature of which of the following neurodegenerative diseases? Parkinson's disease Creutzfeldt-Jacob disease Alzheimer's disease Huntington's disease

AD Alzheimer's disease is defined as dementia without an antecedent cause such as stroke or brain trauma. Features of the disease include loss of cholinergic neurons in the hippocampus and frontal cortex and the presence of amyloid plaques. These plaques are due to the misfolding of the β-amyloid protein and the excessive phosphorylation of microtubule transport protein, Tau. The exact mechanism as to how these plaques cause neurodegeneration remains unknown although it is expected that neurodegeneration is a result of initiating apoptosis, causing an inflammatory response or predispositioning cells to excitotoxicity and oxidative stress.

In vascular smooth muscle cells Depolarization of the membrane allows Ca2+ entry via voltage-gated channels Inositol triphosphate, a product of phospholipase C activation, releases intracellular Ca2+ from the sarcoplasmic reticulum Ca2+ combines with calmodulin to activate myosin light-chain kinase Depolarization of the membrane allows Ca2+ entry via voltage-gated channels and Ca2+ combines with calmodulin to activate myosin light-chain kinase All possible answers are correct

ALL

Which of the following determine the degree of movement of a pharmacological agent between compartments of the body? Partition constant Degree of ionization Size pH All of the above

ALL

Which of the following is an example of a ligand-gated receptor: β1 cardiac receptors Nicotinic receptors Nicotinic receptors and GABAA receptors in the brain GABAA receptors in the brain All possible answers are correct

ALL

Memantine is utilized to treat: Alzheimer's disease Methanol Poisoning Huntington's disease Myasthenia Gravis

AZ

If a drug has a half-life of 10 hours and is taken orally, how long will it take until the subject achieves a steady state drug concentration?

According to Rang and Dale (p. 132), "With repeated dosage or sustained delivery of a drug, the plasma concentration approaches a steady value within three to five plasma half-lives." Following this, the drug in question is expected to reach its steady state concentration in 30-50 hours. According to the "Module2_Pharmokinetics_A branch of pharmacology" document in this course, "it takes approximately four half lives to achieve steady state." Following this, the drug in question is expected to reach its steady state half life in 40 hours.

Which of the following pharmacological agents inhibits carbonic anhydrase? Losartan Spironolactone Acetazolamide Captopril

Acetazolamide

Transmitter that carries excitatory signal from the preganglionic neuron to the postganglionic neuron in the autonomic nervous system: Norepinephrine Norepinephrine and Epinephrine Acetylcholine and Norepinephrine Acetylcholine Epinephrine

Acetylcholine

The two main neurotransmitters that govern the autonomic nervous system are noradrenaline (also referred to as norepinephrine) and which of the following? Dopamine Glycine Serotonin Acetylcholine

Acetylcholine Although serotonin and glycine can be found in the nervous system, they are not one of the two neurotransmitters released from the autonomic preganglion and postganglion neurons.

What does Tacrine do?

Acetylcholinesterase reversible inhibitor for AD. : Tacrine ---Not CNS selective. Therefore can cause nausea and abdominal cramps.

Cholinergic neurons produce and release what neurotransmitter?

Ach

The parasympathetic nervous system releases what neurotransmitter at both the autonomic ganglion and the neuroeffector junction?

Ach

the two main neurotransmitters of the autonomic NS are

Ach and noradrenaline-aka-norepinephrine (NA)

All of the following molecular effects have been associated with ethanol consumption except Enhance γ-amino butyric acid (GABA) release presynaptically Activate glutamate ionotropic receptor Enhance glycine receptor function Inhibit NMDA receptor activation

Activate glutamate ionotropic receptor

Which of the following statements about the NMDA receptor is correct? Activated by acetylcholine Effects potentiated by diazepam (valium) Activation requires binding of glutamate and glycine Belongs to the G Protein Coupled Receptor superfamily

Activation requires binding of glutamate and glycine

Blood pressure is NOT regulated by which of the following Cardiac output Peripheral vascular resistance Mean left ventricular stroke volume All provided answers attribute to blood pressure

All provided answers attribute to blood pressure

G Protein Couple Receptor - activates Gq and leads to the PLC-mediated generation of DAG and IP3 inhibits adenylyl cyclase through Gi decreasing cAMP blocking Ca2+ and K+ channels alternative signal transduction pathway in blood vessels (influx of Ca2+) what receptor?

Alpha-adrenergic receptor

Which of the following compounds is approved for the treatment of a stroke caused by a thrombotic episode? Alteplase Chlorpromazine Ropinirole Entacopone

Alteplase............ is a recombinant tissue plasminogen activator approved for use in patients that have experienced a stroke due to thrombosis of a major cerebral artery. It is not an approved therapy for patients that have experienced a stroke as a result of hemorrhage. Alteplase dissolves the thrombotic plaque restoring blood flow to the brain.

Antiarrhythmic drugs. Class III: K+ channel blockers Prolong action potential by prolonging repolarizationIncreases QT interval Can cause Torsade de pointes (prolonged repolarization resulting in polymorphic ventricular tachycardia with a long QT interval thought to be caused by an early depolarization).

Amiodarone: Utilized to treat tachycardia associated with Wolff-Parkinson-White syndrome, a syndrome in which accessory connections between the atrium and ventricle are 6utilized to propagate an action potential as compared to the normal route of conduction through the AV node. Sotalol: Utilized to treat paroxysmal ventricular tachycardia and suppress arrrhythmic ventricular ectopic beats.

Which of the following is NOT true of an SNP? An SNP is not very common SNP is an abbreviation for single nucleotide polymorphism SNPs include insertions, deletions, and substitutions SNP can be defined as a sequence variation that occurs when a single nucleotide is altered

An SNP is not very common Single nucleotide polymorphisms (SNP) are common in the population. They occur at about one in every 100 to 300 base pairs. SNPs can appear in coding or noncoding regions. Thus, they can have drastic effects in relation to disease or cause no apparent effect at all.

What outcome would result from topical administration of an α1 antagonist to the eye?

An alpha1 antagonist applied to the eye would have an indirect effect. It would cause miosis, which is constriction of the pupil of the eye; it would prevent the contraction of the iris radial muscle and therefore inhibit pupil dilation.

Explain the mechanism of action of captopril. ACE inhibitors produced a dry cough as unwanted side effect. Explain the existence of a dry cough following the administration of an ACE inhibitor.

Angiotensin is a peptide hormone that gets activated by renin (released by the kidneys) to angiotensin I. Angiotensin I gets converted to angiotensin II by angiotensin converting enzyme (ACE). The result of high levels of AngII is increased blood volume and therefore increased blood pressure. Any compound that inhibits ACE will decrease blood pressure. Captopril is an angiotensin-converting enzyme inhibitor used to treat hypertension. Another pathway in which ACE is involved, however, is the conversion of bradykinin to inactive metabolites. In the absence of ACE, bradykinin levels increase and cause bronchoconstriction. A persistent cough is probably linked to suppression of kininase II activity, which is followed by accumulation of kinins, substance P and prostaglandins. [1]

Spironolactone is utilized in the treatment of heart failure due to the ability of the drug to Inhibit the sympathetic nervous system Antagonize aldosterone receptor Increase cardiac contractile force Cause vasodilation

Antagonize aldosterone receptor Spironolactone is an aldosterone receptor antagonist. Aldosterone is released as a response to the renin-angiotensin-aldosterone system. Renin is released from the juxtaglomerular apparatus as a result of lowered renal pressure. Renin acts on angiotensinogen to produce angiotensin I, which is then converted to angiotensin II by the enzyme ACE. Angiotensin II binds to AT1 receptors causing the release of aldosterone from the adrenal cortex. Aldosterone binds to mineral corticoid nuclear receptors in the distal tubule and collecting duct of the kidney. Activation of these receptors increases the expression of the Na+/K+ pump and the epithelial Na+ channel.

Tacrine may produce a small improvement in patients with Alzheimer's disease because it Inhibits cholinesterase Activates cholinergic nicotinic receptors Antagonizes N-methy-D-aspartate receptors Activates dopamine D1 receptors

Antagonizes N-methy-D-aspartate receptors Tacrine is a cholinesterase inhibitor given to compensate for the loss of cholinergic neurons evidenced in patients with Alzheimer's disease. If the enzyme responsible for the metabolism of acetylcholine is blocked, acetylcholine transmission is enhanced, and cognitive function is improved.

The EC50 refers to the drug concentration At which one-half the maximum response is achieved Tolerance is likely to be observed Which is directly proportional to the drug's affinity for its receptor At which one-half the maximum response is achieved and is directly proportional to the drug's affinity for its receptor Required to produce the maximum physiological effect

At which one-half the maximum response is achieved

G Protein Couple Receptor - third cytoplasmic loop coupled to a G protein activates Gs increasing cAMP and activating cAMP-dependent kinase what receptor

B1 B2 and B3 adrenergic recptor

There are two classes of nuclear receptors. Which of the following is true about class I nuclear receptors that control gene transcription? Interact with nucleolar RNA Only act to inhibit DNA transcription Only act to stimulate DNA transcription Bind to hormone response elements of DNA

Bind to hormone response elements of DNA

The diuretic effect of amiloride is due to which of the following? Blocking apical sodium channels Inhibiting apical sodium pumps Inhibiting the sodium chloride transporter Blocking aldosterone receptors

Blocking apical sodium channels

The antidepressant effect of mirtazapine is produced as a result of Activating serotonergic receptors Activating presynaptic noradrenergic receptors Blocking presynaptic noradrenergic receptors Blocking neuronal reuptake of norepinephrine

Blocking presynaptic noradrenergic receptors

A new diuretic is being studied in the human volunteers. Compared to placebo, the new drug increases urine volume, decreases urinary Ca2+, and decreases serum K+. If this new drug has a similar mechanism of action to an established diuretic, it probably Blocks aldosterone receptors in the collecting duct Inhibits carbonic anhydrase in the proximal convoluted tubule Blocks the Na+/Cl- co-transporter in the distal convoluted tubule Acts as an osmotic diuretic

Blocks the Na+/Cl- co-transporter in the distal convoluted tubule

What two fundamental cardiovascular parameters ultimately determine blood pressure? For each of these two parameters, name one antihypertensive drug that targets the parameter and describe its mechanism of action

Blood pressure is determined by cardiac output and peripheral vascular resistance. Cardiac output is determined by ejection fraction (or really, stroke volume) from the left ventricle, which is in part governed by filling rate during diastole. Cardiac output is also determined by heart rate. Stroke Volume x Heart Rate = Cardiac Output. Peripheral vascular resistance is determined by vessel diameter and blood volume. The more blood volume, the higher the blood pressure. The tighter the blood vessel, the higher the blood pressure. To treat hypertesion, one would want to provide the patient with sources of nitric oxide (which is released by blood vessel endothial cells to dilate vessels). Nitroglycerine given sublingually is one option. Or other exogenous nitrates. This will decrease vascular resistance. Or you can give a diuretic, like furosemide, to lower blood volume. You might also give a beta blocker like propanolol. These drugs antagonize beta adrenergic receptors on the heart, which will prevent the rate at which the heart can depolarize and contract. This will lower the heart rate, and therefore cardiac output.

Which of the following only have innervation of the sympathetic nervous system? Blood vessels Sweat glands Salivary glands Blood vessels and sweat glands Blood vessels and salivary glands

Blood vessels and sweat glands

Botox is a prescription medicine that is injected into the muscles of the face to prevent severe crow's feet lines and frown lines between the eyebrows in adults. What is the mechanism of action of Botulinum toxin? Discuss the side effects that can be life threatening.

Botulism toxin blocks the export of acetylcholine from the nerve terminal by blocking VMAT and SNAP. Acetylcholine is an abundant neurotransmitter involved in voluntary motor functions, but also in a wide array of autonomic processes. Too much of this toxin could inhibit basic functions, like movement or even breathing! The majority of the time, the body is being run by the autonomic system dependent on widespread use of acetylcholine.

ailure of the sinoatrial node to initiate an action potential that may result in a slower heart rate = ________________ heart block asysotolic arrest

Bradyarrhythmia

Activation of the parasympathetic nervous system results in which of the following? An increase in heart rate Vasoconstriction Bronchoconstriction Relaxation of the GI tract Mydriasis

Bronchoconstriction

_________nervous system consists of the brain and the spinal cord.

CNS

The initiation of an action potential is due to the influx of _____and _________from nearby depolarized cells through gap junctions.

Ca2+ and Na+

One disturbance of cardiac rhythm is identified as delayed after depolarization. This results due to an increased influx of what ion or ions? Sodium Potassium Both sodium and potassium Calcium

Calcium Abnormally elevated calcium levels triggers an influx of sodium due to the Na+ / Ca2+ pump that exchanges 1 calcium ion for the inward flux of three sodium ions. This result in a net influx of positive charge and the propagation of an action potential before one would normally occur.

A partial agonist is defined as a drug that Can only occupy a small fraction of its receptors Has low affinity for its receptor Increases the number of spare receptors Can only produce a submaximal response Requires high doses to produce a maximal response

Can only produce a submaximal response A partial agonist as opposed to a full agonist produces a response that is less than the maximal response. This effect is not due to a lack of binding. For example, tolazoline produces a barely identifiable response even though it is bound to 100% of the receptors as observed by a radio-ligand binding assay. The lack of a maximal response can be attributed to a higher affinity of a partial agonist to an inactive resting receptor conformation then to an active receptor conformation as postulated by the two-state-receptor model.

Why is Candesartan a better antihypertensive agent then Captopril?

Captopril is an ACE (angiotensin converting enzyme) inhibitor. This comes with side effects, such as elevated levels of bradykinin, which can result in coughing. Candesartan interferes with AngII's ability to bind to its receptor. This is a more direct intervention.

T/F The accumulation of bradykinin as a result of ACE inhibition produces a dry cough in patients taking captopril.

Captopril is an ACE inhibitor. ACE, besides converting angiotensin I to angiotensin II, also inactivates bradykinin. Without ACE activity, bradykinin accumulates resulting in bronchoconstriction producing a dry cough.

what does carbidopa do?

Carbidopa = decarboxylase inhibitor decrease dopamine catabolism for PD

Postganglionic parasympathetic neurons are classified as Serotonergic Cholinergic Adrenergic Dopaminergic

Cholinergic Parasympathetic neurons release acetylcholine and are thus classified as cholinergic neurons. This is true for both preganglionic and postganglionic parasympathetic neurons.

