Al-Kut University College Pharmacology Lectures 2022 PDF

# 1440هـ 2018م ## Al- Kut university collage ### Pharmacology Lectures #### 2022 #### Fourth stage #### By Dr. Taif M Maruish ##### BSc Pharm., MSc.(Pharmacology & Toxicology), Ph.D. ##### Pharmacology & Toxicology ### Antihypertensive Drugs #### Lec 5 #### 5/10/2022 # 11/1/2022 ## Diuretics ### Am...

# 1440هـ 2018م ## Al- Kut university collage ### Pharmacology Lectures #### 2022 #### Fourth stage #### By Dr. Taif M Maruish ##### BSc Pharm., MSc.(Pharmacology & Toxicology), Ph.D. ##### Pharmacology & Toxicology ### Antihypertensive Drugs #### Lec 5 #### 5/10/2022 # 11/1/2022 ## Diuretics ### Amiloride MIDAMOR ### Bumetanide BUMEX ### Chlorthalidone GENERIC ONLY ### Eplerenone INSPRA ### Ethacrynic acid EDECRIN ### Furosemide LASIX ### Hydrochlorothiazide MICROZIDE ### Indapamide GENERIC ONLY ### Metolazone GENERIC ONLY ### Spironolactone ALDACTONE ### Triamterene DYRENIUM ### Torsemide DEMADEX ## B-Blockers ### Acebutolol GENERIC ONLY ### Atenolol TENORMIN ### Betaxolol GENERIC ONLY ### Bisoprolol GENERIC ONLY ### Carvedilol COREG, COREG CR ### Esmolol BREVIBLOC ### Labetalol TRANDATE ### Metoprolol LOPRESSOR, TOPROL-XL ### Nadolol CORGARD ### Nebivolol BYSTOLIC ### Pindolol GENERIC ONLY ### Propranolol INDERAL LA, INNOPRAN XL ## ACE INHIBITORS ### Benazepril LOTENSIN ### Captopril GENERIC ONLY ### Enalapril VASOTEC ### Fosinopril GENERIC ONLY ### Lisinopril PRINIVIL, ZESTRIL ### Moexipril GENERIC ONLY ### Quinapril ACCUPRIL ### Perindopril GENERIC ONLY ### Ramipril ALTACE ### Trandolapril GENERIC ONLY ## Angiotensin II ### Receptor Blockers ### Azilsartan EDARBI ### Candesartan ATACAND ### Eprosartan GENERIC ONLY ### Irbesartan AVAPRO ### Losartan COZAAR ### Olmesartan BENICAR ### Telmisartan MICARDIS ### Valsartan DIOVAN ## Renin Inhibitors ### Aliskiren TEKTURNA # Hypertension Hypertension is defined as either a sustained systolic blood pressure of greater than 140 mm Hg or a sustained diastolic blood pressure of greater than 90 mm Hg. Hypertension results from increased peripheral vascular arteriolar smooth muscle tone, which leads to 1. increased arteriolar resistance 2. Reduced capacitance of the venous system. In most cases, the cause of the increased vascular tone is unknown. Elevated blood pressure is a common disorder, affecting approximately 30% of adults in the United States. Although many patients have no symptoms, chronic hypertension can lead to heart disease and stroke. # 11/1/2022 Hypertension is also an important risk factor in the development of chronic kidney disease and heart failure. The incidence of morbidity and mortality significantly decreases when hypertension is diagnosed early and is properly treated. Hypertension is classified into four categories for the purpose of treatment management. | Systolic mm Hg | Diastolic mm Hg | |:---:|:---:| | <<120 | <80 | | 120-129 | <80 | | 130-139 | 80-89 | | ≥140 | ≥90 | ### Figure 16.2 ### Classification of blood pressure # Etiology of Hypertension Although hypertension may occur secondary to other disease processes, more than 90% of patients have essential hypertension (hypertension with no identifiable cause). A family history of hypertension increases the likelihood that an individual will develop hypertension. The prevalence of hypertension increases with age but decreases with education and income level. Non-Hispanic blacks have a higher incidence of hypertension than do both non-Hispanic whites and Hispanic whites. Persons with diabetes, obesity, or disability status are all more likely to have hypertension than those without these conditions. In addition, environmental factors, such as a stressful lifestyle, high dietary intake of sodium, and smoking, may further predispose an individual to hypertension. # 11/1/2022 # 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 arterial intima (endothelium). Cardiac output depend on heart rate and stroke volume ### Figure 16.3 ### Major factors influencing blood pressure. # To regulate the Arterial blood pressure we need to control: 1. Cardiac output 2. Peripheral vascular resistance. Cardiac output and peripheral resistance are controlled mainly by 1. The baroreflexes and the sympathetic nervous system 2. The renin-angiotensin-aldosterone system. Most antihypertensive drugs lower blood pressure by 1. Reducing cardiac output. 