NAME: HOLY MWANSA

STUDENT ID: 003-484

PROGRAM: BNMWSC
MODULE: PHARMACOLOGY ASSIGNMENT
DUE DATE: 13/03/20
QUESTION: Discuss in detail the therapeutic strategies in the management of
angina pectoris including the following:
1. Brief pathophysiology of angina pectoris
2. Types of angina
3. Classes of drugs
4. Examples of drugs in each class
5. Mechanism of action
6. Side effects
7. Drug interactions
8. Contraindications
INTRODUCTION
Angina also called as pectoris is that the chest pain which is caused by inadequate coronary
blood flow to the myocardium. When coronary blood flow cannot deliver sufficient oxygen
to support cardiac oxidative metabolism (reduced oxygen supply/demand ratio), the
myocardium becomes hypoxic. This triggers pain receptors within the heart, which results in
the classical presentation of chest pain and the sensation of substernal heaviness or pressure.

PATHOPHYSIOLOGY OF PECTORIS ANGINA

Angina pectoris is the result of myocardial ischemia caused by an imbalance between

myocardial blood supply and oxygen demand. Angina may be a common presenting
symptom among patients with arteria disease. Myocardial ischemia develops when coronary
blood flow becomes inadequate to fulfill myocardial oxygen demand. Angina pectoris is that
the common clinical manifestation of myocardial ischemia.  It is caused by chemical and
mechanical stimulation of sensory afferent nerve endings in the coronary vessels and
myocardium. Heart rate, myocardial inotropic state, and myocardial wall tension are the
major determinants of myocardial metabolic activity and myocardial oxygen demand. These
nerve fibres extend from the first to fourth thoracic spinal nerves, ascending via the spinal
cord to the thalamus, and from there to the cerebral cortex. Adenosine is that main chemical
mediator of anginal pain. During ischemia, ATP is degraded to adenosine, which causes
arteriolar dilation and angina pain. Adenosine induces angina mainly by stimulating the A1
receptors in cardiac afferent nerve endings. Myocardial ischemia can result from

(1) a reduction of coronary blood flow caused by fixed and/or dynamic epicardial coronary
artery (conductive vessel) stenosis,

(2) abnormal constriction or deficient relaxation of coronary microcirculation (resistance

vessels), or

(3) reduced oxygen-carrying capacity of the blood. During ischemia ATP is degraded to
adenosine which after diffusion to the extracellular space, causes arteriolar dilation and
anginal pain. Increases in the heart rate and myocardial contractile state result in increased
myocardial oxygen demand. Increases in both afterload aortic pressure and preload
ventricular end-diastolic volume result in a proportional elevation of myocardial wall tension
and, therefore, increased myocardial oxygen demand. Oxygen supply to any organ system is
determined by blood flow and oxygen extraction.

TYPES OF ANGINA
  Stable angina pectoris.
 Prinzmetal’s /Variant angina pectoris.

 Unstable angina pectoris.

STABLE ANGINA PECTORIS

Is caused by narrowed arteries due to atherosclerosis and When cardiac work increases (in
exercise), the obstruction of flow and inadequate oxygen delivery results in the accumulation
of acidic metabolites and ischemic changes that stimulate myocardial pain endings.

 due to obstruction of coronaries by atheroma.

 constitutes about 90% of angina cases.
 Rest usually leads to complete relief of the pain within 15 minutes.

PRINZMETAL/ VARIANT ANGINA

Is caused by a transient spasm in a coronary artery

 due to reversible spasms of coronaries usually at the site of an atherosclerotic

plaque.

 Spasm may occur at any time, even during sleep.

 may deteriorate into unstable angina

 responsible for less than 10% of cases.

UNSTABLE ANGINA

Is due to spasm and partial obstruction of coronaries.

 Is thought to be Immediate precursor of myocardial infarction.

 Is characterized by increased frequency and severity of attacks that result from

a combination of atherosclerotic plaques, platelet aggregation at fractured
plaques, and vasospasm.

 is treated as a medical emergency

 Is more severe and lasts longer than stable angina

  Episodes of pain tend to be changing in the character increasing severity
(cresendo angina), frequency, duration as well as precipitating factors.

CLASSES OF DRUGS AND EXAMPLES OF EACH

1. Organic nitrates. Examples of drugs {Glyceryl trinitrate, isosorbide dinitrate,

and isosorbide-5-mononitrate}

2. Beta-adrenoceptor antagonists (beta-blockers) Examples of drugs {Acebutolol,

Atenolol, Betaxolol, Bisoprolol and Carteolol.

3. Calcium channel blockers. Examples of drugs. Examples of drugs {Amlodipine,

Diltiazem, Felodipine and Isradipine.}

4. Potassium channel openers. Example of drugs {Diazoxide vasodilator, Minoxidil

vasodilator, Nicorandil vasodilator and Pinacidil.

Mechanism of action of Organic nitrate

• Nitrates relax all types of smooth muscles [vascular and non-vascular] and also have a
direct relaxant effect on vascular smooth muscles, and the dilation
of coronary vessels improves oxygen supply to the myocardium.

