Anti-anginal Drugs Flashcards
The underlying pathology of severe angina is…
…severe atherosclerotic affliction of larger coronary arteries
Unstable/variant angina is caused by
recurrent localized coronary vasospasms which maybe superimposed on coronary artery disease.
Drugs useful in treatment of stable angina work to
primarily reduce cardiac work by directly acting on the heart or reducing preload to cause a redistribution of blood to ischemic areas.
Drugs useful in treatment of unstable angina work to
primarily relieve the causative coronary spasms.
The symptoms of angina include
Chest pain
Referred pain
breathlessness, sweating, and nausea , vomiting and pallor in some cases.
“Autonomic symptoms” could present as increased the pulse rate and the blood pressure, pallor ,vomiting.
Typical locations for referred pain in angina are
arms (often inner left arm), shoulders, and neck into the jaw.
Major risk factors for angina include:
cigarette smoking
diabetes
high cholesterol
high blood pressure
sedentary lifestyle etc
Tests used to detect angina:
ECG, Cardiac enzymes e.g troponin, coronary angiogram
Classes of antiangina drugs
Nitrates
Beta blockers
Calcium channel blockers
K channel openers
Short-acting nitrates:
Glycerol trinitrate (GTN)
nitroglycerine.
Long-acting nitrates
Isosorbide dinitrate (short acting)
Isosorbide mononitrate
Erythrityl tetranitrate
Penta erythritol tetranitrate
The mechanism of relief of angina is by
- vasodilatory effect on larger coronary vessels to counteract coronary spasm in variant angina
- reduction of cardiac work in classical angina by action on peripheral vasculature through increase in blood supply to ischemic areas are the focus of nitrates.
Uses of nitrates
- Congestive heart failure- Causes venous pooling of blood to reduce the preload , decrease end diastolic volume and thus improve left ventricular function.
- Myocardial infarction
- Interventional cardiac procedures like percutaneous coronary angioplasty to dilate coronaries
Biliary Colic - Esophageal spasm- relives pain, taken before a meal to facilitate feeding in esophageal achalasia
RODA for GTN
- Transdermal patch for steady delivery for 24hrs, starts working within 60mins and has a high bioavailability.
- Intravenous route is rapid, steady, a titratable infusion.
- Sublingual spray or tablet : Sublingual route us useful for aborting an imminent attack. It may be crushed under the teeth and spread over the buccal mucosa. Acts within 1-2mins as it bypasses hepatic circulation where 90% is metabolized.
- Sustained release oral capsules for chronic prophylaxis.
Adverse effects of nitrates
- Headache and head fullness. Tolerance occurs after continued use
- Flushing, weakness, sweating, palpitation, dizziness and fainting
- Methemoglobinemia
- Rashes- rare more common with pentaerythritol tetranitrate
Drug interactions of nitrates
- Sildenafil causes a dangerous potentiation of nitrate – hypotension
- Additive effect when nitrates are administered with other vasodilators.
MOA of beta blockers in angina
They do not dilate coronary arteries or affect total coronary flow. They act by reducing cardiac work and O2 consumption via decrease in heart rate, inotropic state and blood pressure, thereby reducing the myocardial oxygen demand below the level that would provoke an angina attack.
How to use beta blockers for prophylaxis
Not to be used alone but with CCB±Nitrates that take care of vasospasm.
CCB MOA
- It dilates arterioles and has some α-adrenergic blocking property, decreasing the total peripheral resistance and blood pressure.
- It has cardiodepressant effect, slows AV conduction but cardiac output is maintained by reflex sympathetic stimulation.
Adverse effects of CCB
Nausea
Constipation
Hypotension
Bradycardia
Flushing
Headache
DI of CCB
It should not be administered with beta blockers due to additive sinus depression and conduction defects.
Pharmacological action of nifedipine
It has minimal effects on direct cardiac depression
Side effects of nifedipine
- Palpitation
- Flushing
- Ankle edema
- Hypotension
- Headache
- Drowsiness
- Nausea.
- It has relaxant effect on the bladder and thus increase voiding difficulty in elderly males.
Effects of CCBs on vascular smooth muscle
- Vasodilation of systemic arterial smooth muscle, reducing systemic BP
- Vasodilation of coronary arteries smooth muscle, increasing blood supply to heart
MOA of K-channel blockers
- It acts by activating the ATP sensitive K+ channels thus hyperpolarizing vascular smooth muscle.
- It also acts as an nitric oxide donor like nitrates causing relaxation of blood vessels by increasing cGMP.
- There is a combined arterial dilation coupled with venodilation.
Which class of anti angina drugs are associated with pharmacological pre-conditioning?
K-channel openers
What is pharmacological preconditioning?
When certain drugs mimic the protective effects of ischemic preconditioning. Here, Ischemia followed by reperfusion protects the tissues against subsequent prolonged ischemic events.
Explain the pharmacological conditioning of nicorandil
Nicorandil among other drugs protect the heart against acute myocardial infarction when used before the onset of acute myocardial infarction.
Examples of K channel openers
Nicorandil
Pinacidil
Cromakalim
MOA of pharmacological conditioning by nicorandil
It shows its beneficial effects of myocardial protection through the mechanism of ischemic preconditioning by opening of mitochondrial adenosine 5′-triphosphate-sensitive K+channels.
Other anti angina drugs
Dipyridamole
Trimetazidine
Oxyphedrine
Ranolazine
Ivabradine
MOA of nitrates
- Organic nitrates are rapidly denitrated enzymatically by glutathione S-transferase in the smooth muscle to release the reactive free radical nitric oxide (NO).
- NO activates cytosolic guanylyl cyclase which acts on converting GTP to cGMP.
- cGMP activates the cyclic GMP- dependent protein kinase (or PKG) that activates the myosin light chain phosphatase causing a dephosphorylation of myosin light chain kinase (MLCK).
- The contraction of smooth muscles is dependent on phosphorylated/ active MLCK and so in the dephosphorylated state, there is relaxation.