Which of the following are only innervated by the parasympathetic nervous system? Arteries Ciliary muscle of the eye The salivary glands The sweat glands

Ciliary muscle of the eye

Of the following pharmacological agents, which diminishes the firing of sympathetic neurons by exerting its effects within the central nervous system? Metoprolol Nifedipine Amiodarone Clonidine

Clonidine

Sedation is a side effect of which of the following drugs used for the treatment of hypertension? Losartan Acetazolamide Furosemide Clonidine

Clonidine

oral has highest _____max IV has lowest _____max

Cmax (and highest Tmax!) Tmax (and highest Cmax!)

A 16-year-old man snorted cocaine for the first time at a party. A few minutes later he felt euphoric, and friend noted that his pupils were dilated. What molecular actions most likely mediated the mydriasis (pupil dilation)?

Cocaine is a noradrenergic autonomic drug that blocks the norepinephrine transporters, thereby blocking reuptake of noradrenaline. This led to excessive stimulation of the alpha receptor and pupil dilation.

Which of the following is true about the autonomic nervous system? Composed of a two neuron system Connects the central nervous system to skeletal muscle Governs processes under voluntary control Can function without the central nervous system

Composed of a two neuron system

Which of the following is true of the effects of the parasympathetic nervous system? Constricts bronchial smooth muscle Dilates pupil Increases heart rate Secretion of renin from the kidney

Constricts bronchial smooth muscle Bronchial smooth muscle is only innervated by the parasympathetic nervous system.

Which of the following is a true statement about nicotinic cholinergic receptors? Activated by the release of acetylcholine from sympathetic postganglionic neurons A selective agonist for one subtype is used to treat dementia Classified as a G protein coupled receptor Contains two binding sites for acetylcholine

Contains two binding sites for acetylcholine

At cholinergic synapses, acetylcholine is inactivated in the synaptic cleft by all of the following EXCEPT: Reuptake into the presynaptic nerve Degradation by the enzyme acetylcholinesterase Conversion into ATP Absorption by nearby supporting cells (such as glial cells)

Conversion into ATP Neurotransmitter concentrations in the synapse are controlled to keep the action of the neurotransmitter brief and localized. The enzyme acetylcholinesterase hydrolyzes acetylcholine inactivating the neurotransmitter. Acetylcholine activity is also halted by removal from the synapse by the presynaptic neuron and the surrounding non-neuronal cells.

Curare is a competitive antagonist to nicotinic acetylcholine receptors. South American Indians dipped arrows in curare to paralyze animals while hunting. Curare is a strong base with a pKa slightly higher than 10. Explain why meat from animals killed with these arrows was safe to eat in regards to curare absorption.

Curare is strongly basic, with its pKa higher than 10. Physiological pH is typically around 7.0, but varies--especially in the stomach, where curare would enter after being ingested. If the pH is lower than the pKa (in this scenario, it will definitely be lower, regardless of stomach or small intestine location) the compound will become protonated/ionized, and will be unable to cross the lipid barrier. Curare's charge renders it too hydrophilic to passively diffuse through the gut epithelium in order to reach systemic circulation where it would then get delivered to neuromuscular junctions.

What dopamine receptor family? Contains the D1 and D5 receptor subtype Both subtypes stimulate Gs activating adenylyl cyclase D1 is most abundant in the CNS D1 is involved in the mesolimbic dopaminergic reward pathway

D1-like family

Contains D2 D3 and D4 receptor subtypes Activate Gi or Go inhibiting adenylyl cyclase, activating K+ channels hyperpolarizing the cell and blocking voltage-gated Ca2+ channels D2 is autoinhibitory when presynaptic D2 found in chemoreceptor trigger zone is responsible for dopamine agonist causing nausea and dopamine antagonist having an antiemetic effect

D2-like family

Nitroglycerin, besides reducing coronary artery spasm and redistributing blood to ischemic areas of the heart, is utilized therapeutically to treat stable angina due to the ability to do which of the following? Increase blood pressure Constrict vessels in the heart Decrease cardiac oxygen consumption Increase stroke volume

Decrease cardiac oxygen consumption

A patient with acute-onset cirrhosis of the liver presents evidence of hypoalbuminemia. In addition, an inflammatory response has resulted in increased levels of acid glycoprotein. Which of the following events is most likely to occur? Increased acidic drug binding and increased basic drug binding Increased acidic drug binding and decreased basic drug binding Decreased acidic drug binding and increased basic drug binding Decreased acidic drug binding and decreased basic drug binding None of the above

Decreased acidic drug binding and increased basic drug binding

Nitroglycerin relieves typical angina pectoris partly due to Increasing blood pressure Decreasing cardiac oxygen consumption Dilating coronary arterioles Increasing cardiac stroke volume

Decreasing cardiac oxygen consumption (reduced cariac work) Nitroglycerin relaxes smooth muscle through nitric oxide signaling. The relaxation of smooth muscle is greatest in veins, which reduces the venous pressure and thus reduces preload. However, nitroglycerin also relaxes larger muscular arteries and thus reduces afterload. Together this reduces cardiac work and thus reduces the consumption of oxygen since cardiomyocytes main source of energy is via aerobic metabolism.

A partial agonist that binds to a full agonist's binding site will affect an agonist's dose-response curve by: Shifting the curve to the right Decreasing the maximal response achieved Shifting the curve to the left Increasing the maximal response achieved

Decreasing the maximal response achieved

The herbal preparation, St. John's wart, is a weak monoamine oxidase inhibitor. How could this herbal preparation molecularly attribute to an elevated mood?

Depression is heterogeneous cluster of both emotional and biological symptoms. The leading theory regarding depression is that it is caused by a deficit of monoamine neurotransmitters like norepinephrine and serotonin. Monoamine oxidase in the central nervous system is found within the neuron, and it regulates the concentration of neuronal monoamines in the cyptoplasm. St. John's wart--a weak monoamine oxidase inhibitor--may act to prevent monoamine oxidase from disabling monoamine neurotransmitters. This would allow more monoamine neurotransmitters to accumulate in the cell and potentially leak spontaneously into the synapse, thereby elevating the mood.

Which of the following occurs as a result of the production of diacylglycerol? Activation of adnylate cyclase Activation of protein kinase A Activation of protein kinase C Activation of guanylate cyclase Increase in intracellular calcium

Diacylclycerol (DAG) is produced as a result of the hydrolysis of phosphatidylinositol (4,5) bisphosphate (PIP2) by membrane-bound phospholipase C. DAG is formed and remains attached to the membrane as a highly lipophilic molecule. Protein kinase C is activated by DAG resulting in the phosphorylation of a number of substrates.

Most drugs are absorbed in the gut by which process? Diffusion through lipid Diffusion through aquaporins Carrier-mediated transport Pinocytosis

Diffusion through lipid Most drugs are absorbed via simple diffusion or diffusion through the lipid. Only very small molecules will be able to enter the circulation from the GI tract through the channels created by aquaporins. Most drugs are too big to enter an aquaporin channel. Although there are some drugs that enter the GI tract via carrier-mediated transport such as levodopa, the number of drugs that do so are limited.

Why should a diuretic that decreases plasma K+ levels not be used with digoxin?

Digoxin inhibits sodium-potassium ATPase (which moves 3 Na+ out for 2 K+ in), causing a higher intracellular concentration of Na+. This increased concentration of Na+ indirectly inhibits the Na+/Ca2+ exchanger that moves Na+ in and Ca2+ out of the cell. Given this indirect inhibition of the Na+/Ca2+ exchanger, intracellular levels of Ca2+ remain high--promoting increased contractility of the heart. Diuretics, by the manner in which they reduce fluid retention, may cause low potassium because more potassium will remain in the collecting duct of the nephron, which will promote more fluid volume in the urine and therefore lower the amount of potassium and other solutes in the blood. A change in potassium level can induce digoxin toxicity. This is because digoxin competes with potassium on the sodium-potassium pump. [1] If there is less potassium around generally to compete with digoxin, then digoxin's potency will increase and one may suffer from digoxin toxicity.

Symp effect on lungs?

Dilate bronchioles

Which of the following statements is NOT true about enterohepatic circulation? Evidence with morphine Describes a linear process of drug excretion Does not occur with glucuronide conjugated drugs Responsible for diminishing drug action

Does not occur with glucuronide conjugated drugs Enterohepatic circulation describes the cyclic process whereby which drugs become conjugated to bile and excreted into the intestine only to be released from bile in the intestine by intestinal enzymes and absorbed a second time through the GI tract. Enterohepatic circulation acts as a reservoir for drugs and thus prolongs the action of drugs as is the case with morphine.

The VD of amlodipine is equal to 16 L/kg. How much should one prescribe if the desired plasma concentration is 50 μg/L?

Dose = Vd x (concentration in blood) Dose = 16L/kg x 50ug/L Dose = 800ug/kg Dose = .8mg/kg

Drug A has an EC50 of 11nM and a maximum effect of 97%. Drug B has an EC50 of 75nM and a maximum effect of 100%. Drug C has an EC50 of 300 nM and a maximum effect of 37%. Compare Drugs A, B and C. Make sure to identify which drug is the most potent and which drug is the most efficacious.

Drug A is more potent than Drug B and Drug C. It is more efficacious than Drug C, but less than Drug B. Drug A, is a pretty good drug. Drug B is more efficacious than Drug A and Drug C. Itis less potent than Drug A, but more potent than Drug C. Drug B is the best drug because it has the most efficacy. Drug C is less potent that Drug B and Drug C. It is less efficacious than Drug B and Drug C. Drug C is the worst drug.

Drug P has a volume of distribution of 150 liters. Indicate below the implications that derive from this observation: Drug P's distribution involves large amounts in body tissues Drug P is subject to extensive first-pass metabolism Drug P's distribution in the body is largely confined to the plasma and Drug P is subject to extensive first-pass metabolism Drug P is subject to extensive first-pass metabolism and Drug P's distribution involves large amounts in body tissues Drug P's distribution in the body is largely confined to the plasma

Drug P's distribution involves large amounts in body tissues

Of the following list, which does not describe a pharmacokinetic process? Alteration of a drug by liver enzymes Drug metabolites are removed in the urine Movement of drug from the gut into general circulation Drug causing dilation of coronary vessels Drug readily deposited in fat tissue

Drug causing dilation of coronary vessels

Of the following, which will increase if absorption from the gut is decreased? Duration of action Oral bioavailability Peak plasma drug concentration Volume of distribution

Duration of action

Bosentan antagonizes which of the following? Angiotensin AT1 receptors Vasopressin receptors Endothelin ETA and ETB receptors Nitric oxide receptors

Endothelin ETA and ETB receptors Bosentan is a mixed antagonist of the endothelin receptors. Bosentan is an indirectly acting vasodilator used to treat pulmonary hypertension.

Bosentan is a vasoactive drug utilized clinically to treat pulmonary hypertension as an Endothelin receptor agonist Endothelin receptor antagonist Vasopressin receptor agonist Vasopressin receptor antagonist

Endothelin receptor antagonist

Routes of Administration oral rectal sublingual

Enteral

In the parasympathetic nervous system, neurotransmitter action is terminated by Diffusion from the synapse Enzymatic degradation Active reuptake into presynaptic nerves Endocytosis Inactivation by inhibitors

Enzymatic degradation

Which of the following is not one of the four superfamilies of receptors? Nuclear Hormone Receptor Enzyme Receptor G Protein Coupled Receptors Cytokine Receptors

Enzyme Receptor

Describe the steps outlined in the metabolism of Ethanol and Methanol.

Ethanol gets converted by alcohol dehydrogenase to acetaldehyde. Acetaldehyde gets converted by aldehyde dehydrogenase to acetic acid. Methanol gets converted to formaldehyde by alcohol dehydrogenase. Formaldehyde gets converted to formic acid by aldehyde dehydrogenase. Ethanol can be used to treat methanol poisoning, since they share the same enzymes.

An excess of glutamate results in neuronal excitotoxicity as a result of which of the following essential factors? Enhanced synthesis of adenosine triphosphate Decrease in intracellular calcium Inhibition of intracellular proteases and lipases Excessive levels of intracellular calcium

Excessive levels of intracellular calcium Glutamate, a ubiquitous central nervous system neurotransmitter, is toxic to neurons. When left unregulated, glutamate concentrations reach levels in which glutamate is available to activate NMDA, AMPA and metabotropic receptors. The activation of AMPA receptors depolarizes the cell opening voltage-gated calcium channels. Cellular depolarization also releases the magnesium blockaded of NMDA receptors allowing bound glutamate to activate the channel non-selectively allowing cations to enter the cell including calcium. Additionally, glutamate activates metabotropic receptors that through inositol triphosphate signaling cause the release of calcium stores from the endoplasmic reticulum. The activation of all three of these receptors results in an excess of intracellular calcium, an essential factor of neuronal excitotoxicity.

The final step in the release of norepinephrine from sympathetic neurons is Diffusion Docking Synthesis Exocytosis Loading

Exocytosis

A non-mutated version of an enzyme is classified as an extensive metabolizing allele. Pharmacogenomics gives this allele an activity score of 1. An individual with two normal alleles would then have a total activity score of 2 and be considered an _____________________

Extensive metabolizer

More sodium in the lumen of the kidney results in an increase in blood pressure. True False

False

T/F A missense mutation is classified as a non-synonymous small nucleotide polymorphism in which all amino acid codons downstream of the polymorphism are changed.

False

T/F A synonymous single nucleotide polymorphism does not result in an alteration in the amino acid sequence and thus has no potential consequences.

False

T/F Acetylcholine is stored in vesicles, which reside in the soma (cell body) of the cholinergic neuron.

False

T/F Agonists have zero intrinsic activity.

False

T/F Angiotensin II is a vasodilator.

False

T/F Blood Vessels and salivary glands have only one type of innervation. True False

False

T/F CMAX is greatest upon oral drug administration.

False

T/F GABA and glycine are excitatory neurotransmitters in the central nervous system.

False

T/F Inhibitory neurons of hierarchical systems in the central nervous system utilize the neurotransmitter glutamate.

False

T/F Neurotransmitters are released from the synaptic knob following an influx of K+.

False

T/F Noncompetitive Antagonist by definition can be surmounted with high concentrations of agonist.

False

T/F Sotalol is utilized to treat tachycardia associated with Wolff-Parkinson-White syndrome.