• Relax both arteries and veins but more effective on veins and they have no direct
effect on cardiac or skeletal muscles.

• Are denitrated to release of nitric oxide and Nitrate  Nitric oxide (mediated by
glutathione S-transferase)

• The nitric oxide released stimulates guanylyl cyclase which leads to formation of
cyclic GMP and Cyclic GMP causes smooth muscle relaxation.

• In platelets cyclic GMP decreases platelet aggregation.

Side effects of nitrate

• Tachycardia (baroreceptor reflex)

• Orthostatic hypotension (direct extension of venodilator effect)

• Throbbing headache (from meningeal artery vasodilatation)

• Facial or cutaneous flushing

Drug interaction of nitrate

Interact with sildenafil and similar drugs (these drugs inhibit degradation of cGMP):
synergistic relaxation of vascular smooth muscle with potentially dangerous hypotension and
hypoperfusion of critical organs.

Contradiction of nitrate

Nitrates are contraindicated in increased intracranial pressure (however, they can be used
safely in increased intraocular pressure).

Mechanism of action Beta-adrenoceptor antagonists (beta-blocker)

• They decrease both heart rate & myocardial contractility with resultant decrease in
myocardial oxygen requirement at rest and in exercise and so improve exercise
tolerance.

Side effects of beta-blocker

Sedation, fatigue, sleep alteration, depression, bradycardia, AV blockade, heart failure and
worsen the asthma.

Drug interaction of beta-blocker

Beta blockers can interact with certain other cardiac drugs, including calcium

channel blockers and some drugs used to treat arrhythmias (irregular heart beat). ... Nitrates
or beta blockers are usually recommended first for people with stable angina.

Contradiction of beta-blocker

Beta blockers are considered ineffective, or contraindicated for variant angina (it may worsen

such attacks by blocking some β2 receptors that produce vasodilator effects, leaving α-
mediated effects unopposed.

Mechanism of action of calcium channel blockers

• Block voltage-gated “L-type” calcium channels (channel most important in cardiac

and smooth muscle) and they reduce electrical conduction within the heart.

• Reduce intracellular calcium concentration and muscle contractility (vascular smooth

muscle and myocardium)
Side effects of calcium channel blockers

• Constipation, nausea and dizziness (all)

• Headache, pretibial edema and flushing (dihydropyridines)

• Heart failure, AV blockade and sinus node depression (diltiazem and verapamil)

Drug interaction of calcium channel blockers

Calcium channel blockers are frequently added to β-adrenoceptor blocker therapy in patients

with exercise-induced angina pectoris in order to further reduce the frequency and severity of
anginal and although information is lacking on whether this combination also reduces
morbidity and mortality.

Contradiction of calcium channel blockers

Calcium channel antagonists are also contraindicated in patients with known hypersensitivity

to the drug or its components. Other contraindications include sick sinus syndrome (except in
patients with an artificial pacemaker), severe hypotension, acute myocardial infarction, and
pulmonary congestion.

Mechanism of action of Potassium channel opener

• Activates potassium channels and also causes release of nitric oxide

• Potassium opener are drugs that activate or open ATP-sensitive K +-channels in

vascular smooth muscles.

• Act by inhibition of potassium efflux through cell membranes. blockade of potassium

channels prolongs the duration of action potentials. they are used as anti-arrhythmia
agents and vasodilator agents. Potassium channels that are responsible for phase 3
repolarization. Blocking these channels slows (delays) repolarization, which leads to
an increase in action potential duration and an increase in the effective refractory
period (ERP).

Side effects of potassium channel blockers

 headache,
 flushing and
 dizziness.
Drug interaction of potassium channel blocker

These drugs are effective arterial dilators, potassium-channel openers are used in the
treatment of hypertension. They are generally used in conjunction with a beta-blocker and
diuretics to attenuate the reflex tachycardia and retention of sodium and fluid, respectively.

Contraindications of potassium channel blocker

reflex cardiac stimulation can precipitate angina in patients with coronary artery disease. One
of the most noted side-effects of minoxidil is hypertrichosis, a thickening pigmentation of the
body hair and therefore this drug is more common used for treating baldness. Minoxidil
produces T-waves changes in a high percentage (-60%) of patients under chronic treatment

Conclusion

As been described, angina is not a disease but a symptom indicating heart disease. It required
a long-term treatment in order to prevent angina from recurrence and should be taken
seriously. So, the role of pharmacist is very essential by helping the patients in managing
their life and educating them on angina in order to lead them to healthier life.

REFFERANCE

1. Williams, H. & Stevens, M. (2002) Chronic stable angina. Pharm.J.. 269:363-365

2. National Heart Lung and Blood Institute, Disease and Condition Index. Angina.

3. Khan, M.G., Topol, E.J., Saksena, S. & Goodwin, J.F. (1996) Heart Disease Diagnosis
and Therapy, A Practical Approach. William & Wilkins, Baltimore. Pages 133-183.

4. Lily L. S. Pathophysiology of Heart Disease: A Collaborative Project of Medical

Student & Faculty. 3rd Edition (2203) Lippincott. William & Wilkins.