2. Decreasing peripheral resistance. # 11/1/2022 # A. Baroreceptors and the sympathetic nervous system Baroreflexes act by changing the activity of the sympathetic nervous system. Therefore, they are responsible for the rapid, moment-to moment regulation of blood pressure. A fall in blood pressure causes pressure sensitive neurons (baroreceptors in the aortic arch and carotid sinuses) to send fewer impulses to cardiovascular centers in the spinal cord. This prompts a reflex response of increased sympathetic and decreased parasympathetic output to the heart and vasculature, resulting in vasoconstriction and increased cardiac output. ### Figure 16.4 ### Response of the autonomic nervous system and the renin-angiotensin-aldosterone system to a decrease in blood pressure # B. Renin-angiotensin-aldosterone system The kidney provides long-term control of blood pressure by altering the blood volume. Baroreceptors in the kidney respond to reduced arterial pressure (and to sympathetic stimulation of ẞ1-adrenoceptors) by releasing the enzyme renin. Low sodium intake and greater sodium loss also increase renin release. Renin converts angiotensinogen to angiotensin I, which is converted in turn to angiotensin II, in the presence of angiotensin-converting enzyme (ACE). Angiotensin II cause 1. Vasoconstrictor, constricting both arterioles and veins, resulting in an increase in blood pressure. 2. Preferential vasoconstrictor action on the efferent arterioles of the renal glomerulus, increasing glomerular filtration. 3. Stimulates aldosterone secretion, leading to increased renal sodium reabsorption and increased blood volume, which contribute to a further increase in blood pressure. # TREATMENT STRATEGIES The goal of antihypertensive therapy is to reduce cardiovascular and renal morbidity and mortality. For most patients, the blood pressure goal when treating hypertension is a systolic blood pressure of less than 130 mm Hg and a diastolic blood pressure of less than 80 mm Hg. Current recommendations are to initiate therapy with a thiazide diuretic, ACE inhibitor, angiotensin receptor blocker (ARB), or calcium channel blocker. However, initial drug therapy choice may vary depending on the guideline and concomitant diseases # 11/1/2022 ### Figure 16.6 ### Treatment of hypertension in patients with concomitant diseases. [Note: Angiotensin receptor blockers (ARBs) are an alternative to angiotensin converting enzyme (ACE) inhibitors.] # DIURETICS Thiazide diuretics can be used as initial drug therapy for hypertension unless there are compelling reasons to choose another agent. Regardless of class, the initial mechanism of action of diuretics is based upon decreasing blood volume, which ultimately leads to decreased blood pressure. Low-dose diuretic therapy is safe, inexpensive, and effective in preventing stroke, myocardial infarction, and heart failure. Routine serum electrolyte monitoring should be done for all patients receiving diuretics # A. Thiazide diuretics Thiazide diuretics, such as hydrochlorothiazide and chlorthalidone lower blood pressure initially by increasing sodium and water excretion. This causes a decrease in extracellular volume, resulting in a decrease in cardiac output and renal blood flow. With long-term treatment, plasma volume approaches a normal value, but a hypotensive effect persists that is related to a decrease in peripheral resistance. Thiazides are useful in combination therapy with a variety of other antihypertensive agents, including B-blockers, ACE inhibitors, ARBs, and potassium-sparing diuretics. With the exception of metalazone thiazide diuretics are not effective in patients with inadequate kidney function (estimated glomerular filtration rate less than 30 mUmin/m2). Loop diuretics may be required in these patients. Thiazide diuretics can induce hypokalemia, hyperuricemia, and, to a lesser extent, hyperglycemia in some patients. ### Figure 16.7 ### Actions of thiazide diuretics. # 11/1/2022 # B. Loop diuretics The loop diuretics (furosemide, torsemide, bumetanide, and Ethacrynic acid act promptly by blocking sodium and chloride reabsorption in the kidneys, even in patients with poor renal function or those who have not responded to thiazide diuretics. Loop diuretics cause decreased renal vascular resistance and increased renal blood flow. Like thiazides, they can cause hypokalemia. However, unlike thiazides, loop diuretics increase the calcium content of urine, whereas thiazide diuretics decrease it. These agents are rarely used alone to treat hypertension, but they are commonly used to manage symptoms of heart failure and edema. # C. Potassium-sparing diuretics Amiloride and triamterene are inhibitors of epithelial sodium transport at the late distal and collecting ducts, and spironolactone and eplerenone are aldosterone receptor antagonists. All of these agents reduce potassium loss in the urine. Aldosterone antagonists have the additional benefit of diminishing the cardiac remodeling that occurs