False

T/F Sympathetic neurons terminating on the SA node of the heart release acetylcholine on muscarinic receptors.

False

T/F The clearance of ethanol follows zero order kinetics in which a constant fraction of ethanol is eliminated per unit time.

False

T/F The functional activity score for a nonfunctional allele is 1.

False

T/F The population frequency distribution curve depicting the effect of a drug in which a single trait contributes to the observed phenotype will be unimodal-skewed, with no distinct differences among the genotypic groups.

False

T/F The sinoatrial node, the main pacemaker of the heart, creates an action potential via continual stimulation from the sympathetic or parasympathetic pathway.

False

T/F The somatic nervous system governs consciously controlled functions with two neurons connected in series.

False

T/F Two drugs that have similar half-lives will have similar volumes of distributions.

False

T/F Verapamil is a potassium channel blocker utilized to treat hypertension.

False

T/F 5-Fluorouracil administration is complicated by polymorphisms identified in both the drug target and the enzyme responsible for its metabolism.

False 5-Fluorouracil is utilized to treat solid tumors. Currently, identified polymorphisms in the population that effect the administration of 5-FU are only evident in dihydropyrimidine dehydrogenase, the enzyme responsible for its metabolism.

T/F An irreversible antagonist can be surmounted with excess amount of agonis

False An irreversible antagonist binds to a receptor in such a way that it cannot be easily removed from the receptor. Typically, irreversible antagonists contain reactive groups that form strong covalent bonds with the receptor. Therefore, an excess amount of agonist will not be able to displace or surmount an irreversible antagonist from the receptor. Note that an irreversible antagonist is also referred to as a non-competitive antagonist.

T/F Sympathetic preganglionic neurons leave the central nervous system at the thoracic and sacral spinal roots.

False Anatomically, the parasympathetic and sympathetic neurons leave the central nervous system at distinct locations. The sympathetic preganglionic neurons exit the central nervous system through the thoracic and lumbar spinal nerves. The parasympathetic preganglionic neurons, on the other hand, exit the central nervous system through the cranial and sacral spinal nerve roots.

T/F Molecules that are able to transverse the blood brain barrier are not at risk of being transported back into the bloodstream via P-glycoprotein and ATP-driven efflux transporters.

False Any molecule that is able to cross the blood brain barrier either by passive diffusion as is the case for small non-polar molecules or with the use of transporters are subject to be pumped back out of the brain. The main efflux pumps responsible for the export of molecules out of the brain are the P-glycoprotein and the ATP-driven efflux transporter.

T/F Dose-response curves and concentration-effect curves can be used to measure the affinity of a drug for the receptor.

False Binding curves measure with radio-ligands are utilized to quantify the affinity of a drug to a receptor. Dose-response curves do not reveal receptor occupancy but the physiological response produced as a result of the amount of agonist administered. Because the response is not directly proportional to receptor occupancy, a dose-response curve cannot reveal drug affinity. Note: A concentration-effect curve is produced as a result of an experiment performed in a test tube while a dose-response curve is acquired as a result of an experiment performed in a live organism.

T/F An individual with one copy of a chromosome encoding for an abnormal plasma cholinesterase resulting in deficiency of the enzyme is sensitive to suxamethonium.

False Suxamethonium is inactivated in the plasma by the enzyme cholinesterase. A mutation has been identified in the cholinesterase gene that yields a modified version of the enzyme that does not effectively metabolize suxamethonium. This results in prolong action of suxamethonium in the body yielding sensitivity to the effects of suxamethonium. However, one normal copy of the plasma cholinesterase gene is enough to detoxify the clinical doses of suxamethonium. Therefore, this condition is autosomal recessive, and one must have two abnormal copies in order to experience suxamethonium sensitivity.

T/F The higher the affinity of a drug for a receptor, the higher the dissociation constant (abbreviated KA in the textbook).

False Therefore, the higher the affinity of a drug for the receptor, the lower the value.

T/F Baroreceptors are important for long-term control of blood pressure.

False - it's just short term

T/F If drug A has a greater potency compared to drug B, you can predict that drug A will also have a greater efficacy.

False!

T/F Small muscular arteries and arterioles are the main capacity vessels.

False. Veins contain a large fraction of the total blood volume and are therefore the capacity vessels. Arteries and arterioles, on the other hand, are the main resistance vessels.

Activation of AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propianic acid) receptors results in Fast excitatory neurotransmission Slow excitatory neurotransmissio Fast inhibitory neurotransmission Slow inhibitory neurotransmission

Fast excitatory neurotransmission

Name a location in the body that can accumulate lipid-soluble drugs, has little or no receptors, and can hold distributed drugs like barbiturates.

Fat

A 2-year-old boy was admitted to the emergency department after having ingested several tablets of propranolol, which he had found in his father's dresser drawer. Vital signs on admission were blood pressure 85/50 mm Hg, heart rate 40 beats per minute, respiratory rate 20/min. The boy received an intramuscular injection of glucagon a hormone that activates glucagon receptors in the heart, causing a significant increase in heart contractility. Which of the following terms best defines the antagonism between glucagon and propranolol? Competitive Pharmacokinetic Functional Chemical

Funcitonal

Which of the following pharmacological agents inhibits the Na+/K+/2Cl- transporter? Acetazolamide Hydrochlorothiazide Spironolactone Furosemide

Furosemide

What are the benefits of co-administering furosemide with spironolactone?

Furosemide is a powerful diuretic and results in increased delivery of sodium to the distal portions of the nephron (by blocking the K+Na+/2Cl- co-transporter). The increased delivery of Na+ to the distal nephron results in a loss of protons and K+ ions. Spironolactone is a potassium-sparing diuretic. It acts by inhibiting aldosterone from activating channels that permit the reabsorption of Na+ from the collecting tubule, thereby increasing the Na+ and volume of fluid that gets excreted in the urine. Thus, spironolactone promotes additional retention of the Na+ solute without affecting K+ levels by blocking the transporter that would otherwise work to reabsorb Na+ for the excretion of K+. This promoted better management of K+ levels. Mismanaged K+ levels can present a danger to the patient.

Adrenergic receptors are classified as what type of receptor? G protein coupled receptor Ligand-gated ion channel Voltage-gated ion channel Nuclear receptor Enzyme receptor

G protein coupled receptor

Which of the following receptor type is activated by proteolytic cleavage and inactivated by phosphorylation? G-protein coupled receptor Kinase-linked receptor Voltage-gated ion channel Nuclear receptor Ligand-gated ion channel

G-protein coupled receptors are normally activated as a result of agonist binding, however four types of protease-activated G-protein coupled receptors (PARs) have also been identified. Proteases cleave the end of the N-terminal tail of PARs and expose five or six residues that act as a "tethered agonist." Note that a PAR can only be activated once. Inactivation of this type of a PAR occurs by further proteolytic cleavage which frees the tethered ligand OR by the process of desensitization. The process of desensitization starts with phosphorylation of the receptor. Phosphorylated residues of a G-protein coupled receptor are binding sites for β-arrestin. Bound β-arrestin targets a G-protein coupled receptor for receptor internalization removing the receptor from the membrane.

Which of the following receptor types contains seven transmembrane helices? Nicotinic acetylcholine receptors Ligand-gated ion channels Kinase-linked receptors G-protein coupled receptors Nuclear receptors

G-protein coupled receptors have a very distinct heptahelical molecular structure. G-protein coupled receptors consist of a single polypeptide chain with seven transmembrane α-helices, an extracellular N-terminal domain and an intracellular C-terminal domain.

Which of the following is NOT a slow-acting neurotransmitter of the central nervous system? Dopamine GABA Norepinephrine Acetylcholine

GABA Dopamine, norepinephrine and acetylcholine is considered a slow-acting neurotransmitter being that it acts on a g-protein coupled receptor. Time is required for the signal transduction pathways to produce a response as part of the activation of a g-protein coupled receptor. Acetylcholine is included as both a slow and fast acting neurotransmitter due to its effects on both fast response producing ligand-gated ion channels and the slower response producing g-protein coupled receptors. GABA is the only neurotransmitter in this list that only acts on ion channels.

Main inhibitory CNS neurotransmitters

GABA (γ-aminobutyric acid--widesprain in CNS) and Glycine (in spinal cord and brainstem)

What kind of receptor? Ligand-gated ion channels permeable to Cl- Activation cause hyperpolarization of the cell = inhibitory post-synaptic potential Pentamers consisting of two α subunits, two β subunits and one γ subunit Positive allosteric modulation by benzodiazepines (sedative anxiolytic and anticonvulsant agents) and barbiturates. Barbiturates are no longer used clinically due to potent respiratory depressant effects.

GABAa receptor

What kind of receptor? GPCR dimer conjoined at the C-terminal tails Once GPCR binds GABA, while the other activates Gi / Go inhibiting voltage gated Ca2+channels, adenylyl cyclase and opening K+ channels

GABAb receptors

The enteric nervous system is primarily concerned with the regulation of Male sex organs Gastrointestinal motility The urinary tract Vascular smooth muscle Respiration

GI motility

Which of the following is a positive allosteric modulator for the NMDA (N-methyl-D-aspartate) receptor? Glutamate Glycine GABA Barbiturates

GLycine

Of the four receptor superfamilies which is the largest?

GPCR

Slow neurotransmitters and neuromodulators act on which of the following targets? Enzymes G-protein coupled receptors Ionotropic receptors Ligand-gated ion channels

GPCRs Slow neurotransmitters and neuromodulators such as dopamine and serotonin target g-protein coupled receptors. Time is required for the signal transduction pathways to produce a response as part of the activation of a g-protein coupled receptor. Note that ligand-gated ion channels are also classified as ionotropic receptors.

A drug taken in excess in an attempt to overdose has a large volume of distribution. Can this drug be readily removed by dialysis, a process whereby only free drug is removed from the plasma? Why or why not?

Given a certain dose, the higher the volume of distribution, the more widely that drug is found throughout the body's tissues (and is not limited to the blood). The drug that was taken has a large volume of distribution, indicating that the amount of that drug that can readily be removed from the plasma by dialysis is limited. Despite the low relative quantities of drug found in the plasma, we have no further information about the how the drug was administered, and to what degree the drug is bount to albumin, and to what degree it has been through Phase 1 metabolic processes--such as hydrolysis--and Phase 2 metabolic processes--such as conjugation of active groups to inactive or polar groups that could have been excreted through the urine. In short, given high distribution of the drug throughout the body, in absolute terms, most of the drug will not be readily eliminated by dialysis.

Which of the following is a fast-acting neurotransmitter of the central nervous system? Nerve Growth Factor Glutamate Prostanoids Dopamine

Glutamate Fast chemical modulators in the central nervous system include glutamate, GABA and acetylcholine. Fast-acting neurotransmitters are released from a neuron and travel short distances to interact with an ion channel on the post-synaptic neuron. Acetylcholine is included as both a slow and fast acting neurotransmitter due to its effects on both fast responding ligand-gated ion channels and the slower responding g-protein coupled receptors. Dopamine is considered a slow-acting neurotransmitter being that it acts on the slower responding g-protein coupled receptor.

Widespread throughout the central nervous system and spinal cord Synthesized from glucose as part of the Krebs cycle Stored in synaptic vesicles Transmission terminated by carrier-mediated reuptake into presynaptic neurons or neighboring astrocytes.

Glutamate main excitatory neurotransmitte

An ultra rapid metabolizer that has one copy of an allele which encodes for an enzyme with normal activity and a second that encodes for an ultra rapid metabolizing enzyme will have a total functional activity score of 0 1 2 Greater than 2

Greater than 2

Which of the following is true of amiodarone pharmacokinetically? Extensively bound to albumin Is rapidly metabolized and excreted Blocks K+ channels Has a very long elimination half-life

Has a very long elimination half-life Amiodarone is used to treat tachycardia associated with Wolff-Parkinson-White syndrome. It is also effective in many other supraventricular and ventricular tachyarrhythmias, however the serious adverse effects (ie. thyroid abnormalities, pulmonary fibrosis, skin rashes, GI disturbance, hepatitis) that accompany amiodarone limit its use. Additionally, amiodarone is extensively bound in tissues equating to a long elimination half-life somewhere between 10 to 100 days. Although the mechanism of action includes blocking K+ channels involved in repolarization, this is not a pharmacokinetic attribute of amiodarone.

Anything that is absorbed from the GI tract is first routed to the liver before reaching the systemic circulation. This occurs via the hepatic portal vein. Metabolizing enzymes can be found elsewhere in the body but are only considered to be a part of first pass metabolism if the drug contacts these enzymes before reaching the systemic circulation (arterial circulatio

Hepatic First Pass Metabolism

A 2-year-old boy was admitted to the emergency department after having ingested several tablets of propranolol, which he had found in his father's dresser drawer. Vital signs on admission were blood pressure 85/50 mm Hg, heart rate 40 beats per minute, respiratory rate 20/min. The boy received an intramuscular injection of glucagon a hormone that activates glucagon receptors in the heart, causing a significant increase in heart contractility. What type of antagonism is described in this clinical situation?

His blood pressure was low, his heart rate low, and respiratory rate low. The boy needed a pick me up. Propranolol must be inhibiting a constitutively active receptor. The injection of glucagon is a competitive antagonist relative to propranolol. It competes for the active site on the receptor, but may not have any intrinsic activity at it.

The expansion of a trinucleotide repeat is a feature of which of the following neurodegenerative diseases? Alzheimer's disease Creutzfeldt-Jacob disease Huntington's disease Parkinson's disease

Huntington's disease Huntington's disease is an inherited disorder as a result of a trinucleotide repeat in the huntingtin gene. The exact function of the soluble cytosolic protein encoded by the huntingtin gene remains unknown. However, the expansion of the CAG trinucleotide results in a string of glutamine residues reducing the solubility of the protein causing the huntingtin protein to form aggregates. This aggregation is believed to be responsible for the neurodegeneration experienced in individuals with Huntington's disease.

Which of the following is not a Phase II reaction? Glucuronidation Hydrolysis Methylation Sulfation

Hydrolysis

Large doses of hydrochlorothiazide can cause which of the following? Hyperkalemia Hypokalemia Hyperchloremia Hypochloremia

Hypokalemia

Lidocaine belongs to what class of antiarrythmic (antidysrhythmic) drugs? Class I Class II Class III Class IV

I

arenteral route of administration where the drug is injected into the blood stream.

