| Drug Class: Erectile Dysfunction / BPH Drugs |
Be patient. We'll get it up before too long. |
| Reference: A work in progress |
| Drug Class: Endogenous Renal Vasodilators |
Mechanism of Action:
|
| Reference: Kadowitz's handout |
| Drug Class: Endogenous Renal Vasoconstrictors |
Mechanism of Action:
|
| Reference: Kadowitz's handout |
ACE Inhibitors
| Drug: Benazepril (Lotensin ®), Captopril (Capoten ®), Enalapril (Vasotec ®), Fosinopril (Monopril ®), Lisinopril (Prinivil, Zestril ®), Quinapril (Accupril ®), Ramipril (Altace ®) |
| Drug Class: ACE Inhibitor, Antihypertensive |
| Mechanism of Action: Inhibits peptidyl dipeptidase (Angiotensin Converting Enzyme). This prevents the conversion of angiotensin I to angiotensin II. ACE also inactivates bradykinin, a potent vasodilator that works in part by stimulating the release of nitric oxide and prostacyclin. ACE inhibition can thereby elevate bradykinin levels in addition to lowering Ang II levels. Ang II is one of the most potent vasoconstrictors known. |
| Indications: Treatment of hypertension, useful for CHF, reduce glomerular damage in diabetes. |
| Side Effects: acute renal failure in patients with bilateral renal artery stenosis, hyperkalemia due to aldosterone suppression, allergic respons to sulfhydryl group on captopril, severe hypotension in patients who are hypovolemic due to diuretics, salt restriction of GI fluid loss. Dry cough (believed to be caused by bradykinin & substance P). |
| Contraindications: When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. |
Drug Interactions: potassium supplements or K-sparing diuretics can result in hyperkalemia. NSAIDs may impair the hypotensive effect by blocking bradykinin-mediated vasodilation (mediated at least in part by PGs). |
| Reference: Katzung's text & Kadowitz's handout |
Angiotensin Receptor Blockers
| Drug: Irbesartan (Avapro ®), Losartan (Cozaar ®), Valsartan (Diovan ®) |
| Drug Class: Ang II - AT1 receptor blockers, Antihypertensive |
| Mechanism of Action: Block AT1 receptors. They have no effect on bradykinin metabolism & are therefore more selective blockers on angiotensin effects compared to ACE inhibitors. They have the potential for more complete inhibition of Ang II action compared to ACE inhibitors because there are enzymes other than ACE that can generate Ang II. |
| Indications: Hypertension. It may be used alone or in combination with other drugs. |
| Contraindications: Similar to ACE inhibitors, pregnancy. When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. |
| Side Effects: Cough & angioedema, but less common compared to ACE inhibitors. |
| Reference: www.rxlist (Irbesartan, Losartan, Valsartan) & Katzung's text |
| Drug: Saralasin |
| Drug Class: Ang II antagonist / partial agonist (peptide) |
| Mechanism of Action: partial agonist / antagonist at the AT1 receptor |
| Indications: detection of renin-dependent hypertension & other hyperreninemic states |
| Pharmacokinetics: must be given i.v. |
| Side Effects: pressor response when Ang II levels are low |
| Reference: Katzung's text |
| Drug: Acetazolamide (generic, Diamox ®) |
| Drug Class: diuretic (carbonic anhydrase inhibitor) |
| Mechanism of Action: a potent carbonic anhydrase inhibitor. The diuretic effect of acetazolamide is due to its action in the kidney on the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. The result is renal loss of HCO 3 ion, which carries out sodium, water, and potassium. Alkalinization of the urine and promotion of diuresis are thus effected. Alteration in ammonia metabolism occurs due to increased reabsorption of ammonia by the renal tubules as a result of urinary alkalinization. Carbonic anhydrase inhibitors were the forerunners of modern diuretics. |
| Indications: adjunctive treatment of: edema due to congestive heart failure; drug- induced edema; centrencephalic epilepsies (petit mal, unlocalized seizures); chronic simple (open- angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where delay of surgery is desired in order to lower intraocular pressure. Acetazolamide is also indicated for the prevention or amelioration of symptoms associated with acute mountain sickness in climbers attempting rapid ascent and in those who are very susceptible to acute mountain sickness despite gradual ascent. |
