Antihypertensive Pharmacology Flashcards
(23 cards)
Diuretic Agents
What do they do?
What ones can we use?
Act on nephron to increase urine output
Can use:
Thiazides (hydrochlorothiazide) - block NCC in distal conv. Tubule
Loop diuretics (furosemide) - block NKCC in ascending loop of Henle
Potassium-sparing diuretics (spironolactone)
ACE Inhibitors
Example
Actions
Overall effect
Example - Ramipril
Actions:
1) inhibits vasoconstriction
2) inhibits aldosterone secretion
3) inhibits NaCl reabsorption
4) increases vasodilation via bradykinin
Overall effect: decreased SVR and increased Na and H2O excretion (decreased preload)
ACE inhibitor
- adverse effects
- contraindications
Adverse effects:
- Cough (due to bradykinin)
- hyperkalemia (due to reduced aldosterone)
- renal dysfunction (decreased renal blood flow)
- hypotension
- angioedema (rare, due to bradykinin)
Contraindications:
- pregnancy (teratogenic and increased complications)
- renal artery stenosis
Angiotensin Receptor Blockers
Example
Actions
Overall effect
Example - Losartan
Actions:
1) inhibits vasoconstriction
2) inhibits aldosterone secretion
3) inhibits NaCl reabsorption
4) no effect on bradykinin metabolism
Overall effect:
Decreased SVR, increased Na and H2O excretion (decreased preload)
ARBs
Adverse effects:
Contraindications:
Adverse effects:
- Less cough and angioedema
- dizziness and hypotension (most common side effects)
- hyperkalemia (due to reduced aldosterone)
- renal dysfunction
Contraindications:
Pregnancy (teratogenic)
Renin Inhibitors
Example
Actions
Overall effect
Example - Aliskiren
Actions:
1) inhibit vasocontriction
2) inhibits aldosterone secretion
3) inhibits NaCl reabsorption
Overall effect:
- decreased SVR, increased Na and H2O excretion (decreased preload)
Renin Inhibitors
Adverse effects:
Contraindications:
Adverse effects:
1) diarrhea (unknown mechanism)
2) angioedema (rare)
Contraindications:
- pregnancy (teratogenic)
Calcium Channel Blockers
Examples:
Actions
Action:
1) decreases smooth muscle contraction (decreased SVR)
2) decreases cardiac conduction and contractility (decreased HR and CO)
3) blocks Ca-signaling to adrenal cortical cells to release aldosterone
Examples:
1) dihydropyridines - amlodipine
2) non-hydropyridines:
A) benzothiazepines (diltiazem)
B) Phenylalkylamines (verapamil)
Dihydropyridine Ca-channel blockers
Example:
Action:
Overall effect:
Example - amlodipine
Act primarily on vasculature as a vasodilator
- weak effect on cardiac Ca-Channels
Overall effect:
Decreased SVR, a slight decrease in cardiac contractility
Non-Dihydropyridine Ca-channel blockers
Example:
Action:
Overall effect:
Example:
Two subclasses:
- Benzothiazepines (diltiazem)
- Phenylalkylamines (verapamil)
Action:
Affect cardiac and vascular Ca-channels (cardiac > vascular)
Overall effect:
- Decreases HR and contractility and SVR
Ca-Channel blockers
Adverse effects:
Contraindications:
Adverse effects:
- dizziness and headache
- flushing, peripheral edema, reflex tachycardia
- bradycardia, hypotension
Contraindications:
- dihydropyridines - conditions worked by tachycardia (e.g. severe aortic stenosis)
- non-dyhydropyridines
A) conduction disorders (wolff-Parkinson-White syndrome, AV block)
B) Acute congestive heart failure
- pregnancy (use nifedipine instead)
Adrenergic effect receptors
B1 receptors — increased contraction, HR and renin secretion
B2 — bronchodilation, vasodilation of Sk. Muscle arterioles (sm muscle relaxation)
B3
A1 - vasoconstriction and venoconstriction of non-skeletal muscle vessels (smooth muscle contraction)
A2
Beta-blockers
Examples:
Actions:
Overall effect:
Examples - propranolol, metoprolol
Actions:
1) decreases SNS activity
2) decreases HR and contractility
3) decreases renin secretion
Overall effect: decreased HR and CO
Beta-blocker classification
Cardioselective B-blockers - only block B1 receptors
- metoprolol, atenolol, bisprolol
Non-Cardioselective B-blockers - blocks all B receptors
- propranolol (B1, B2)
Mixed a and B-blockers
- carvedilol, labetalol (a1, B1, B2)
Partial Agonists
- acebutolol (partial B1 agonist)
Beta-blocker
Adverse effects:
Contraindications:
Adverse effects:
- fatigue (due to increase CO)
- bradycardia
- bronchoconstriction (B2 blockade)
- rebound hypertension (if abruptly discontinued)
Contraindications:
- asthma (especially if non-Cardioselective agent)
- bradycardia or 2nd or 3rd degree heart block
- acute congestive heart failure
Alpha-1 blockers
Examples
Actions
Overall effect
Examples - prazosin, terazosin
Actions:
1) decreases vasoconstriction (arteries and arterioles)
2) decreases venoconstriction (veins)
Overall effects - decreased SVR
Alpha-1 blockers
Adverse effects:
Orthostatic hypotension
Not typically used for hypertension (used to treat benign prostatic hypertrophy)
Direct Vasodilators:
Example
Action
Overall effect
Example: hydralazine
Action:
- arteriolar vasodilation
- mechanism is uncertain (possibly opens potassium channels)
Overall effect: decreased SVR
Direct Vasodilators
Adverse effects:
Reflex tachycardia
Flushing
Hypotension
Immunological lupus-like reaction
Not commonly used for hypertension
Central-acting agents
Example:
Action:
Overall effect:
Adverse effects:
Example - clonidine
Action - inhibit presynaptic release of NE
Overall effect - decreased HR, VS, and SVR
Adverse effects:
- sedation (central inhibition of NT release)
- dry mouth
- Orthostatic hypotension
- rebound hypertension (if abruptly discontinued)
Not commonly used for hypertension
Why treat Hypertension?
Untreated increases risk for:
Morbidity (57 million disability-adjusted life years)
- coronary artery disease, heart failure, stroke, peripheral vascular disease, kidney injury, vision loss
Mortality - 7.5 million deaths annually
Which antihypertensive to use?
- in absence of cardiovascular risk factors or disease
Low-dose thiazides are first line
- ACE inhibitors and Ca-Channel blockers may be equally as effective, but lower evidence
Which antihypertensive to use?
- in heterogeneous populations with cardiovascular risk factors or disease
Can use RAAS inhibitors, Ca-Channel blockers, thiazides and beta blockers
- thiazides caused less HF and stroke than RAAS inhibitors
- Ca-channel blockers increased HF but decreased stroke compared to RAAS inhibitors
- increase in HF exceeded the decrease in stroke
