Pharmacology

Question 1

What is the MOA of Calcium channel blockers?

Answer 1

Blocks entry of calcium into muscle cells, causing vasodilation. This leads to decreased myocardial force generation (negative inotropy), decrease in heart rate (negative chronotropic) and decrease in conduction velocity within the heart (negative dromotropic)

Question 2

List 2 examples of non-dihydropyridines CCBs

Answer 2

Diltiazem & verapamil

Question 3

List 3 examples of dihydropyridines CCBs

Answer 3

1) Amlodipine
2) Felodipine
3) Nifedipine
4) Nicardipine

Question 4

List 3 indications for verapamil

Answer 4

1) Supraventricular tachycardia
2) Hypertension
3) Angina

Question 5

MOA of Beta blockers

Answer 5

Beta blockers inhibits activation of adenylyl cyclase -> decreased cAMP levels -> reduced activation of calcium channel -> reduced Ca conc. in cells -> reduction in contraction of muscle cells

Question 6

List 3 non-selective beta-blockers

Answer 6

1) Propranolol
2) Pindolol
3) Carvedilol

Question 7

List 3 beta-1 selective beta blockers

Answer 7

1) Atenolol
2) Bisprolol
3) Metoprolol

Question 8

Beta-1 adrenergic receptors are predominantly found in?

Answer 8

Heart muscles

Question 9

List 3 beta-blockers specifically approved to treat heart failure

Answer 9

1) Bisoprolol
2) Metoprolol
3) Carvedilol

Question 10

List at least 3 indications for beta-blockers

Answer 10

1) Hypertension
2) Heart failure
3) Following myocardial infarction
4) Abnormal heart rhythm
5) Anxiety disorders

Question 11

List 3 adverse effects of beta-blockers

Answer 11

1) Hypotension
2) Bradycardia
3) AV nodal block
4) Reduced exercise capacity
5) Bronchoconstriction (especially in asthmatics)

Question 12

Explain why beta-blockers (especially non-selective) are contraindicated in asthmatics

Answer 12

B2 receptors are found in the bronchus to mediate bronchodilation. Use of beta-blockers, especially non-selective ones will lead to bronchoconstriction

Question 13

MOA of ACE-I (hint: 3 pathways)

Answer 13

ACE-inhibitors inhibits ACE from converting angiotensin I to angiotensin II -> reduced angiotensin II leads to:
1) reduced vasoconstriction, hence reduced peripheral vascular resistance
2) reduced aldosterone secretion, hence reduced Na/water retention
3) reduces inactivation of bradykinin, which will activate nitric oxide and prostaglandins, causing vasodilation

=> overall reduces BP

Question 14

List 3 examples of ACE-inhibitors

Answer 14

1) Captopril
2) Enalapril
3) Ramipril
4) Lisinopril

Question 15

List 3 indications of ACE-inhibitors

Answer 15

1) Hypertension
2) Heart failure
3) Following myocardial infarction
4) Renal insufficiency- reduces aldosterone which provides kidney protective effects

Question 16

List 5 adverse effects of ACE-inhibitors

Answer 16

1) Severe hypotension
2) Acute renal failure
3) Hyperkalemia
4) Angioedema
5) Dry cough - due to reduction of inactivation of bradykinin which leads to release of substance P -> causes airway smooth muscles to constrict leading to bronchoconstriction and cough

Question 17

ACE-I/ARBs are contraindicated in which patient population?

Answer 17

Pregnancy

Question 18

What are the advantages of ARBs over ACE-I?

Answer 18

Less/no dry cough; less angioedema

Question 19

List 3 examples of ARBs

Answer 19

Losartan, valsartan, candesartan, irbesartan, telmisartan, eprosartan

Question 20

Beta blockers are contraindicated in which patient populations?

Answer 20

1) Asthmatics
2) Diabetes - patients cannot recognize when they are in hypoglycemic state when taking BBs, unable to take action to restore glucose levels

Question 21

CCBs are contraindicated in which patient population?

Answer 21

Congestive heart failure

Question 22

How does prostaglandins affect renal blood flow?

Answer 22

It increases renal blood flow

Question 23

Loop diuretics targets which part of the nephrons?

Answer 23

Loop of Henle

Question 24

A unit of the kidney is known as?

Answer 24

Nephron

Question 25

In the thin descending loop of henle, water is extracted by what force (1)? And how is it created (2)?

Answer 25

1) Osmostic force
2) Created in the hypertonic medullary interstitium

Question 26

The thick ascending limb of the loop of henle actively reabsorbs what?

Answer 26

NaCl

Question 27

For the following sections of the nephron, state whether they are permeable/impermeable to water:

1) Proximal convoluted tubule
2) Thin descending limb of loop of henle
3) Thick ascending limb of loop of henle
4) Distal convoluted tubue

Answer 27

1) Proximal convoluted tubule- permeable to water
2) Thin descending limb- permeable to water
3) Thick ascending limb - nearly impermeable to water
4) Distal convoluted tubule - relatively impermeable to water

Question 28

Where does the bulk of water resorption occur in the nephrons?

Answer 28

At the collecting ducts

Question 29

In the thick ascending limb of loop of henle, what is the cotransporter that transports NaCl?

Answer 29

Na/K/2Cl co-transporter

Question 30

Which transporter does loop diuretics inhibit?

