drug treatment of angina

8/6/2019 Drug Treatment of Angina

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DRUG TREATMENT OF

ANGINA


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WHAT IS ANGINA PECTORIS?

Condition occurs when oxygen supply

to the heart is insufficient to meet its

demands

Paroxysmal chest pain which often

radiates


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TYPES OF ANGINA?

Three types:

1. Typical (exertional, classic, stable)

most common form (90%)

due to vessel occlusion(atherosclerosis)

Attacks usually occur during exercise(climbing stairs, etc.) when oxygendemand exceeds supply


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TYPES OF ANGINA?

2. Variant [rest angina]

due to vasospasm

Attacks often occur during rest (e.g., atnight)


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TYPES OF ANGINA?

3. Unstable angina

Increased frequency & severity of attacks

Caused by atherosclerotic plaques,platelet aggregation at fractured plaques(clots) & vasospasm

High risk for myocardial infarction


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ANTI-ANGINAL DRUGS

1. Nitrates

2. Calcium channel blockers

3. -blockers


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ORGANIC NITRATES (Nitroglycerin)

MOA OF Nitroglycerin:

Nitrates are metabolised to release nitric oxide (NO)

NO causes Venodilation - primary mechanism

Venodilation results in decreased preload(decreasedventricular chamber size, end diastolic pressure, fiber

tension) = decreased work

Decreased preload results in decreased O2 demand


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SIDE EFFECTS OF NITROGLYCERIN

orthostatic hypotension

headache

dizziness

tachycardia (baroreceptor mediated)


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USE OF ORGANIC NITRATES

Nitrates are the mainstay of therapy for the immediate relief of

angina

Low doses (usually sublingual tablets) for acute attacks & forprophylaxis

Patches used for prolonged prophylaxis

Tablets oral high dose; first-pass metabolism

Duration of action 10-30 min

Tolerance develops with long term use (commonly nightly

nitrate free gaps of ~8 hrs are used)


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BETA BLOCKERS (Propranolol)

MOA:

Block beta receptors on the heart resulting in HRand force of contraction BP

Reduced oxygen consumption (demand) due to

reduced heart rate (esp. during exercise), reducedforce of contraction & reduced blood pressureduring exercise.


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USES OF PROPRANOLOL

1) Only for prophylaxis of exertionalangina

2) Ineffective (or contraindicated) forvariant angina ---- (may make attacks

worse)

3) Often combined with other drug types


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SIDE EFFECTS OF PROPANOLOL

fatigue insomnia

erectile dysfunction

Avoid use in patients with:

Asthma / bronchospastic disorders

bradycardia

Depression

CALCIUM CHANNEL BLOCKERS


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CALCIUM CHANNEL BLOCKERS

(Amlodipine)

MOA ofAmlodipine:

Blocks calcium influx via L-type channels in cardiac andvascular smooth muscle; produce decreased force ofcontraction of the heart and vasodilation

preload, afterload, oxygen consumption by theheart

Increase coronary blood flow (useful in vasospasticangina)


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SIDE EFFECTS OF CA 2+ CHANNEL BLOCKER

Constipation Nausea

Flushing

dizziness

AVN & SAN depression (more common

w/ verapamil)


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USEFUL DRUG COMBINATIONS

Nitrate + blocker Different mechanism of action - additive efficacy

blocker can prevent reflex tachycardia &positive inotropic effects caused by nitrates


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USEFUL DRUG COMBINATIONS

Add a CCB w/ a blocker + Nitrate Different mechanisms of action - additive efficacy

CCB may cause improvement if there is a

vasospastive component to the angina

blocker can prevent reflex tachycardia caused bynitrate or CCB (& further lower HR & BP)


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DRUG TREATMENT OF

CONGESTIVE HEART FAILURE


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WHAT IS CONGESTIVE HEART

FAILURE (CCF)?

failure of the heart to provide sufficient cardiac output to meetthe physiological needs of the body

Congestive describes abnormal accumulation of venous blood

and edema (lungs and legs). Leads to breathlessness andswelling of legs

Chronic or acute


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CCF

CCF: pumping action of ventricles is impaired resulting

in back pressure of blood, with congestion of the lungsand liver


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CAUSES OF CCF

Ischemic heart disease

Hypertension

Valvular heart disease

Cardiomyopathies

These conditions prevent the heart from providing sufficientoutput


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TREATMENT OF CCF

Treatment objectives:

1. Reduce congestion ( edema)

2. Improve cardiac contraction and relaxation


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DRUGS USED TO TREAT CCF

1. Cardiac glycosides

2. Angiotensin converting enzyme

inhibitors (ACE inhibitors)

3. Angiotensin receptor blockers

4. -Blockers


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CARDIAC GLYCOSIDES (Digoxin)

Extracted from the foxglove plant

(Digitalis spp.)