| Contraindications: contraindicated in situations in which sodium and/or potassium blood serum levels are depressed, in cases of marked kidney and liver disease or dysfunction, in suprarenal gland failure, and in hyperchloremic acidosis. it is contraindicated in patients with cirrhosis because of the risk of development of hepatic encephaiopathy. Long- term administration of acetazolamide is contraindicated in patients with chronic noncongestive angle- closure glaucoma since it may permit organic closure of the angle to occur while the worsening glaucoma is masked by lowered intraocular pressure. |
| Pharmacokinetics: oral or parenteral administration |
| Side Effects: paresthesias, particularly a “tingling” feeling in the extremities, hearing dysfunction or tinnitus, loss of appetite, taste alteration and gastrointestinal disturbances such as nausea, vomiting and diarrhea; polyuria, and occasional instances of drowsiness and confusion. Metabolic acidosis and electrolyte imbalance may occur. |
Reference: www.rxlist.com |
| Drug: Indapamide (generic, Lozol ®) |
| Drug Class: antihypertensive & diuretic |
| Mechanism of Action: Its antihypertensive mechanism of action is not clearly understood but possibly involves both renal and extra-renal effects. |
| Indications: Indapamide tablets are indicated for the treatment of hypertension, alone or in combination with other antihypertensive drugs. |
| Contraindications: Pregnancy - The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unnecessary hazard |
| Pharmacokinetics: oral administration. Onset: 1-2 weeks after multiple doses. Peak levels: 2 hr. Duration: Up to 8 weeks with multiple doses. t1/2: 14 hr. Nearly 100% is absorbed from the GI tract. Excreted through the kidneys (70% with 7% unchanged) and the GI tract (23%). |
| Major drug interactions: may produce additive effects when given with other antihypertensives, may enhance lithium toxicity, may decrease the arterial response to catecholamines / norepi. |
Reference: www.rxlist.com & www.healthdigest.org/drugs |
| Drug: Chlorothiazide (generic, Diuril ®) |
| Drug Class: thiazide diuretic |
Mechanism of Action: Chlorothiazide increases excretion of Na & Cl in the distal convoluted tubule. Natriuresis may be accompanied by some loss of potassium and bicarbonate.Thiazides enhance Ca reabsorption in the distal convoluted tubule, perhaps by Na/Ca exchange. The effects of loop diuretics, thiazides & K-sparing diuretics depend on renal prostaglandin production & can be inhibited by NSAIDs under certain conditions |
| Indications: 1) hypertension, 2) heart failure, 3) treatment of kidney stones caused by hypercalciuria, 4) nephrogenic diabetes insipidus. |
| Contraindications: Anuria. Hypersensitivity to this or other sulfonamide-derived drugs |
| Pharmacokinetics: After oral use diuresis begins within 2 hours, peaks in about 4 hours, and lasts about 6 to 12 hours. Chlorothiazide is not metabolized but is eliminated rapidly by the kidney. The plasma half-life of chlorothiazide is 45-120 minutes. |
| Side Effects: hypokalemic metabolic alkalosis, hyperuricemia, impaired carbohydrate tolerance, hyperlipidemia (5-15% rise in serum chlosterol & increased LDL), hyponatremia, allergic reactions. |
| Major drug interactions: alcohol, barbiturates & narcotics may potentiate orthostatic hypotension, additive effect with other antihypertensives, decreased response to pressor amines, dosage adjustment of antidiabetic drugs may be necessary. |
Reference: www.rxlist.com |
| Drug: Hydrochlorothiazide (generic, Microzide ®) |
| Drug Class: thiazide diuretic, antihypertensive |
Mechanism of Action: inhibits NaCl reabsorption from the luminal side of epithelial cells in the distal convoluted tubule by blocking the Na/Cl transporter. Thiazides enhance Ca reabsorption in the distal convoluted tubule, perhaps by Na/Ca exchange. The effects of loop diuretics, thiazides & K-sparing diuretics depend on renal prostaglandin production & can be inhibited by NSAIDs under certain conditions |
| Indications: hypertension, heart failure, nephrolithiasis due to idiopathic hypercalciuria & neprogenic diabetes insipidus. |
| Contraindications: excessive use in hepatic cirrhosis, borderline renal failure, or heart failure |
| Side Effects: hypokalemic metabolic alkalosis (hypokalemia), hyperuricemia, impaired carbohydrate tolerance, hyperlipidemia (5-15% rise in serum chlosterol & increased LDL), hyponatremia, allergic reactions. |
| Major drug interactions: the effects of diuretics are dependent on renal prostaglandin production & can be inhibited by NSAIDs under certain conditions. |
Notes: the prototypical thiazide diuretic |
| Reference: www.rxlist.com |
Loop Diuretics (the most efficacious diuretics): "High Ceiling" Diuretics