in heart failure Potassium-sparing diuretics are sometimes used in combination with loop diuretics and thiazides to reduce the amount of potassium loss induced by these diuretics. # ADRENOCEPTOR-BLOCKING AGENTS ẞ-Blockers are a treatment option for hypertensive patients with concomitant heart disease or heart failure. ## A. Actions The B-blockers reduce blood pressure primarily by decreasing cardiac output. They may also decrease sympathetic outflow from the central nervous system (CNS) and inhibit the release of renin from the kidneys, thus decreasing the formation of angiotensin II and the secretion of aldosterone. The prototype ẞ-blocker is propranolol, which acts at both ẞ1 and ẞ2 receptors. Selective blockers of ẞ1 receptors, such as metoprolol and atenolol, are among the most commonly prescribed β-blockers. Nebivolol is a selective blocker of ẞ-1 receptors, which also increases the production of nitric oxide, leading to vasodilation. The selective ẞ-blockers may be administered cautiously to hypertensive patients who also have asthma. The non- selective ẞ-blockers are contraindicated in patients with asthma due to their blockade of ẞ-mediated bronchodilation. β-Blockers should be used cautiously in the treatment of patients with acute heart failure or peripheral vascular disease ## Pharmacokinetics The B-blockers are orally active for the treatment of hypertension. Propranolol undergoes extensive and highly variable first-pass metabolism. Oral ẞ- blockers may take several weeks to develop their full effects. Esmolol, metoprolol, and propranolol are available in intravenous formulations. # 11/1/2022 ## Adverse effects 1. Common effects: The ẞ- blockers may decrease libido and cause erectile dysfunction, which can severely reduce patient compliance. 2. Alterations in serum lipid patterns: Non cardioselective ẞ- blockers may disturb lipid metabolism, decreasing high-density lipoprotein cholesterol and increasing triglycerides. 3. Drug withdrawal: Abrupt withdrawal may induce severe hypertension, angina, myocardial infarction, and even sudden death in patients with ischemic heart disease. Therefore, these drugs must be tapered over a few weeks in patients with hypertension and ischemic heart disease ### Figure 16.9 ### Some adverse effects of B-blockers. ## Beta-Blockers | | Negative ISA | Positive ISA | |:----------|:-------------|:------------:| | Non-selective | -Propranolol | -Pindolol | | | -Sotalol | -Oxprenolol | | | -Timolol | | | Selective | -Atenolol | -Celiprolol | | | -Metoprolol | -Acebutolol | | | -Bisoprolol | | | With alpha-blocking activity | -Carvedilol | -Labetalol | ### Figure 16.8 ### Actions of ẞ-adrenoceptor-blocking agents. # Therapeutic uses The primary therapeutic benefits of B-blockers are seen in - Hypertensive patients with concomitant heart disease, such as supraventricular tachyarrhythmia {for example, atrial fibrillation), - previous myocardial infarction, - stable ischemic heart disease, and - chronic heart failure. Conditions that discourage the use of B-blockers include - reversible bronchospastic disease such as asthma, - second- and third-degree heart block, and - severe peripheral vascular disease. # ACE INHIBITORS ACE inhibitors such as captopril, enalapril, and lisinopril are recommended as first-line treatment of hypertension in patients with a variety of compelling indications, including high coronary disease risk or history of diabetes, stroke, heart failure, myocardial infarction, or chronic kidney disease. ## A. Actions The ACE inhibitors lower blood pressure by reducing peripheral vascular resistance without reflexively increasing cardiac output, heart rate, or contractility. These drugs block the enzyme ACE, which cleaves angiotensin I to form the potent vasoconstrictor angiotensin II ACE is also responsible for the breakdown of bradykinin, a peptide that increases the production of nitric oxide and prostacyclin by the blood vessels. Both nitric oxide and prostacyclin are potent vasodilators. Vasodilation of both arterioles and veins occurs as a result of decreased vasoconstriction (from diminished levels of angiotensin II) and enhanced vasodilation (from increased bradykinin). ACE inhibitors also decrease the secretion of aldosterone, resulting in decreased sodium and water retention. ACE inhibitors reduce both cardiac preload and afterload, thereby decreasing workload on the heart. ## __B.__ Therapeutic uses ACE inhibitors slow the progression of diabetic nephropathy and decrease albuminuria and, thus, have a compelling indication for use in patients with diabetic nephropathy. Beneficial effects on renal function may result from decreasing intraglomerular pressures, due to efferent arteriolar vasodilation. ACE inhibitors are a standard in the care of a patient following a myocardial infarction and first-line agents in the treatment of patients with systolic dysfunction. # 11/1/2022 ## __B.