Anti-Anginal Drugs

Nicorandil reduces afterload and preload, while in the coronary circulation it dilates both the large epicardial and smaller resistance vessels. Because Nicorandil is an anteriolar dilator and hence primarily decrease after load.

Hydralazine and minoxidil reduce afterload by relaxing arteriolar smooth muscle. The venodilators and diuretics are used to decrease preload. The venodilators include nitroglycerine and isosorbide dinitrite. Drugs that reduce both prelod and afterload include nitroprusside, prazosin, ACE inhibitors and angiotensin II receptor blockers.

Ans. is ‘c’ i.e., Variant angina

We all know that attacks of variant angina occur due to coronary vasospasm.

So, the drugs which relieve coronary vasospasms will be used in variant angina (C.C.B.’s, Nitrates)

β blockers are contraindicated in these patients because 13 blockers, instead of dilating the coronary arteries constrict the coronary arteries (due to unopposed a mediated constriction).

Remember,

blockers are useful in classical angina. (They cause favourable redistribution of blood)

Ans. is ‘b’ i.e., Variant angina

“All CCBs are effective in reducing frequency and severity of classical as well as variant angina”.

Due to these cardiodepressant effects, it is C/I in the following conditions.

           Sick sinus syndrome (causes cardiac arrest)

           A- V block (Accentuate conduction defects)

           Congestive heart failure

           Hypotensive states

           Ventricular tachycardias

           AF with accessory pathway or WPW syndrome.

o Other conditions in which Verapamil is C/I.

           Digoxin toxicity —> Increases plasma digoxin level by decreasing its excretion, toxicity can develop.

           Quinidine and disopyramide —> Both these drugs have cardiac depressant action.

Verapamil is not used with β blockers because their depressant effect on SA and AV node may add up.

β

Ans. is ‘a’ i.e., Nitrates & ‘b’ i.e., CCBs

Ans. is ‘b’ i.e., Nitrates

Treatment of variant angina

Drugs are :

1.       Nitrates

2.       Calcium channel blockers (verapamil, diltiazem)

o Nitroglycerin is considered the drug of choice for the patient with variant angina.

o Prazosin a selective a-blocker may also be used because it prevents a mediated vasospasm.

o β-blocker’s are contraindicated because they cause constriction of coronary artery due to unopposed a mediated vasoconstriction.

Prevention of variant angina

o In contrast Nitrates are not used for the prevention of variant angina because of delevelopment of tolerance.

o CCBs are the DOC for prevention.

Ans. is ‘a’ i.e., Propranolol

o P-blocker’s are contraindicated because they cause constriction of coronary artery due to unopposed a mediated vasoconstriction.

Ans. is ‘d’ i.e., Lidocaine by bolus infusion

Ans. is ‘b’ i.e, Angina

o The drug that inhibit fatty acid oxidation is Trimetazine.

o These drugs are partial  inhibitors of FA oxidation

o These drugs also inhibit lipid peroxidation —> Reduce the generation of free radicals

o These drugs are indicated for the treatment of chronic angina pectoris who failed to respond to standard antianginal therapy.

Ans. is ‘d’ i.e., Hypotension is an established adverse effect

• Ranolazine is an effective newer anti-anginal drug but unlike CCBs and beta-blockers it does not significantly alter the heart rate or blood pressure.
• It is a piperazine derivative.

o Ranolazine appears to have other promising non-anginal effects, including glycemic control, improvement in endothelial function and decreases the incidence of atrial fibrillation and other arrhythmias.

o Ranolazine has been generally well tolerated in clinical trials its most common adverse effects are nausea, constipation and dizziness.

About option b

o Most of the text books have mentioned that ranolazine can be used as add-on therapy in chronic stable angina. o However, it has recently been approved as first line agent:

” Previously limited by its FDA indication to use in angina in combination with a calcium channel blocker, beta blocker or nitrate; ranolazine is now approved for use as a first line agent in chronic angina”. .. The Heart. org.

Ans. is ‘b’ i.e., Oxyfedrine

Drugs that exacerbate Angina

o Amphetamines                      o Alpha blocker                    o Beta agonists                     o Beta blockers withdrawal

o Dipyridamol                           o Vasopressin                       o Ergotamine                        o Decongestants

o Excessive thyroxine                 o Hydralazine                       o Methysergide                     o Minoxidil

o Nifedipine                            o Nicotine and cocaine            o Oxytocin                           o Sumatriptan

o Theophylline

Answer is A (Beta Blockers)

‘Hypertension: A companion to Braunwald’s Heart Disease (Elsevier) 2007/335

Beta-blockers are the first line drugs of choice for treatment of hypertension in patients with coronary artery disease & stable angina

`Beta blockers are the first line choice when treating hypertension in a patient with coronary artery disease’ — Evidence Based Medicine Guidelines (John Wiley & Sons)

‘Beta blockers reduce angina symptoms, improve mortality and lower BP, and they should be the drugs offirst choice in hypertensive patients with CAD and stable angina’ — ‘Hypertension: A companion to Braunwald’s Heart Disease’

Ans. A: Nitroglycerin

Their mechanism of action is systemic venodilation with concomitant reduction in LV end diastolic volume and pressure, thereby reducing myocardial wall tension and oxygen requirements.

Complications are a pulsating feeling in the head, postural dizziness.

