Drugs to Treat Hypertension

  1. Primary (essential) hypertension
    • –most common form
    • –no identifiable cause
    • –a chronic progressive disorder
    • –drugs lower BP but do NOT treat underlying cause
  2. Secondary hypertension
    • –has identified primary cause
    • –some people can be cured by treating cause
  3. Consequences of Hypertension
    • •heart disease (left ventricular hypertrophy, myocardial infarction, angina pectoris)
    • •kidney disease
    • •blindness and stroke
    • •degree of injury related to degree of elevation
    • •injury can occur during asymptomatic stage
  4. Management of Essential Hypertension I: Lifestyle Modifications
    • •weight reduction—leads to a reduction in blood pressure in 60%–80% of overweight people, restrict calories and keep fat intake <30% of diet; body mass index (BMI) should be ≤ 27
    • •sodium restriction—can decrease blood pressure and enhance drug therapy
    • •alcohol restriction—excessive intake increases blood pressure; limit to 1 oz/day
    • •exercise—regular exercise can decrease blood pressure by 10 mm Hg
    • •smoking cessation—smoking is a major risk for cardiovascular disease and may impair the ability of antihypertensives to protect against cardiovascular disease; benefits seen by 1 year after stopping
    • •maintenance of potassium and calcium intake—
    • –potassium lowers blood pressure
    • –calcium is needed for overall good health but has only a modest effect on blood pressure
  5. Sympathetic baroreceptor reflex
    reflex circuit (baroreceptor reflex) keeps arterial pressure at preset level on a second-by second basis; opposes attempts to reduce arterial pressure with drugs
  6. Alpha 1
    adrenergic receptors cause vasoconstriction
  7. Alpha 2
    adrenergic receptors act both in the brain and in the periphery in a feedback inhibitory manner to decrease sympathetic tone
  8. Beta 1
    adrenergic receptors increase heart rate and contractility, and stimulate renin secretion by the kidneys
  9. Beta 2
    • adrenergic receptors dilate skeletal muscle vasculature during fight or flight response
    • •with concomitant a1-receptor mediated vasoconstriction in the organs, blood is shunted to the muscles
  10. Renal regulation of blood pressure
    • –a decrease in arterial pressure decreases GFR, which promotes retention of sodium, chloride, and water to increase blood volume
    • –increased blood volume increases venous return to the heart, which increases cardiac output and arterial pressure
    • –these actions opposes the renal effects of diuretics and other agents that act on the vasculature to lower arterial pressure
  11. Diuretics—Mainstay of antihypertensive therapy:
    thiazides: hydrochlorothiazide
    • –most commonly used, as monotherapy or in combination
    • –work by reduction of blood volume and arterial resistance (a direct effect on vasculature)
    • –adverse effects: hypokalemia, dehydration, hyperglycemia, and hyperuricemia
  12. Diuretics—Mainstay of antihypertensive therapy:
    loop diuretics (high ceiling):furosemide
    • –reserved for patients requiring greater diuresis than with thiazides, and for patients with low GFR
    • –adverse effects: hypokalemia, dehydration, hyperglycemia, and hyperuricemia; also a risk of hearing loss
  13. Diuretics—Mainstay of antihypertensive therapy
    potassium-sparing diuretics … triamterene or spironolactone
    • –least effective but balance the potassium loss by thiazides or loop diuretics
    • –most significant adverse effect is hyperkalemia, do NOT use with potassium supplements or with ACE inhibitors
  14. Sympatholytics
    suppress influence of sympathetic nervous system on heart, blood vessels, and other structures
  15. Sympatholytics:
    b-adrenergic blockers (non-selective propranolol is prototype, metoprolol has b1 selectivity)
    • –goal is to block the b1 receptors that increase heart rate, myocardial contractility and renal renin secretion
    • –most widely used of the sympatholytic drugs
    • –some drugs have Intrinsic Sympathomimetic Activity (means they are partial agonists, can’t block “too much”)
    • –can cause bradycardia and heart block, and other non-cardiac adverse effects including depression, insomnia, bizarre dreams and sexual dysfunction
  16. Sympatholytics:
    Centrally-acting a2 agonists (clonidine is the prototype)
    • –these agents act in the brain to decreases sympathetic nervous system tone
    • –dry mouth and sedation are major adverse effects
  17. Sympatholytics:
    a1-adrenergic antagonists (prazosin is the prototype)
    • –these agents block the principal receptors causing vasoconstriction
    • –orthostatic hypotension is a major adverse effect, can be especially pronounced with the first dose
  18. Sympatholytics:
    a1/b blockers
    combine both the benefits and adverse effects of the selective receptor blockers
  19. Sympatholytics:
