Antihypertensive Drugs Lecture 9 Chapter 39 Antihypertensive Drugs

Antihypertensive Agents Hypertension (HTN) - An inc. in BP such that systolic is > 140 mm/hg & diastolic > 90 mm/hg on 2 or more occasions after initial screening Essential HTN = most common. About 90% of clients. * Exact Origin - unknown. Contributing Factors - family hx, hyperlipidemia, African American background, diabetes, obesity, aging, stress, excessive ETOH & smoking. Secondary HTN is about 10% of HTN, related to endocrine or renal disorders

Renin-angiotensin system Kidneys and blood vessels strive to regulate and maintain a “normal” BP. The kidneys regulate blood pressure via the renin-angiotensin system. Renin (from the renal cells) stimulates production of angiotensin I & then AT- II (a potent vasoconstrictor), causes the release of aldosterone (adrenal hormone that promotes sodium retention and then water retention). Retention of sodium and water causes fluid volume to increase, thus elevating blood pressure. N.E. , an adrenal hormone of the sympathetic nervous system, increases blood pressure.

Hypertension Non-Pharmacological - Should be first line of treatment. If successful, no meds. may be needed. * Stress reduction techniques, exercise, salt restriction, dec. in ETOH intake, no smoking, wt. reduction Systolic pressure >140 mm/hg = antihypertensive meds started Pt. education & compliance very important as in a good history

Hypertension Pharmacological therapy - Individualized * Want to start at lowest possible doses of meds. * Reduce risk factors, even while on meds. - lifestyle changes may allow the client to decrease medications. * suggested after 1 yr. of therapy to dec. dose to determine if less drug dose possible Step care hypertensive approach to treatment developed several years ago - Classified by 4 stages based on BP range. Pg. 695 table 39-1 Individualized approach is also used - more modified to each client. Pg. 696 - Table 39-3

STEPPED – CARE APPROACH Diuretic, Beta Blocker, Calcium blocker, Angiotensin-converting enzyme Step 2 Diuretic with beta blocker Sympatholytics Step 3 Direct-acting vasodilator Sympatholytic with diuretic Step 4 Adrenergic neuron blocker Combinations from steps I, II & III

Antihypertensive Agents Drugs used to treat Hypertension: Diuretics - * Promote Na depletion  dec. in extra cellular fluid (ECF) * First line drug for Rx of mild HTN * Hydrochlorothiazide (HydroDIURIL) most frequently prescribed for first line Rx of mild HTN * Can be used alone or w/ other antiHTN agents

ANTIHYPERTENSIVE AGENTS SYMPATHOLYTICS (SYMPATHETIC DEPRESSANTS) 1. BETA-ADRENERGIC 2. CENTRAL ACTING SYMPATHOLYTICS 3. ALPHA-ADRENERGICS 4. ADRENERGIC NEURON BLOCKERS 5. ALPHA & BETA ADRENERGIC BLOCKERS

Antihypertensive Agents 1) Beta-Adrenergic Blockers (Beta Blockers) Atenolol (Tenormin), Metoprolol (Lopressor) - Beta-1 cardio selective Nadolol (Corgard), Propranolol (Inderal) - Nonselective Beta-1, Beta-2 - Step 1 or 2 Rx - may be combined w/ a diuretic - Reduces cardiac output (CO) by diminishing sympathetic nervous system response

Antihypertensive Agents Beta Blockers - With continued use the vascular resistance diminished & BP lowered - Reduces HR & contractility - Reduces renin release from kidneys Nonselective = inhibits Beta-1 (heart) & Beta-2 (bronchial) receptors - HR slows & BP decreases - Bronchoconstriction occurs Cardio selective - Preferred - acts mainly on Beta-1 receptors & bronchospasms less likely - not absolute protection *Use cautiously in clients w/ pulmonary history*

Antihypertensive Agents 2) Centrally Acting Sympatholytics (Adrenergic Blockers) Clonidine HCL (Catapres), Methyldopa (Aldomet) - Stimulate Alpha-2 receptors  dec. sympathetic activity dec. epi., norepi. & dec.renin release  dec. peripheral vascular resistance - Can be used w/ other agents - Clonidine = a new transdermal preparation - provides a 7 day duration of action - Used w/ diuretics – to prevent NA+ and fluid retention - Do not D/C drug abruptly - HTN crisis possible

