Antihypertensive Drugs: Pharmacology for Nursing PDF

Antihypertensive drug Antihypertensive Drugs Pharmacology for Nursing Dr. Heba Khader Hypertension Categories  Hypertension is defined as an arterial pressure greater than 140/90 mm Hg in adults on at least three consecutive visits to the doctor's office...

Antihypertensive drug Antihypertensive Drugs Pharmacology for Nursing Dr. Heba Khader Hypertension Categories  Hypertension is defined as an arterial pressure greater than 140/90 mm Hg in adults on at least three consecutive visits to the doctor's office.  The risks of damage to kidney, heart, and brain are directly related to the extent of blood pressure elevation. Mechanisms for controlling blood pressure  Arterial blood pressure is regulated within a narrow range to provide adequate perfusion of the tissues without causing damage to the vascular system, particularly the endothelium.  Arterial blood pressure is directly proportional to cardiac output and peripheral vascular resistance. Mechanisms for controlling blood pressure  Cardiac output and peripheral resistance, in turn, are controlled mainly by two overlapping control mechanisms:  The baroreflexes  The renin-angiotensin-aldosterone system  Baroreflexes  Baroreceptors are sensors located in the blood vessels of all vertebrate animals. They are a type of mechanoreceptor sensory neuron that is excited by stretch of the blood vessel.  Baroreceptors act immediately as part of a negative feedback system called the baroreflex.  Baroreflexes act by changing the activity of the autonomic nervous system. Therefore, they are responsible for the rapid, moment-to moment regulation of blood pressure.  1. Reduced blood pressure 2. Beta1 activation 3. Low sodium intake or excessive sodium loss Need more time Beta Blocker s Aldosteron increases sodium CO Renin and water retention ADH: Anti diuretic Increases blood hormone pressure Hypertension treatment  The goal of antihypertensive therapy is to reduce cardiovascular and renal morbidity and mortality.  Mild hypertension can sometimes be controlled with a single drug, but most patients require more than one drug to achieve blood pressure control. Drugs used in hypertension 1. Diuretics 2. Sympathoplegic agents  Beta blockers  Alpha blockers  Centrally acting adrenergic drugs 3. Agents that block production or action of angiotensin  Angiotensin Converting Enzyme Inhibitors (ACEIs)  Angiotensin Receptor blockers (ARBs)  Renin inhibitor 4. Vasodilators  1. Diuretics  Diuretics lower blood pressure by depleting the body of sodium and reducing blood volume.  Diuretics can be used as first-line drug therapy for hypertension unless there are compelling reasons to choose another agent.  Low-dose diuretic therapy is safe, inexpensive, and effective in preventing stroke, myocardial infarction, and congestive heart failure, all of which can cause mortality.  The diuretics most important for treating hypertension are the thiazides (eg, hydrochlorothiazide) and the loop diuretics (eg, furosemide). Sites of action of diuretic drugs 1. Diuretics 1. Thiazide diuretics are appropriate for most patients with mild or moderate hypertension and normal renal and cardiac function. 2. loop diuretics such as furosemide are more powerful diuretics are necessary in severe hypertension; 3. Potassium-sparing diuretics (e.g, spironolactone) are useful both to avoid excessive potassium depletion and to enhance the natriuretic effects of other diuretics.  All diuretics should not be administered late in the day. Thiazide diuretics  Therapeutic Uses: 1. Essential hypertension (primary indication): Thiazides are drugs of first choice. 2. Edema associated with mild to moderate heart failure.  Need adequate kidney function (ineffective when GFR is low)  cannot be used to promote fluid loss in patients with severe renal impairment. Thiazide diuretics  Actions:  Increase Na+, Cl- and K+ excretion  Decrease Ca++ excretion  They promote the reabsorption of Ca+>>>> decrease Ca+ content of urine>>>> beneficial for patients with calcium oxalate stones in the urinary tract. Thiazide diuretics  Side effects:  Hypokalemia (increases digoxin toxicity)  Hypercalcemia  Hyperuricemia Hyperglycemia  Hyponatremia (It can be prevented by reducing the dose of the drug or limiting water intake).  Hypersensitivity Loop Diuretics  Ex: furosemide  More powerful diuretics reserved for cases that require massive diuresis.  