2. ANGINA: Angina pectoris = Ischemic Heart Disease.
Angina pectoris is a syndrome
characterized by
uncomfortable sensation in the
chest or neighbouring anatomic
structure resulting from an
imbalance between oxygen supply
and demand, and is most
commonly caused by the inability
of atherosclerotic coronary arteries
to perfuse the heart under
conditions of increased myocardial
oxygen consumption.
3. Classification of Angina Pectoris:
Stable or typical angina: the
most common form of angina.
consequence of coronary
atherosclerosis.
presents in physical activity,
emotional stress etc.
predictable, reproducible
(exertion).
worse in cold conditions and
after meals
Unstable angina (crescendo/pre-
infarction angina)
- intermediate state between stable angina
and MI
-a presentation of “acute coronary
syndromes” (ACS)
-may appear unexpectedly, at rest
-often not associated with physical activity
-usually a consequence of severe coronary
atherosclerosis possibly complicated by a
rupture and thrombus formation
Prinzmetal angina (variant/vasospastic angina): an uncommon form of
angina Consequence of coronary artery spasm, occurs at rest, patients
may be younger, with lower risk, typical ECG profile
4. E
T
I
O
L
O
G
Y
Sedentary Lifestyle Genetic factor
Arteriosclerosis
Gender(Male)
Hypertension
Obesity
Some other factors are associated with angina – 1. Positive family history 2. Smoking
3. Alcohol 4. Age 5. Drug abuse 6. Stress 7. Myocardium hypoxia.
5. Pathophysiology:
Patent Lumen
Normal Endothelial function
Platelets aggregation
inhibited
No overt plaques
Intense Vasospasm
Plaque ruptured
Platelet aggregation
Thrombus formation
Unopposed vasoconstriction
Lumen narrowed by plaque
Inappropriate vasoconstriction
6. During ischemia, ATP is degraded to adenosine, which, after diffusion to
the extracellular space, causes anginal pain.
Myocardial ischemia develops when coronary blood flow becomes
inadequate to meet myocardial oxygen demand
This causes myocardial cells to switch from aerobic to anaerobic
metabolism, with a progressive impairment of metabolic, mechanical,
and electrical functions.
Studies have shown that adenosine may be the main chemical mediator
of anginal pain.
8. DIAGNOSIS OF ANGINA:
Electrocardiogram (ECG or EKG). Each beat of your heart is triggered by an electrical
impulse generated from special cells in your heart. An electrocardiogram records these
electrical signals as they travel through your heart.
Stress test. Sometimes angina is easier to diagnose when your heart is working harder.
During a stress test, you exercise by walking on a treadmill or pedaling a stationary
bicycle. Your blood pressure and ECG readings are monitored as you exercise.
Other tests also may be done at the same time as a stress test. If you're unable to
exercise, you may be given drugs that cause your heart to work harder to simulate
exercising followed by an imaging test.
Echocardiogram. An echocardiogram uses sound waves to produce images of the
heart. Your doctor can use these images to identify angina-related problems, including
heart muscle damage due to poor blood flow.
Nuclear stress test. A nuclear stress test helps measure blood flow to your heart
muscle at rest and during stress.
9. Chest X-ray. This test takes images of your heart and lungs. This is to look for other
conditions that might explain your symptoms and to see if you have an enlarged heart.
Blood tests. Certain heart enzymes slowly leak out into your blood if your heart has
been damaged by a heart attack. Samples of your blood can be tested for the presence
of these enzymes
Coronary angiography. Coronary angiography uses X-ray imaging to examine the inside
of your heart's blood vessels. It's part of a general group of procedures known as
cardiac catheterization.
Cardiac computerized tomography (CT) scan. In a cardiac CT scan, you lie on a
table inside a doughnut-shaped machine.
An X-ray tube inside the machine rotates around your body and collects images of your
heart and chest, which can show if any of your heart's arteries are narrowed or if your
heart is enlarged.
Cardiac MRI. In a cardiac MRI, you lie on a table inside a long, tubelike machine that
produces detailed images of your heart's structure and its blood vessels.
11. MOA: Entry of Ca2+ through L-type calcium channels lead to activation of myosin light
chain kinase, which then leads to phosphorylation of light chain myosin, finally
resulting actin-myosin cross bridging – and contraction of vascular smooth muscle –
resulting in vasoconstriction. • CCB blocks calcium channels – resulting – vasodilation –
predominantly arteriolar smooth muscle.