| Drug: Furosemide (generic, Lasix ®) |
| Drug Class: loop diuretic |
| Mechanism of Action: selectively inhibit NaCl reabsorption in the thick ascending limb of the loop of Henle. Loop diuretics also induce renal prostaglandin synthesis, which participate in their renal actions. Furosemide also increases renal blood flow & (by an unknown mechanism) reduce pulmonary congestion and left ventricular filling pressure in heart failure (this effect occurs prior to producing a change in urinary output, and also in anephric patients). The effects of loop diuretics, thiazides & K-sparing diuretics depend on renal prostaglandin production & can be inhibited by NSAIDs under certain conditions. |
| Indications: acute pulmonary edema, other edematous conditions, acute hypercalcemia, hyperkalemia, acute renal failure, anion overdosage (e.g. toxic ingestion of fluoride, bromide, iodide). |
| Contraindications: patients who are allgeric to sulfonamides. Do not use "overzealously" in hepatic cirrhosis or borderline renal failure or heart failure. |
| Pharmacokinetics: rapidly absorbed, eliminated by tubular secretion & glomerular filtration. Duration of effect is 2-3 hours (half life depends on renal function). NSAIDs and probenecid compete for secretion. |
| Side Effects: hypokalemia. Toxicity: hypokalemic metabolic alkalosis, ototoxicity (dose related & usually reversible), hyperuricemia, hypomanesemia, allergic reactions (skin rash, eosinophilia). |
| Major drug interactions: NSAIDs (eg. indomethacin) can interfere with the actions of loop diuretics by interfering with prostaglandin synthesis. This interference is minimal in norma subjects, but may be significant in patients with nephrotic syndrome or hepatic cirrhosis. |
Reference: www.rxlist.com, Katzung's text |
| Drug: Ethacrynic acid (Edecrin ®) |
| Drug Class: loop diruetic |
Mechanism of Action: acts on the ascending limb of the loop of Henle and on the proximal and distal tubules. Urinary output is usually dose dependent and related to the magnitude of fluid accumulation. Water and electrolyte excretion may be increased several times over that observed with thiazide diuretics, since ethacrynic acid inhibits reabsorption of a much greater proportion of filtered sodium than most other diuretic agents. Therefore, ethacrynic acid is effective in many patients who have significant degrees of renal insufficiency. The effects of loop diuretics, thiazides & K-sparing diuretics depend on renal prostaglandin production & can be inhibited by NSAIDs under certain conditions |
| Indications: indicated for treatment
of edema when an agent with greater diuretic potential than those commonly
employed is required. Examples include: 1. Treatment of the edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. 2. Short- term management of ascites due to malignancy, idiopathic edema, and lymphedema. 3. Short- term management of hospitalized pediatric patients, other than infants, with congenital heart disease or the nephrotic syndrome. 4. Intravenous ethacrynic acid is indicated when a rapid onset of diuresis is desired, e.g., in acute pulmonary edema, or when gastrointestinal absorption is impaired or oral medication is not practicable. |
| Contraindications:anuria. If increasing electrolyte imbalance, azotemia, and/ or oliguria occur during treatment of severe, progressive renal disease, the diuretic should be discontinued. |
| Pharmacokinetics: Onset of action is rapid, usually within 30 minutes after an oral dose of ethacrynic acid or within 5 minutes after an intravenous injection of ethacrynic acid. After oral use, diuresis peaks in about 2 hours and lasts about 6 to 8 hours. |
| Side Effects: hypokalemic metabolic alkalosis (hypokalemia), ototoxicity, hyperuricemia, hypomagnesemia, allergic reactions, dehydration. |
| Major drug interactions: Lithium generally should not be given with diuretics because they reduce its renal clearance and add a high risk of lithium toxicity. Ethacrynic acid may increase the ototoxic potential of other drugs such as aminoglycoside and some cephalosporin antibiotics. NSAIDs may interfere with the actions of diuretics. |
Reference: www.rxlist.com, Katzung's text |
| Drug:Torsemide (Demadex ®) |
| Drug Class: loop diuretic |
| Mechanism of Action: acts from within the lumen of the thick ascending portion of the loop of Henle, where it inhibits the Na+/K+/2CI--carrier system. Torsemide increases the urinary excretion of sodium, chloride, and water |