They are necessary: 1. in severe hypertension that cannot be controlled by other duiretics 2. in renal insufficiency, when glomerular filtration rate is less than 30 or 40 mL/min 3. in cardiac failure or cirrhosis, in which sodium retention is marked. 4. Pulmonary edema associated with CHF. Loop Diuretics  Actions:  Increase Na+, Cl-, K+ and Ca++ excretion  Side effects:  Ototoxcity, reversible (esp. with aminoglycoside antibiotics)  Hyperuricemia  Acute hypovolemia (severe and rapid reduction in blood volume)  Hypokalemia  Hyperglycemia  Hypersensitivity (All loop diuretics, with the exception of ethacrynic acid, are sulfonamides.) Potassium-sparing Diuretics  E.g, spironolactone  They are not very efficacious diuretics. They commonly used in combination with other diuretics, for their potassium- sparing properties. 2. Sympathoplegic agents  Sympathoplegic agents lower blood pressure by reducing peripheral vascular resistance, inhibiting cardiac function, and increasing venous pooling in capacitance vessels. (The latter two effects reduce cardiac output.)  These agents are further subdivided according to their putative sites of action in the sympathetic reflex arc to: A. Beta blockers B. Alpha blockers C. Centrally acting adrenergic drugs  A. Beta blockers  Mechanism of action involves reduction in cardiac output and suppression of renin release A. Beta blockers  The non-selective β blockers such as propranolol can be used to treat hypertension.  Selective blockers of β1 receptors, such as metoprolol and atenolol are among the most commonly prescribed β- blockers.  Nebivolol is a selective blocker of β1 receptors, which also increases the production of nitric oxide leading to vasodilation.  The selective β-blockers may be administered cautiously to hypertensive patients who also have asthma.  The nonselective β-blockers, such as propranolol and nadolol, are contraindicated in patients with airway diseases due to their blockade of β2-mediated bronchodilation.  Adverse effects include fatigue, bradycardia, insomnia and disturbances in glucose metabolism. B. Alpha 1 blockers  Prazosin, doxazosin, and terazosin.  Mechanism of action is by dilating vessels which decrease peripheral vascular resistance.  Side effects include reflex tachycardia and orthostatic hypotension.  Labetalol and carvedilol block α1, β1, and β2 receptors. C. Centrally acting adrenergic drugs Clonidine and methyldopa  α2-agonists that reduce the central adrenergic outflow, decreasing the firing rate of the sympathetic nerves and the amount of norepinephrine release.  Not a first-line or second line treatment.  Methyldopa was widely used in the past but is now used primarily for hypertension during pregnancy.  The most common side effects of methyldopa are sedation particularly at the onset of treatment. 3. Agents that block production or action of angiotensin  Agents that block production or action of angiotensin and thereby reduce peripheral vascular resistance and blood volume. A. Angiotensin Converting Enzyme Inhibitors (ACEIs) B. Angiotensin Receptor blockers (ARBs) C. Renin inhibitor  1. Reduced blood pressure 2. Beta1 activation 3. Low sodium intake or excessive sodium loss Aldosteron increases sodium and water retention ADH: Anti diuretic Increases blood hormone pressure A. ACEIs A. ACEIs  The ACE inhibitors lower blood pressure by reducing peripheral vascular resistance without reflexively increasing cardiac output, rate, or contractility.  These drugs block the ACE that cleaves angiotensin I to form the potent vasoconstrictor angiotensin II.  By reducing circulating angiotensin II levels, ACE inhibitors also decrease the secretion of aldosterone, resulting in decreased sodium and water retention.  The converting enzyme is also responsible for the breakdown of bradykinin. ACEIs also reduce the rate of bradykinin inactivation.  ACE inhibitors decrease angiotensin II and increase bradykinin levels.  Vasodilation occurs as a result of the combined effects of lower vasoconstriction caused by diminished levels of angiotensin II and the potent vasodilating effect of increased bradykinin. ACEIs Pharmacokinetics  Ex: enalapril, captopril, ramipril.  All ACE inhibitors are adequately absorbed following oral administration.  Because the presence of food may decrease absorption, they should be taken on an empty stomach. ACEIs adverse effects  Common side effects include:  Dry cough especially at night (ACE cough)  Skin rash  Hypotension  Hyperkalemia (Potassium levels must be monitored, and potassium supplememts or spironolactone are contraindicated).  