Ans. C: Evening

If nocturnal angina is a predominant symptom, long term nitrates can be given at the end of the day

Nitrates:

• They cause vasodilation, flushing, headache, dizziness, met-hemoglobinemia
• Decreases preload and afterload
• Decreases myocardial oxygen consumption
• Causes reflex tachycardia, hypotension
• Long acting nitrates are not used chronically as tolerance develops
• *Shortest acting NITRITE: Amyl nitrite
• Shortest acting nitrate: Nitroglycerine
• Longest acting nitrate: Penta-erythritol-nitrate

Ans. a. Fasudil

Ans. is ‘c’ i.e., Beta blocker

Use of beta blocker and long acting nitrate combination is rational in classical angina because :

1. Tachycardia due to nitrate is blocked by beta blocker
2. The tendency of beta blocker to cause ventricular dilatation is countered by nitrate
3. The tendency of beta blocker to reduce the total coronary flow is opposed by nitrate

Ans. is ‘c’ i.e.,  Total coronary flow

Pharmacological actions of nitrates

• The only major action is direct nonspecific smooth muscle relaxation. The most prominant action is exerted on vascular smooth muscles.
• Preload reduction – Nitrates dilate veins more than arteries decreased venous return (preload) → decreased end diastolic size and pressure → decreased O₂ consumption.
• Afterload reduction – Nitrates also produce some arteriolar dilatation → slightly decreased total peripheral resistance (afterload).
• Redistribution of coronary flow –
• There are two types of vessels in coronary circulation.

1. Larger conducting arteries which run epicardially and send perforating branching to deeper tissue (endocardium).
2. Smaller resistance arterioles – These are the perforating branches of larger conducting arteries. These arterioles supply blood to endocardium. Ischemia causes dilatation of these vessles by autoregulatory mechanism.

Nitrates preferentially dilate bigger conducting vessels. This pattern of action cause favourable redistribution of blood to ischemic zone because the smaller resistance vessels in ischemic zone are dilated by autoregulatory mechanism, while smaller resistance vessels in non ischemic zone are not dilated  → blood supply of ischemic zone is increased.

• Nitrates do not appreciably increase total coronary flow in angina patients.
• The dilator effect on larger coronary vessels is the principal action of nitrates benefiting variant angina by counteracting coronary spasm.
• In classical angina, primary effect is to reduce cardiac wark.
• Other smooth muscles – Nitrates cause relaxation of bronchi, biliary tract, esophagus → can be used in biliary colic and esophageal spasm.

Mechanism of action

• Organic nitrates are rapidly denitrated enzymatically in the smooth muscle cell to release nitric oxide (NO) which activates cytosolic guanyl cyclase → rcGMP  → Vasodilatation.
• Veins express greater amount of the enzyme that generates NO from organic nitrates than arteries – Account for the predominant venodilatory effect.

Remember

• The NO generated from nitrates activates cGMP production in platelets as well mild antiaggregatory effect.

Ans. a. Fasudil

Ans. is ‘b’ i.e., Ranolazine 

Ranolazine

• Ranolazine is an effective newer anti-anginal drug but unlike CCBs and beta-blockers it does not significantly alter the heart rate or blood pressure.
• Ranolazine alters the trans-cellular late sodium current and affects the sodium dependent calcium channels during myocardial ischaemia thus prevents calcium overload, resulting in reduced oxygen demand, and prevent angina.
• Ranolazine is useful as add-on therapy in chronic stable angina which is refractory to more standard anti-anginal medication. However, it is not found to be useful in acute coronary syndrome.
• Ranolazine should be used in combination with amlodipine, l3-blockers or nitrates. It should not be used as an alternative to n-blocker therapy in patients otherwise eligible for this form of therapy.
• Ranolazine appears to have other promising non-anginal effects, including glycemic control, improvement in endothelial function and decreases the incidence of atrial fibrillation and other arrhythmias.
• Ranolazine may increase the QT interval and hence it should not be used in patients with long- QT syndrome and
• should be used with caution when combined with other medications that increase the QT interval.
• Ranolazine has been generally well tolerated in clinical trials its most common adverse effects are nausea, constipation and dizziness.

Ans. is ‘c’ i.e., GTN 

PHARMACOLOGICALTREATMENT OF STABLE (CLASSICALANGINA)

• For immediate pre-exertional prophylaxis and acute attack
• Sublingual glyceral trinitrate (Drug of choice)
• Acts by decreasing preload (LV filling pressure → myocardial oxygen demand).
• Also cause redistribution of blood flow to the ischemic zone by dilating conducting coronary vessels.
• Nifedipine by bite capsule
• Decrease myocardial oxygen demand by decreasing contractility and arterial pressure.
• Also dilates coronary artery.

For long term prophylaxis

• fl-blockers (DOC)
• They reduces the myocardial oxygen demand by inhibiting the increase in heart rate, arterial pressure and myocardial contractility caused by adrenergic stimulation.
• CCBs 
• Are used if coronary spasm is suspected or P-blockers are contraindicated.
• Long acting nitrates o Usually avoided because of development of tolerance.
• Nicorandil (Potassium-channel opener)
• Decreases preload (venodilatation) and L.V. filling pressure –> myocardial oxygen demand.
• ACE inhibitors
• Particularly useful in patient at increased risk, especially if DM or LV dysfunction is present, and in those who have not achieved adequate control of blood pressure by 13-blockers.

Ans. is ‘a’ i.e., Nitroglycerine 

Treatment of variant angina

• Prinzmetal’s variant angina is due to spasm of coronary vessels.
• The drugs which dilate the coronary vessels, are the main treatment of Prinzmental’s angina.
• Drugs are :

1. Nitrates
2. Calcium channel blockers (verapamil, diltiazem)

• Nitroglycerin is considered the drug of choice for the patient with variant angina.
• Prazosin a selective a-blocker may also be used because it prevents a mediated vasospasm.
• ii-blocker’s are contraindicated because they cause constriction of coronary artery due to unopposed a mediated vasoconstriction.

Prevention of variant angina

• In contrast Nitrates are not used for the prevention of variant angina because of delevelopment of tolerance.
• CCBs are the DOC for prevention.