IV admin accurate immediate onset skips 1st pass metab. can't reverse toxic dose

Antiarrhythmic drugs. Class I: Na+ channel Blocks high-frequency excitation of the myocardium that occurs in tachycardia without preventing heart from beating normally. This is due to blockade of more frequently used Na+ channels.

Ia: Disoyramide Ib: Lidocaine Ic: Flecainide and Encainade

Which of the following compounds blocks the activity of the Bcr-Abl fusion protein and is used to treat haematological malignancies such chronic myeloid leukemia? Irinotecan Trastuzumab Imatinib Thiopurine Tamoxifen

Imatinib

Imatinib is effective for the treatment of chronic myeloid leukemia by inhibiting which of the following receptor type? Ligand-gated ion channel Nuclear receptor Voltage-gated ion channel G-protein coupled receptor Kinase-linked receptor

Imatinib is a small-molecule tyrosine kinase inhibitor. Specifically, it inhibits an oncogenic cytoplasmic kinase, BCR-Abl1. BCR-Abl1 is a fusion gene that is a result of a chromosomal translocation between chromosome 9 and 22. The result is an uncontrolled tyrosine kinase that signals the cells to continuously divide.

Explain the side effects associated with taking the antidepressant, Imipramine, which includes dry mouth and constipation.

Imipramine is a tricyclic antidepressant that blocks the reuptake of norepinephrine and serotonin, but which also antagonizes muscarinic acetylchoine receptors. It is not selective, so side effects may include dry mouth and constipation. A selective serotonin reuptake inhibitor may be the better choice, as SSRIs tend to have fewer side effects.

Minoxidil activates potassium channels which in turn leads to Increased potassium influx Membrane depolarization Inactivation of calcium channels Increased calcium influx

Inactivation of calcium channels When potassium channels open, potassium rushes out of the cell hyperpolarizing the membrane. The hyperpolarization of the membrane inactivates the voltage-gated calcium channels.

Single nucleotide polymorphisms in the noncoding region could cause all of the following deleterious effects EXCEPT: Incorporation of a premature stop codon Misregulation of mRNA processing Altered gene expression DNA replication machinery binding disturbed

Incorporation of a premature stop codon

Dobutamine an adrenergic β1 receptor agonist is utilized to treat heart failure. Although the exact mechanism remains unknown, it is useful because of its ability to do what? Cause both cardiac stimulation and vasoconstriction Prevent cardiac stimulation and cause vasoconstriction Increase heart rate more than contractile force Increase contractile force more than heart rate

Increase contractile force more than heart rate

Why could β3 adrenoceptor agonists potentially be utilized to treat obesity? Can suppress appetite Increase thyroid function Increase thermogenesis Inhibit the digestion of fats Uncouple oxidative phosphorylation

Increase thermogenesis

An individual with four copies of an enzyme as opposed to the normal two will yield Increased enzymatic activity Decreased enzymatic activity Increased clearance of the enzyme Decreased clearance of the enzyme

Increased enzymatic activity

A delayed after-depolarization event occurs as a consequence of Increased intracellular potassium Increased intracellular calcium Increased intracellular sodium Decreased intracellular chloride

Increased intracellular calcium

The mechanism of the most successful therapy for treating depression is one that Enhances the amount of glutamate in the synaptic cleft Increases the level of monoamines in the central nervous system Antagonizes post-synaptic cholinergic receptors Inhibits neurogenesis

Increases the level of monoamines in the central nervous system

Vasodilation by nitroglycerin and other organic nitrates, such as isosorbide mononitrate, occur as a result of what molecular event? Increasing the formation of cyclic AMP Increasing the formation of cyclic GMP Blocking calcium channels Blocking adrenergic β receptors Activating potassium channels

Increasing the formation of cyclic GMP

Disulfiram can be used as aversion therapy to discourage people from consuming ethanol based on its ability to do what molecularly? Inhibit the mesolimbic dopaminergic reward pathway Inhibit ethanol withdrawal symptoms Inhibit aldehyde dehydrogenase Inhibit alcohol dehydrogenase

Inhibit aldehyde dehydrogenase

Which of the following is true of insulin receptors? Bind and activate intracellular kinases Phosphorylate DNA transcription factors Contain tyrosine kinase in their intracellular domain Exhibit phosphatase activity Linked to guanylate cyclase

Insulin receptors belong to the kinase-linked receptors superfamily. Specifically, insulin receptors are receptor tyrosine kinases containing a tyrosine kinase domain intracellularly.

type of agonist. Drug that binds to the same site as an agonist and elicits the opposite effect to that of a normal agonist.

Inverse agonist. Unlike antagonists, inverse agonists do have an effect in the absence of an agonist. Have negative intrinsic activity. pushes curve to the left.

highly permeable to Ca2+ Activation promotes Ca2+ efflux into the cell Activation requires glycine and glutamate binding and removal of Mg2+blockade Membrane depolarization removes Mg2+ blockade Slow component of excitatory synaptic potential Involved in long term potentiation

Ionotropic glutamate receptors N-methyl-D-asparatic acid (NMDA) receptor

a receptor type in the CNS. Co-localized with NMDA receptors Fast component of excitatory post-synaptic potential Permeable to Na+ and K+

Ionotropic glutamate receptors -amino-3-hydroxy-5-methylisoxazole-4-propianic acid (AMPA) receptor

a receptor type in the CNS. Limited distribution . Fast component of excitatory post-synaptic potential Permeable to Na+ and K+

Ionotropic glutamate receptors 1) Kainate receptor

Which of the following statements is true about rectal administration? Is only used for localized effects Provides nearly 100% bioavailability Is suitable for patients experiencing nausea or vomiting Is subject to a high degree of first-pass metabolism

Is suitable for patients experiencing nausea or vomiting Rectal administration is utilized for individuals that are unable to take medications orally due to nausea, inability to swallow, or restrictions on eating. Roughly 50 percent of rectally administered drug will reach the portal vein via the superior hemorrohdial artery, and will thus undergo hepatic first pass metabolism.

________________________ is a result of the build up of fatty acids in the coronary arteries, vessels that supply oxygenated blood to the heart muscle.

Ischemic heart disease

T/F The parasympathetic and sympathetic nervous system produce opposing effects on the salivary glands.

It is incorrect to simplify the autonomic nervous system as two opposing branches. There are some instances where the parasympathetic and sympathetic branches produce similar effects. In addition, some target organs are innervated by only one branch of the autonomic nervous system.

Which of the following is true about transdermal administration? It is only used for localized effects. It provides rapid and complete absorption. It is most suitable for highly polar drugs. It is not subject to first pass hepatic metabolism.

It is not subject to first pass hepatic metabolism. Transdermal administration requires that a drug diffuse through many layers of epidermis before reaching the systemic circulation. For this reason a drug must be lipophilic in order for absorption to occur which will not occur rapidly. Transdermal administration can be used for localized effects but this is not the only use for transdermal administration. Refer to Table 2.2 in the handout for a list of drugs administered transdermally that are not utilized for local effects.

The influx of ions, as mentioned above, changes the transmembrane potential. As a result, voltage sensitive transient outward _________________change conformation yielding an open state allowing for the movement of ___ ions out of the cardiac cell. The efflux of ions through these channels is short lived due to rapid inactivation of these channels. The rapid inactivation, evidenced by the notch in the action potential, is denoted as __________.

K+ channels; K+; phase 1.

However, the efflux of _______ through delayed-rectifier channels increases with time repolarizing the cell as observed in _______. The most common form of congenital long QT syndrome is due to a mutation in the genes that encode for the ____ channels responsible for the repolarizing current.

K+ ions; phase 3; K+

Which of the following was not mentioned as an inducers of microsomal enzymes in the text? Ketoconazole Rifampicin Ethanol Carbamazepine

Ketoconazole A number of drugs are known to induce the cytochrome P450 metabolizing enzymes. Carbamazepine, ethanol and rifampicin are among the list. Ketoconazole, on the other hand, is a competitive inhibitor. It binds reversibly to the ferric form of CYP3A4.

Which organ controls blood volume? Kidney Central nervous system Peripheral nervous system Heart

Kidney

Dasatinib and Imatinib inhibit what receptor superfamily? Nuclear Receptor G-protein coupled receptor Kinase-linked receptor Ligand-gated ion channel

Kinase-linked receptor Dasatinib and Imatinib are usted to treat haematological malignancies. They are both tyrosine kinase inhibitors that fall under the kinase-linked receptor superfamily.

According to the following table which drug is extracted by the liver the LEAST when taken orally? Drug Oral Bioavail Clearance Vd Diazepam 100% 1.62 L/h/70kg 77 L/70kg Labetalol 18% 105 L/h/70kg 660 L/70kg Morphine 24% 60 L/h/70kg 230 L/70kg Warfarin 93% 61.8 L/h/70kg 6.8 L/70kg

Labelalol bound up in the tissues the most* cleared the fastest least orally avail

The dissociation constant can be defined by all of the following except? Reciprocal of association constant Abbreviated as KA or KD Concentration of drug at which 50% of the available receptors are occupied Large for a high-affinity drug Quantification of affinity of a drug for a receptor

Large for a high-affinity drug

5-HT3 receptors belong to which receptor superfamily? G protein coupled receptor Kinase-linked receptor Ligand-gated ion channel Nuclear receptor

Ligand-gated ion channel

Nicotinic receptors are classified as what type of receptor? G protein coupled receptor Ligand-gated ion channel Voltage-gated ion channel Nuclear receptor Enzyme receptor

Ligand-gated ion channel

what does Entacopone do?

Lipophilipic COMT inhibitor decreases dopamine catabolism for PD

What organ is responsible for "first-pass effect" metabolism? Kidney Heart Liver Brain

Liver

Noradrenergic cell bodies cluster predominantly in the pons and are denoted as the Nucleus basalis Raphe nuclei Nigrostriatal pathway Locus coeruleus

Locus coeruleus

ciliary musle controlled by what receptors? result of each?

M2 M3 = contracts (for near vision) beta2 = relaxes (for far vision)

iris circular muscle controlled by what receptor? result?

M2 and M3 pupil constriction (miosis)

What contaminant found in a heroin substitute was found to cause irreversible destruction of dopaminergic neurons and Parkinson's like symptoms? MSG MPTP Rotenone Memantine

MPTP

________________ dopaminergic pathway effects behavioral associated with an emotional response.

Mesocortical

____________________ dopaminergic pathway is involved in emotion and drug-induced reward or euphoria.

Mesolimbic Amphetamines and cocaine activate mesolimbic dopaminergic reward pathways.Both block the reuptake of dopamine yielding accumulation of dopamine in the synapse, amplifying the signal.

Why could ethanol be prescribed to an individual that is experiencing methanol poisoning?

Methanol uses the same set of enzymes for its metabolism that ethanol does: alcohol dehydrogenase and aldehyde dehydrogenase. Administration of ethanol in the event of methanol poisoning will let ethanol compete for alcohol dehydrogenase and inhibit the formation of formaldehyde from methanol. Formaldehyde is a highly toxic intermediate metabolite of methanol.

Antiarrhythmic drugs. β-adrenergic receptor antagonists (β-blockers) Hinder sympathetic activity on the heart that would otherwise include Increased force of contraction Increased heart rate Increased automaticity

Metoprolol and atenolol (selective for β1 receptors and thus not as contraindicative with asthma)

Of the following pharmacological agents, the activation of K+ channels in vascular smooth muscle mediates vasodilation? Hydralazine Nitroprusside Captopril Minoxidil

Minodixil

Which of the following statements is true about mitochondrial DNA? Mitochondrial DNA is transcribed into messenger RNA Mitochondrial DNA does not utilize the nucleotide thymidine Mitochondrial DNA is heritable only from the father Mitochondrial DNA does not contain mutations

Mitochondrial DNA is transcribed into messenger RNA DNA is found both within the nucleus and the mitochondria. Mitochondrial DNA is inherited from the mother since the ovum is the only source of mitochondria for the gamete. Mitochondrial DNA is similar in composition to the chromosomal DNA found within the nucleus. Mutations can be found in mitochondrial DNA as indicated by the book chapter. Refer to the section entitled aminoglycoside toxicity.

Which of the following receptors is a G Protein Coupled Receptor? Nicotonic receptor Muscarinic receptor NMDA receptor AMPA receptor

Muscarinic

____________________ acetylcholine receptors mediate behavioral effects associated with acetylcholine.

Muscarinic

Constriction of bronchi is typically produced by activation of Muscarinic M1 receptors Muscarinic M2 receptors Muscarinic M3 receptors Adrenergic beta-2 receptors Adrenergic beta-1 receptors

Muscarinic M3 receptors

Scopolamine utilized to treat motion sickness is a Muscarinic receptor antagonist Selective α2 antagonist β1 and β2 antagonist Nicotinic receptor antagonist

Muscarinic receptor antagonist

Which of the following contribute to the development of Alzheimer's disease? Mutations in the apoE4 gene Decreased expression of γ-secretase Decreased production of Aβ42 peptides Mutation in synuclein gene

Mutations in the apoE4 gene One familial form of Alzheimer's disease has been found to be associated with a mutation in the apoE4 gene. This gene encodes for a lipid transport protein responsible for the clearance of Aβ peptides. One Aβ peptide, Aβ40, is produced normally in small amounts within the central nervous system. However, in individuals with Alzheimer's disease a variable Aβ peptide, Aβ42, is produced in excess and is found to have a stronger tendency to aggregate and form amyloid plaques than the Aβ40 peptide itself. The two Aβ peptide variants are cleaved from the amyloid precursor protein, APP, a membrane protein found in many cells. APP is cleaved by several secretases. γ-secretase in particular is rather inefficient and is responsible for the variable lengths of Aβ peptides evident in Alzheimer's.

Myasthenia gravis is caused by Mutated G protein Autoantibodies against a receptor Defective signal transmission pathway Abnormal amino acid sequence of a receptor Down-regulation of nuclear receptors

Myasthenia gravis is an autoimmune disease that results in autoantibodies against the nicotinic acetylcholine receptor. You will learn more about this disorder and the current therapeutics that result in the autonomic pharmacology module.