Angioedema is a rare but potentially life- threatening side effect (Because of the risk of angioedema and first dose syncope, ACEIs are first administered in the physician’s office with close supervision.  ACEIs inhibitors are fetotoxic and should not be used in pregnant women. B. Angiotensin Receptor Blockers (ARBs)  Losartan is the prototype drug. Other drugs are candesartan, valsartan and irbesartan.  ARBs are extremely potent competitive antagonists of the angiotensin type 1 (AT1) receptor.  Like ACEIs, produce vasodilation and blocks aldosterone secretion, but have no effect on bradykinin. B. Angiotensin Receptor Blockers (ARBs)  ARBs are orally active and require only once-a-day dosing.  ARBs have an adverse effect profile similar to that of ACE inhibitors. However, cough and angioedema can occur but are less common  As with ACE inhibitors, ARBs are contraindicated in pregnancy. C. Renin Inhibitor  A selective renin inhibitor, aliskiren.  Aliskiren directly inhibits renin and, thus, acts earlier in the renin-angiotensin-aldosterone system than do ACE inhibitors or ARBs.  Hyperkalemia is significantly more common in patients who received both valsartan and aliskiren.  Adverse effects:  Diarrhea, especially at higher doses.  Cough and angioedema but less often than ACE inhibitors.  As with ACE inhibitors and ARBs, aliskiren is contraindicated during pregnancy. 4. Vasodilators  This class of drugs includes:  The oral vasodilators, e.g: hydralazine, used for long-term outpatient therapy of hypertension.  The parenteral vasodilators, e.g: nitroprusside and fenoldopam used to treat hypertensive emergencies.  The calcium channel blockers, which are used in both circumstances.  The nitrates (nitroglycerine), which are used mainly in angina. 4. Vasodilators  Vasodilators differ from one another with respect to the types of blood vessels they affect: e.g. Hydralazine and CCBs produce selective dilation of arterioles. Nitroglycerine produces selective dilation of veins. Nitroprusside dilates arterioles and veins.  Dilation of arterioles (resistance vessels)  decrease cardiac afterload  Reduce cardiac work.  Dilation of veins  reduce the force with which blood is returned to the heart reduces ventricular filling decreases cardiac preload  decreases the force of ventricular contraction  decreases cardiac work  decrease cardiac output Calcium Channel Blockers (CCBs)  Mechanism of action:  Calcium-channel antagonists block the inward movement of calcium by binding to calcium channels in the heart and in smooth muscle of the coronary and peripheral arteriolar vasculature.  This causes relaxation of cardiac and vascular smooth muscles which decrease cardiac output and vascular resistance. Calcium Channel Blockers (CCBs)  The calcium-channel blockers are divided into: 1. Dihydropyridines (DHP)  mainly affect vessels  Nifedipine, amlodipine, felodipine, isradipine, nicardipine, and nisoldipine  Clevidipine is a newer member of this group that is formulated for intravenous use only. 2. Non- Dihydropyridines (non-DHP)  affect cardiac and vessels effect  Verapamil and diltiazem  Side effects include:  Constipation (verapamil).  Bradycardia (verapamil and diltiazem)  Dizziness, headache, and a feeling of fatigue.  edema Sodium nitroprusside  Rapidly acting vasodilator.  Relaxes both arteriole and venules.  IV administration (rapid acting within 30 sec) and short acting (3 minutes).  Decompose on exposure to light. Infusion bottle and tubing should be covered with foil.  Drug of choice in hypertensive emergencies.  Poisonous if given orally because of its hydrolysis to cyanide. Hypertensive emergencies  Hypertensive emergency is a rare but life- threatening situation in which:  the diastolic blood pressure is either greater than 150 mm Hg (with systolic blood pressure greater than 210 mm Hg) in an otherwise healthy person  or greater than 130 mmHg in an individual with preexisting complications, such as encephalopathy, cerebral hemorrhage, left ventricular failure, or aortic stenosis.  If high BP is associated with edema of retina, intracranial hemorrhage, MI, or acute CHF  sever emergency BP must be lowered within 1 hour.  If sever hypertension is present but does not pose an immediate threat of organ damage  reduce BP more slowly (over 24 to 48 hours): because rapid reduction in BP can cause cerebral ischemia, MI, and renal failure. Pressure should be reduced gradually whenever possible. The End