2: Lecture 1 Drugs

Question 1

Main action of Diuretics

Answer 1

Decreased blood volume (via the kidney as retention of water decreases/excretion of water increases)–>decreasing smooth muscle tone

Question 2

2 Main classes of diuretics

Answer 2

1) Thiazides
2) Loop Diuretics

Question 3

Mechanism of Thiazides (diuretics)

Answer 3

ex. Hydrochlorothiazide
Mild-moderate hypertension
Blocks the Na+/Cl- symporter and increases Ca2+ reabsorption–>decreases sodium reabsorption which simultaneously decreases water reabsorption and increases its excretion
Less water reabsorption/more water excretion–>less blood volume–>decrease blood pressure
Orally active

Question 4

Toxicity of Diuretics

Answer 4

ex. hydrochlorothiazide (thiazide) and furosemide (loop diuretic)
K+ depletion (hypokalemia) in patients with arrythmias, infarcts, etc.

Question 5

Mechanism of Loop Diuretics (diuretics)

Answer 5

ex. Furosemide
Moderate-severe hypertension
Blocks the Na+/K+/2Cl- symporter and increases Ca2+ excretion–>decreases sodium reabsorption–>decreases water reabsorption/increases water excretion–>decrease blood volume–>decrease blood pressure
Orally AND intravenously active

Question 6

Main action of Sympathoplegics

Answer 6

Decrease sympathetic discharge by targeting beta-1 adrenergic receptors (in heart) and alpha adrenergic receptors (blood vessels and CNS)

Question 7

4 Main classes of Sympathoplegics

Answer 7

1) Centrally acting agents
2) Ganglion blockers
3) Postganglionic sympathetic neuron blockers
4) Adrenoreceptor blockers

Question 8

Mechanism of Centrally Acting agents (sympathoplegics)

Answer 8

ex. Clonidine
Mild-moderate hypertension
Alpha-2 adrenergic (CNS) selective agonists
Sympathoplegic effect is unknown

Question 9

Toxicity of Centrally acting agents (sympathoplegics)

Answer 9

Minimal, but sudden stop of usage causes severe hypertension

Question 10

Mechanism of Ganglion blockers (sympathoplegics)

Answer 10

Ex. Trimethaphan
Severe Hypertension
Reduce blood pressure by blocking nAChR in autonomic ganglia–>inhibits propagation of sympathetic stimulation signals–>dangerous
Rapid set
VERY TOXIC–>rarely used

Question 11

Mechanism of Postganglionic sympathetic neuron blockers (sympathoplegic)

Answer 11

ex. Reserpine
Blocks the action of monoamine vesicular pump–>lower release of noradrenaline
VERY TOXIC

Question 12

Mechanism of Adrenoreceptor blockers (sympathoplegics)

Answer 12

Alpha-1 and beta-1 adrenergic receptor antagonists
ex. Prazosin and Propranolol
Overall reduces sympathetic drive
Prazosin blocks alpha-1 adrenergic receptor–>reduces sympathetic drive in the blood
Propranolol blocks beta-1 adrenergic receptor–>reduces sympathetic drive in the heart
Mild hypertension (monotherapy)
Moderate-severe hypertension (polypharmacy)

Question 13

Toxicity of Adrenoreceptor blockers (symapthoplegics)

Answer 13

Alpha blockers (prazosin)–>mild toxicity (first dose may cause hypotension and mild tachycardia)
Beta blockers (propranolol)–>moderate toxicity (may cause asthma, bradycardia, heart failure)

Question 14

Main action of Vasodilators

Answer 14

Lower blood pressure by inducing vasodilation of arterioles

Question 15

3 Main classes of Vasodilators

Answer 15

1) Nitrovasodilators
2) K+ channel agonists
3) Ca2+ channel blockers

Question 16

Mechanism of Nitrovasodilators (Vasodilator)

Answer 16

ex. Nitroprusside
Increase activation of soluble Guanylate Cyclase to relax vascular smooth muscle (through release of nitric oxide)
Used for hypertensive emergencies and part of polypharmacy

Question 17

Toxicity of Nitrovasodilators (vasodilator)

Answer 17

Excessive hypotension and tachycardia (nitroprusside)

Question 18

Mechanism of K+ channel agonist (vasodilator)

Answer 18

ex. Diazoxide
Hyperpolarize the cell (by opening K+ channels)–>inhibits sympathetic stimulation–>causes relaxation of smooth muscle
Used in hypertensive emergencies
Part of polypharmacy

Question 19

Toxicity of K+ channel agonists (vasodialtors)

Answer 19

Tachycardia

Question 20

Mechanism of Ca2+ channel blockers (vasodilators)

Answer 20

ex. Verapamil, Diltiazem, Nifedipine
Block L-type Ca2+ channels–>prevents the excitation-contraction coupling

Question 21

3 drugs that can be given simultaneously (vasodilators)

Answer 21

Vasoselective–>Nifedipine
Cardiac and vascular acting–>Verapamil and Diltiazem
These 3 drugs have different allosteric sites so can be given simultaneously to achieve an additive effect

Question 22

2 Main classes of Angiotensin Antagonists

Answer 22

1) ACE inhibitors
2) Angiotensin receptor inhibitors

Question 23

Mechanism of ACE inhibitors (Angiotensin antagonists)

Answer 23

ex. Captopril
Prevent action of ACE (angiotensin converting enzyme)–>no conversion of angiotensin I to angiotensin II–>decrease of angiotensin II action—>decrease in arteriolar constriction and resistance
Also prevent breakdown of bradykinin (responsible for vasodilation)
More bradykinin–>more vasodilation–>less peripheral vascular resistance–>decrease in blood pressure

Question 24

Toxicity of ACE inhibitors (angiotensin antagonist)

Answer 24

ex. Captopril
cough, severe renal damage in fetus

Question 25

Mechanism of Angiotensin receptor inhibitors (angiotensin antagonist)

Answer 25

ex. Losartan
Allow for action of aldosterone on kidney, but prevent action of angiotensin II on peripheral cardiovascular resistance
milder toxicity than ACE inhibitors