Antianginal drugs

Definition :

The term angina, or angina pectoris is used to describe a sudden, temporary substernal pain caused by transient (15 sec. to 15 minutes) and reversible myocardial ischemia.

Which may radiate to the left shoulder, neck, and/or the flexor surface of the left arm.

Anginal pain results from a temporary imbalance between the ability of the coronary arteries to supply oxygenated blood to cardiac muscle and the oxygen requirements of the tissue leading to ischemia.

- Angina (heavy weight or pressure or pain in the chest) occurs when blood (oxygen, nutrient) supply to the heart is limited as a result of :

- Disruption of coronary blood flow because of vasospasm or platelet aggregation

- Increased demand for oxygen evoked by physical exertions

- A combination of both

Factors affecting myocardial oxygen demand and oxygen supply

Oxygen demand

Oxygen supply=

>

Coronary blood flow

Ventricular volume

LV pressure

Wall tension

Heart rate

Contractile state

Aortic pressure

Coronary vascular resistance

TYPES OF ANGINA

There are 3 major types of angina.

(1) ATHEROSCLEROTIC ANGINA.

(2) VASOSPASTIC ANGINA.

(3) UNSTABLE ANGINA.

ATHEROSCLEROTIC ANGINA

Also known as angina of effort or classical angina.

Associated with atheromatus plaque.

Rest usually leads to prompt relief.

It may deteriorate into unstable angina.

Unstable angina

Unstable angina : Characterized by increasing frequency of pain, the episodes also tend to be more intense and longer lasting than stable angina.

Unstable angina is associated with plaque disruption and superimposed partial thrombosis, distal embolization of the thrombus, and/or vasospasm.

UNSTABLE ANGINA

Characterized by increase frequency and severity of attacks caused by repeated episodes of diminished coronary blood flow.

It is thought to be the immediate precursor of a myocardial infarction and is treated as a medical emergency.

Unstable angina is sometimes called pre-infarction angina.

VASOSPASTIC ANGINA

Also known as Rest angina or variant angina or Prinzmetal’s angina.

It involves the reversible spasm of coronary arteries.

The spasm can occur any time, even during sleep.

It may deteriorate into unstable angina.

Therapeutic strategies

The primary goal in the treatment of angina is not the relief of anginal pain. The primary goal is to restore the balance between oxygen supply and oxygen demand, thereby reversing or preventing myocardial ischemia.

The defect that cause anginal pain is inadequate coronary oxygen delivery relative to the myocardial oxygen requirement. This defect can be corrected in 2 ways :

(1) increasing oxygen delivery.(2) reducing oxygen requirements.

Pharmacologic therapy includes the(1)Nitrates(2)Calcium channel blockers.(3)Beta blockers.

MYOCARDIAL REVASCULARIZATION corrects coronary obstruction either by bypass grafting or by angioplasty.

ANTIANGINAL DRUGS

ORGANIC NITRATES.

1)Isosorbide dinitrate.

2)Isosorbide mononitrate.

3)Nitroglycerine.

BETA BLOCKERS.

1)Acebutolol

2)Atenolol

3)Metaprolol

4)Propranolol

Ca+ Channel Blockers.

1) Amlodipine

2) Diltiazem

3) Nifedipine

4) Verapamil

NITRATES

MECHANISM OF ACTION:

Denitration of the nitrates within smooth muscle cells release nitric oxide (NO), which stimulates guanylyl cycla

se,

Causes an increase in the second messenger of cGMP,

Leads to smooth muscle relaxation probably by dephosphorylation of myosin light chain phosphate.

ANTIANGINAL DRUGS

Nitrates: Direct relaxation of vascular smooth muscle

Although venous effects predominate at low doses, nitroglycerin produces dilation of both arterial and venous beds.

Dilation of the postcapillary vessels, including large veins, promotes peripheral pooling of blood and decreases venous return to the heart, reducing left ventricular end-diastolic pressure (decreased preload).

Arteriolar relaxation produced at higher doses reduces systemic vascular resistance and arterial pressure (decreased afterload).

Myocardial oxygen consumption or demand is decreased by both the arterial and venous effects of nitroglycerin, and a more favorable supply-demand ratio can be achieved.

Effects on CVS.

It has 2 effects :

1. First, it causes dilation of the large veins resulting in pooling of blood in the veins,

2. Second, it dilates the coronary vasculature providing an increase blood supply to the heart muscle.

Nitroglycerin: Oral (not generally used because extensively metabolized in liver)

Sublingual,

Transdermal

Isosorbide: oral, (not redialy metabolized by the liver.)

Time of onset varies from one minute for nitroglycerin to more than one hour for isosorbide mononitrate.

Adverse Effects.

Headache Postural hypotension Facial flushing Tachycardia

TOLERANCE Tolerance develop rapidly, it can be overcome by providing a

daily nitrate free intervals ,typically 10-12 hrs usually at night. Nitroglycerine patches are worn for 12 hrs then removed for 12 hrs.

BETA BLOCKERS

Mechanism of Action:-

Effective in the prophylaxis of atherosclerotic angina attacks. It decrease heart rate , cardiac force and blood pressure.

The effectiveness of beta blockers in the treatment of angina is attributable to a fall in myocardial consumption.

This is due to negative chronotropic effect and inotropic effect and reduction of arterial blood pressure.

This all leads to increase in systolic ejection period and increase in left ventricular and diastolic volume , this tends to increase oxygen consumption.

Clinical use:-

Use only for prophylactic therapy of angina and

not used in acute attack.

Can be use in combination with nitroglycerine to compensate the undesirable effects evoked by the nitrates.

Beta blockers are contraindicated in vasospastic angina.

Reasons for Using Nitrates and Beta Blockers in Combination in Angina

Beta Blockers prevent reflex tachycardia and contractility produced by nitrate-induced hypotension.

Nitrates prevent any coronary vasospasm produced by Beta Blockers.

Nitrates prevent increases in left ventricular filling pressure or preload resulting from the negative inotropic effects produced by Beta Blockers.

Nitrates and Beta Blockers both reduce myocardial oxygen consumption by different mechanisms.

Nitrates and Beta Blockers both increase subendocardial blood flow by different mechanisms

CALCIUM CHANNEL BLOCKERS

Mechanism of action:-

Calcium is essential for muscular contraction, the entry of extracellular calcium initiate the contraction of myocardium cells .

Calcium channel blockers decreases smooth muscle tone and vascular resistance by blocking voltage gated calcium channels

Nifedipine is important for vasospastic angina.

A/E: flushing , headache, hypotension and peripheral edema

The end…..