Antianginal drugs

Jomanah A. Hmood

What is angina pectoris? "angina" means ("strangling") , and

the pectus means ("chest")therefore be can translated as:

" a strangling feeling in the chest”

Angina pectoris : is the chest discomfort that

occurs when the heart is not getting enough blood.

Angina is a symptom of myocardial ischemia

This imbalance may result from:

Decrease supply

Spasm of vascular smooth muscle

increase demand : exertion

Atherosclerosis in the coronary artery

What the patient with angina feels??

pain, pressure, fullness,

or squeezing in the center of the chest

Some patients (women, elderly, and diabetic) may have different symptoms,

such as: shortness of breath A feeling of indigestion or heartburn nausea sweating dizziness fatigue Palpitations

which may be radiate to

neck

shoulder

jaw

arm

angina

stable unstable vasospastic

Stable anginaCalled “ typical angina” ►►most common

Caused by▼

The fixed obstruction of coronary artery by atherosclerosis

▼

Blood supply ↕ when heart ↑ work

Stable angina

• Physical exertion • Emotion • Exposure to very cold temperatures1. ↑work load2. Coronary vasoconstriction3. Sympatheticoadrenal hormones• Heavy meals• Smoking.

Stable angina

Occurs when the heart must work harder.

Usually lasts a short time (5 minutes or less).

Is relieved by rest or medicine.

Why is called “stable”angina?

1. Frequency of chest pain. 2. Amount of effort needed to trigger it .

↓↓Don’t change from day to day or week to

week .

Unstable angina

Between stable | MI Characterized by :

1. ↑ frequency, duration and intensity .2. Often occurs at rest, while sleeping at

night, or with little physical exertion.3. lasts more than 20(as long as 30

minutes).4. Not relieved by rest .

atherosclerosis

Arterial wall thickeningEndothelium damage → cholesterol crosses

→ white blood cells stream in to digest the LDL cholesterol → formation of plaque

• Which may be grow until block the artery• Or rupture and allowing blood to clot inside

an artery.

Prinzmetal “ variant “

It is coronary vasospasm

Uncommon “ 2% of cases of angina”

Occurs at rest “during the night or early morning hours”

response to medication “coronary vasospasm”.

What diagnostic tests might pt has?

•Blood tests•Electrocardiogram (EKG or ECG)•Exercise stress test•Cardiac catheterization•Coronary angiogram

angina can be prevented:

Antianginal drugs action:

Variant angina

Organic nitrates

Organic nitrates

Are simple nitric and nitrous acid esters of glycerol .

Used for all types of angina

Examples:

1. Isosorbide dinitrate →solid2. Isosorbide mononitrates→solid3. Nitroglycerin →volatile → therefore it

must be kept in tightly closed glass containers

pharmacokinetics

• Nitroglycerin: rapidly disappears from the blood

• half-life: only a few minutes• Excretion: largely by extrahepatic

mechanisms.• Isosorbide dinitrate, in contrast, must first be

converted in the liver to active mononitrates.• half-life : 4 to 6 hours

Mechanism of action

• Nitrates work by dilating both arteries and veins, both in the heart and elsewhere.

1. Inhibit coronary spasm → variant angina

stable angina1. Relax veins → ↓preload

adverse effects

1. Headache : 30-60% of patients. 2. Postural hypertension 3. Facial flushing high doses4. Tachycardia

Tolerance

• "Decrease in the effect of a drug•when administered in a long-acting form“

Is dose-dependent

•Disappears in 24 h. after stopping the drug•The mechanisms of nitrate tolerance are therefore likely to be multifactorial,

involving vascular biochemical changes, physiologic compensation, and possibly receptor regulation .

• result from vascular depletion of critical sulfhydryl groups, which are necessary to bring about vasorelaxation from nitrates.

•   While this mechanism of nitrate tolerance probably operates when isolated blood vessels are exposed to high concentrations of nitrate in vitro

•Use of angiotensin converting enzyme inhibitors and diuretics in conjunction with nitrates may alleviate the development of tolerance

B- blockers

B- blockers • Lowering the rate and force of contractility

• Suppress the activation of heart by blocking B1 receptors

Heart work↓ Oxygen demand↓

B- blockers

They reduce oxygen demand both During exertion and at rest

beta blockers are effective in improving the amount of exercise that can be performed

without developing angina .

