Angina Pectoris

1. Drugs Used in the
Treatment of Angina
Pectoris
By:Dr.M.Usman Khalid
DPT,MS-NMPT

2. Angina pectoris
• Angina pectoris refers to a strangling or
pressure-like pain caused by cardiac ischemia.
• The pain is usually located substernally but is
sometimes perceived in the neck, shoulder
and arm, or epigastrium.

3. Classification

4. PATHOPHYSIOLOGY OF ANGINA
A. Types of Angina
1. Atherosclerotic angina: Atherosclerotic angina is also
known as angina of effort or classic angina. It is associated
with atheromatous plaques that partially occlude one or more
coronary arteries.
• When cardiac work increases (eg, in exercise), the
obstruction of flow and inadequate oxygen delivery results
in the accumulation of metabolites, eg, lactic acid, and
ischemic changes that stimulate myocardial pain endings.
• Rest, by reducing cardiac work, usually leads to complete
relief of the pain within 15 min.
• Atherosclerotic angina constitutes about 90% of angina
cases.

5. 2. Vasospastic angina
• Vasospastic angina, also known as rest angina,
variant angina, or Prinzmetal’s angina, is
responsible for less than 10% of angina cases.
• It involves reversible spasm of coronaries,
usually at the site of an atherosclerotic plaque.
Spasm may occur at any time, even during
sleep.
• Vasospastic angina may deteriorate into
unstable angina.

6. 3. Unstable angina
• A third type of angina—unstable or crescendo
angina, also known as acute coronary
syndrome—is characterized by increased
frequency and severity of attacks that result from
a combination of atherosclerotic plaques, platelet
aggregation at fractured plaques, and vasospasm.
• Unstable angina is thought to be the immediate
precursor of a myocardial infarction and is treated
as a medical emergency.

7. DETERMINANTS OF CARDIAC OXYGEN
REQUIREMENT

8. THERAPEUTIC STRATEGIES
• The defect that causes anginal pain is
inadequate coronary oxygen delivery relative
to the myocardial oxygen requirement.
• This defect can be corrected—at present—in 2
ways: by increasing oxygen delivery and by
reducing oxygen requirement.

9. THERAPEUTIC STRATEGIES
• A newer strategy attempts to increase the
efficiency of oxygen utilization by shifting the
energy substrate preference of the heart from
fatty acids to glucose.
• Drugs that may act by this mechanism are
termed partial fatty acid oxidation inhibitors
(pFOX inhibitors) and include ranolazine and
trimetazidine.

10. NITRATES
• Nitroglycerin (the active ingredient in dynamite) is
the most important of the therapeutic nitrates and
is available in forms that provide a range of
durations of action from 10–20 min (sublingual for
relief of acute attacks) to 8–10 h (transdermal for
prophylaxis).
• The efficacy of oral (swallowed) nitroglycerin
probably results from the high levels of glyceryl
dinitrate in the blood.

11. • Nitroglycerin (glyceryl trinitrate) is rapidly
denitrated in the liver and in smooth muscle.

12. B. Mechanism of Action
• Nitrates release nitric oxide (NO) within smooth
muscle cells, probably through the action of the
mitochondrial enzyme aldehyde dehydrogenase-2
(ALDH2).
• NO stimulates soluble (cytoplasmic) guanylyl
cyclase and causes an increase of the second
messenger cGMP (cyclic guanosine
monophosphate); the latter results in smooth
muscle relaxation by stimulating the
dephosphorylation of myosin light-chain
phosphate.

14. C. Organ System Effects
• 1. Cardiovascular—Smooth muscle relaxation
by nitrates leads to an important degree of
venodilation, which results in reduced cardiac
size and cardiac output through reduced
preload.
• Relaxation of arterial smooth muscle may
increase flow through partially occluded
epicardial coronary vessels.

15. • Venodilation leads to decreased diastolic heart
size and fiber tension. Arteriolar dilation leads to
reduced peripheral resistance and blood pressure.
• These changes contribute to an overall reduction
in myocardial fiber tension, oxygen consumption,
and the double product.
• Thus, the primary mechanism of therapeutic
benefit in atherosclerotic angina is reduction of
the oxygen requirement.

16. 2. Other organs
• Nitrates relax the smooth muscle of the
bronchi, gastrointestinal tract, and
genitourinary tract, but these effects are too
small to be clinically significant.
• Intravenous nitroglycerin (sometimes used in
unstable angina) reduces platelet aggregation.
• There are no clinically useful effects on other
tissues.

17. D. Clinical Uses
• The standard form for treatment of acute
anginal pain is the sublingual tablet or spray,
which has a duration of action of 10–20 min.
• Sublingual isosorbide dinitrate is similar with a
duration of 30 min.
• Transdermal formulations (ointment or patch)
can maintain blood levels for up to 24 h.
• Tolerance develops after 8–10 h.

18. E. Toxicity of Nitrates and Nitrites
• Tachycardia (from the baroreceptor reflex),
orthostatic hypotension (a direct extension of
the venodilator effect), and throbbing
headache from meningeal artery vasodilation.
• Nitrates interact with sildenafil and similar
drugs promoted for erectile dysfunction.

19. • Nitrites are of significant toxicologic
importance because they cause
methemoglobinemia at high blood
concentrations.

20. Mechanism of interaction between nitrates and drugs
used in erectile dysfunction.

21. F. Nitrites in the Treatment of Cyanide Poisoning
• The iron in methemoglobin has a higher affinity for cyanide
than does the iron in cytochrome oxidase.
• Nitrites convert the ferrous iron in hemoglobin to the ferric
form, yielding methemoglobin.
• Therefore, cyanide poisoning can be treated by a 3-step
procedure: (1) immediate inhalation of amyl nitrite,
followed by (2) intravenous administration of sodium
nitrite, which rapidly increases the methemoglobin level to
the degree necessary to remove a significant amount of
cyanide from cytochrome oxidase. This is followed by (3)
intravenous sodium thiosulfate, which converts
cyanomethemoglobin resulting from step 2 to thiocyanate
and methemoglobin.

22. CALCIUM CHANNEL-BLOCKING DRUGS
• Mechanism of Action: Calcium channel
blockers block voltage-gated L-type calcium
channels, the calcium channels most
important in cardiac and smooth muscle, and
reduce intracellular calcium concentration and
muscle contractility.

24. Effects and Clinical Use
• Calcium blockers relax blood vessels and, to a
lesser extent, the uterus, bronchi, and gut.
• Nifedipine and other dihydropyridines evoke
greater vasodilation, and the resulting
sympathetic reflex prevents bradycardia and
may actually increase heart rate.
• All the calcium channel blockers in sufficient
dosage reduce blood pressure and reduce the
double product in patients with angina.

25. Toxicity
• The calcium channel blockers cause
constipation, pretibial edema, nausea,
flushing, and dizziness. More serious adverse
effects include heart failure, AV blockade, and
sinus node depression.

26. BETA-BLOCKING DRUGS
• Beta blockers are used only for prophylactic
therapy of angina; they are of no value in an
acute attack.
• They are effective in preventing exercise-
induced angina but are ineffective against the
vasospastic form.