Antihypertensive Agents 3) Alpha - Adrenergic Blockers Prazosin HCL (Minipress) - Blocks alpha adrenergic receptors vasodilatation & a dec. in BP - Helps maintain renal blood flow - Useful in clients with lipid abnormalities - decs. VLDL & LDL - responsible for build-up of fatty plaques in arteries & incs. HDL (friendly) - Can cause Na & H2O retention - diuretics may be added

ANTIHYPERTENSIVE AGENTS Safe for diabetics, do not affect respiratory function. Used in HTN, refractory CHF, Benign prostatic hypertrophy (BPH) Side effects – dizziness, drowsiness, HA, N, V, &D., impotence, vertigo, urinary frequency, tinnitus, dry mouth Adverse - Orthostatic hypotension, palpitations, tachycardia When taken with ETOH or other antihyper.  severe hypotension

Antihypertensive Agents 4) Adrenergic Neuron Blockers (Peripherally acting sympatholytics) * Potent drugs that block norepi. form sympathetic nerve endings  a dec. in norepi.  dec. in BP * Decrease in both cardiac output & peripheral vascular resistance Reserpine (Serpasil) & guanethidine (Ismelin) - Potent - used for severe HTN * Step IV drugs - alone or with diuretics to dec. peri. edema * Common SE = Orthostatic Hypotension*

Antihypertensive Agents 5) Alpha-1 & Beta-1 Adrenergic blockers Carteolol (Cartrol), Labetalol (Trandate) - Blocks both alpha-1 & beta-1 receptors - Block alpha-1 = dilation of arterioles & veins -Effect on alpha receptors stronger than on beta receptors so have a dec. BP & pulse rate - Block beta-1 lead to decreased HR & AV contractility - Large doses could block beta-2 receptors  inc. in air way resistance - Do not give to severe asthmatics. AV block SE = Orthostatic Hypotension, GI, nervousness, dry mouth&fatigue

Antihypertensive Agents Direct - Acting Arteriolar Vasodilators - potent Hydralazine (Apresoline) - Mod. to severe HTN Sodium Nitroprusside (Nipride) - Very potent - for hypertensive Emergencies - Act by relaxing smooth muscles of bld. vessels - mainly arteries  vasodilation  - Inc. blood flow to brain & kidneys - With vasodilation the BP dec., Na & H2O retained  peripheral edema. Diuretics used to counter this SE - SE = numerous - tachycardia, palpitations, edema, dizzy, GI bleeding

Antihypertensive Agents Angiotensin Antagonists - Angiotensin-Converting Enzyme Inhibitors (ACE inhibitors) Captopril (Capoten), Enalapril (Vasotec), Lisinopril (Zestril) - Prevents conversion of Angiotensin I to angiotensin II (vasoconstrictor) & blocks release of aldosterone. Aldosterone promotes Na retention & K excretion. Block aldosterone & Na excreted, but H2O & K retained - Used to treat HTN primarily, - but not a 1st line drug. Also used in heart failure. - SE = hyperkalemia & 1st dose hypotension (more common with comb. Diuretic & ACE inhibitor.

Antihypertensive Agents Angiotensin II receptor Antagonists (Blockers) - A - II Blockers Losartan (Cozaar) - Newer drugs similar to ACE inhibitors + prevent release of aldosterone (Na+ retaining hormone) - Act on renin - angiotensin system - Diff between ACE &AII is A-II blockers block angiotensin from angiotensin I receptors found in many tissues - blocks at receptor site. - A-II blockers cause vasodilation & dec. peripheral resistance

ACE inhibitors inhibit the enzyme necessary for the conversion of A-I to A-II A-II blockers - block angiotensin II from receptors in blood vessels, adrenals, and all other tissues.

Antihypertensive Agents Calcium Channel Blockers Verapamil (Calan), Nifedipine (Procardia), Diltiazem (Cardizem) - Free calcium muscle contractility, peripheral resistance & BP . So, Calcium blockers - Dec. calcium levels & promote vasodilation - Drugs can be used w/ clients prone to asthma - SE. Flushing, HA, dizzyness, ankle edema, bradycardia, AV node block,

Math 80 mg = 200mg Cross multiply 1 ml X ml A dosage of 200 mg must be prepared from a solution strength of 80 mg. per ml. How many mls. should be given? 80 mg = 200mg Cross multiply 1 ml X ml 80 X = 200 mg Immediately divide by the number on front of X 200 = Reduce the fraction. 5 80 2 2.5 ml