Effects on vascular smooth muscle • Vasodilation of systemic arterial smooth muscle → systemic
blood pressure • Vasodilation of coronary arterial smooth muscle → blood supply to cardiac
muscles.
Cardiac muscle • SA node → rate of nodal discharge • AV node → AV conduction •
heart rate • myocardial contractility • conduction
Pharmacokinetics:
Nifedipine is extensively converted to inactive metabolites and approximately 80% of
nifedipine and metabolites are eliminated via the kidneys
The half-life of nifedipine in plasma is approximately 2 hours
Since hepatic biotransformation is the predominant route for the disposition of
nifedipine, the pharmacokinetics may be altered in patients with chronic liver
disease
Side Effects: Dizziness Flushing Headache Transient hypotension Peripheral edema
Major drug interactions:
Cimetidine (80% increase in nifedipine plasma levels)
12. Pharmacokinetics:
Oral administration.
Plasma elimination half-life is approximately 3.0 to 4.5 hours.
Side Effects: Hypotension, AV conduction block, Bradycardia ,Constipation
Major drug interactions:
Diltiazem can produce additive effects with other antihypertensive drugs & with
cardiac effects of beta blockers
Contraindications:
Hypotension, AV block (2nd- or 3rd-degree) or sick sinus syndrome, except in the presence of a
functioning ventricular pacemaker, Acute MI, Pulmonary congestion, Lactation
Indications:
1. Vasospastic & Classic Angina (prophylactic treatment)
2. Hypertension
3. Control of ventricular rate in atrial fibrillation of flutter
Diltiazem
14. Aspirin: AE- Irritation in stomach and intestine, Feel like thrown up, Heartburn, Ringing
of ears, Haemorrhage in skull, Decrease blood platelet, Anaemia, Decrease WBC. CI-
GI bleeding, Coagulation disorder, G6PD deficiency, Thrombocytopenia,
Hypersensitivity reaction, Renal dysfunction, Asthma, Reye’s syndrome. DI- Alcohol,
Anti Coagulant, Anti diabetic produce hypoglycaemia, Ibuprofen USE- Treatment of
exertional and unstable angina, Ischemic stroke, Preventing and treating Heart attack,
as an analgesic.
Clopidogrel: AE- Easy bleeding, Abdominal pain, Diarrhoea, Fainting, Fever, Headache,
Serious bleeding in gut, eye, stomach or brain may occour.CI- Allergic disease, Peptic
ulcer, Bleeding from eye or brain, Recent surgery, Serious trauma, Liver disease,
Haemophilia, Pregnancy. DI- Anti depressant, PPI’s, Ibuprofen, Naproxen or aspirin.
USE- Unstable angina, Preventing and treating Heart attack, Peripheral Vascular
disease.
Abciximab: AE- Nausea, Vomiting, Minor bleeding, Irritation at the injection site,
Serious bleeding is the main serious side effect. CI- Bleeding within last 6 weeks,
Stroke in the last 2 years, Brain tumour or blood vessel problems in the brain,
Thrombocytopenia, Pregnancy, Liver disease, Inflammatory bowel disease. DI-
Dextran, Anti coagulant, NSAIDs(Ibuprofen, naproxen), Anti platelet
drugs(dipyridamole, ticlopidine). USE-It’s a type of blood thinner, Used in balloon
angioplasty, coronary stent placement, preccutaneous coronary intervention,
15. Glycolysis and
Beta oxidation of Fatty acid
Acetyl - CoA HMG - CoA
HMG – CoA Reductase
Inhibitor – Atrovastatin.
Mevalonate
Cholesterol
VLDL and Bile acid
LIPID LOWERING DRUGS: HMG COA REDUCTASE INHIBITORS
Statins: AE- Headache, Nausea, Vomiting, Constipation, Diarrhoea, Rash, Muscle pain,
Liver failure and rhabdomyolysis, Memory loss, Amnesia. CI- Liver disease, Pregnancy,
DI- Protease inhibitor(Ritonavir), Antibiotics(Erythromycin, Clarithromycin), Calcium
channel blockers, Grape juice. USE- Treating Atherosclerosis that causes chest pain,
Strokes, Heart attacks.