Bradykinin is a vasodilator by stimulating which of the following? Nitric oxide production Conversion of angiotensinogen to angiotensin I Agonizing noradrenergic receptors on blood vessels of the viscera Endothelin production

NO production

parasympathetic effect on adrenal medulla

NOTHING

parasympathetic effect on liver

NOTHING

sympathetic effect on pancreas

NOTHING

However once a threshold potential is reached, the cell becomes depolarized causing a conformational change in voltage-dependent ______________ yielding an open pore conformation allowing for the influx of ten million ________ ions to enter a cell per second. The surge is short lived, but the transmembrane potential quickly reaches 65 millivolts. The rise in the transmembrane potential at this stage is denoted as ____________.

Na+ channels; Na+; phase 0K+ channels

The metabolism of ethanol may lead to a depletion of which of the following when ethanol is consumed in large amounts? Tryptophan Acetaldehyde Adenosine triphosphate Nicotinamide adenine dinucleotide (NAD+)

Nicotinamide adenine dinucleotide (NAD+)

____________________ acetylcholine receptors are mostly presynaptic and facilitate the release of other neurotransmitters such as dopamine, glutamate, and GABA.

Nicotinic

___________________dopaminergic pathway controls posture and movement.

Nigrostriatal

Imipramine blocks the neuronal reuptake of Only norepinephrine Only serotonin Norepinephrine and serotonin Norepinephrine, serotonin, and acetylcholine

Norepinephrine and serotonin

A 73-year old man recently diagnosed with Alzheimer disease started a therapy with a drug that acts mainly on the central cholinergic system. Which of the following brain regions was most likely involved in the therapeutic effect of the drug in this patient? Nucleus basalis Substantia nigra Locus ceruleus Central raphe nucleus

Nucleus basalis

Underlying mechanisms of Cardiac Arrhythmias After depolarization: Spontaneous activity in normally quiescent cells Two Types 1) Delayed After Depolarization 2) Early After Depolarization Delayed after depolarizations occur during phase 4 of the action potential, before another action potential would normally occur. Cause: abnormal increase in intracellular Ca2+ Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a congenital syndrome in which delayed after depolarizations are induced by exercise. Genetic cause = Mutation in ryanodine receptors (IP3 activated Ca2+ channel located on the sarcoplasmic reticulum). Effects: Increased Ca2+ triggers the Na+/Ca2+ exchanger resulting in the influx of 3 Na+ ions in exchange for one Ca2+ ion out of the cell resulting in depolarization.

OK

Underlying mechanisms of Cardiac Arrhythmias Early after depolarizations occur during phase 2 or phase 3. Phase 2 early after depolarizations occur as a result of an inward flux of Ca2+ while phase 3 early after depolarizations result due to an influx of Na+ ions. Cause: A deficiency of K+ in the blood, hypokalemia, or hypercalcaemia. Effect: Hypercalcaemia delays repolarization of phase 3, which increases the entry of Ca2+.

OK

Why is it advised that some pharmacological agents be ingested orally in the presence food?

Oral administration involves the swallowing of a whole drug; the absorption of that drug typically occurs in the small intestine. Orally administered drugs are typically absorbed via passive transfer that is determined by the ionization of the drug as well as its lipid solubility. Typically, around 75% of a drug is absorbed in 1-3 hours after ingestion, however absorption rates vary greatly. Factors affecting absorption include gut content, gastrointestinal motility, the size of the drug particle as well as its formulation, and splanchnic blood flow. For example, if gut motility is too fast, the drug won't be absorbed. Food increases splanchnic blood flow, thereby increasing drug absorption.

L-carbadopa is utilized to treat: Alcoholism Depression Glaucoma Parkinson's disease

PD

CNS >> cholinergic >> Ach on Nicotinic Receptor >>>> cholinergic >>> Ach on Target Organ

Parasympathetic NS

What disease characterized by Degeneration of dopaminergic neurons in the substantia nigra and degeneration of nerve terminals in the corpus striatum

Parkinson's symptoms: Suppression of voluntary movement, tremor at rest, muscle rigidity, and variable cognitive impairmentFeature of disease: appearance of lewy bodies, abnormal aggregates of α-synucleinsynaptic protein inside neurons

The utilization of genetic information of an individual in order to preselect the most effective and least toxic pharmacological agent and dosing regimen is known as: Personalized medicine Idiosyncratic response Pharmacogenomics Pharmacokinetics

Personalized medicine Pharmacogenomics is the study of the genetic factors that influence drug response. It is a discipline that is still being developed as a core branch of pharmacology. Personalized medicine is an idea that arose as a result of pharmacogenomics. Once we are able to effectively and cheaply sequence individuals genomes, we can potentially use the genetic information retrieved from a patient as a means to chose the most effective and safe drug dose.

Study of the biochemical and physiological effect(s) of drugs and their mechanism of action. For simplicity, pharmacodynamics can be defined as the effect of a drug on the body = _______________?

Pharmacodynamics

__________________is the study of the genetic basis for variation in drug response among individuals or populations. It identifies which variants or combination of variants have a functional consequence for drug effects.

Pharmacogenomics

Study of the bodily absorption, distribution, metabolism and elimination of drugs. For simplicity, pharmacokinetics can be defined as the effect of the body on a drug. = _____________?

Pharmacokinetics

Tamoxifen, utilized to treat breast cancer, is metabolized by CYP2D6. A polymorphism that diminishes the activity of CYP2D6 would alter what property of tamoxifen? Phase I metabolism Phase II metabolism Pharmacodynamics Volume of distribution Rate of absorption

Phase 1 Metabolism

An action potential of cardiomyocytes not belonging to the automatic pacemaker generating regions of the heart consists of four phases. In which phase are L-type calcium channels open? Phase 1 Phase 2 Phase 3 Phase 0

Phase 2 Phase 2 is the plateau phase. The membrane potential doesn't change much during this phase due to the simultaneous influx of Ca2+ and efflux of K+. This is the only phase in which Ca2+ channels are open.

T/F Phase II biotransformation reactions yield drug conjugates that are readily excreted polar molecules.

Phase II metabolizing reactions (also called biotransformation reactions) attach a bulky chemical group to the newly exposed functional moiety. This bulky conjugation causes pharmacological agents to be readily excreted by transforming the chemistry of the compound making the drug more polar. A list of the conjugation groups can be found in the text or in Table 2.3 of the handout.

Which of the following statements is true about phase II drug metabolism (biotransformation)? Phase II metabolism includes oxidation reactions Phase II reactions usually form inactive metabolites Phase II metabolism produces low molecular weight products Phase II metabolism usually takes place in the kidneys

Phase II reactions usually form inactive metabolites

The ability of Sildenafil to promote blood flow depends on which of the following? Phosphodiesterase inhibition elevating cGMP levels Activation of parasympathetic activity Activation of K+ channels promoting hyperpolarization Inhibition of adenylyl cyclase diminishing cAMP levels

Phosphodiesterase inhibition elevating cGMP levels

Some full agonists are able to elicit a maximal response without acquiring 100% occupancy of the receptor pool. This is a result of what phenomenon? Tolerance Presence of spare receptors Tachyphylaxis Desensitization

Presence of spare receptors The spare receptor hypothesis is a result of work performed by Stephenson in 1956. He observed that a full maximal response was achieved even though a small fraction of the available receptors on the surface were occupied. This revealed that there was a reserve in the mechanism linking response to receptor occupancy.

Which signal transduction pathway associated with the kinase-linked receptor superfamily is most important in cell division, growth, and differentiation? Guanylate cyclic signal pathways Ras/Raf/Map kinase Phospholipase C pathway Eicosanoid signal pathway

Ras/Raf/Map kinase

The process of re-excitation of cardiac tissue before the propagation of the next cardiac action potential is referred to Ectopic automaticity Atrioventricular block Re-entry Bradycardia

Re-entry Re-entry occurs as a result of myocardial damage that disturbs the normal pattern of conduction. This allows for the propagation of an action potential to migrate in a pattern that would allow for the re-excitation of cardiomyocytes before a subsequent action potential is propagated by the pacemaker regions of the heart. This can result in the continuous circulation of action potentials.

The enteric nervous system Receives input only from the parasympathetic nervous system Cannot function without the central nervous system Releases several peptide neurotransmitters and nitric oxide Receives input only from the sympathetic nervous system Has cell bodies lying in plexuses outside the intestinal wall

Receives input only from the sympathetic nervous system s

Four main protein targets for drug action include:

Receptors Ion channels Enzymes Carrier molecules

Which of the following statements is true about neurotrophic factors? Released by cholinergic neurons Regulate neuron growth and gene expression Act on ligand-gated ion channels only Include glutamate

Regulate neuron growth and gene expression Neurotrophic factors are released from non-neuronal cells such as astrocytes. The target of neurotrophic factors are tyrosine kinase linked receptors that are responsible for neuronal growth and gene expression.

Activation of adrenergic beta-2 receptors produces Contraction of the iris sphincter muscle Lacrimal gland secretion Relaxation of the ciliary muscle Relaxation of the iris sphincter muscle Contraction of the ciliary muscle

Relaxation of the ciliary muscle

Which of the following compounds blocks the vesicular monoamine transporter (VMAT)? Metyrosine Baclofen Reserpine Yohimbine

Reserpine

Which of the following statements best describes the condition of tachyphylaxis? Responsiveness increased rapidly after administration of a drug Responsiveness decreased rapidly after administration of a drug Responsiveness increased rapidly after maintenance of a drug Responsiveness decreased rapidly after maintenance of a drug

Responsiveness decreased rapidly after maintenance of a drug

Prozac belongs to what class of antidepressant drugs? Tricyclic antidepressants Selective serotonin reuptake inhibitors Monoamine oxidase inhibitor Serotonin and norepinephrine reuptake inhibitors

Selective serotonin reuptake inhibitors

Selegiline is included as a potential treatment of Parkinson's related symptoms because selegiline Acts as a muscarinic acetylcholine receptor antagonist Slows the progression of Parkinson's disease Inhibits cholinesterase Selectively inhibits type B monoamine oxidase

Selectively inhibits type B monoamine oxidase Selegiline is a monoamine oxidase type B inhibitor. Unlike nonselective monoamine oxidase inhibitors that inhibit both type A and B, selegiline lacks the unwanted peripheral side effects associated with the degradation of catecholamines such as norepinephrine, serotonin and dopamine.

Which of the following mutations does not result in a change in the amino acid sequence Non-synonymous Missense Sense Frameshift

Sense

Psychotic and obsessive-compulsive behavior is associated with which receptor? Metabotrophic glutamate receptor Nicotinic receptor Serotonin receptor Ionotrophic glutamate receptor

Serotonin receptor

The concurrent administration of Prozac with a monoamine oxidase inhibitor such as Moclobemide is most likely to cause hyperthermia and muscle rigidity, a condition known as Prion disease Creutzfeld-Jacob disease Excessive dopamine condition Serotonin syndrome

Serotonin syndrome

A man recently diagnosed with hypertension started a therapy with hydrochlorothiazide, one tablet daily. Hydrochlorothiazide is an acidic drug with a pKa of about 9. Which of the following parts of the digestive tract most likely represents the main site of absorption of that drug? Small intestine Oral mucosa Stomach Colon

Small intestine

Which route of administration is typically utilized for Nitroglycerin in which drug is absorbed into the blood through tissues under the tongue? Sublingual Intravascular Enteral Oral

Sublingual

The process of long-term potentiation includes all of the following except: Activation of nitric oxide synthase Sustained blockade of N-methyl-D-aspartate receptors Activation of protein kinases by calcium Retrograde feedback by nitric oxide

Sustained blockade of N-methyl-D-aspartate receptors

Approximately one in 2500 individuals have a polymorphic variant in the plasma cholinesterase gene resulting in a prolonged and more intense drug effect upon administration of what drug? Warfarin Suxamethonium Tamoxifen Morphine Thiopurine

Suxamethonium

CNS >> cholinergic >> Ach on Nicotinic Receptor >>>> noradrenergic >>> NA on Target Organ

Sympathetic NS

Autonomic Nervous System is subdivided into the _________ and _______________.

Sympathetic and Parasympathetic

Which of the following nomenclature correctly denotes a polymorphism in the TPMT gene? CYP2D6*4 TPMT*2 TPMT*4xN A80P

TPMT*2

abnormally rapid heart beats = __________________ atrial fibrillation Supraventricular Tachycardia Ventricular tachycardia and Ventricular Fibrillation:

Tachyarrhythmia

Digoxin increases myocardial contraction by acting on β-adrenergic receptor The Na+/K+ ATPase L-type voltage-gated Ca2+ channels Na+/K+/2Cl- cotransporter

The Na+/K+ ATPase

Describe the Philadelphia chromosome. What is it? How is it formed? What drug or drugs have been designed to inhibit the activity of the fusion protein that is produced as a result of the formation of the Philadelphia chromosome? How does this relate to pharmacogenomics?

The Philadelphia chromosome is one of the most studied translocations. It is found in 90% of those with chronic myelogenous leukemia (CML). It is a translocation between the ABL proto-oncogene portion of Chromosome 9 to Chromosome 22; it is placed adjacent to Chromosome 22's breakpoint cluster regions (BCR) portion in exchange for another part of Chromosome 22. Together, BCR-ABL code for a protein that permits the cell to bypass signals that control normal cell growth. The result is malignancy and chronic myelogenous leukemia. BCR-ABL codes for a tyrosine kinase able to phosphorylate molecules. BCR-ABL can phosphorylate the thereby activate a cancer protein leading to uncontrolled growth. Dasatinib is a tyrosine kinase inhibitor. It binds to the ATP binding site on BCR-ABL to competitively inhibit its activity in phosphorylating proteins. A mutation in BCR-ABL (T315I) serves as a barrier to dasatinib's inhibition. Therefore, patients with CML who have this variant do not benefit from the drug.

Which of the following statements is true about Warfarin? The drug target for Warfarin is an acetyltransferase Warfarin is utilized to reduce the size of tumors Warfarin is rarely prescribed in the United States The administration of Warfarin is complicated by a polygenic affect

The administration of Warfarin is complicated by a polygenic affect

A drug has a volume of distribution of 300 Liters. What can we infer from this observation? The drug is confined largely in the plasma The drug is subject to extensive first-pass metabolism The drug is distributed mainly in body tissues None of the above

The drug is distributed mainly in body tissues

Which of the following is not one of the four receptor superfamilies? Kinase-linked receptors Nuclear receptors G-protein coupled receptors Transport proteins Ligand-gated ion channels

The four receptor superfamilies are G-protein coupled receptors, kinase-linked receptors, nuclear receptors, and ligand-gated ion channels. Transport proteins are of pharmacological importance as a drug target. Transport proteins are responsible for the movement of ions and small organic molecules across cell membranes that are often too polar to pass through the lipid membrane on their own.

