Chapter 19: Antihypertensives Flashcards
What are the mechanisms for controlling blood pressure?
-arterial BP is proportional to CO and PVR
- Baroreceptors and sympathetic nervous system
- fall in BP causes reflex tachycardia; causes vasoconstriction and increased CO - RAA system
- baroreceptors in the kidney respond to a reduction in arterial BP by releasing renin producing angiotensin II which is a potent vasoconstrictor to increase renal blood flow
- aldosterone promotes sodium resorption
What is the MOA, indications, pharmokinetics and adverse effects of thaizide diuretics?
ex: Hydrochlorothiazide, Chlorthalidone
MOA: lower BP by increasing Na+ and H2O excretion causing a decrease in CO and renal blood flow
indications: decrease BP
- used in combination with B-blockers, ACE inhibitors, ARBs, and K+ sparing diuretics
pharmokinetics: orally
adverse effects: induce hypokalemia, hyperuricemia, hyperglycemia, acute gout attacks may be triggered
What is the MOA, indications, pharmokinetics and adverse effects of loop diuretics?
ex: Furosemide, Bumetanide, Torsemide
- act promptly even in patients with poor renal function who have no responded to thiazides or other loop diuretics
- decrease renal vascular resistance and increased renal blood flow
- increase the [Ca2+] of urine whereas thiazide diuretics decrease it
What is the MOA, indications, pharmokinetics and adverse effects of K-sparing diuretics?
ex: Amiloride, Triamterene, Spironolactone, Eplerenone
Amiloride, Triamterene: inhibitors of epithelial Na+ transport at late distal and collecting ducts
Spironolactone, Eplerenone: aldosterone receptor antagonist
- reduce K+ loss through urine
- spironolactone has the benefit of diminishing cardiac remodeling that occurs in heart failure
What is the MOA, indications, pharmokinetics and adverse effects of K-sparing diuretics?
ex: Amiloride, Triamterene, Spironolactone, Eplerenone
Amiloride, Triamterene: inhibitors of epithelial Na+ transport at late distal and collecting ducts
Spironolactone, Eplerenone: aldosterone receptor antagonist
- reduce K+ loss through urine
- spironolactone has the benefit of diminishing cardiac remodeling that occurs in heart failure
What is the MOA, indications, pharmokinetics and adverse effects of B-blockers?
ex: Propanolol, Metoprolol, Atenolol , Nebivolol
MOA: decrease BP by decreasing CO
indications: hypertensive patients, hypertensive patient with concomitant disease, supraventricular tachyarrhytmia, previous MI, angina pectoris, and chronic heart failure
- more effective in treating white people than black people and younger people than elderly patients
pharmokinetics: orally; propanolol undergoes extensive first pass metabolism
adverse effects: bradycardia, hypotension, fatigue, insomnia, sexual dysfunction
What is the MOA, indications, pharmokinetics and adverse effects of ACE inhibitors?
ex: Enalapril, Lisinopril
MOA: reduce BP by reducing peripheral vascular resistance without increasing CO, rate or contractility as a reflex
- prevents breakdown of bradykinin
- reduce cardiac preload and afterload which decreases the work of the heart
indications: when first line agents such as diuretics or B blocker are contraindicated or ineffective
- +diuretics: same effect in white and black patients
- +ARBs: slow progression of diabetics nephropathy and decrease albuminuria
- decrease intraglomerular pressure due to efferent arteriolar vasodilation
- therapy started 24 hours after the end of the infarction
- first line agents in treatment of patients with systolic dysfunction
Chronic therapy achieves lower BP, regression of left ventricular hypertrophy and prevents ventricular remodelling after MI
adverse effects: dry cough, hyperkalemia, skin rash, hypotension, fever
What is the MOA, indications, pharmokinetics and adverse effects of Angiotensin II- Receptor Blockers?
ex: Losartan
MOA: block AT1 receptors; produce arteriolar and venous dilation, block aldosterone secretion; do not increase bradykinin levels;
indications: decrease nephrotoxicity of diabetes
adverse effects: similar to ACE inhibitors (low cough incidence and angioedema incidence); fetotoxic
What is the MOA, indications, pharmokinetics and adverse effects of renin inhibitors?
ex: Aliskiren
MOA: directly inhibits renin and acts earlier in the RAA system than ACE inhibitors or ARBs
indications: combined with other antihypertensives
adverse effects: diarrhea at high doses; contraindicated in pregnancy
What is the MOA, indications, pharmokinetics and adverse effects of Ca2+ channel blockers?
ex: Amlodipine, Verapamil, Nifedipine
MOA: preferred when first line agents are ineffective or contraindicated; block inward movement of calcium by binding L type channels in heart and smooth muscle of the coronary and peripheral arteries
- causes vascular smooth muscle to relax
- do not dilate veins
indications: treating hypertension in patients with angina or diabetes; hypertensive patients who also have asthma, diabetes, angina or peripheral vascular disease
pharmokinetics: oral dose
adverse effects: constipation in patients treated with Verapamil, flushing, dizziness, headache, fatigue, hypotension
What is the MOA, indications, pharmokinetics and adverse effects of Alpha-Adrenoceptor blocking agents?
ex: Prazosin, Doxazosine, Terazosin
MOA: decrease peripheral vascular resistance and lower arterial BP by causing relaxation of arterial and venous smooth muscle
indications: mild/moderate hypertension and prescribed in combination with pronanolol or a diuretic
pharmokinetics:
adverse effects: water retention, postural hypotension, reflex tachycardia and first-dose syncope
What is the MOA, indications, pharmokinetics and adverse effects of centrally acting adrenergic drugs?
MOA:
What is the MOA, indications, pharmokinetics and adverse effects of Alpha-Adrenoceptor blocking agents?
ex: Prazosin, Doxazosine, Terazosin
MOA: decrease peripheral vascular resistance and lower arterial BP by causing relaxation of arterial and venous smooth muscle
indications: mild/moderate hypertension and prescribed in combination with pronanolol or a diuretic
adverse effects: water retention, postural hypotension, reflex tachycardia and first-dose syncope
What is the MOA, indications, pharmokinetics and adverse effects of the centrally acting adrenergic drugs Clonidine?
MOA: decreases firing rate of sympathetic nerves and decreases amount of NE released
indications: treatment of hypertension that hasn’t responded to two or more drugs
- doesn’t decrease renal blood flow or GFR
pharmokinetics: orally; renally excreted
adverse effects: Na+ and water retention (given with a diuretic), sedation, dry mouth, constipation
What is the MOA, indications, pharmokinetics and adverse effects of the centrally acting adrenergic drugs alpha-Methyldopa?
MOA: alpha2 agonist to diminish adrenergic outflow from the CNS resulting in reduced TPR and decreased BP; CO is not decreased and blood flow to vital organs is not decreased
indications: hypertensive patients with renal insufficiency; useful in hypertensive pregnant patients
adverse effects: sedation and drowsiness