Answer 30

Na/K/2Cl transporter in the thick ascending limb of loop of henle

Question 31

Explain the function of the Na/K/2Cl co-transporter in the thick ascending loop of henle

Answer 31

1) Facilitates absorption of Na, K and Cl from the lumen (where the urine is formed) into the cell
2) This leads to excess K+ accumulation within the cell, causing back diffusion of K+ back into the lumen
3) Lumen now has a positive electric potential which drives the reabsorption of Mg and Ca via the paracellular pathway, into the blood

Question 32

Explain the MOA of loop diuretics

Answer 32

1) Selectively inhibits luminal Na/K/2Cl transporter -> causing increase in Mg and Ca excretion in the urine
2) Induce renal prostaglandin synthesis
3) Furosemide increases renal blood flow

Question 33

List 4 side effects of loop diuretics

Answer 33

1) Hypokalemic metabolic alkalosis
2) Ototoxicty - avoid using together with aminoglycoside antibiotic (due to ototoxicity S.E. as well)
3) Hyperuricemia - prevents urea from getting into the lumen, hence increase conc in blood
4) Hypomagnesemia - due to reduced reabsorption of Mg back into the blood

Question 34

Which ion (1) is actively reabsorbed in the distal convoluted tubule and what facilitates its reabsorption (2)?

Answer 34

1) Ca ions
2) Apical Ca channel and basolateral Na/Ca exchanger

Question 35

What transporter does thiazide diuretics inhibit?

Answer 35

Blocks Na/Cl transporter in the distal convoluted tubule

Question 36

Explain the MOA of thiazide diuretics

Answer 36

1) Inhibits NaCl reabsorption in the distal convoluted tubule by blocking the Na/Cl transporter -> NaCl remains in the urine
2) Enhance Ca reabsorption in the distal convoluted tubule

Question 37

Explain the relationship between thiazide diuretics and NSAIDs

Answer 37

Action of thiazides depend in part on renal prostaglandin synthesis. NSAIDs can interfere with the actions of thiazide diuretics by reducing prostaglandin synthesis -> DDI

Question 38

Explain the relationship between NSAIDs and loop diuretics

Answer 38

Loop diuretics can induce renal prostaglandin synthesis. NSAIDs can interfere with the actions of loop diuretics by reducing prostaglandin synthesis -> DDI

Question 39

List 3 examples of thiazide diuretics

Answer 39

1) Hydrochlorothiazide
2) Indapamide
3) Chlorthalidone

Question 40

List 3 side effects of thiazide diuretics

Answer 40

1) Hypokalemic metabolic alkalosis
2) Hyperuricemia (due to upset of ionic balance, hence increased urea in blood)
3) Hyperglycemia
4) Hyperlipidemia
5) Hyponatremia

Question 41

Explain the 3 main MOA of digoxin

Answer 41

1) Inhibits Na/K/ATPase pump in myocytes -> increase intracellular Na -> increase Ca influx -> increase contractility
2) Suppression of SA and AV nodal conductions -> increase refractory period and decrease conduction velocity -> decrease heart rate (direct effect)
3) Enhances vagal tone (i.e. increase parasympathetic activity), which slows down AV node conduction -> decrease heart rate

Question 42

Comment on the volume of distribution of digoxin

Answer 42

1) Large volume of distribution as it is extensively distributed to peripheral tissues
2) Has a distinct distribution phase of 6-8h where pharmacologic effects are delayed and do not correlate well with serum concentrations during this phase
3) Volume of distribution is increased (i.e. increased toxicity) in scenarios like hypokalemia and hyperthyroidism

Question 43

Does digoxin have a long or short half life?

Answer 43

Long half life of 36-48h in normal renal function, up to 5 days in severe renal impairment

Question 44

List 5 characteristics of amiodarone

Answer 44

1) high affinity to tissues
2) Large volume of distribution
3) Long half-life of 40-60 days
4) Bears similar structure to thyroid hormones; deiodination during metabolism creates a source of iodine
5) High potential for DDIs (e.g. warfarin, digoxin, statins) - inhibits CYP 1A2, 2D6, 2C9, 3A4

Question 45

List down 5 lab monitoring components required for amiodarone, and the monitoring intervals

Answer 45

1) Thyroid function test (think: iodine)
2) Liver function test
3) Chest X-ray
4) ECG
5) Physical exam

Monitoring intervals: at baseline & Q6 monthly or more often if deranged or if patient complains of symptoms

Question 46

List down 7 different organs that amiodarone can cause side effects in

Answer 46

1) Opthalmic: hence eye exam is recommended if there is visual impairment at baseline, or if it develops during treatment
2) GI (PO route): n/v, abdominal discomfort; counsel to take after food
3) Dermatological: photosensitivity (counsel on sun protection), blue-gray skin discoloration
4) Thyroid: causes thyroid function derangements
5) Lungs: can cause pulmonary toxicity- routine chest x-rays required
6) Liver: deranged LFTs, hepatitis, cirrhosis
7) CNS: neuropathy, numbness, paraesthesias

Question 47

Which classes of anti-arrhythmic drugs carries the risk of torsades de pointes?

Answer 47

Vaughan Williams Classification:
1) Class IA
2) Class III (amiodarone, sotalol)

Question 48

Explain the role of sotalol in treatment of arrhythmias

Answer 48

1) Has both non-selective beta-blocking and Class III (vaughan williams classification) effects
2) Racemic mixture:
- L-isomer: class II and III effects
- D-isomer: only class III effects

Question 49

List 3 lab monitoring parameters for sotalol (anti-arrhythmia lecture)

Answer 49

1) Renal function
2) QTc prolongation
3) Pulse rate and blood pressure