Compare dose-response curves for codeine in which one individual has a fully functional CYP2D6 and another individual has a polymorphism in CYP2D6 that decreases the affinity for codeine. Explain the shift or lack of shift that takes place in the dose response curve.

The individual possessing the fully functional CYP2D6 gene would show a particular dose response curve that we may use as a reference curve. Codeine is a prodrug metabolized by the CYP2D6 enzyme. Without this enzyme, codeine is less potent. Thus, any polymorphism that decreases CYP2D6's affinity for codeine will push the dose response curve to the right of the reference curve. In sum, the dose response curve of the individual with a polymorphism in CYP2D6 that decreases the affinity of the enzyme for codeine will lie to the right of curve of the fully fucntional CYP2D6.

When plotting plasma drug concentration (y-axis) versus time (x-axis), what are the advantages of using a log scale for the y-axis rather than a linear scale?

The log scale enables better viewing of certain components. It spreads out the function so we can see what is occurring more clearly.

Which of the following occurs as a result of agonist binding to a ligand-gated ion channel? You Answered The open channel conformation is altered Channel ion selectivity is altered Channel conductance increases The rate of channel closing increases The number of open channels increase

The number of open channels increase Ligand-gated ion channels are also referred to as ionotropic receptors. When an agonist binds, the channel opens and ions are allowed to flow down their concentration gradient.

A patient has come into the ER complaining of joint pain, unexplainable bruising and blood in the urine. During his examination, he mentions that he is not taking any other medication besides warfarin to treat his chronic atrial fibrillation. What is the most likely pharmacogenomic explanation for his symptoms? Would you suggest increasing or decreasing the dose of warfarin?

The patient may have been on a "normal" dose of warfain and then experienced some underlying change. He may have lower levels of Vitamin K, thereby lowering the competition for warfarin on its target (which uses vitamin K to make clotting factors), thereby increasing the potency of his warfarin dose. The best thing to do would be to give the patient a competitive antagonist to warfarin, like Vitamin K, or another drug that would--hopefully--rapidly induce the expression of cytochrome P450 enzyme, which is a necessary phase 1 metabolizer of many drugs, including warfarin. This would decrease the potency of warfarin. They could also just lower his dose of warfarin, since it's obviously being too effective as an anti-coagulant and has caused bleeding.

Of the following statements, which of the following is true for a drug that follows first-order elimination kinetics? The amount eliminated per unit time is constant Elimination is proportional to the drug concentration in the plasma Elimination involves a rate-limiting enzymatic reaction that is saturated The rate of elimination is proportional to the plasma concentration

The rate of elimination is proportional to the plasma concentration

Explain the renin angiotensin aldosterone system and how the signaling pathway results in an increase in cardiac output. Start with the release of renin from the juxtaglomerular apparatus.

The renin-angiotensin alsosterone system (RAAS) is a system that regulates blood pressure and also controls fluid balance. It is a hormonal system. Low blood pressure due to low blood volume. The RAS system is activated by a decrease in blood flow volume to the kidneys. Renin gets released from the juxtaglomerular apparatus. Renin converts angiotensinogen, released by the liver, to angiotensin I. Angiotensin converting enzyme converts angiotensin I to angiotensin II. Angiotensin II is a peptide that causes vasoconstriction, while also stimulating the release of aldosterone from the adrenal cortex. It does this by binding AT1 receptors, which signals for the release of aldosterone. Aldosterone causes renal tubules to reabsorb more sodium and water so that blood volume may be increased. This is due to the increased expression of Na+/K+ pump and the epithelial Na+ channel. Because cardiac output is the mean ventricular ejection volume multiplied by heart beats per minute, by increasing blood volume, the amount of blood filling the heart and subsequently being ejected will also increase, thereby increasing cardiac output on a whole.

Which of the following genetic loci are routinely screened as recommended by the FDA before drug administration? Acetyltransferase Thiopurine-S-methyltransferase (TPMT) Plasma cholinesterase Warfarin

Thiopurine-S-methyltransferase (TPMT) Thiopurine-S-methyltransferase (TPMT) is found in the plasma. TPMT is an enzyme that detoxifys thiopurine drugs used in the treatment of leukemias. Low TPMT activity results in bone marrow toxicity in the presence of these drugs, whereas high TPMT activity yields thiopurine drugs highly ineffective. Before administration of a thiopurine drug, it is recommended by the FDA that a clinician screen for the three most common disruptive TPMT genes (TPMT*3A, TPMT*3C, and TPMT*2). Prescreening allows the clinician to access the safety and efficacy of a thiopurine before drug administration. This allows toxicity to be avoided and/or a more effective treatment to be utilized.

What is the purpose of producing inactive prodrugs? To increase drug absorption To decrease hepatic drug metabolism To increase drug half-life To reduce drug toxicity

To increase drug absorption The parent compound of a prodrug is inactive upon absorption. The drug only becomes activated following the process of metabolism. One purpose of producing a prodrug is to overcome hurdles associated with drug delivery.

Route of administration pulmonary ocular

Topical

Some breast cancers overexpress the human epidermal growth factor receptor abbreviated HER2. The following drug would only be useful if the tumor tissue was screened and found to contain the HER2 genetic variant. Tamoxifen 5-fluorouracil Trastuzumab Suxamethonium

Trastuzumab Trastuzumab is a monoclonal antibody that binds to HER2 and antagonizes the receptor. This is an effective treatment for breast cancers in which this receptor is overexpressed.

Acetylcholine is synthesized and stored in the synaptic knob of cholinergic neurons.

True

T/F An individual who has two non-functional alleles will have an activity score of zero.

True

T/F Ethanol is a CNS depressant.

True

T/F Homotropic interactions are a type of presynaptic modulation in which the release of a neurotransmitter from a neuron is affected by the binding of the same neurotransmitter to receptors located on the neuron itself.

True

T/F Nitric Oxide dilates blood vessels.

True

T/F Pharmacodynamics describes the effect a pharmacological compound has on the body.

True

T/F Pharmacodynamics is the study of the biochemical and physiological effects of drugs and their mechanisms of action.

True

T/F Pharmacogenetics is the study of genetic factors that underlie variation in drug response.

True

T/F Sympathetic neurons terminating on sweat glands release acetylcholine on muscarinic receptors.

True

T/F The FDA recommends that 5-fluorouracil not be used for patients with solid tumors that have a deficiency in dihydropyrimidine dehydrogenase (DPYD).

True

T/F The enteric nervous system can function independently of the central nervous system.

True

T/F The population frequency distribution displaying a drug's effect in which a single trait contributes to the observed phenotype will appear multi-modal.

True

T/F The predominant tone in most organ systems is the parasympathetic nervous system.

True

T/F The smaller the KD the more tightly bound a Drug-Receptor complex.

True

T/F The third cytoplasmic loop of the M2 muscarinic receptor is associated with the inhibitory G protein, Gi.

True

T/F Tricyclic antidepressants produce unwanted side effects including dry mouth and constipation as anticholinergics inhibiting parasympathetic innervation.

True

T/F Verapamil is not used therapeutically to treat heart failure.

True

T/F All neurons leaving the central nervous system release acetylcholine, which acts on nicotinic receptors.

True Although there are some exceptions, there are a few general rules surrounding the neurotransmitters utilized by the parasympathetic and sympathetic branches of the autonomic nervous system.

T/F Complete heart block is a condition in which the atria and ventricle beat independently of one another.

True Heart block results as a consequence of fibrosis or ischemic damage to the conducting system. Normally, the electrical conducting impulse originates in the sinoatrial node and is conducted through the atria to the atrioventricular node through the bundle of His and purkinje fibers to the ventricles. Interruption of this conduction system results in the atria and ventricles beating independently of each other. The atria will contract as governed by the faster pacemaker in the sinoatrial node while the ventricles will beat at a slower rate dependent on the pacemaker available downstream of the damaged tissue.

T/F Sweat glands have only sympathetic innervation.

True It is incorrect to simplify the autonomic nervous system as two opposing branches. There are some instances where the parasympathetic and sympathetic branches produce similar effects. In addition, some target organs are innervated by only one branch of the autonomic nervous system.

T/F Noradrenaline is synthesized in noradrenergic nerve terminals.

True Neurotransmitters are synthesized in the nerve terminals of the neurons that secrete them.

___________________________ dopaminergic pathway controls endocrine secretions.

Tuberohypophyseal or tuberoinfundibular Dopamine inhibits prolactin secretion but increases growth hormone secretion.

An individual with more than two copies of a metabolizing enzyme as a result of a copy number variant polymorphism is classified as a Intermediate metabolizer Fast metabolizer Extensive metabolizer Poor metabolizer Ultra-rapid metabolizer

Ultra-rapid metabolizer

Which of the following can produce a therapeutic response? A drug that is: Concentrated in the bile Unbound to plasma proteins Not absorbed from the GI tract Bound to plasma albumin

Unbound to plasma proteins

Five hundred milligrams of a pharmacological compound was administered to a 70-kg subject. Later the measured in the plasma to be 1 μg/mL. Calculate the volume of distribution in Liters.

Vd = Drug amt/plasma concentration Vd = (500mg)/(1ug/ml) Vd = (500mg)/(.001mg/ml) Vd= (500mg)/1mg/L) Vd=500L

Antiarrhythmic drugs. Class IV: Calcium channel blockers Since the propagation of an action potential depends on the influx of Ca2+, class IV antiarrhythmic drugs slow conduction via the sinoatrial and atrioventricular nodes. Calcium is also an essential component for the excitation-contraction coupling of cardiac muscle.

Verapamil: Utilized to slow the rate of atrial fibrillation. Note: Nifedipine and Diltiazem are used to treat angina and hypertension.

can be defined as the fluid volume that would be required to contain all of the drug in the body if the concentration in the tissues is the same as the concentration in the blood. amt of drug in the body / concentration in the blood.

Volume of distribution Vd

A pharmacogenetic response to a drug can be due to a mutation disrupting the function of all the following except: Phase I enzyme Phase II enzymes Membrane Transporters Warfarin

Warfarin

Which of the following statements is true about Warfarin? Warfarin is utilized to treat breast cancer Warfarin is metabolized by the cytochrome P450 enzyme, CYP2D6 Warfarin is the most widely used drug for which pharmacogenomics testing is proposed Warfarin administration is only complicated by a pharmacokinetic polymorphism

Warfarin is the most widely used drug for which pharmacogenomics testing is proposed Warfarin is an anticoagulant used to treat heart attacks, strokes and blood clots. The administration of warfarin is complicated by a polymorphism in the drug target, vitamin K epoxide reductase, and by a polymorphism in the enzyme responsible for its metabolism, CYP2C9. Lack of efficacy and serious adverse events are commonly observed in subjects taking warfarin. Warfarin is the most widely used drug for which pharmacogenetic testing is being considered.

If the number of receptors in a tissue is increased in response to reduced receptor stimulation, does the maximum response to a transmitter always increase? Why or why not?

Yes. This is due to sensitization. It's not clear that a maximum biological response to receptor stimulation in such circumstances is ALWAYS the case, but due to a low amount of stimulation (or no stimulation of a receptor, in the case of a severed nerve), the receiving end of the system would increase the quantity of available receptors, as though it is "searching" for the missing input. Once found, the biological response--such as in the case of pain--is enhanced. Just as too many inputs can result in desensitization in receptors, too few and result in increased biological response.

___________can be defined as the movement of a drug from its site of administration into the central compartment (plasma) and the extent to which it occurs.

absorption

1) Nucleus basalis of Meyert Cluster appearing in the forebrain. Distinguishable by really large cell bodies. Project throughout the cerebral cortex Believed to be responsible for arousal 2) Septohippocampal nucleus Believed to be responsible in memory Main cholinergic input to the hippocampus 3) Pedunculopontine and laterodorsal tegmental nuclei Interneurons in corpus striatum

acetylcholine function: : Learning, memory, arousal, and motor control.

what does Sumatriptan do?

agonists to 5-HT1D used to treat migraine

Major biding protein carrier for acidic drugs (such as warfarin, NSAIDs, sulfonamides

albumin! Liver disease cause hypoalbuminemia.Hypoalbuminemia will increase the unbound fraction of drug and thus increase the potency of a drug.

skeletal muscle controlled by what receptors? results of each?

alpha 1 = contriction and Beta2 = dilation

skin and mucosa controlled by what receptor? result?

alpha 1 and alpha 2 constriction

iris radial muscle controlled by what receptor result?

alpha1 pupil dilation (mydriasis)

Which of the following pharmacological agents have been approved for stroke as a result of thrombosis? Alteplase Disulfiram Presenilin Selegiline

alteplase

Palliative Treatment for _________________ 1) Prolong acetylcholine action by inhibiting acetylcholine degradation 2) NMDA receptor antagonist: memantine

alzheimer's

Degeneration of several neurotransmitter systems First and most pronounced reduction occurs in the cholinergic neuronal system of the nucleus basalis

alzheimer's features of the disease: presence amyloid plaques as a result of increased deposits of β-amyloid protein and intraneuronal neuro-fibrillary tangles (filaments of phosphorylated Tau, a microtubule protein involved in the transport of materials along axons).

what does ondasterone do?

an antagonist of 5-HT3, used to treat vomiting

nitroglycerine given for

angina

A type of ischemic heart disease, ______________________, midsternal chest pain that may radiate along the inner portion of one or both arms, or to the back. Angina pectoris is the primary symptom of ischemic heart disease.

angina pectoris imbalance between the supply and demand of oxygen in the myocardium.Demand increases as heart rate, ventricular contractility, and ventricular wall tension increases. caused by narrowing of coronary artery.