__ Therapeutic uses. Chronic treatment with ACE inhibitors achieves sustained blood pressure reduction, regression of left ventricular hypertrophy, and prevention of ventricular remodeling after a myocardial infarction. ACE inhibitors are first-line drugs for treating heart failure, hypertensive patients with chronic kidney disease, and patients at increased risk of coronary artery disease. All of the ACE inhibitors are equally effective in the treatment of hypertension at equivalent doses. # Pharmacokinetics All of the ACE inhibitors are orally bioavailable as a drug or prodrug. All but captopril and lisinopril undergo hepatic conversion to active metabolites, so these agents may be preferred in patients with severe hepatic impairment. Fosinopril is the only ACE inhibitor that is not eliminated primarily by the kidneys. Therefore, it does not require dose adjustment in patients with renal impairment. Enalaprilat is the only drug in this class available intravenously. ## Adverse effects 1-The dry cough, which occurs in up to 10% of patients, is thought to be due to increased levels of bradykinin and substance P in the pulmonary tree, and it occurs more frequently in women. The cough resolves within a few days of discontinuation. 2-Angioedema is a rare but potentially life-threatening reaction that may also be due to increased levels of bradykinin. 3-Potassium levels must be monitored while on ACE inhibitors, and potassium supplements and potassium- sparing diuretics should be used with caution due to the risk of hyperkalemia. 4-Serum creatinine levels should also be monitored, particularly in patients with underlying renal disease. However, an increase in serum creatinine of up to 30% above baseline is acceptable and by itself does not warrant discontinuation of treatment. 5-ACE inhibitors can induce fetal malformations and should not be used by pregnant women. ### Figure 16.10 ### Effects of various drug classes on the renin-angiotensin-aldosterone system. Blue = drug target enzymes; red = drug class. ### Figure 16.11 ### Some common adverse effects of the ACE inhibitors. # ANGIOTENSIN II RECEPTOR BLOCKERS The ARBs, such as losartan and irbesartan, block the AT1 receptors, decreasing the activation of AT1 receptors by angiotensin II. Their pharmacologic effects are similar to those of ACE inhibitors in that they produce arteriolar and venous dilation and block aldosterone secretion, thus lowering blood pressure and decreasing salt and water retention ARBs do not increase bradykinin levels. They may be used as first-line agents for the treatment of hypertension, especially in patients with a compelling indication of diabetes, heart failure, or chronic kidney disease Adverse effects are similar to those of ACE inhibitors, although the risks of cough and angioedema are significantly decreased. ARBs should not be combined with an ACE inhibitor for the treatment of hypertension due to similar mechanisms and adverse effects. These agents are also teratogenic and should not be used by pregnant women. # RENIN INHIBITOR A selective renin inhibitor, aliskiren is available for the treatment of hypertension. Aliskiren directly inhibits renin and, thus, acts earlier in the renin-angiotensin-aldosterone system than ACE inhibitorsor ARBs. Aliskiren should not be combined with an ACE inhibitor or ARB in the treatment of hypertension. Aliskiren can cause diarrhea, especially at higher doses. It also causes cough and angioedema but less often than ACE inhibitors. As with ACE inhibitors and ARBs, Aliskiren is contraindicated during pregnancy. Aliskiren is metabolized by CYP3A4 and is subject to many drug interactions. # 11/1/2022 # CALCIUM CHANNEL BLOCKERS Calcium channel blockers are a recommended first-line treatment option in black patients. They may also be useful in hypertensive patients with diabetes or angina. High doses of short-acting calcium channel blockers should be avoided because of increased risk of myocardial infarction due to excessive vasodilation and marked reflex cardiac stimulation. ## A. Classes of calcium channel blockers The calcium channel blockers are divided into three chemical classes, each with different pharmacokinetic properties and clinical indications | | | |:----------------|:--------------------| | Calcium channel blockers | | | Phenilalkylamines | Verapamil | | Benzothiazepines | Diltiazem | | | | | | 1 st generation | | | Nifedipine | | | | | Dihydropyridines | 2nd generation | | | Isradipine | | | Nicardipine | | | Felodipine | | | | | | 3rd generation | | | Amlodipine | # 1. Diphenylalkylamines: Verapamil is the only member of this class that is available in the United States. Verapamil has significant effects on both cardiac and vascular smooth muscle cells. It is also used to treat angina and supraventricular tachyarrhythmias and to prevent migraine and cluster headaches. ### Figure 16.12 ### Actions of calcium channel blockers. ### AV = atrioventricular. # 2. Benzothiazepines: Diltiazem is the only member of this class that is currently approved in the United States. Like verapamil, diltiazem affects both cardiac and vascular smooth muscle cells, but it has a less pronounced negative inotropic effect on the heart compared to that of verapamil. Diltiazem has a favorable side effect profile. # 3. Dihydropyridines: This class of calcium channel blockers includes nifedipine (the prototype), amlodipine, felodipine,isradipine ,nicardipine,and nisoldipine. These agents differ in pharmacokinetics, approved uses, and drug interactions. All dihydropyridines have a much greater affinity for vascular calcium channels than for calcium channels in the heart. They are, therefore, particularly beneficial in treating hypertension. The dihydropyridines have the advantage in that they show little interaction with other cardiovascular drugs, such as digoxin or warfarin, which are often used concomitantly with calcium channel blockers. # 11/1/2022 ## Actions The intracellular concentration of calcium plays an important role in * maintaining the tone of smooth muscle * and in the contraction of the myocardium. Calcium channel antagonists block the inward movement of calcium by binding to L-type calcium channels in the heart and in smooth muscle of the coronary and peripheral arteriolar vasculature. This causes vascular smooth muscle to relax, dilating mainly arterioles. Calcium channel blockers do not dilate veins. ## C. Therapeutic uses In the management of hypertension, CCBs may be used as an initial therapy or as add-on therapy. They are useful in the treatment of - hypertensive patients who also have asthma, - diabetes, and/or - peripheral vascular disease, because unlike B-blockers, they do not have the potential to adversely affect these conditions. All CCBs are useful in the treatment of angina. In addition, diltiazem and verapamil are used in the treatment of atrial fibrillation. # 11/1/2022 ## D. Pharmacokinetics Most of these agents have short half-lives (3 to 8 hours} following an oral dose. Sustained-release preparations are available and permit once-daily dosing. Amlodipine has a very long half-life and does not require a sustained-release formulation. ## Adverse effects - First-degree atrioventricular block and constipation are common dose-dependent side effects of verapamil. - Verapamil and diltiazem should be avoided in patients with heart failure or with atrioventricular block due to their negative inotropic (force of cardiac muscle contraction}and dromotropic (velocity of conduction} effects. - Dizziness, headache, and a feeling of fatigue caused by a decrease in blood pressure are more frequent with dihydropyridines - Peripheral edema is another commonly reported side effect of this class. - Nifedipine and other dihydropyridines may cause gingival hyperplasia. ### Figure 16.13 ### Some common adverse effects of the calcium channel blockers. # 11/1/2022 # a-ADRENOCEPTOR-BLOCKING AGENTS - a- Adrenergic blockers used in the treatment of hypertension include prazosin, doxazosin, and terazosin. - These agents produce a competitive block of a1-adrenoceptors. - They decrease peripheral vascular resistance and lower arterial blood pressure by causing relaxation of both arterial and venous smooth muscle. - These drugs cause only minimal changes in cardiac output, renal blood flow, and glomerular filtration rate. Therefore, long-term tachycardia does not occur, but salt and water retention does. # α-ADRENOCEPTOR-BLOCKING AGENTS Reflex tachycardia and postural hypotension often occur at the onset of treatment and with dose increases, requiring slow titration of the drug in divided doses. Due to weaker outcome data and their side effect profile, a-blockers are no longer recommended as initial treatment for hypertension but may be used for refractory cases. a1-blockers with greater selectivity for the prostate are used in the treatment of benign prostatic hyperplasia # 11/1/2022 # α/β -ADRENOCEPTOR-BLOCKING AGENTS - Labetalol and carvedilol block a1, ẞ1, and ẞ2 receptors. - Carvedilol, although an effective antihypertensive, is mainly used in the treatment of heart