2: Lecture 1 Drugs Flashcards
Main action of Diuretics
Decreased blood volume (via the kidney as retention of water decreases/excretion of water increases)–>decreasing smooth muscle tone
2 Main classes of diuretics
1) Thiazides
2) Loop Diuretics
Mechanism of Thiazides (diuretics)
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
Toxicity of Diuretics
ex. hydrochlorothiazide (thiazide) and furosemide (loop diuretic)
K+ depletion (hypokalemia) in patients with arrythmias, infarcts, etc.
Mechanism of Loop Diuretics (diuretics)
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
Main action of Sympathoplegics
Decrease sympathetic discharge by targeting beta-1 adrenergic receptors (in heart) and alpha adrenergic receptors (blood vessels and CNS)
4 Main classes of Sympathoplegics
1) Centrally acting agents
2) Ganglion blockers
3) Postganglionic sympathetic neuron blockers
4) Adrenoreceptor blockers
Mechanism of Centrally Acting agents (sympathoplegics)
ex. Clonidine
Mild-moderate hypertension
Alpha-2 adrenergic (CNS) selective agonists
Sympathoplegic effect is unknown
Toxicity of Centrally acting agents (sympathoplegics)
Minimal, but sudden stop of usage causes severe hypertension
Mechanism of Ganglion blockers (sympathoplegics)
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
Mechanism of Postganglionic sympathetic neuron blockers (sympathoplegic)
ex. Reserpine
Blocks the action of monoamine vesicular pump–>lower release of noradrenaline
VERY TOXIC
Mechanism of Adrenoreceptor blockers (sympathoplegics)
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)
Toxicity of Adrenoreceptor blockers (symapthoplegics)
Alpha blockers (prazosin)–>mild toxicity (first dose may cause hypotension and mild tachycardia)
Beta blockers (propranolol)–>moderate toxicity (may cause asthma, bradycardia, heart failure)
Main action of Vasodilators
Lower blood pressure by inducing vasodilation of arterioles
3 Main classes of Vasodilators
1) Nitrovasodilators
2) K+ channel agonists
3) Ca2+ channel blockers
Mechanism of Nitrovasodilators (Vasodilator)
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
Toxicity of Nitrovasodilators (vasodilator)
Excessive hypotension and tachycardia (nitroprusside)
Mechanism of K+ channel agonist (vasodilator)
ex. Diazoxide
Hyperpolarize the cell (by opening K+ channels)–>inhibits sympathetic stimulation–>causes relaxation of smooth muscle
Used in hypertensive emergencies
Part of polypharmacy
Toxicity of K+ channel agonists (vasodialtors)
Tachycardia
Mechanism of Ca2+ channel blockers (vasodilators)
ex. Verapamil, Diltiazem, Nifedipine
Block L-type Ca2+ channels–>prevents the excitation-contraction coupling
3 drugs that can be given simultaneously (vasodilators)
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
2 Main classes of Angiotensin Antagonists
1) ACE inhibitors
2) Angiotensin receptor inhibitors
Mechanism of ACE inhibitors (Angiotensin antagonists)
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
Toxicity of ACE inhibitors (angiotensin antagonist)
ex. Captopril
cough, severe renal damage in fetus