Which of the following is not a type of kinase-linked receptor? Receptor tyrosine kinase Receptor serine/threonine kinase Cytokine receptor Angiotensin-converting receptor

angiotensin-converting receptor

Quinidine inhibits a cytochrome P450 metabolizing enzyme, CYP2D6 as an Negative allosteric modulator Inverse agonist Antagonist Partial agonist

antagonist Quinidine binds to the active site of CYP2D6 and blocks the binding and subsequent metabolism of other substrates. Quinidine is not a substrate itself in that it does not become metabolized. Therefore, quinidine has no intrinsic activity and by definition is considered an antagonist to CYP2D6.

what does Benzotropine do?

antagonized muscarinic ach receptors for PD

A way small molecules cross cell membranes Diffusion through aqueous pores Diameter is too small for most drugs but small enough for ethanol and glycerolSimple and Aqueous diffusion are forms of passive transport. Mole move across the cell membrane from an area of high concentration to lower concentration.

aqueous diffusion

Which of the following mechanisms is utilized by a drug that permeates across epithelial tight junctions powered by a concentration gradient? Aqueous diffusion Simple diffusion Facilitated transport Endocytosis and Exocytosis Pinocytosis

aqueous diffusion

Which cells convert glutamate to glutamine. Glutamine is then released and taken up by the presynaptic neurons for conversion back into glutamine.

astrocytes

Which of the following arrhythmias is verapamil utilized for? Ventricular tachycardia Atrial fibrillation Cardiac asystole Ventricular fibrillation

atrila fibrillation

The peripheral nervous system is subdivided into the somatic and ____________ nervous system.

autonomic

Governs functions that occur without conscious control such as: Cardiac Output, Blood Flow Distribution, and Digestion.

autonomic ns

A reduction in cardiac output is sensed via ________________________ (stretch receptors). An increase in blood pressure, however, activates the stretch receptor increasing the rate of firing and compensated by an enhancement of parasympathetic activity.

baroreceptors

γ-amino butyric acid (GABA) effects are potentiated by Tacarine Ketamine Amantadine Benzodiazepines

benzos

The inhibition of carbonic anhydrase in proximal renal tubular cells causes a loss of: Hydrogen ions Glucose Bicarbonate Ions Glycine

bicarbonate

The amount of administered drugs that enter the circulation, and is therefore available to the site of action, is defined as what? Bioavailability Bioequivalence Drug absorption Clearance Half-life

bioavailability

AUC oral / AUC iv =

bioavailability, denoted as F. it's not solely a characteristic of a drug, instead bioavailability also depends on the presence and activity of liver enzymes which varies from patient to patient as well as enzymes found in the gut.

which organs/systems have only one type of innervation?

blood vessels and sweat glands

Which of the following is NOT a second messenger associated with the G-protein coupled receptor? Diacylglycerol cAMP cGMP Inositol trisphosphate

cGMP

Levodopa, a pharmacological agent utilized to alleviate symptoms of Parkinson's disease, is administered in combination with a peripheral dopa decarboxylase inhibitor such as: Entacopone Benztropine Amantadine Carbidopa

carbidopa Carbidopa is a dopa decarboxylase inhibitor. It is administered with levodopa in order to prevent the conversion of levodopa to dopamine outside of the central nervous system. This eliminates the side effects experienced as a result of excess dopamine in the periphery. In addition, the dose of levodopa required to produce an effect can be decreased 10-fold.

_______________________ = heart Rate x Mean Left Ventricular Stroke Volume

cariac output

what does LSD do?

causes hallucinations. agonized serotonin receptors.

type of antagonism . The result of one drug acting on another preventing binding to a receptor. Typically, interactions are a result of ionic binding of the chemical antagonist to a second compound.

chemical antagonism e.g. The effects of heparin, an anticoagulant, can be halted by the addition of protamine sulfate.

nerve fibers that produce and release Ach are

cholinergic

_________________can be defined as a measure of the body's EFFICIENCY in eliminating drug from the systemic circulation. mL/min per kg

clearance clearance = rate of elimination / concentration of drug

Dopamine reuptake in the presynaptic nerve terminals is inhibited by? Levodopa Cocaine Entacopone Amantadine

cocaine

drug that competes with an agonist or endogenous compound for the primary binding site on a receptor but lacks intrinsic efficacy = _______________ does what to the curve?

competitive antagonist (reversible) pushes curve to the right

parasympathetic effect on bladder

contracts

The major functions of noradrenergic pathways in the central nervous system include? Control of mood Pleasure and reward Appetite Sleep

control of mood

Depression is associated with the elevation of which of the following? Cortisol Norepinephrine Brain-derived neurotrophic factor γ-amino butyric acid (GABA)

cortisol

A 24-year-old woman was admitted to the hospital after a car accident and was diagnosed with neurogenic shock due to a spinal cord injury. An emergency treatment was started that included the administration of norepinephrine. Which of the following expected effects of the drug was most likely mediated by the activation of peripheral postsynaptic β receptors? Decreased renin secretion Adjustment of the eye for near vision Bronchodilation Urinary contraction

cronchodilation

The Jak/Stat pathway associated with the kinase-linked receptor superfamily responds to activation by which of the following? Steroid hormones Human growth hormone Cytokines Nitric oxide

cytokines

what does Ecstasy do?

displaces serotinin in synaptic vesicles, depleting serotonin supplies.

___________can be defined as the movement of a pharmacological compound from the central compartment (organs and systems with high perfusion rates) to the target site via the blood stream.

distribution Rate of delivery to the target site is dependent on 1.cardiac output 2.regional blood flow 3.capillary permeability brain kidneys and liver get most of the drug first, such they get lots of blood!

Vd x concetration in the blood = _______?

dose

Any component of a cell that can bind a drug and elicit an effect. = ________________?

drug receptor

Cellular macromolecule or macromolecular complex with which the drug molecule interacts with to elicit a cellular response. = ______________?

drug target

_________________can be defined as the pharmacokinetic process whereby which drugs are excreted from the bod

elimination

Phase I metabolizing enzymes (CYP450s) and their reactions occur primarily in the _________________________.

endoplasmic reticulum oxidation reduction hydrolysis

what does Adamantine do?

enhances dopamine release for PD

For acute sever type I hypersensitivity reactions the first-line of treatment is: Norepinephrine Dopamine Epinephrine Isoproterenol Phenylephrine

epinephrine

A way small molecules cross cell membranes Utilization of membrane bound carrier proteins (transporters) No energy requiredHere molecules combine with carrier proteins which then diffuse across the cell membraneTransporters become saturated, therefore the amount of carriers limits the rate of diffusionRare route for drugsoLevodopa and fluorouracil

facilitated transport

T/F A partial agonist has the same efficacy as a full agonist, but takes longer to achieve this effect.

false

T/F Degeneration of dopaminergic neurons in the nigrostriatal pathway is associated with the development of Alzheimer's disease.

false

T/F Lipophilic drugs are eliminated efficiently by the kidney.

false Lipophilic drugs can easily diffuse through the plasma membrane. Drugs that are lipophilic will be reabsorbed back into the bloodstream and avoid elimination by simple diffusion.

T/F A pharmacological compound bound to albumin is filtered from the blood in the kidney by glomerular filtration.

false. Bound drug is too big to be filtered through the pores of glomerular capillaries. Drugs with a molecular weight under 20,000 are able to be filtered. Albumin alone has a molecular weight of 68,000.

T/F The somatic nervous system governs involuntary functions.

flase

Type of agonist. A drug that produces a maximal response at full receptor occupancy

full agonist. drug that produces a maximal response at full receptor occupancy

What kind of receptor? Pentameric ligand-gated Cl- channel Activation causes an influx of Cl- ions resulting in hyperpolarization Tetanus toxin blocks glycine release resulting in limited to no stimulation Result = excessive reflux hyperexcitability and violent muscle spasms due to lack of inhibition.

glycine receptor

GPCR homodimer cross-linked by disulfide bridge Extracellular domain contains a venus fly trap-like structure to which glutamate binds Located postsynaptically Activation causes an increase in Ca2+ intracellularly

group 1 Metabotropic glutamate receptor

GPCR homodimer cross-linked by disulfide bridge Extracellular domain contains a venus fly trap-like structure to which glutamate binds Located presynaptically and function as inhibitory autoreceptorsInhibit Ca2+ channels inhibiting neurotransmitter release Reduce synaptic transmission Some are located postsynaptically and inhibit adenylyl cyclase

group 2 Metabotropic glutamate receptor

__________is a measure of the rate of 50% elimination of a drug from the systemic circulation.

half life

_____________________= occurs as a result of diminished perfusion of peripheral tissues inadequate to meet the needs of the organs of the body.

heart failure

estradiol given for

hormone replacement therapy

testosterone given for

hormone replacement therapy.

Which of the following is a Phase I reaction? Sulfation Glucuronidation Methylation Hydrolysis

hydrolysis Phase I reactions include hydrolysis, oxidation and reduction. Glucuronidation, sulfation and methylation are all phase II reactions.

clonidine given for

hypertension

What does Levodopa do?

increases dopamine synthesis for PD

_______________ is a type of polymorphism that is produced as a result of an insertion or deletion of one or more nucleotides in either the coding or noncoding region of the genome. If occurring in the coding region, these types of polymorphisms most commonly produce frameshift mutations.

indel frameshift copy number variants duplication inversion

Variations of activity could be imagined such that an allele containing a polymorphism could provide intermediate activity and be considered an intermediate metabolizing allele. has an activity score less than one but greater than zero. An individual containing two intermediate metabolizing alleles would have an activity score greater than zero but less than two and would be considered an _____________

intermediate metabolizer

parenteral route of administration where the drug is injected into the muscleThe rate of absorption is dependent on the rate of blood flow to the site of injection. Absorption can be increased with the addition of hyaluronidase, an enzyme that breaks down the intercellular matrix. Absorption can be decreased by adding adrenaline or epinephrine.

intramuscular admin can give a lot sustained release painful at site absorption varies site to site

________is a result of the effect of pH on drug absorption.

ion trapping

Which of the following pharmacological agents blocks NMDA (N-methyl-D-aspartate) receptors? Kainite Bromocriptine Ketamine Barbiturates

ketamine

Of the four receptor superfamilies, which does the insulin receptor belong?

kinase linked receptors

Cholinergic pathways in the central nervous system are associated with which function? Learning and memory Mood and emotion Appetite Drug dependence

learning and memory

Of the four receptor superfamilies, which is also referred to as ionotropic receptors?

ligand gated ion channels

The majority of serotonin receptors are metabotropic G protein coupled receptors except for the 5-HT3 family, which is a ___________________________________.

ligand-gated Na+ and K+ channel

Weak electrical stimulation resulting in a minimal release of glutamate only causes a response from the AMPA receptor resulting in channel opening, an influx of Na+, and slight membrane depolarization. The sole activation of AMPA receptors is a consequence of the blockage of NMDA receptor ion channels with Mg2+. However, when way too much glutamate is released from the presynaptic axon due to stronger presynaptic electrical stimulation or increased frequency of glutamate release, the depolarization of the membrane from AMPA receptors is great enough to expel the Mg2+ from the NMDA receptor ion channel. The NMDA channel can then respond to glutamate and allow the influx of Na+ and more importantly the influx of Ca2+. (NMDA receptor has the highest permeability to Ca2+ and thus the influx of Ca2+ into the cell as a result of glutamate is mainly due to the NMDA receptor.) Increased intracellular Ca2+ levels, as a result of activated NMDA receptors promotes a variety of responses intracellularly including the activation of several kinases. The calcium/calmodulin dependent protein kinase (CAM kinase) is one kinase that becomes activated The calcium-calmodulin complex then binds and activates CAM kinase resulting in the phosphorylation of existing AMPA receptors in the membrane, increasing the conductance of Na+. CAM kinase also promotes the release of intracellular stores of AMPA receptors into the membrane. Together these two events result in an enhanced response to glutamate as compared to the response obtained with the same stimulus before the activation of NMDA receptors. This physiological change is one of the mechanisms responsible for long-term potentiation.

long term potentiation

_________________________is a prolonged enhancement of synaptic transmission at various CNS synapses following a short burst of high-frequency presynaptic stimulation.

long-term potentiation

Of the following drugs, which is utilized to treat hypertension in pregnant women? Candesartan Aliskiren Methyldopa Captopril

methyldopa Methyldopa has not been documented to have adverse effects on the baby unlike angiotensin II receptor blockers such as candesartan and ACE inhibitors such as captopril. Therefore, methyldopa is used to treat hypertension in pregnant women.

Scopolamine given for

motion sickness

Which of the following is NOT governed by the autonomic nervous system? Movement Cardiac output Digestion Blood flow

movement

Receptor type: G Protein Couple Receptor - third cytoplasmic loop coupled to a G protein5 subtypes: M1 M2 M3 M4 M5Subtypes based on pharmacological specificities and amino acid/gene sequence. what receptor?

muscarinic receptors

Atropine, when administered topically yields which of the following effects? Decreased intraocular pressure Conjunctivitis Miosis Mydriasis Lacrimation

myadriasis

All of the following could result from poisoning by an organophosphate nerve gas or insecticide except: Excessive saliva production Mydriasis (pupil dilation) Diarrhea Overactive bladder

mydriasis

___________________is a form of ischemic heart disease in which a coronary artery is completely occluded by a thrombotic event resulting in diminished oxygen supply to a region of the heart.

myocardial infarction

Drug that does not compete with the agonist for the primary binding site on a receptor but is still able to block or reduce the effect of an agonist or endogenous compound. = ________________? does what to curve?

negative allosteric agonist. pushes curve to the right

Receptor type: Ligand-gated ion channel Has two acetylcholine binding sites (both need to be occupied to cause an effect)Allows the influx of Na+ and sometimes Ca2+ and an efflux of K+ End result = depolarization of cell membraneIn skeletal muscle, depolarization initiates an action potential causing contraction what receptor?

nicotinic receptor

drug with affinity for a receptor in which the inhibitory effect cannot be surmounted regardless of agonist concentration. = ___________ does what to the curve?

non-competitive antagonist (irreversible) depresses curve

nerve fibers that produce and release NA are

noradrenergic

____________________ is Inactivated by monoamine oxidase, aldehyde reductase and catechol-O-methyl transferase. it's released diffusely in CNS The most prominent cell body cluster is known as the LOCUS COERULEUS and is found in the PONS

norepinephrine (noradrenaline) Involved in arousal and attention, blood pressure regulation (noradrenergic synapses in medulla form part of the baroreceptor reflex pathway), and mood. May be important in major depression.

