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Anti-Hypertensives Drug (B-blockers (Adverse Effects (Bradycardia,…
Anti-Hypertensives Drug
Treatment Strategies
Combine 2 therapy
= if BP is inadequately controlled, a 2nd drug is added (to to minimize adverse effects)
Combine 2 from beginning
= patients with BP>160/100 should start with 2 anti-HPT simultaneously
Monotherapy
= initiate with thiazide diuretic/ARBs/CCBs/ACEI
A-Adrenoceptor Blocker
Mechanism of Action
competitively block A1-adrenoceptors, decrease PVR by relaxing arterial & venous smooth muscle, lower BP
Adverse Effects
may cause reflex tachycardia & postural hypotension
no longer recommended as anti-HPT, but may used for refractory (resistant/unmanageable) cases & other condition (benign prostatic hyperplasia)
Examples
A1 selective (Doxazosin, Prazosin, Terazosin)
ACE Inhibitors
Mechanism of Action
lowers BP by reducing PVR without increasing CO, HR or contractility
decrease Ang II & increase bradykinin levels, decrease aldosterone secretion, results in water and sodium retention
reduce both preload and afterload, decreasing cardiac work
Examples
Captopril, Benazepril, Enalapril, Fosinopril, Lisinopril, Moexipril, Quinapril, Perindopril, Rampril, Trandolapril
Therapeutic Uses
used in patients with diabetic nephropathy, slows the progression & decrease albuminuria
decrease intra-glomerular pressures due to efferent arteriolar vasodilation
Adverse Effects
Hypotension (in hypovolemic state)
Dry cough, rash, fever, altered taste
Hyperkalemia, angioedema (may be due to increased levels of bradykinin)
Teratogenic (should not be used by pregnant women)
Diuretics
Mechanism of Action
decrease blood volume, decrease BP
Examples
Thiazide (Hydrochlorothiazide, Chlorthalidone), Loop diuretics (Furosemide, Torsemide), Potassium-sparring (Aldosterone antagonist [Spironolactone, Eplerenone], Sodium channel blocker [Triamterene, Amiloride])
B-blockers
Mechanism of Action
decreasing CO, decrease sympathetic outflow from CNS, inhibit renin release
Precautions
Selective B-blockers administered cautiously to HPT patients who also have asthma, Non-selective B-blocker are contraindicated in patients with asthma
should be used cautiously in patients with acute HF or peripheral vascular disease
Examples
Selective B1 blocker (Acebutolol, Atenolo, Betaxalol, Bisoprolol, Esmolol, Metoprolol, Nebivolol), Non-selective B-blocker (Propanolol, Nadolol, Timolol)
Therapeutic Uses
Used in HPT patients with concomitant heart disease (atrial fibrillation, previous MI, angina pectoris & chronic HF)
Adverse Effects
Bradycardia, hypotension
CNS side effects (fatigue, lethargy, insomnia)
decrease libido & cause erectile dysfunction
non-cardio selective B-blocker may disturb lipid metabolism
CCBs
Examples
Dihydropyridines (Nifedipine, Amlodipine, Felodipine), Nondihydropyridine (Verapamil, Diltiazem)
Mechanism of Action
block inward movement of Calcium by binding to L-type calcium channels in heart & smooth muslce of coronary & peripheral arteriolar vasculature, causes dilation of arterioles (CCBS do not dilate veins)
Therapeutic Uses
useful for HPT patients with asthma, diabetes, and/or peripheral vascular disease
useful in treating angina
nondihydropyridine useful in treatment of tachyarrhythmia
Verapamil= constipation (10%), first degree atrioventricular block, gingival hyperplasia,,,,, should be avoided in patients with HF or atrioventricular block due to negative inotropic & dromotropic (velocity of conduction) effects
Dihydropyridines= dizziness, headache, fatigue,,,,,,,,,high doses of short acting CCBs should be avoided because of increased risk of MI due to excessive vasodilation & marked reflex cardiac stimulation
ARBs
Mechanism of Action
block AT1 receptors, decreasing activation of AT1 receptors by Ang II
produce arteriolar & venous dilation, block aldosterone secretion, thus lower BP & decrease salt & water retention,
do not increase bradykinin levels
Indications
used in patients with diabetes, HF and CKD
Examples
Losartan, Candesartan, Eprosartan, Irbesartan, Olmesartan, Telmisartan, Valsartan
Adverse Effects
risks of cough and angioedema are significantly reduced
ARBs and ACEI cannot be combined together
teratogenic (should not be used by pregnant women)
Renin Inhibitor
Examples
Aliskiren
Mechanism of Action
directly inhibits renin, lowers BP
Adverse Effects
should not be combined with ACEI/ARBs
can cause diarrhea (high doses) cough & angioedema but less often than ACEI
contra-indicated during pregnancy
Centrally-Acting Adrenergic Drug
Mechanism of Action
acts centrally as A2 agonist to produce inhibition of sympathetic vasomotor centers, decreasing sympathetic outflow to periphery, leads to reduced TPR, decreased BP
Indication
used in patients who have renal disease = does not decrease renal blood flow or glomerular filtration
Examples
Clonidine
Adverse Effects
Sedation, dry mouth, constipation
withdrawn slowly to prevent rebound HPT
Vasodilators
Mechanism of Action
relaxation of vascular smooth muscle decrease peripheral resistance, so decrease BP
however, it produce reflex stimulation of heart (increase myocardial contractility, HR), prompt angina pectoris, MI or cardiac failure
increase renin conc, results in sodium and water retention (edema)
the side efects can be blocked by concomitant use of diuretic & B-blocker (reduce CO)
Adverse Effects
Headache, tachycardia, nausea, sweating, arrhythmia, angina
Lupus-like syndrome (can occur with high dose but reversible upon drug discontinuation)
Examples
Hydralazine