    adrenergic neuron blockers
    –only used in special cases due to adverse effects (severe orthostatic hypotension in the case of the norepinephrine release inhibitors, guanethidine and guanadrel, and severe depression in case of the neurotransmitter depleter, reserpine)
  20. Direct-acting vasodilators
    • —decrease blood pressure by dilating arterioles
    • –these agents cannot be used as monotherapy due to salt and water retention (i.e., must also take a diuretic)
    • –hydralazine can cause a lupus-like syndrome while minoxidil can cause pericardial effusion/cardiac tamponade
  21. Calcium channel blockers
    • —decrease blood pressure by dilating arterioles
    • –the dihydropyridines (e.g., nifedipine) are the best vasodilators, but can cause significant ankle edema and reflex tachycardia requiring the addition of a diuretic and b-adrenergic blocker, respectively
  22. Angiotensin converting enzyme (ACE) inhibitors
    • •lower blood pressure by preventing conversion of angiotensin I to its active form, angiotensin II… (e.g., captopril)
    • –adverse effects are persistent cough, first-dose hypotension, and hyperkalemia –cause fetal harm during the 2nd and 3rd trimesters of pregnancy
  23. Angiotensin II receptor antagonists (ARBs)
    • •work very much like ACE inhibitors, but block action of angiotensin II at its receptors (e.g., losartan)
    • –relatively devoid of serious adverse effects (can cause angioedema), but also are harmful to a 2nd and 3rd trimester fetus
    • –considerably more expensive than “off patent” diuretics and b-blockers
  24. Direct renin inhibitors (aliskiren)
    –newest, less adverse effects than ACE inhibitors but do cause fetal harm, role is emerging
  25. Patients in Special Populations:
    African Americans
    hypertension is a major health problem, lifestyle changes most important; b-blockers and ACE inhibitors are less effective than in whites but other drugs work well
  26. Patients in Special Populations
    Children and adolescents
    secondary hypertension is more prevalent than in adults so attempt to treat cause; do NOT give ACE inhibitors or ARBs to sexually active girls
  27. Patients in Special Populations:
    older adults
    •65% incidence in people over age 60, with increased prevalence of isolated systolic hypertension; use b-blockers and diuretics to decrease risk of stroke and myocardial infarction
  28. Ways to promote compliance
    • •educate the patient
    • •teach self-monitoring
    • •minimize side effects (e.g., don’t take diuretics at bedtime J)
    • •establish a collaborative relationship
    • •simplify the regimen, and try to keep the drugs affordable (e.g., off-patent diuretics and b-blockers)
    • •other measures—give positive reinforcement, involve family members, schedule convenient office visits, and follow up missed appointments
  29. Drugs for Hypertensive Emergencies:
    •When DBP >120 mm Hg, the elevated blood pressure can cause papilledema, intracranial hemorrhage, myocardial infarction, and/or acute congestive heart failure
    • –if the increase occurred abruptly, an emergency exists and need to decrease blood pressure quickly (< 1 hr)
    • –if no obvious crisis, reduce blood pressure over a few days
  30. Drugs for Hypertensive Emergencies:
    Sodium nitroprusside
    • –the mainstay for acute, severe hypertension demanding a rapid but controlled reduction in blood pressure
    • •a direct-acting vasodilator that relaxes smooth muscle of arterioles and veins
    • •effects begin immediately and fade fast when drug is discontinueddo not use longer than 72 hours or toxic effects can occur
  31. Drugs for Hypertensive Emergencies
    5-min half-life, causes dilation by activating peripheral dopamine receptors on arterioles
  32. Drugs for Hypertensive Emergencies
    —blocks a and b adrenergic receptors
  33. Drugs for Hypertensive Emergencies
    —calcium channel blocker approved 2008 with ultrashort half-life
  34. Drugs for Hypertensive Disorders of Pregnancy:
    chronic hypertension
    • –present prior to pregnancy or before 20th week of gestation
    • •goal is to minimize risk of hypertension to mother
    • •ACE inhibitors and ARBs are contraindicated during pregnancy because of fetal harm continue drugs previously used or start methyldopa
  35. Drugs for Hypertensive Disorders of Pregnancy
    • –develops after 20th week of pregnancy:
    • •characterized by increased blood pressure, proteinuria, and generalized edema; may see liver dysfunction and coagulation abnormalities
    • •preeclampsia can progress to a convulsive phase (= eclampsia)
    • –if close to term, treat with delivery
    • –otherwise, use hydralazine (5 mg bolus) and repeat 3 times every 20 minutes; if pressure is too high, may need nifedipine or labetalol
    • –may also need to treat with anticonvulsants such as magnesium sulfate
Card Set
Drugs to Treat Hypertension
Pharm: Drugs to Treat Hypertension