Download Antihypertensive Drugs

Introductory Clinical
Pharmacology
Chapter 41
Antihypertensive Drugs
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Blood Pressure
• Normal = sys<120 and diastolic <80
• Prehypertension 120-139/80-89
• Stage 1 hypertension 140-159/ 90-99
• Stage 2 hypertension >159 or >99
• For every 20mmgh increase in systolic BP from ages 4069, mortality from ischemic heart disease and stroke
doubles.
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Blood Pressure
• BP= CO x SVR Vascular resistance influenced by alpha1
receptors (norepinepherine), calcium channels, AT2
receptors (RAAs vasoconstriction and sodium and water
retention w/potassium excreteion
• CO= HR x SV
Stroke volume=preload (aldosterone)
– HR influenced by β1 receptors
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Copyright © 2008 Lippincott Williams & Wilkins.
Blood Pressure
• Force of blood against arterial walls
• Normal: <120/<80
• Hypertension
– Essential vs. secondary
– Increases risk of heart disease, CHF, RF, blindness,
stroke
– African Americans twice as likely as Caucasians
– Essential cannon be cured but can be controlled
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Non-Pharmacologic Control of HTN
• Weight loss
• Stress reduction
• Smoking cessation
• Regular aerobic exercise
• Decrease sodium and sugar intake
• Increase potassium intake
• DASH diet
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Antihypertensive Drugs
• ACE inhibitors: captopril, enalapril, lisinopril
• ARBs: Losartan, valsartan
• Nitrates: nitroglycerin, isosorbide dinitrate
• Calcium channel blockers: verapamil, nifedipine, diltiazem
• Alpha adrenergic blockers: phentolamine,
phenoxybenzamine, prazosin, terazosin
• Adrenergic neuron blockers: reserpine, guanethidine,
guanadrel
• Centrally acting agents: clonidine, guanabenz, methyldopa
• Other: hydralazine, minoxidil, nitroprusside,diazoxide,
nesiritide
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Pharmacologic control of BP
• Diuretics decrease preload
• Beta Blockers (-lols)decrease contractile state of the heart and
heart rate (decrease cardiac output)
• ACE inhibitors (-prils) Block AT2 via ACE inhibition
• ARBs ( sartans) block AT2 receptors
• Calcium Channel blockers (dipines and others) block calcium
channels on peripheral vessels
• Alpha 1 Blockers (-osins) are rarely used for HTN
• Alpha 2 agonists (catapres) work in hypothalamus
• Other: hydralazinie, nitroprusside, morphine, NTG: direct
vasodilators for hypertensive crises
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Vasodilators
• May dilate arterioles, veins or both
• Uses: essential hypertension, hypertensive crisis,
angina, heart failure, MI, production of controlled
hypotension during surgery
• Adverse effects: postural hypotension, reflex
tachycardia, expansion of blood volume
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Hydralazine (Apresoline)
• Selective dilation of arterioles
 peripheral resistance,  BP,  HR,  myocardial
contractility
• Used for Essential HTN, usually in conjunction with a βblocker and a diuretic; hypertensive crisis, heart failure
• Adverse effects: reflex tachycardia, Increased blood volume,
SLE like syndrome, headache, dizziness, weakness, fatigue
• Use with β-blocker prevents reflex tachycardia, diuretics prevent
blood volume expansion
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Renin-Angiotension-Aldosterone System
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Ace Inhibitors
• Benazepril, captopril, enalapril, lisinopril, ramipril,
fosinopril
• Prevent conversion of Angiotensin I to Angiotensin II
• Use: hypertension, HF, diabetic neuropathy, MI.
Prevention of adverse CV events in patients at risk
• Excreted by the kidneys. Dosages must be reduced in
patients with kidney disease.
• SE: Hypotension, hyperkalemia, hypoglycemia, cough,
angioedema
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Angiotensin Receptor Blockers
• Losartan, valsartan, candesartan irbesartan
telmisartan, olmesartan
• Action of the angiotensin II receptor antagonists:
Block the binding of angiotensin II at the receptor
sites found in smooth muscle and adrenal gland;
this stops renin angiotensin system and lowers blood
pressure
• Uses: Used for the treatment of hypertension; some
drugs are used only in severe cases of hypertension;
two antihypertensive drugs may be given together
to achieve a better response
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Antihypertensive Drugs:
Contraindications
• Antihypertensive drugs are contraindicated in
patients with known hypersensitivity to the
individual drug
• ACEIs: Contraindicated in patients with impaired
renal function, congestive heart failure, salt or
volume depletion, bilateral stenosis, or angioedema,
also during pregnancy or lactation
• Use of the ACEIs and the angiotensin II receptor
blockers during the second and third trimester of
pregnancy is contraindicated because use may
cause fetal or neonatal injury or death
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Beta Blockers
• Acebutolol, atenolol, carvedilol, esmolol, labetalol,
bisoprolol, metoprolol, bisoprolol
• Epinepherine stimulates β1 receptors on heart  HR BP
and increases strength of contraction
• Β2 stimulation causes tremors, bronchodilation vasodilation of
large arteries in legs.
• Non-selective β-blockers affect heart, skeletal muscle, lungs and
arteries (propranolol, nadolol, timolol, carvedilol, pindolol)
• Β1 selective blockers block receptors on heart so that heart rate
falls, blood pressure falls, cardiac workload decreases. (atenolol,
metoprolol, betaxolol, bisoprolol)
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Uses of Beta-blockers
• Decrease palpitations during panic attacks
• Decrease essential tremors
• Decrease situational anxiety
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Beta1 Agonists
• Stimulate β1 receptors to increase HR and contractility
– Dobutamine
– Dopamine
– Levophed
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Calcium Channel Blockers
• Class 1: Verapamil
– Blocks calcium channels primarily on the coronary
vessels and AV node
– Increases blood flow to heard and decreases
impulses through AV node. Used to decrease
workload of heart, slows rate, treat HTN, angina, afib
• Class 2 Diltiazem
– Dilates calcium channels on the coronary and
peripheral vessels
– Uses: a fib, HTN, angina, vasospasm
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Class 3 Calcium Channel Blockers
• -dipines: amlodipine, felodipine, nifedipine,
• Peripheral vessel calcium channel blockers
• Uses: HTN, vasospasm (Prinzmetals’s angina,
Reynaud’s)
• SE: Verapamil causes significant consipation, diltiazem
less
– Dipines: headaches, hypotension, peripheral and
pedal edema
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• True/False
• 1.
Blood pressure is the force of the blood against the walls of the arteries.
• 2.
A hypertensive emergency is a case of extremely high blood pressure in
which blood pressure must be lowered immediately to prevent damage to the target
organs.
• 3. Risk factors for hypertension include diabetes, obesity, smoking and family
history of CVD.
• 4.
A systolic pressure of less than 120 mmHg and a diastolic pressure of less
than 80 mmHg (120/80) are considered abnormal.
• 5.
The hypotensive effects of most antihypertensive drugs are increased when
administered with diuretics and other antihypertensives.
• Fill-in-the-Blank
• 1.
________________ is defined as a systolic pressure between 120 and 139
mmHg or a diastolic pressure between 80 and 89 mmHg.
• 2.
When a direct cause of the hypertension can be identified, the condition is
described as ________________ hypertension.
• 3.
_________________ promotes the retention of sodium and water, which
may contribute to a rise in blood pressure.
• 4.
_________________ hypotension occurs when the individual has a significant
drop in blood pressure (usually 10 mmHg systolic or more) when assuming an
upright position.
• 5.
Nitroprusside and diazoxide are drugs used to treat patients with a
_________________ emergency.
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