www.pharmaqz.com 1

HYPERTENSION DENNIS GEORGE

CONSULTANT PHARMACIST

www.pharmaqz.com

www.pharmaqz.com 2

Hypertension

Hypertension is blood pressure elevated enough to perfuse tissues and organs

Primary (or essential) hypertension, in which no specific cause can be identified, constitutes 90% of all cases of systemic hypertension. Th e average age of onset is about 35 years.

Secondary hypertension, resulting from an identifiable cause, such as renal disease or adrenal hyperfunction,

www.pharmaqz.com 3

CLASSIFICATION

www.pharmaqz.com 4

Blood pressure = (stroke volume X heart rate) X total peripheral vascular resistance (TPR)

www.pharmaqz.com 5

Predisposing factors

a. Family history of essential hypertension, stroke, and premature cardiac disease.

b. Patient history of intermittent elevations in blood pressure.

c. Racial predisposition. Hypertension is more common among African Americans than

Whites.

d. Obesity. Weight reduction has been shown to reduce blood pressure in a large proportion of

hypertensive patients who are 10% above ideal body weight.

e. Smoking, resulting in vasoconstriction and activation of the sympathetic nervous system, is a

major risk factor for cardiovascular disease.

www.pharmaqz.com 6

Predisposing factors

f. Stress

g. High dietary intake of saturated fats or sodium

h. Sedentary lifestyle

i. Diabetes mellitus

j. Hyperlipidemia

k. Major risk factors according to the JNC-7 include smoking, diabetes mellitus, age ( 55 for

men; 65 for women), family history of cardiovascular disease, and dyslipidemia.

l. Target-organ damage/clinical cardiovascular disease according to the JNC-7 includes heart

disease (e.g., left ventricular hypertrophy, angina, prior MI, heart failure), stroke or transient

ischemic attacks, nephropathy, peripheral artery disease, and retinopathy.

www.pharmaqz.com 7

Treatment

Candidates for treatment

(1) All patients with a diastolic pressure of 90 mm Hg, a systolic pressure of 140 mm Hg,or a combination of both should receive antihypertensive drug therapy.

(2) For those patients with a diastolic pressure of 80 to 89 mm Hg or a systolic pressure of 120 to 139 mm Hg (prehypertension), no drug treatment is indicated unless the patient has a compelling indication. However, lifestyle modifications, such as weight reduction, dietary sodium reduction, increased physical activity, and moderation of alcohol consumption, should be initiated.

For patients with hypertension who have diabetes or renal disease, the blood pressure goal recommended by the JNC-7 is 130/80 mm Hg.

www.pharmaqz.com 8

Pharmacological treatment

most hypertensive patients will require two or more antihypertensive drugs.

Thiazide diuretics should be considered initial agents for treatment unless there are compelling indications for other medications.

Agents such as ACE inhibitors, angiotensin-receptor blockers, -blockers, and calcium channel blockers have all been recommended for patients who cannot receive a thiazide diuretic or in combination with a thiazide diuretic for adequate control of blood pressure. This may include the use of ACE inhibitors in hypertensive patients having systolic dysfunction after a MI, a diabetic nephropathy patient who might benefit from an ACE inhibitor in combination with a diuretic, or a patient with HF.

www.pharmaqz.com 9

Diuretics: Thiazide diuretic

Antihypertensive effects are produced by directly dilating the arterioles and reducing the total fluid volume.

Thiazide diuretics increase the following:

(a) Urinary excretion of sodium and water by inhibiting sodium and chloride reabsorption in the distal convoluted (renal) tubules

(b) Urinary excretion of potassium and, to a lesser extent, bicarbonate

(c) The effectiveness of other antihypertensive agents by preventing re expansion of extracellular and plasma volumes

www.pharmaqz.com 10

Diuretics: Thiazide diuretic

NSAIDs, interact to diminish the antihypertensive effects of the thiazide diuretics.

Precautions and monitoring effects

(a) Potassium ion (K) depletion may require supplementation, increased dietary intake,or the use of a potassium-sparing diuretic, such as spironolactone

(b) Uric acid retention may occur; this is potentially significant in patients who are predisposed to gout and related disorders.

(c) Blood glucose levels may increase, which may be significant in patients with

diabetes.

(d) Calcium levels may increase because of the potential for retaining calcium ions.

www.pharmaqz.com 11

Diuretics: Loop diuretics

These agents are indicated when patients are unable to tolerate thiazides, experience a loss of thiazide effectiveness, or have impaired renal function (clearance <30 mL/min).

act primarily in the ascending loop of Henle; hence, they are called “loop” diuretics. By acting within the loop of Henle, they decrease sodium reabsorption.Their action is more intense but of shorter duration (1 to 4 hrs) than that of the thiazides

As with the thiazides, the antihypertensive effect of loop diuretics may be diminished by NSAIDs.

must be monitored closely for signs of hypovolemia

Transient deafness has been reported. If the patient is taking a potentially ototoxic drug (e.g., an aminoglycoside antibiotic), another class of diuretic (e.g., a thiazide diuretic) should be substituted

www.pharmaqz.com 12

Diuretics: Potassium-sparing diuretics

They are indicated for patients in whom potassium loss is significant and supplementation is not feasible. These agents are often used in combination with a thiazide diuretic because they potentiate the effects of the thiazide while minimizing potassium loss.