A similar drug is ouabain

The main action of digoxin is on the heart

MOA OF DIGOXIN


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MOA OF DIGOXIN

IN CCF digoxin:

force of contraction of the heart

MOA:

binds to Na+/K+ ATPase pump and inhibits it

Increases intracellular Na+ concentrations resulting in increased

intracellular Ca2+

concentrations

Increased intracellular calcium concentration results in increased

storage in the sarcoplasmic reticulum, which increases the FOC of theheart


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MOA OF DIGOXIN

Digoxin also slows AV conduction allowing for

improved ventricular filling in CCF. Also useful

in Supraventricular tachycardia

DIGOXIN


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DIGOXIN

Digoxin given op or iv

Half life=36 hrs

Interactions with amiodarone, verapamil

Side effects: hypokalemia*, abdominal

discomfort, nausea and vomiting


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ACE INHIBITORS (Captopril, Enalapril,

Lisinopril)

First line therapy for CCF

MOA:

Inhibits ACE, hence inhibits the conversion of angiotensin I toangiotensin II

Reduces cardiac afterload

Prevents aldosterone mediated Na retention (reduces cardiac

preload)

Increase cardiac output


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ACE INHIBITORS

T Adverse effectsElimination

captopril 4hrs Hypotension,

cough

Renal and

hepatic

enalapril 30-35hrs same Renal andhepatic

lisinopril >30hrs same renal


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ANGIOTENSIN RECEPTOR BLOCKERS

(losartan)

MOA: block the effects of angiotensin II

at the angiotensin receptor

Role in the treatment of CCF not well

ascertained


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BETA BLOCKERS

These agents have paradoxical benefit in CCF

increases cardiac output

Their MOA in CCF is not well understood

Suspected mechanism is up-regulation of Beta

one receptor expression on the heart


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BETA BLOCKERS

Selective beta-1 antagonist

Metoprolol

Bisprolol

Reduces deathrate in CCF

Non-selective

beta antagonist

carvedilol Reduces deathrate in CCF


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DRUGS AFFECTING THE

BLOOD


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DRUGS AFFECTING THE BLOOD

1. Anti-coagulant drugs

2. Thrombolytic drugs

3. Anti-platelet drugs

4. Vitamin K and plasma fractions

COAGULATION CASCADE


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COAGULATION CASCADE


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ANTI-COAGULANTS (heparin, warfarin)

1. Injectable anticoagulant: heparin (IV & SC).

MOA: Inhibits thrombin by activating anti-thrombin III

Low molecular weight heparin

Unwanted effects include haemorrhage, osteoporosis,hypersensitivity rxns


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ANTI-COAGULANTS (heparin, warfarin)

2. Oral anticoagulant: warfarin

MOA: Inhibits the enzymic reduction of vitamin Kto its active form Hydroquinone which isnecessary for the formation of certain clotting

factors.

II, VII, IX, X

Unwanted effects include haemorrhaging,teratogenicity, hepatotoxicity


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CLINICAL USES OF ANTI-COAGULANTS

Prevention of:

Deep vein thrombosis

Thrombosis on prosthetic heart valves

Clotting during haemodialysis or bypasssurgery

THROMBOLYTIC DRUGS


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THROMBOLYTIC DRUGS

(streptokinase, anistreplase)

Clot-busting drugs: dissolve clots

Also referred to as fibrinolytics

MOA: increase fibrinolysis by increasingthe formation of plasmin from

plasminogen

THROMBOLYTIC DRUGS


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THROMBOLYTIC DRUGS

(streptokinase, anistreplase)

Streptokinase: protein extracted fromstreptococci which activates plasminogen(clots +circulation)

Anistreplase (APSAC): anisolyated

plasminogen-streptokinase activatorcomplex.

- form of streptokinase with 4x longer T

- prebound to a plasminogen molecule


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ANISTREPLASE

ROA: iv

Side effects: allergic rxns, hypotension

given within 3hrs after ischemic stroke

IV (acute attacks)-to dissolve clot


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ANTI-PLATELETS (aspirin)

Aspirin MOA:

Inhibits cyclo-oxygenase enzymes and

hence the synthesis of thromboxanes

Prevents platelet aggregation through

inhibition of thromboxane A2*


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COX

PGG2& PGH2 ] endoperoxidases-

-------------

--------

Arachidonic Acid

Thromboxane A2

ASPIRIN

ASPIRIN PHARMACOKINETICS


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ASPIRIN PHARMACOKINETICS

Orally well absorbed: weak acid

50-80% PPB

Low dose T=4hrs, high dose T=15hrs

hydrolysed by esterases in plasma and liver (75%) to salicylate(active) and acetic acid

ASPIRIN/SIDE EFFECTS


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ASPIRIN/SIDE EFFECTS

Git effects

Hypersensitivity

Prolonged bleeding time

nephrotoxicity

Interactions with warfarin, uricosuric agents


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CLINICAL USES OF ASPIRIN

Mycocardial infarction

Following coronary bypass grafting

Ischemic brain damage (stroke)

VITAMIN K


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VITAMIN K

Fat soluble vitamin

Essential for formation of clotting factors II, VII, IX

and X

Natural vitamin K given orally or iv

Synthetic (menadiol sodium phosphate) mainly op

Used in the treatment/prevention of bleeding and in

vitamin K deficiencies

drug treatment of angina

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