Antihypertensives 2 Flashcards
What are the B- Blockers?
Propranolol / Metoprolol / Atenolol / Pindolol
• Propranolol - Non-selective b1 &b2 receptor antagonist
• Metoprolol & atenolol (most widely used) - Selective b1 receptor antagonists
• Pindolol
Non-selective b1 and b2 partial agonist with intrinsic sympathomimetic activity (preferred b-blocker in pregnancy)
What is the B-blocker mechanism of action
MOA • Reduce BP by decreasing cardiac output, contractility & heart rate
• Blunt sympathetic reflex with exercise
• Inhibit both release of norepinephrine and renin (b1 R) which will decrease in angiotensin II & aldosterone secretion)
What are the adverse effects of B-Blockers?
- Bradycardia, CNS effects (fatigue, lethargy, insomnia, hallucinations), hypotension, decreased libido & impotence
- Disturb lipid metabolism ( decrease HDL & increase TAGs)
- Hypoglycemia (via b 2 blockade)
- Drug withdrawal (abrupt withdrawal may induce angina, MI or sudden death in patients with heart disease) which leads to a taper off dose in these patients
- Propranolol is contraindicated in asthmatics and COPD patients
What are a1- Blockers?
Prazosin / Doxazosin
• Competitively block a1 -adrenoceptors
•decrease peripheral vascular resistance & decrease arterial BP by
relaxing both arterial & venous smooth muscle
- Cause minimal changes in cardiac output, renal blood flow & GFR which leads to no long-term tachycardia
- Na+ & H20 retention does occur
- Effective in lowering BP but more side effects than other antihypertensives
What is the clinical applications of a1-blockers?
- Hypertension (due to side-effect profile, development of tolerance & advent of safer antihypertensives, a-blockers are seldom used in treatment of hypertension)
- Reserved as alternative agents for unique situations, such as men with benign prostatic hyperplasia
- Have been used in heart failure (but not commonly)
What are the adverse effects of a1-Blockers?
• Orthostatic hypotension (which may lead to syncope)
upon first-dose or large increases in dose
• Concomitant use of a b-blocker may be necessary to blunt short-term effect of reflex tachycardia
• Dizziness, drowsiness, headache, lack of energy, nausea,
and palpitations,
• Doxazosin shown to increase rate of congestive HF
What are the mixed a- and B-blocer?
Labetalol
- Oral & parenteral admin.
- Used in hypertension management (safe in pregnacy)
- IV labetalol = rapid reduction in BP which leads to useful in hypertensive emergencies
A dvantages
• increase in BP associated with a1-blockade is not associated with reflex increase in HR or cardia coutput
adverse effect: • Orthostatic hypotension may be a problem (first use or
high doses)
WHat are the effects of Clonidine as a central a2 agonist
- Reduces sympathetic outflow by acting on presynaptic a2 adrenergic autoreceptors
- Resultant decrease in peripheral vascular resistance & cardiac output which causes a decrease BP
- DOES NOT decrease renal blood flow or GFR
- Used in hypertension management, including hypertensive crises (other drugs with fewer side effects are now generally preferred)
What are the adverse effects of Central a2 agonists?
- Drowsiness, dry mouth, dizziness, headache & sexual dysfunction occur commonly
- Rebound hypertension may occur following abrupt withdrawal (avoid concomitant use with b-blockers)
Methyldopa effects?
Central a2 agoinst
- a2 -agonist converted to a-methyldopamine and a- methylnorepinephrine centrally to diminish sympathetic outflow in CNS
- decrease peripheral resistance & decrease BP (cardiac output NOT decrease )
- DOES NOT decrease renal blood flow or GFR
• Usually treatment of choice for pregnancy-induced
hypertension • Used in hypertension management (other drugs with
fewer side effects are now generally preferred)
Methyldopa adverse effects?
- Sedation, drowsiness, dizziness, nausea, headache, weakness, fatigue, sexual dysfunction
- Nightmares, mental depression, vertigo (infrequent)
- Development of positive Coombs test (10-20% patients on long-term treatment (>1 year)). Can result in hemolytic anemia, hepatitis & drug fever
What are the direct vasodilators?
