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Antianginal Antianginal AgentsAgents

Dr.Shadi-SarahroodiDr.Shadi-Sarahroodi

Pharm.D & PhDPharm.D & PhD

Qom University of Medical sciencesQom University of Medical sciences

IranIran

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Angina Pectoris (Chest Angina Pectoris (Chest Pain)Pain)

When the supply of oxygen and When the supply of oxygen and nutrients in the blood is nutrients in the blood is insufficient to meet the demands insufficient to meet the demands of the heart, the heart muscle of the heart, the heart muscle achesaches..


Types of AnginaTypes of Angina

Atherosclerotic angina Atherosclerotic angina (also called classic or effort angina)(also called classic or effort angina)

Vasospastic anginaVasospastic angina(also called Prinzmetal’s or variant angina)(also called Prinzmetal’s or variant angina)

Unstable anginaUnstable angina(also called preinfarction or crescendo (also called preinfarction or crescendo angina)angina)


Antianginal Agents:Antianginal Agents:

Therapeutic ObjectivesTherapeutic Objectives Increase blood flow to ischemic heart muscleIncrease blood flow to ischemic heart muscle

and/orand/or Decrease myocardial oxygen demandDecrease myocardial oxygen demand


Antianginal AgentsAntianginal Agents

NitratesNitrates Beta blockersBeta blockers Calcium channel Calcium channel

blockersblockers


intracellular conversion to nitrite ions, and then to intracellular conversion to nitrite ions, and then to nitric oxidenitric oxide

activates guanylate cyclase activates guanylate cyclase and increases the and increases the cells' cyclic guanosine monophosphate cells' cyclic guanosine monophosphate (cGMP).(cGMP).

Elevated cGMP ultimately leads to Elevated cGMP ultimately leads to dephosphorylation of the myosin light chaindephosphorylation of the myosin light chain, , resulting in vascular resulting in vascular smooth muscle relaxationsmooth muscle relaxation


Organic NitratesOrganic Nitrates

Ferid Murad


Antianginal Agents: Antianginal Agents: NitratesNitrates

Available forms:Available forms:SublingualSublingual OintmentsOintments

BuccalBuccal Transdermal patchesTransdermal patches

Chewable tabletsChewable tablets Inhalable spraysInhalable sprays

CapsulesCapsules Intravenous Intravenous solutionssolutions


BENEFITS OF BENEFITS OF NITRATESNITRATES Reduce myocardial oxygen demand by dilating veins and Reduce myocardial oxygen demand by dilating veins and

increase venous pooling of blood increase venous pooling of blood

Increase systemic arteriolar vasodilation (intravenous Increase systemic arteriolar vasodilation (intravenous forms only) forms only)

Directly dilate undiseased coronary arteries, helping Directly dilate undiseased coronary arteries, helping restore blood flow deep within myocardial tissues restore blood flow deep within myocardial tissues

Decrease ventricular wall tension due to increased venous Decrease ventricular wall tension due to increased venous pooling pooling

Improve exercise tolerance Improve exercise tolerance


Antianginal Agents: Antianginal Agents: Nitrates Nitrates

NitroglycerinNitroglycerin Prototypical nitratePrototypical nitrate Large first-pass effect with PO formsLarge first-pass effect with PO forms Used for symptomatic treatment of ischemic Used for symptomatic treatment of ischemic

heart conditions (angina)heart conditions (angina) IV form used for BP control in perioperative IV form used for BP control in perioperative

hypertension, treatment of CHF, ischemic hypertension, treatment of CHF, ischemic pain, pain, and pulmonary edema associated with acute and pulmonary edema associated with acute MIMI


Antianginal Agents: Antianginal Agents: Nitrates Nitrates isosorbide dinitrate isosorbide dinitrate

(Isordil, Sorbitrate, Dilatrate SR)(Isordil, Sorbitrate, Dilatrate SR) isosorbide mononitrate isosorbide mononitrate

(Imdur, Monoket, ISMO)(Imdur, Monoket, ISMO)

Used for:Used for: Acute relief of anginaAcute relief of angina Prophylaxis in situations that may provoke Prophylaxis in situations that may provoke

anginaangina Long-term prophylaxis of anginaLong-term prophylaxis of angina



Antianginal Agents: Antianginal Agents: Nitrates Nitrates

Side EffectsSide Effects HeadacheHeadache

– Usually diminish in intensity and Usually diminish in intensity and frequency with continued usefrequency with continued use