MOA:
17. MOA: It selectively inhibits the funny current (If) in sinoatrial nodal tissue, resulting in
a decrease in the rate of diastolic depolarization and, consequently, the heart rate, a
mechanism that is distinct from those of other negative chronotropic agents. Thus, it
has been evaluated and is used in select patients with systolic heart failure and chronic
stable angina without clinically significant adverse effects
AE- Blurred vision, Slow down the Heart rate, Palpitation, Change Heart rhythm,
Vertigo, Shortness of Breath, Muscle cramp, Increased blood Uric acid and Creatinine
level. CI- Caution in patients with symptoms of tiredness or shortness of breath,
chronic retinal (eye) disease, chronic heart failure, moderate liver disease, severe renal
disease, mild to moderate low blood pressure. Pregnancy and Brest feeding women.
DI- Ketoconazole, Itraconazole, Clarithromycin, Telithromycin, Erythromycin, Nelfinavir,
Ritonavir, Nefazodone. USE- Mild to severe chronic heart failure. Stable angina,
Chronic Heart failure.
18. Ischemia
Increased Late I Na
Na+ Overload
Ca++ Overload
Diastolic Relaxation Failure
(Increased diastolic tension)
Extra vascular Compression
Renolazine inhibits the late
inward Na+ current.
LATE SODIUM CHANNEL BLOCKER
Renolazine: AE- Dizziness, Nausea,
Constipation, Headache, Swelling in
hands, ankles, or feet, Slow, fast, or
irregular heartbeats, Tremors, Blood in
the urine and Shortness of breath. DI-
Clarithromycin, Ritonavir, Fluconazole,
Cyclosporine, Rifampin, Phenytoin,
Carbamazepine, Simvastatin. CI-
Hepatic impairment, Pregnancy- C,
USE- Treatment of Chronic angina and
also potentially used in other
cardiovascular conditions.
20. Sites of action of beta blockers in the treatment of angina. Beta blockers exert the majority of
their effects on heart tissue by antagonizing beta-1 receptors (the subtype most heavily
expressed in heart tissue). Beta blockers will block the effects of circulating and neuronal
catecholamines, which have the greatest effect on heart rate and ventricular contractility.
Reductions in both heart rate and contractility will reduce the work of the heart, resulting in a
decrease in myocardial oxygen demand, which is “anti-ischemic”. In addition, beta blockers also
produce a reduction in total peripheral resistance, with an associated decrease in blood
pressure & afterload. These effects also contribute to decreased work of the heart & myocardial
oxygen demand.
21. Indications:
Angina of effort (classic angina) but NOT vasospastic angina
Contraindications:
Asthma & other bronchospastic conditions
Severe bradycardia
AV block
Severe unstable LV failure
Beta Bockers are Contraindicated in Vasospastic Angina.
Side Effects:
increase in end-diastolic volume & increased ejection time, which ends up increasing
oxygen requirements, which partially offsets the beneficial effects to
reduce oxygen demands. This can be balanced by the concomitant use of nitrates
Others - fatigue, impaired exercise tolerance, insomnia, unpleasant dreams, erectile
dysfunction.
22. Side Effects are flushing, palpitation, weakness, headache, dizziness, nausea and vomiting. Large
painful aphthous ulcers in the mouth, which heal on stopping nicorandil have been reported.
23. Mechanism of Action of DP. DP increases local concentrations of adenosine, which stimulates
adenylyl cyclase in platelets leading to increased intracellular cAMP levels. In addition, by
inhibiting PDE, DP prevents the breakdown of cAMP. Increased intracellular levels of cAMP keep
platelets from being activated. Furthermore, by inhibiting PDE in the vascular wall, DP increases
PGI2 production and vascular smooth muscle cGMP levels, leading to vasodilation
Related to Antianginal Drugs
24. Summary of Maintenance Therapy for Angina
Acute Emergency Treatment of Angina
Oxygen
Nitroglycerin
Aspirin
Morphine-reduces central anxiety and relieves pain
Chronic Stable Angina of Effort
Long-acting Nitrates
Calcium Channel Blockers
Beta Blockers
Vasospastic (Variant) Angina
Nitrates
Calcium Channel Blockers
Unstable Angina Management
Antiplatelet agents, Nitroglycerin, Beta-blocker, ACE-inhibitor, Statin or other lipid-lowering
agent if applicable, In high-risk patients: catheter-based myocardial revascularization.
