Drugs Affecting Circulation: Antihypertensives ...Mosby items and derived items © 2008, 2002 by...

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Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Chapter 20 Drugs Affecting Circulation: Antihypertensives, Antianginals, Antithrombotics

Transcript of Drugs Affecting Circulation: Antihypertensives ...Mosby items and derived items © 2008, 2002 by...

Page 1: Drugs Affecting Circulation: Antihypertensives ...Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Chapter 20 Drugs Affecting Circulation:

Mosby items and derived items © 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.

Chapter 20

Drugs Affecting Circulation:

Antihypertensives, Antianginals,

Antithrombotics

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Epidemiology and Etiology of

Hypertension

Primary: Unknown etiology

Secondary: Due to known disease process

Adversely affects numerous organs Termed cardiovascular disease (CVD)

Diagnosis: Two or more seated BP taken on different days

Increased risk of: Left ventricular (LV) hypertrophy, angina, myocardial

infarction (MI), heart failure, stroke, peripheral arterial disease (PAD), retinopathy, and renal failure

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Pathophysiology of Hypertension

Arterial blood pressure

Product of cardiac output (CO) and total

resistance

Preload is major factor in systolic blood

pressure (SBP)

Affects venous capacitance

Afterload is major factor in diastolic blood

pressure (DBP)

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Hypertensive Crisis

Patient with BP > 180/120 mmHg

Hypertensive urgency

No signs/symptoms of organ complication

Hypertensive emergency

Acute, chronic, or progressive organ injury

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Hypertension Pharmacotherapy

First-line agents:

Angiotensin-converting enzyme inhibitors (ACEIs)

Angiotensin II receptor blockers (ARBs)

Calcium channel blockers (CCBs)

β Blockers

Thiazide-type diuretics

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Hypertension Pharmacotherapy

(cont’d)

Second-line agents

Vasodilators

α Blockers

α2 Agonists

Antiadrenergics

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Hypertension Pharmacotherapy

(cont’d)

Angiotensin-converting enzyme inhibitors

Suppress renin-angiotensin-aldosterone system

• Block conversion of angiotensin I to angiotensin II

Hemodynamic effect

• Reduce peripheral arterial resistance (PAR)

• Increase CO

• Increase renal blood flow

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Hypertension Pharmacotherapy

(cont’d)

Indicated for:

• Hypertension (HTN), heart failure, systolic dysfunction,

MI prevention, LV dysfunction, and diabetic neuropathy

Generally decrease SBP and DBP 15-25%

Most common side effect is dry cough

Significant interaction with nonsteroidal

antiinflammatory drugs (NSAIDs)

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Hypertension Pharmacotherapy

(cont’d)

Angiotensin II receptor blockers

Angiotensin II type 1 receptor agonists

• Receptors found in vascular smooth muscle, myocardium,

brain, kidney, liver, uterus, adrenal glands

Indicated for HTN and treatment of heart failure

Slightly “weaker” than ACEIs

Side effects: Orthostatic hypotension, hyperkalemia,

neutropenia, nephrotoxicity, and fetotoxicity

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Hypertension Pharmacotherapy

(cont’d)

Calcium channel blockers

Cause coronary and peripheral vasodilation via L-

channel blockade

Verapamil and diltiazem

• Negative chronotropic and inotropic effects

• Long-acting formulations (target circadian rhythm)

• High incidence of constipation

• Side effects

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Hypertension Pharmacotherapy

(cont’d)

β Blockers

Method of action

Indications

• Essential HTN, angina, dysrhythmias, MI prevention,

chronic heart failure

• Also: Migraine prophylaxis and alcohol withdrawal

May induce bronchospasm and render β-agonist

ineffective

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Hypertension Pharmacotherapy

(cont’d)

Diuretics

Five classes

• Thiazide and thiazide-like agents

• Loop diuretics

• K-sparing agents

Used for HTN

• Carbonic anhydrase inhibitors (CAIs)

• Osmotics

Interact with NSAIDs

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Hypertension Pharmacotherapy

(cont’d)

Potassium-sparing diuretics

• Weak if used alone

• Additive effect with thiazides

• Amiloride (Midamor) and triamterene (Dyrenium)

• Side effects

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Hypertension Pharmacotherapy

(cont’d)