Tachycardia, postural hypotensionTachycardia, postural hypotension Tolerance may developTolerance may develop facial flushing, and tachycardiafacial flushing, and tachycardia


ToleranceTolerance

blood vessels become blood vessels become desensitizeddesensitized to vasodilationto vasodilation

daily daily “nitrate-free interval”“nitrate-free interval” typically typically 10 to 12 hours10 to 12 hours, usually at , usually at

nightnight, because demand on the , because demand on the heart is decreased at that timeheart is decreased at that time

variant angina worsens early in the morning, variant angina worsens early in the morning, perhaps due to circadian catecholamine surgesperhaps due to circadian catecholamine surges


Antianginal Agents: Antianginal Agents: Beta BlockersBeta Blockers


Antianginal Agents: Antianginal Agents: Beta BlockersBeta Blockers

Mechanism of ActionMechanism of Action Decrease the HRDecrease the HR, resulting in decreased , resulting in decreased

myocardial oxygen demand and increased myocardial oxygen demand and increased oxygen delivery to the heartoxygen delivery to the heart

Decrease myocardial contractilityDecrease myocardial contractility, helping to , helping to conserve energy or decrease demandconserve energy or decrease demand


Propranolol is the prototype: not Propranolol is the prototype: not cardioselectivecardioselective

metoprolol or atenolol, are metoprolol or atenolol, are preferredpreferred


All β-blockers are nonselective at All β-blockers are nonselective at high doses and can inhibit βhigh doses and can inhibit β22 receptors.receptors.

Important in asthmatics.Important in asthmatics.


contraindicationcontraindication

AsthmaAsthma DiabetesDiabetes severe bradycardiasevere bradycardia peripheral vascular diseaseperipheral vascular disease chronic obstructive pulmonary chronic obstructive pulmonary

disease. disease.


Do not discontinue β-blocker therapy Do not discontinue β-blocker therapy abruptlyabruptly. .

The dose should be gradually tapered The dose should be gradually tapered off over off over 5 to 10 days 5 to 10 days to avoid to avoid rebound angina rebound angina or or hypertensionhypertension.].]


Antianginal Agents: Antianginal Agents: Calcium Channel Calcium Channel BlockersBlockers


Mechanism of ActionMechanism of Action

Calcium influx is increased Calcium influx is increased in in ischemia because of the membrane ischemia because of the membrane depolarization that hypoxia depolarization that hypoxia producesproduces

In turn, this promotes the activity of In turn, this promotes the activity of several adenosine triphosphate–several adenosine triphosphate–consuming enzymes, thereby consuming enzymes, thereby depleting energy stores and depleting energy stores and worsening the ischemiaworsening the ischemia


Antianginal Agents: Antianginal Agents: Calcium Channel Calcium Channel BlockersBlockers Cause peripheral arterial vasodilationCause peripheral arterial vasodilation Reduce myocardial contractility Reduce myocardial contractility

(negative inotropic action)(negative inotropic action) Result: decreased myocardial oxygen Result: decreased myocardial oxygen

demanddemand


NifedipineNifedipine

a dihydropyridine derivativea dihydropyridine derivative arteriolar vasodilatorarteriolar vasodilator OralOral Usually: extended-release tablets.Usually: extended-release tablets. Hepatic metabolismHepatic metabolism Eliminate in both urine and the Eliminate in both urine and the

fecesfeces


Side EffectsSide Effects

FlushingFlushing HeadacheHeadache HypotensionHypotension peripheral edema as peripheral edema as all all calcium-channel blockerscalcium-channel blockers are are

with with constipationconstipation is a problem is a problem


VerapamilVerapamil

Slows AV conductionSlows AV conduction decreases heart rate, contractility, decreases heart rate, contractility,

blood pressure, and oxygen demandblood pressure, and oxygen demand contraindicatedcontraindicated in patients with in patients with

preexisting depressed cardiac preexisting depressed cardiac function or AV conduction function or AV conduction abnormalitiesabnormalities


DiltiazemDiltiazem

slow AV conductionslow AV conduction decrease the rate of firing of the decrease the rate of firing of the

sinus node pacemakersinus node pacemaker metabolized by the livermetabolized by the liver


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