Hydralazine / Minoxidil
• Not used as first-line antihypertensives
• Direct acting smooth muscle relaxants
• Produce reflex tachycardia, increase plasma renin which leads to Na+ &H20 retention
2• Major side effects can be blocked if combined with diuretic
& b-blocker
Hydralazine?
- Acts mainly on arterioles
- Used to treat pregnancy induced hypertension / pre- eclampsia
- Used in management of hypertension as last-line therapy
what are the adverse effects of Hydralazine
- Fluid retention & reflex tachycardia are common
- Reversible lupus-like syndrome
- Headache, nausea, sweating, flushing • Usually administered with b-blocker & thiazide
Minoxidil and its adverse effects?
- Causes direct peripheral vasodilatation of arterioles
- Oral treatment for severe-malignant hypertension (refractory to other treatments
- Causes hypertrichosis (also used topically to treat male pattern baldness)
- Reflex tachycardia & fluid retention may be severe (combine with loop diuretic & b-blocker)
epoprostenol: class and function?
prostaglandin used to treat pulmonary hypertension
- Synthetic PGI2
- Lowers peripheral , pulmonary, and coronary resistance
- Given via continuous infusion
- Adverse effects include flushing, headache, jaw pain, diarrhea and arthralgias
Bosentan?
Used in Pulmonary Hypertension
• Nonselective endothelin receptor blocker
• Blocks both the initial transient depressor (ET
prolonged pressor (ETB ) responses to endothelin
• Pregnancy category X
Sildenafil
used to treat pulmonary hypertension
- Inhibitor of phosphodiesterase 5 (PDE5)
- Increased cGMP which leads to smooth muscle relaxation
- Adverse Effects: headache, flushing, dyspepsia, cyanopsia
- Contraindications: Nitrates
Sodium Nitroprusside function
used in hypertensive crisis
- Prompt vasodilation & reflex tachycardia
- Causes peripheral vasodilation by direct effects on arterial & venous smooth muscle
Sodium Nitroprusside adverse effect?
A dverse effects
• Hypotension (overdose), goose bumps, abdominal cramping, nausea, vomiting, headache
• Cyanide toxicity (rare)
Nitroprusside metabolism leads to cyanide ion
Can be treated with sodium thiosulfate infusion which leads to nontoxic thiocyanate
Labetalol. function
• Combined a and b blocker
DOES NOT cause reflex tachycardia
Contraindications
Asthma, COPD, patients with 2nd or 3rd-degree AV block or bradycardia
Fenoldopam function?
- Peripheral dopamine-1 (D1) receptor agonist
- Evokes arteriolar dilation
- IV infusion for hypertensive emergency •t 1/2= 30 min
Maintains or increases renal perfusion as lowers BP
- Promotes naturesis
- Safe to use in all hypertensive emergencies (particularly beneficial in patients with renal insufficiency)
Contraindications: Glaucoma
Nicardipine
- Calcium-channel blocker
- IV infusion for hypertensive emergency
Evokes reflex tachycardia
Nitroglycerin
- Vasodilator (more effect on veins than arteries)
- Drug of choice for hypertensive emergencies in patients with cardiac ischemia or angina, or after cardiac bypass surgery
- Hypotension = most serious side effect
Diazoxide function and adverse effect?
• Arteriolar dilator
• Prevents vascular smooth muscle contraction by opening K+ channels and stabilizing membrane potential
Adverse Effects
Hypotension, reflex tachycardia, Na+ & H20 retention
• Inhibits insulin release and can be used to treat hypoglycemia secondary to insulinoma
Other options for Hypertensive crisis?
Phentolamine -Drug of choice for patients with catecholamine- related emergencies
Esmolol -Often used for aortic dissection or postoperative hypertension
Hydralazine -Drug of choice in treating hypertensive emergencies in pregnancy related to eclampsia