Thiazide and thiazide-like diuretics

• Increase Na and Cl excretion

• Dose-ceiling effect

• 2 to 4 weeks to elicit full effect

• Side effects

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Hypertension Pharmacotherapy

(cont’d)

Loop diuretics

• Decrease Na reabsorption at ascending limb of loop of

Henle

• Indicated for chronic heart failure, ascites, renal failure,

pulmonary edema, hypercalcemia, hypermagnesemia,

syndrome of inappropriate antidiuretic hormone

• Second-line treatment for management of HTN

• Cause frequent urination

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Hypertension Pharmacotherapy

(cont’d)

Aldosterone antagonists

Spironolactone (Aldactone) and Eplerenone (Inspra)

Spironolactone is weak, often used with other

antihypertensives

• Adverse effects: Impotence, gynecomastia, deep voice,

menstrual irregularities, hirsutism, gastrointestinal upset, rash,

drowsiness

Eplerenone

• Indicated for HTN and post-MI heart failure

• Minimal adverse sexual side effects

• Higher risk of hyperkalemia

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Hypertension Pharmacotherapy

(cont’d)

Centrally acting adrenergic agents

Affect CO and peripheral resistance

Negative inotrope/negative chronotrope

α2 Agonists are effective, but riddled with side

effects

• Clonidine transdermal is most effective and least toxic

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Hypertension Pharmacotherapy

(cont’d)

α1-Adrenergic antagonists

Cause arterial and venous dilation

• Decrease preload and afterload

First-dose phenomenon

• Initial doses low and at bedtime

Indicated for HTN, benign prostatic hyperplasia,

heart failure, and Raynaud’s vasospasm

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Hypertension Pharmacotherapy

(cont’d)

Antiadrenergic agents

Second-line drugs

Reserpine

• Depletes postganglionic norepinephrine

• May cause: Sedation, depression, psychosis, peptic ulcers,

nasal stuffiness

Guanethidine (Ismelin) and Guanadrel (Hylorel)

• Substitute neurotransmitters

• May cause orthostatic hypotension, sexual dysfunction,

explosive diarrhea

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Hypertension Pharmacotherapy

(cont’d)

Vasodilators Hydralazine (Apresoline) and minoxidil (Rogaine,

Loniten)

Second-line treatment for HTN because of side effects

Act on vascular smooth muscle to decrease total peripheral resistance

• May cause reflex tachycardia, renin release, increased CO

• Often given with β blocker and loop diuretic

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Epidemiology, Etiology, and

Pathophysiology of Angina

“Chest pain”

Symptom of myocardial ischemia

Imbalance of myocardial O2 supply and demand

May present as: Heavy weight or pressure on chest

Burning sensation

Shortness of breath (SOB)

Pain over sternum, left shoulder, or lower jaw

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Pharmacotherapy for Angina

Nitrates

Nitroglycerin dilates coronary arteries and

collaterals (mostly venous effect)

Indications: Angina, acute MI, HTN

Formulations: Oral, IV, ointment, transdermal,

translingual, sublingual

• Sublingual: Q 5 minutes x 3, then seek care

Adverse effects: Tachycardia, palpitations,

hypotension, dizziness, flushing, headache

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Pharmacotherapy for Angina (cont’d)

Ranolazine (Ranexa)

Indicated for chronic angina not responding to

other medications

Shifts energy production from fatty acid oxidation

to glucose oxidation (uses less O2)

500 mg BID (maximum, 1 g BID)

Contraindicated in hepatic dysfunction

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Antithrombotic Agents

Formation and elimination of acute coronary

thrombus

Formation initiated by injury to endothelium

Platelets adhere to site of injury, release

chemicals that cause further aggregation, forming

unstable thrombus

Eventually forms insoluble fibrin clot

• Must be removed by fibrinolytic system for homeostasis

to be maintained

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Antithrombotic Agents (cont’d)

Anticoagulant agents

Heparins: Unfractionated heparin and low

molecular weight heparin

• Indicated for venous thromboembolism, pulmonary

embolism, atrial fibrillation (AF), disseminated

intravascular coagulation (DIC), and peripheral arterial

embolism

• Extracted from porcine intestinal mucosa

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Antithrombotic Agents (cont’d)

Anticoagulant agents (cont’d)