| Indications: treatment of edema associated with congestive heart failure, renal disease, or hepatic disease. Use of torsemide has been found to be effective for the treatment of edema associated with chronic renal failure. Chronic use of any diuretic in hepatic disease has not been studied in adequate and well-controlled trials. Torsemide intravenous injection is indicated when a rapid onset of diuresis is desired or when oral administration is impractical. Torsemide is indicated for the treatment of hypertension alone or in combination with other antihypertensive agents. |
| Contraindications: hypersensitivity to torasemide or sulfonylureas. |
| Pharmacokinetics:oral or parenteral administration. the elimination half-life of torsemide is approximately 3.5 hours. Torsemide is cleared from the circulation by both hepatic metabolism (approximately 80% of total clearance) and excretion into the urine (approximately 20% of total clearance in patients with normal renal function). |
| Side Effects: hypokalemic metabolic alkalosis (hypokalemia), ototoxicity, hyperuricemia, hypomagnesemia, allergic reactions, dehydration. |
| Major drug interactions: Demadex and salicylates compete for secretion by renal tubules, patients receiving high doses of salicylates may experience salicylate toxicity. Lithium clearance is reduced, elevating the risk of lithium toxicity. |
Reference: www.rxlist.com |
2 Epithelial Na channel (ENaC) inhibitors
| Drug: Triamterene (Dyrenium ®) |
| Drug Class: antihypertensive / diuretic (potassium-sparing) |
Mechanism of Action: it blocks Na entry through Na-selective ion channels in the apical membrane of the collecting tubule. Since K secretion is coupled with Na entry in this segment, it is also K-sparing. The effects of K-sparing diurects depend on renal prostaglandin production & can be inhibited by NSAIDs under certain conditions. |
| Indications: treatment of edema associated with congestive heart failure, cirrhosis of the liver, and the nephrotic syndrome; also in steroid-induced edema, idiopathic edema, and edema due to secondary hyperaldosteronism. Triamterene may be used alone or with other diuretics either for its added diuretic effect or its potassium-conserving potential. It also promotes increased diuresis when patients prove resistant or only partially responsive to thiazides or other diuretics because of secondary hyperaldosteronism. |
| Contraindications: anuria. It also should not be given to patients receiving other potassium-sparing agents such as spironolactone, amiloride hydrochloride, or other formulations containing triamterene. |
| Pharmacokinetics: Most patients will respond to triamterene during the first day of treatment, however the maximum therapeutic effect may not be seen for several days. Duration of diuresis depends on several factors, especially renal function, but it generally tapers off 7 to 9 hours after administration. Triamterene is primarily metabolized to the sulfate conjugate of hydroxytriamterene. |
| Side Effects: WARNING - Abnormal elevation of serum potassium levels (greater than or equal to 5.5 mEq/liter) can occur with all potassium-sparing agents, including triamterene. Hyperkalemia is more likely to occur in patients with renal impairment, and diabetes (even without evidence of renal impairment), elderly or severely ill patients. Since uncorrected hyperkalemia may be fatal, serum potassium levels must be monitored at frequent intervals especially in patients receiving triamterene, when dosages are changed or with any illness that may influence renal function. |
| Major drug interactions: lithium (increases it's toxicity), potentiates other antihypertenstive drugs. Potassium-sparing agents should be used with caution in conjunction with angiotensin-converting enzyme (ACE) inhibitors and beta blockers due to an increased risk of hyperkalemia. NSAIDs may interefere with the actions of most diuretics. |
Reference: www.rxlist.com |
| Drug: Amiloride (Midamor ®) |
| Drug Class: potassium-sparing diuretic |
| Mechanism of Action: exerts its potassium sparing effect through the inhibition of sodium reabsorption through ion channels in the distal convoluted tubule, cortical collecting tubule and collecting duct; this decreases the net negative potential of the tubular lumen and reduces both potassium and hydrogen secretion and their subsequent excretion. It is NOT an aldosterone antagonist, and exerts effects even in the absence of aldosterone. |
