Lecture 9Chapter 39

Antihypertensive Drugs

AntihypertensiveAgents

• 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 APPROACHStep 1

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 AgentsBeta Blockers

- With continued use the vascular resistance diminished & BP lowered

- Reduces HR & contractility - Reduces renin release from kidneysNonselective = inhibits Beta-1 (heart) & Beta-2 (bronchial)

receptors - HR slows & BP decreases - Bronchoconstriction occursCardio 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 blockSE = 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.

AntihypertensiveAgents

• 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

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