Spironolactone is particularly useful in patients with hyperaldosteronism,as it has direct antagonistic effects on aldosterone (aldosterone-receptor blocker).

Less potent than the thiazides and loop diuretics.

promote potassium retention.

Coadministration with ACE inhibitors or potassium supplements significantly increases the risk of hyperkalemia

www.pharmaqz.com 13

Diuretics: Potassium-sparing diuretics

should be avoided in patients with acute renal failure and used with caution in patients with impaired renal function (monitor serum creatinine) because they can retain potassium.

Triamterene should not be used in patients with a history of kidneystones or hepatic disease

www.pharmaqz.com 14

Beta Blocker

a) Relative cardioselective activity. blockers have a greater tendency to occupy the 1-receptor in the heart, rather than the 2-receptors in the lungs.

(b) Intrinsic sympathomimetic activity. These agents have the ability to release catecholamines and to maintain a satisfactory heart rate. Intrinsic sympathomimetic activity may also prevent bronchoconstriction and other direct -blocking actions

www.pharmaqz.com 15

Beta Blocker

Propranolol was the first -adrenergic blocking agent shown to block both 1- and 2-receptors. The usual daily dose range is 40 to 160 mg. It is available both as a rapid-acting product and a long-acting product (Inderal-LA®)

Metoprolol (Lopressor®) show relative cardioselective blocking activity, with relatively less blockade of the beta2-receptors in the lung when compared to propranolol. The usual daily dose is 50 to 100 mg. A sustained- release form of the drug is now available, as the succinate salt (Toprol XL®), which requires less frequent dosing (daily vs. once or twice daily for immediate-release metoprolol).

Atenolol (Tenormin®) was the first -adrenergic blocking agent to combine oncedaily dosing (nadolol) with relative cardioselective blocking activity (metoprolol).The usual daily dose is 25 to 100 mg.

www.pharmaqz.com 16

Beta Blocker

Bisoprolol (Zebeta®) is a -adrenergic blocking agent that is cardioselective and has no intrinsic sympathomimetic activity. It allows for once-daily dosing, and the usual daily dose is 2.5 to 10 mg

Carvedilol (Coreg®) is a -adrenergic blocking agent that has -blocking properties as well as -blocking properties, with a resultant vasodilation. Th e drug is administered twice daily with a starting dose of 6.25 mg titrated at 7- to 14-day intervals to a dose of 25 mg twice daily. Usual daily doses are 12.5 to 50 mg daily.

www.pharmaqz.com 17

Choice of antihypertensive agent

www.pharmaqz.com 18

Choice of antihypertensive agent

www.pharmaqz.com 19

Peripheral alpha1-adrenergic blockers

prazosin (Minipress®), terazosin (Hytrin®),and doxazosin (Cardura®)

Used for hypertensive patients who have not responded to initial antihypertensive therapy

The alpha1-blockers (indirect vasodilators) block the peripheral postsynaptic alpha1-adrenergic receptor, causing vasodilation of both arteries and veins. Also, the incidence of reflex tachycardia is lower with these agents than with the vasodilator hydralazine

First-dose phenomenon. A syncopal episode may occur within 30 to 90 mins of the first dose; similarly associated are postural hypotension, nausea, dizziness, headache,palpitations, and sweating. To minimize these eff ects, the first dose should be limited to a small dose (1 mg) and administered just before bedtime

Additional adverse effects include diarrhea, weight gain, peripheral edema, dry mouth, urinary urgency, constipation, and priapism.

www.pharmaqz.com 20

Centrally active alpha-agonists

Methyldopa, Clonidine

act primarily within the CNS on 2-receptors to decrease sympathetic outflow to the cardiovascular system

Methyldopa decreases total peripheral resistance through the aforementioned mechanism while having little effect on cardiac output or heart rate (except in older patients).

Common untoward effects include orthostatic hypotension, fl uid accumulation (in the absence of a diuretic), and rebound hypertension on abrupt withdrawal. Sedation is a common finding upon initiating therapy and when increasing doses; however, the sedative effect usually decreases with continued therapy.

www.pharmaqz.com 21

Centrally active alpha-agonists

Clonidine

Clonidine is effective in patients with renal impairment, although they may require a reduced dose or a longer dosing interval.

Clonidine stimulates 2-receptors centrally, decreasing vasomotor tone and heart rate.

Intravenous administration causes an initial paradoxical increase in pressure (diastolic and systolic) that is followed by a prolonged drop. As with methyldopa, abrupt withdrawal can cause rebound hypertension

Clonidine has a tendency to cause or worsen depression, and it heightens the depressant effects of alcohol and other sedating substances

www.pharmaqz.com 22

THANKS FOR WATCHING

www.pharmaqz.com

www.pharmaqz.com 23

www.pharmaqz.com 24

www.pharmaqz.com 25