| Indications: adjunctive treatment with thiazide diuretics or other kaliuretic-diuretic agents in congestive heartfailure or hypertension to: a. help restore normal serum potassium levels in patients who develop hypokalemia on the kaliuretic diuretic b. prevent development of hypokalemia in patients who would be exposed to particular risk if hypokalemia were to develop, e. g., digitalized patients or patients with significant cardiac arrhythmias. |
| Contraindications: hyperkalemia, other potassium-sparing agents, anuria, acute or chronic renal insufficiency, hypersensitivity |
| Pharmacokinetics: usually begins to act within 2 hours after an oral dose. Its effect on electrolyte excretion reaches a peak between 6 and 10 hours and lasts about 24 hours. Peak plasma levels are obtained in 3 to 4 hours and the plasma half-life varies from 6 to 9 hours. Amiloride HCI is not metabolized by the liver but is excreted unchanged by the kidneys & in the stool. |
| Side Effects: WARNING Like other potassium-conserving agents, amiloride may cause hyperkalemia (serum potassium levels greater than 5.5 mEq per liter) - see triamterene side effects. |
| Major drug interactions: ACE inhibitor or beta blocker (hyperkalemia), lithium (increased Li toxicity), NSAIDs (decreased diuretic effects) |
Reference: www.rxlist.com |
2 Mineralocorticoid Receptor Antagonists
| Drug: Spironolactone (generic, Aldactone ®) |
| Drug Class: diuretic (potassium-sparing) |
| Mechanism of Action: a specific pharmacologic antagonist of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Spironolactone causes increased amounts of sodiumand water to be excreted, while potassium is retained. Spironolactone acts both as a diuretic and as an antihypertensive drug by this mechanism. |
| Indications: primary hyperaldosteronism, edematous conditions, essential hypertension, hypokalemia, reducing edema (& mortality) in CHF |
| Contraindications: patients with significant renal impairment, hyperkalemia, routine use in pregnancy is unwise, |
| Pharmacokinetics: Spironolactone is rapidly and extensively metabolized. Sulfur-containing products are the predominant metabolites and are thought to be primarily responsible, together with spironolactone, for the therapeutic effects of the drug. Spirnonolactone has a short half-life of ~1-2 hrs, but it's active metabolites have half-lives of ~15 hrs. |
| Side Effects: gynecomastia, agranulocytosis, spironolactone has been shown to be a tumorigen in rats |
| Major drug interactions: ACE inhibitors and beta blockers (may produce severe hyperkalemia), reduced effect of pressor amines, lithium (should not be given with diuretics), NSAIDS (can reduce the effectiveness of diuretics), digoxin (increased half-life), corticosteroids (intensifies hypokalemia). |
Reference: www.rxlist.com |
| Drug: Eplerenone (Inspra ®) |
| Drug Class: diuretic (potassium-sparing) |
| Mechanism of Action: same as spironolactone (mineralocoticoid receptor antagonist), but has greater selectivity for the aldosterone receptor than spironolactone. |
| Indications: currently approved for use only in hypertension |
Reference: www.rxlist.com |
| Drug: Hydralazine (generic, Apresoline ®) |
| Drug Class: Vasodilator, Antihypertensive |
| Mechanism of Action: dilates arterioles, but not veins. Cellular mechanism is not well understood. Results in decreased arterial blood pressure (diastolic more than systolic); decreased peripheral vascular resistance; and when used alone can cause a reflex increase in heart rate, stroke volume, and cardiac output. |
| Indications: essential hypertension, alone or in combination with other drugs |
| Contraindications: Hypersensitivity to hydralazine; coronary artery disease; mitral valvular rheumatic heart disease. |
| Pharmacokinetics: Oral or parenteral formulations. Plasma levels of apparent hydralazine decline with a half-life of 3 to 7 hours. Binding to human plasma protein is 87%. Plasma levels of hydralazine vary widely among individuals. Hydralazine is subject to polymorphic acetylation; slow acetylators generally have higher plasma levels of hydralazine and require lower doses to maintain control of blood pressure. Hydralazine undergoes extensive hepatic metabolism; it is excreted mainly in the form of metabolites in the urine. |
| Side Effects: headache, anorexia, nausea, vomiting, diarrhea, palpitations, tachycardia, angina pectoris. With high doses - skin rashes, arthralgia & lupus-like syndrome (reversible). |
| Major drug interactions: MAO inhibitors should be used with caution in patients receiving hydralazine. |
Reference: www.rxlist.com & Katzung's text |
| Drug: Diazoxide (Hyperstat IV ®) |
| Drug Class: Vasodilator, Antihypertensive |