Which of the following receptor type is located entirely intracellularly? G-protein coupled receptor Ligand-gated ion channel Kinase-linked receptor Nuclear receptor Voltage-gated ion channel

nuclear receptor

Of the four receptor superfamilies, which contains a DNA binding domain and primarily regulates gene transcription?

nuclear receptors

topical route of administration in which the drug is placed on the eye.

ocular admin skips first pass metab

Which of the following compounds antagonizes the serotonergic receptor in the medulla in order to treat vomiting as an antiemetic Memantine Tacrine Ondansetron Sumatriptan

ondasterone

Many of the disadvantages surrounding ____________________________ of pharmacological compounds revolves around the limitations associated with incomplete absorption. Transport of a drug through the epithelial cells lining the gastrointestinal tract occurs via simple diffusion (with the exception of a few pharmacological agents which utilize carrier-mediated transport such as levodopa and fluorouracil). The rate at which passive transport occurs in the gastrointestinal tract depends on ionization and lipid solubility of the drug.

oral administration

fentanyl given for

pain

Leave the CNS through the cranial and sacral spinal nerves. Long myelinated preganglionic neurons Preganglionic neurons synapse in or near the effector organ Short unmyelinated postganglionic neurons Effect: discrete and localized response

parasympathetic ns

Route of administration intravenous intramuscular subcutaneous transdermal

parenteral

type of agonist. A drug that produces a lower than maximal response at full receptor occupancy. cannot elicit a max response by itself.

partial agonist. According to the two-state receptor model, a partial agonist has equal affinity for the active and inactive receptor conformation. shifts to the right!

All of the nerves outside of the central nervous system make up the _____________________________.

periferal NS

Antagonism type. ---due to decreasing the concentration of available active drug in the systemic circulation due to an increase in drug metabolism or decrease in drug absorption

pharmacokinetic antagonism e.g. The treatment for tuberculosis, rifampin, induces CYP3A4, an enzyme found in the liver responsible for the metabolism of a number of pharmacological compounds. Specifically, CYP3A4 hydrolyzes the active ingredient in oral contraceptives. If taken concurrently, oral contraceptives are ineffective due to increased metabolism.

______________ is the study of the bodily absorption, distribution, metabolism and elimination of drugs.

pharmacokinetics

The study of the effects of drugs on the function of a living system = _________________

pharmacology

___________reactions introduce or expose a functional polar group on the parent compoun

phase 1 metabolizing

_________________reactions occur in the cytosol.

phase 2 metabolizing use covalent linkages. Phase II reactions result in the addition of an endogenous substrate to yield a more water-soluble compound yielding an increase in polarity.

The next phase of the cardiac action potential, _______________, has a characteristic plateau shape. During this phase, the inward movement of___________creates a depolarizing current that is balanced by an outward repolarizing current governed by the movement of ________ out of the cell. The influx of ions through L-type voltage-gated sensitive ______channels inactivates throughout this phase.

phase 2; Ca2+ ions; K+ ions; Ca2+

type of antagonism that is a result of the administration of a drug that indirectly inhibits the cellular or physiological effect of an agonist.

physiological antagonism e.g. Excessive thyroid hormone can produce a rapid or irregular heart beat. A β-blocker, such as propranolol can be administered to counteract the increased heart rate.

A way small molecules cross cell membranes cell drinking 2Requires energy

pintocytosis

A ________________can be defined as a combinatorial effect of multiple genes on drug response. For a single trait, the population frequency distribution exhibits a multimodalfrequency distribution with relatively distinct separation among low activity, intermediate activity, high activity and ultra high activity groups.

polygenic effect

__________________ is variation in the DNA sequence that persists in a population so that the allele frequency is equal to 1% or greater. Individuals differ from each other approximately every 300-1000 nucleotides.

polymorphism

An allele in which a polymorphism has arisen such that little or no activity is observed would be classified as a poor metabolizing allele. This allele has been designated an activity score of 0. An individual with two poor metabolizing alleles would have a total activity score of 0 and be considered a _______________.

poor metabolizer

Which class of pharmacological compounds causes the agonist dose-response curve to shift to the left?

positive allosteric moulator

A competitive antagonist affects the ________ of an agonist and a non-competitive antagonist affect the _________ of an agonist.

potency efficacy

topical route of administration in which the drug is inhaled into the lungs.

pulmonary admin. rapid absorb skips first pass metab

parasympathetic effect on eye ....

pupil constricts

drug that facilitates or potentiates receptor activation upon agonist binding but does not bind to the primary agonist binding site. = __________? does what to the curve?

pushes curve to the left

________________ = a condition in which a cardiac impulse returns to original site and reexcites the region of the myocardium causing continuous circulation of action potentials independent of normal sinoatrial node conduction. Cause: myocardial damage Effect: AV reentrant tachycardia (Wolff-Parkinson-White syndrome), AV nodal tachycardia, atrial flutter.

re-entry

enteral route of administration in which a drug is placed in the rectal cavity.Rectal administration is utilized in scenarios in which patients cannot take a medication orally due to nausea, inability to swallow or have restrictions on eating.

rectal admin. no need to be awake. can produce local effect about 50% will bypass 1st pass metab but Variable and incomplete absorption

Which of the following statements is true about non-competitive antagonists in the absence of a spare receptor effect? Reduce the efficacy of an agonist Increase the EC50 of an agonist Increase the EC50 and reduce the efficacy of an agonist Reduce the EC50 of an agonist

reduce the efficacy of an agonist

parasympathetic effect on pancreas

release insulin and digestive enzymes

Which drug blocks the movement of noradrenaline (norepinephrine) into the synaptic vesicles? Reserpine 6-hydroxydopamine Guanethidine Methyldopa Bretylium

reserpine

Pharmacogenomic effects are due to polymorphisms in all of the following except: You Answered Noncoding regions Phase I metabolizing enzymes Mitochondrial DNA Vitamin K epoxide reductase Ribosomes

ribosomes

which organ/system have same effect under sympathetic and parasympathetic effect?

salivary glands

synthesized from tryptophan from diet. Main cluster is referred to as the raphe nuclei.

serotonin An enzyme involved in serotonin synthesis, tryptophan hydroxylase is irreversibly inhibited by PCPA (p-chlorophenylalanine) Important role in hallucinations and behavioral changes, sleep, mood, appetite, thermoregulation, vomiting, and control of sensory transmission. also involved in OCD>

For most pharmacological compounds in which a dose-response curve is constructed, what is the shape of the curve if the response is plotted on the y-axis and dose is plotted on the x-axis as the log of the drug concentration?

sigmoidal

A way small molecules cross cell membranes Non-specific diffusion through lipid Does not require energyoRate determined by partition coefficient (degree of lipid solubility) Main mechanism by which drugs transverse the plasma membrane

simple diffusion

_________________ is a type of polymorphism in which a single nucleotide in the genome is altered that may or may not change the amino acid sequence found within the coding and the noncoding region.

single nucleotide polymorphism synonymous non-synonymous missense (a change in a single nucleotide that alters the amino acid ) nonsense sense ( replacement of a single nucleotide does not alter the amino acid ..Potential consequences: diminished transcript production rate, altered protein structure due to misfolding. non-coding SNP (Potential consequences: alternate splicing, altered DNA tertiary structure as a result of chromatin interaction, altered binding of transcription factors, enhancers, topoisomerases and other DNA replication machinery )

The __________________ is the main pacemaker of the heart. the heart. Action potentials are initiated here without the help of neurons attributing to the automaticity of the pacemaker.

sinoatrial node

nicotine given for

smoking cessation

Governs consciously controlled functions such as: Movement, Respiration, and Posture.A single motor neuron(s) connects the central nervous system to the skeletal muscle.

somatic ns

The central nervous system in its entirety contains the brain and the__________________

spinal cord

sympathetic effect on adrenal medulla

srecretion of epinephrine/norepinephrine

Chest pain is predictable. Occurs upon exertion due to increased demand on the heart. Therapeutic goal: decrease cardiac demand, increase oxygen supply by dilating coronary arteries β-adrenergic receptor antagonists Organic nitrates Ca2+ antagonists Statin (treat underlying disease - stabilize the plaque) Aspirin (anti-platelet pharmacological agent) Treats what?

stable angina

To maintain a _____________________ concentration, the rate of administration should be adjusted so that it is equivalent to the rate of clearance (assuming 100% bioavailability).

steady state

what does Bromocriptine do?

stimulates dopamine receptors. it's an agonist. for PD.

sympathetic effect on liver

stimulates glucose production and release

parasympathetic effect on lacrimal glands

stimulates tears

sympathetic effect on lacrimal glands

stimulates tears

parenteral route of administration in which the drug is injected into the subcutaneous layer. As with intramuscular administration, the rate of absorption is dependent on the rate of blood flow to the site of injection.

subcutaneous admin complete absorb helped by heat and massage can regulate absorb with a vasoconstrictor/dilator. e.g. lidocaine given with epinephrine. slow and irritating

enteral route of administration whereby the drug is absorbed into the blood through tissues under the tongue. Common route of administration for nitroglycerin (glyceryl trinitrate).

sublingual admin. rapid absorb. skips stomach and first pass metab! only works for small doses.

The autonomic nervous system is subdivided into the ______________and __________________ nervous systems.

sympathetic and parasympathetic

Leave the CNS through the thoracic and lumbar spinal nerves Short myelinated preganglionic neurons Long unmyelinated postganglionic neurons One preganglionic neuron may synapse with many postganglionic sympathetic neurons diffuse response exception (Adrenal medulla)

sympathetic ns

Neurotransmitters are made in the _________________, stored in ________________, released into the_________ and act on postganglionic neuron receptors or effector organ receptors.

synaptic knob; synaptic vesicles; synapse

_______________________ is long-term adaptive changes in synaptic connectivity and efficacy following physiological alterations in neuronal activity (as in learning and memory) or pathological disturbances.

synaptic plasticity

____________________ is a range of concentrations that falls below the mean effective concentration of an adverse response and above the mean effective concentration for a desired respon

therapeutic window

Underlying mechanisms of Cardiac Arrhythmias Enhanced automaticity Cause: hypokalemia, β-adrenergic stimulation, mechanical stretch of cardiac cells Effects: Increase the slope of phase 4 ok

too little K+ too much B-adregergice stimulation, too much blood in the heart?

parenteral route of administration in which the drug is absorbed through the skin. Absorption is dependent on the surface area and lipid solubility.

transdermal (cutaneous) admin. good absorb, esp with oil vehicle. skips 1st pass metab.

T/F G proteins consist of three subunits (α,β and γ). In the resting state, the α subunit is bound to GDP. When the G-protein coupled receptor becomes activated, the G protein associates with the receptor and GDP falls off leaving space for GTP to bind.

true

T/F The adrenal medulla is connected to the central nervous system via one neuron.

true

T/F Parkinson's disease is more common in agricultural areas than cities.

true Environmental toxins are believed to be one source for the development of Parkinson's disease. Various herbicides have been found to induce Parkinson's like symptoms in animals. For example, rotenone selectively blocks mitochondrial function impairing mitochondrial activity. This impairment produces a resting tremor in animals.

T/F Genes are abbreviated and written in italics.

true Genes are the heritable sequence of DNA that encodes for proteins. The nucleotides that make up a gene dictate the amino acid sequence in the polypeptide chain of a protein. In convenient, genes are abbreviated in accordance to the protein it encodes. To distinguish protein from the genetic sequence, genes are italicized.

T/F Administering nitroglycerin (glyceryl trinitrate) sublingually allows for rapid absorption and drug stability since this route of administration avoids hepatic first pass metabolism.

true. Sublingually administered drugs are absorbed rapidly into the tissues under the tongue. Blood vessels that supply oxygen to this region of the body drain into the superior vena cava, which distributes a drug such as nitroglycerin directly to the systemic circulation.

A 43-year-old man recently diagnosed with an adrenal gland tumor started a treatment with a drug that can cause a pronounced decrease in norepinephrine and epinephrine by blocking the first rate-limiting step in catecholamine biosynthesis. Which of the following enzymes was most likely inhibited by the drug? Dopamine - β -hydroxylase Aromatic L-amino acid decarboxylase Monoamine oxidase Tyrosine hydroxylase

tyrosine hydroxylase

A polymorphism in a metabolizing enzyme that yields greater metabolizing activity than the non-mutated version of the allele is considered an ultra metabolizing allele and has an activity score greater than one. An individual containing two ultra rapid metabolizing alleles would have an activity score greater than two and would be considered an _____________________>

ultra rapid metabolizer

Chest pain occurs in the absence of increased oxygen demand by the myocardium yet originates as a result of an abrupt reduction in blood flow due to a ruptured plaque yielding a platelet-fibrin thrombosis. No occlusion or complete block of the vessel is evident. Therapeutic goal: restore blood supply (pharmacologically or mechanically), prevent thrombosis Organic nitrates Mechanical restoration = coronary stents or bypass surgery Heparin (antithrombotic agent) Antiplatelet agents Clopidogrel Prasugrel Aspirin Treats what?

unstable angina

Chest pain is felt as a result of a coronary artery spasm at rest. This type of angina is very uncommon. Therapeutic goal: reduce the incidence of coronary artery spasms Organic nitrates Vasodilators Ca2+ antagonists Nifedipine and DiltiazemIn Treats what?

variant angina

oIn most organs systems, the parasympathetic nervous system displays the predominant tone. exceptions are?

vasculature, sweat glands, and the ventricular myocardium

blood enters the left atrium from the pulmonary __________ and flows into the left ventricle via the bicuspid valve and out to the systemic circulation through the aortic valve.

vein

An antagonist has Negative intrinsic activity Intrinsic activity similar to inverse agonists Zero intrinsic activity Positive intrinsic activity Intrinsic activity fluctuates according to the receptor target

zero intrinsic activity

Lewy bodies are apparent in individuals with Parkinson's disease as a result of the aggregation of what protein? Presenilin α-synuclein Parkin Tau

α-synuclein Lewy bodies are formed due to the aggregation of α-synuclein. α-synuclein is a synaptic protein believed to play a role in synaptic vesicle recycling that would impair dopamine storage in the neuron. A mutation in α-synuclein has been identified as a cause for one form of familial Parkinson's disease.

Major binding protein carrier for basic drugs

α1-acid glycoprotein Inflammatory diseases such as cancer, arthritis, and myocardial infarction yield an increase in α1- acid glycoprotein.

The general four types of drugs are utilized to treat angina:

β-adrenergic receptor antagonists (β-blockers), organic nitrates, K+ channel activators, Ca2+ channel antagonists.

Which of the following is NOT an ionotropic glutamate receptor? γ-amino butyric acid (GABA) receptors α-amino-3-hydroxy-5-methylisoxazole-4-propianic acid (AMPA) receptors Kainate receptor N-methyl-D-aspartate (NMDA) receptors

γ-amino butyric acid (GABA) receptors