failure. - Carvedilol, as well as metoprolol succinate, and bisoprolol have been shown to reduce morbidity and mortality associated with heart failure. - Labetalol is used in the management of gestational hypertension and hypertensive emergencies. # CENTRALLY ACTING ADRENERGIC DRUGS ## A. Clonidine Clonidine acts centrally as an a2 agonist to produce inhibition of sympathetic vasomotor centers, decreasing sympathetic outflow to the periphery. This leads to reduced total peripheral resistance and decreased blood pressure. Clonidine is used primarily for the treatment of hypertension that has not responded adequately to treatment with two or more drugs. Clonidine does not decrease renal blood flow or glomerular filtration and, therefore, is useful in the treatment of hypertension complicated by renal disease. Clonidine is well absorbed after oral administration and is excreted by the kidney. It is also available in a transdermal patch. ## Adverse effects include - sedation, dry mouth, and constipation, - Rebound hypertension occurs following abrupt withdrawal of clonidine. - The drug should, therefore, be withdrawn slowly if discontinuation is required. ### Figure 16.14 ### Some adverse effects of clonidine. # 11/1/2022 ## B. Methyldopa Methyldopa is an a2 agonist that is converted to methylnorepinephrine centrally to diminish adrenergic outflow from the CNS. The most common side effects of methyldopa are sedation and drowsiness. Its use is limited due to adverse effects and the need for multiple daily doses. It is mainly used for management of hypertension in pregnancy, where it has a record of safety. # VASODILATORS - The direct-acting smooth muscle relaxants, such as hydralazine and minoxidil, are not used as primary drugs to treat hypertension. - These vasodilators act by producing relaxation of vascular smooth muscle, primarily in arteries and arterioles. This results in decreased peripheral resistance and, therefore, blood pressure. - Both agents produce reflex stimulation of the heart, resulting in the competing reflexes of increased myocardial contractility, heart rate, and oxygen consumption. # VASODILATORS - These actions may prompt angina pectoris, myocardial infarction, or cardiac failure in predisposed individuals. - Vasodilators also increase plasma renin concentration, resulting in sodium and water retention. - These undesirable side effects can be blocked by concomitant use of a diuretic (to decrease sodium retention} and a B-blocker (to balance the reflex tachycardia}. # Hydralazine Hydralazine is an accepted medication for controlling blood pressure in pregnancy induced hypertension. Adverse effects of hydralazine include headache, tachycardia, nausea, sweating, arrhythmia, and precipitation of angina - A lupus-like syndrome can occur with high dosages, but it is reversible upon discontinuation of the drug. - Minoxidil treatment causes hypertrichosis (the growth of body hair). This drug is used topically to treat male pattern baldness. ### Figure 16.15 ### Some adverse effects of hydralazine. # HYPERTENSIVE EMERGENCY - Hypertensive emergency is a rare but life-threatening situation characterized by severe elevations in blood pressure (systolic greater than 180 mm Hg or diastolic greater than 120 mm Hg) with evidence of impending or progressive target organ damage (for example, stroke, myocardial infarction). - [Note: A severe elevation in blood pressure without evidence of target organ damage is considered a hypertensive urgency.] - Hypertensive emergencies require timely blood pressure reduction with treatment administered intravenously to prevent or limit target organ damage. # 11/1/2022 - A variety of medications are used, including calcium channel blockers (nicardipine and clevidipine), nitric oxide vasodilators (nitroprusside and nitroglycerin), adrenergic receptor antagonists (phentolamine, esmolol, and labetalol. the vasodilator hydralazine, and the dopamine agonist fenoldopam. - Treatment is directed by the type of target organ damage and/or comorbidities present. # RESISTANT HYPERTENSION - Resistant hypertension is defined as blood pressure that remains elevated (above goal) despite administration of an optimal three-drug regimen that includes a diuretic. - The most common causes of resistant hypertension are poor compliance, excessive ethanol intake, concomitant conditions (diabetes, obesity, sleep apnea, hyperaldosteronism, high salt intake, and/or metabolic syndrome), concomitant medications (sympathomimetics, nonsteroidal anti-inflammatory drugs, or corticosteroids), insufficient dose and/or drugs, and use of drugs with similar mechanisms of action. # 11/1/2022 60 ==End of OCR for page 30==