| Mechanism of Action: a long-acting arteriolar dilator. It prevents smooth muscle contraction by opening potassium channels and stabilizing the membrane potential at a more hyperpolarized voltage. Lowers TPR & systemic arterial blood pressure while producing substantial reflex tachycardia & increase in cardiac output. |
| Indications: occasionally used to treat hypertensive emergencies |
| Pharmacokinetics: Oral or parenteral formulations. Both metabolized & excreted unchanged, h alf life ~24 hrs. Extensive protein binding to serum albumin & to vascular tissue. |
Reference: Katzung's text |
| Drug: Sodium Nitorprusside (generic, Nitropress ®) |
| Drug Class: Vasodilator |
| Mechanism of Action: Dialates both venous & arterial vessels, resulting in reduced TPR & venous return. Activates guanylyl cyclase, etiher by release of NO or by direct stimulation of the enzyme, resulting in increased intracellular cGMP, which lowers intracellular Ca and relaxes vascular smooth muscle. In the absence of heart failure, BP decreases while CO does not change, or decreases slightly. In patients with heart failure & low CO, CO often increases due to afterload reduction. |
| Indications: hypertensive emergencies & severe heart failure |
| Pharmacokinetics: Given i.v. only. Nitroprusside is rapidly metabolized & its effect dissappears within 1-10 mins after discontinuation of i.v. infusion. In aqueous solution the drug is sensitive to light & must be made up fresh before each administration & covered with opaque foil. |
| Side Effects: excessive lowering of blood pressure, accumulation of cyanide (resulting from nitroprusside metabolism) that can cause metabolic acidosis, arrhythmias & death. Administration of sodium thiosulfate as a sulfur donar facilitates the metabolism of cyanide. Hydroxocobalamiin also combines with cyanide to form a nontoxic product. Thiocyanate may accumulate over the course of prolonged administration ( a week or more) & cause weakness, disorientation, convulsions. |
| Note: Nitroprusside is a complex of iron, cyanide groups, and a nitroso moiety. |
Reference: www.rxlist.com & Katzung's text |
| Drug: Minoxidil (generic, Loniten ®) |
| Drug Class: Vasodilator |
| Mechanism of Action: Dialates arterioles but not veins. Opens potassium channels in smooth muscle membranes which stabilizes the membrane at hyperpolarized potentials, making contraction less likely. The effect is produced by minoxidil sulfate, the active metabolite. |
| Indications: Typically not a drug used for initial therapy of hypertension. Must be used with a beta blocker and a loop diuretic to reduce reflex sympathetic stimulation & Na & fluid retention. Because of the potential for serious adverse effects, minoxidil tablets are indicated only in the treatment of hypertension that is symptomatic or associated with target organ damage and is not manageable with maximum therapeutic doses of a diuretic plus two other antihypertensive drugs. |
| Contraindications: pheochromocytoma, because it may stimulate secretion of catecholamines from the tumor through its antihypertensive action |
| Pharmacokinetics: Oral administration for treatment of hypertension, or topical administration (Rogaine ®) to stimulate hair growth. |
| Side Effects: tachycardia, palpitations, angina & edema are observed when doses of beta blockers & diuretics are inadequate. Headache, sweating & hirsutism (hair growth) that is most bothersome in women. |
Reference: www.rxlist.com & Katzung's text |
| Drug: Enalapril (Vasotec ®), Lisinopril (Prinivil, Zestril ®) |
| Drug Class: ACE Inhibitors, Antihypertensive |
| Mechanism of Action: Inhibit peptidyl dipeptidase (Angiotensin Converting Enzyme). |
| Indications: Treatment of normal renin & high renin hypertension, useful for CHF, possibly prevents glomerular damage in diabetes. |
| Side Effects: acute renal failure in patients with bilateral renal artery stenosis, hyperkalemia due to aldosterone suppression, allergic respons to sulfhydryl group on captopril, severe hypotension in patients who are hypovolemic due to diuretics, salt restriction of GI fluid loss. Dry cough (believed to be caused by bradykinin & substance P). |
| Contraindications: When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. |
Drug Interactions: potassium supplements or K-sparing diuretics can result in hyperkalemia. NSAIDs may impair the hypotensive effect by blocking bradykinin-mediated vasodilation (mediated at least in part by PGs). |
| Reference: Katzung's text & Kadowitz's handout |