Heparins: Unfractionated heparin and low

molecular weight heparin (cont’d)

• Goal: Balance unwanted clotting with risk of hemorrhage

• Side effects: Bleeding, thrombocytopenia, hyperkalemia,

osteoporosis, increased liver enzyme tests (LETs)

• Antidote: Protamine sulfate

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Antithrombotic Agents (cont’d)

Anticoagulant agents (cont’d)

Direct thrombin inhibitors

• Desirudin (Iprivask): Indicated for deep vein thrombosis

(DVT)

• Bivalirudin (Angiomax): Indicated for unstable angina

• Argatroban and lepirudin (Refludan): Used for

anticoagulation of patients with heparin-induced

thrombocytopenia type 2 (HIT-2)

• Common adverse side effect: Hemorrhage

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Antithrombotic Agents (cont’d)

Anticoagulant agents (cont’d)

Warfarin (Coumadin)

• Oral anticoagulant for venous thrombosis, pulmonary

embolism (PE), AF, valve replacement, coronary

occlusion

• Daily dosing (delayed onset of 3-5 days)

• International normalized ratio (INR) is standard for

monitoring therapy

• Hemorrhage is common side effect

• Many drugs may increase/decrease effects

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Antithrombotic Agents (cont’d)

Antiplatelet agents

Aspirin

• Reduces platelet aggregation by inhibition of

prostaglandin production

• Antithrombotic indications: Reduce risk of thrombosis,

transient ischemic attack (TIA), or stroke

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Antithrombotic Agents (cont’d)

Antiplatelet agents (cont’d)

Aspirin (cont’d)

• Side effects: Peptic ulcer, renal dysfunction, HTN,

tinnitus, pulmonary dysfunction, and bleeding

• Ibuprofen inhibits pharmacological effect; concurrent

NSAID use may cause fatal gastropathy

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Antithrombotic Agents (cont’d)

Antiplatelet agents (cont’d)

Dipyridamole

• Vasodilator and platelet adhesion inhibitor

• Indicated as an adjunct to warfarin in prevention of

postoperative thromboembolic complications of cardiac

valve replacement

• May potentiate effect of adenosine

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Antithrombotic Agents (cont’d)

Antiplatelet agents (cont’d) Clopidogrel (Plavix)

• Platelet aggregation inhibitor

• Indications: History of MI, stroke, PAD, acute coronary syndrome

• Slightly more effective than aspirin (except for stroke prophylaxis)

• Metabolized by liver

• Steady state in 3 to 7 days

• 75 mg QD (plus aspirin)

300-mg loading dose for acute coronary syndrome (ACS)

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Antithrombotic Agents (cont’d)

Antiplatelet agents (cont’d)

Ticlopidine

• Platelet aggregation inhibitor

• Indicated for stroke

• More effective than aspirin

• Steady state in 14 to 21 days

• Metabolized by liver

• Risk of life-threatening blood dyscrasias

Use only if aspirin/clopidogrel are unacceptable

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Antithrombotic Agents (cont’d)

Antiplatelet agents (cont’d)

Cilostazol and pentoxifylline

• Cause vasodilation and inhibition of platelet aggregation

• Indicated for PAD pain

• Clinical benefits may take up to 12 weeks

• Transient adverse effects: Headache, diarrhea,

dizziness, palpitations

• 100 mg BID on an empty stomach

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Antithrombotic Agents (cont’d)

Antiplatelet agents (cont’d)

Glycoprotein IIb/IIIa inhibitors

• Indicated for ACS

• Abciximab (ReoPro) is “drug of choice”

• Not available in oral formulation (ineffective)

• Bleeding is most common adverse side effect

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Antithrombotic Agents (cont’d)

Thrombolytic agents

Indicated for PE, ischemic stroke, and acute ST

segment elevation MI

Agents: Streptokinase (second line), alteplase,

reteplase, and tenecteplase

• Therapy should begin within 12 hours of symptoms

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Antithrombotic Agents (cont’d)

Thrombolytic agents (cont’d)

Contraindications: Internal bleeding, aortic

dissection, head injury or stroke in last 3 months,

HTN, anticoagulant use

Bleeding is most common adverse effect

• Gastrointestinal, genitourinary, respiratory tract,

retroperitoneal, intracranial