Vasospastic angina

B- blockers

• cardioselective • Atenolol (Tenormin)• Metoprolol (Lopressor, Toprol XL)

• Non selective :• Propanolol • Agents with intrinsic sympathomimetic

activity should be avoided.

side effects Bradycardia breathing difficulties in people who have

asthma or chronic lung disease. fatigue depression and erectile dysfunction.

side effects

• By Using cardioselective beta blockers , many of these side effects can be avoided, because these have relatively little effect on the blood vessels, lungs, and central nervous system.

• But all B-blockers are non selective in high doses.

ß-ADRENERGIC BLOCKERSCONTRAINDICATIONS

•Hypotension: BP < 100 mmHg•Bradycardia: HR < 50 bpm•Chronic bronchitis, ASTHMA•Severe chronic renal insufficiency

Calcium channel blockers

calcium channels• Two voltage-dependent calcium channels:  •  L-type calcium channel ('L' for Long-lasting) • and T-type calcium channels ('T' for Transient) •  L-type channels are important in sustaining an

action potential • while T-type channels are important

ininitiating them. •  L-type channels respond to higher membrane

potentials, open more slowly, and remain open longer than T-type channels.

Calcium channel blockers

• Calcium is essential for muscular contraction

• Ca influx ↑↑ in ischemia because :Hypoxia →membrane depolarization ↑

→ ATP consuming enzymes → ↓energy

Calcium channel blockers

• Therefore, Calcium channel blockers protect tissues by inhibiting the entrance of Ca.

• It is used to treatment of variant angina.• They are effective in treating hypertension

in patients with angina and diabetes. • They don’t dilate the veins.

Calcium channel blockers

• High doses of short-acting calcium channel blockers should be avoided because of → increased risk of MI due to:

• excessive vasodilation • and marked reflex cardiac stimulation.

Nifedipine

•  is a dihydropyridine calcium channel blocker.

• Has minimal effect on cardiac conduction and heart rate.

•  Administrated orally• It undergoes hepatic metabolism .• Eliminated in both urine and feces

Nifedipine

• Its main uses : antianginal (especially in Prinzmetal's

angina)  antihypertensive  Raynaud's phenomenon  painful spasms of the esophagus such as

in cancer and tetanus patients

Side effects

headache Flushing hypotensionsevere constipation and cramps.Peripheral edema Reflex tachycardia in sever peripheral

vasodilation →No sympathetic antagonistic action

verapamil

Verapamil

is an L-type calcium channel blocker of the phenylalkylamine class.

 action: decrease impulse conduction through

the AV node dilate the blood vessel

Verapamil

It has been used in the treatment of :hypertensionangina pectoriscardiac arrhythmiacluster headaches. Verapamil is also used intra-arterially to

treat cerebral vasospasm.

PharmacokineticGiven orally absorption : 90–100% of Verapamil  high first-pass metabolism , bioavailability(10–

35%)   As its metabolites, 70% is excreted in the urine

and 16% in feces; 3–4% is excreted unchanged in urine.

 Half-life : 5–12 hours  not cleared by hemodialysis.excreted in human milk

Side effects

•  headaches,• facial flushing,•  dizziness,•  swelling,• increased urination,• Fatigue• and nausea

diltiazemDiltiazem is a potent vasodilator → increasing

blood flow strong depressor of A-V node conduction →

decreasing the heart rate Its pharmacological activity is somewhat similar

to verapamil.  reduces peripheral resistance and afterload. Because of its negative inotropic effect,

diltiazem causes a modest decrease in heart muscle contractility and reduces myocardium oxygen consumption.

Indications Stable angina (exercise-induced) – diltiazem

increases coronary blood flow and decreases myocardial oxygen consumption, secondary to decreased peripheral resistance, heart rate, and contractility.

Variant angina   coronary dilation.supraventricular tachycardias Atrial fibrillation  hypertension

Contraindications

In congestive heart failure, patients with reduced ventricular function may not be able to counteract the inotropic and chronotropic effects of diltiazem, the result being an even higher compromise of function.

With SA node or AV conduction disturbances : the use of diltiazem should be avoided in patients with SA or AV nodal abnormalities, because of its negative chronotropic and dromotropic effects.

Low blood pressure patients, with systolic blood pressures below 90 mm Hg, should not be treated with diltiazem.