ANTIANGINALANTIANGINAL ((CORONARY ACTIVECORONARY ACTIVE) )

DRUGSDRUGS

ISCHEMIC HEART DISEASEISCHEMIC HEART DISEASE

2,4 mln. people die from IHD annually

ISCHEMIC HEART DISEASEISCHEMIC HEART DISEASE

There are 35 risk factors for development of IHD 3 the most important ones are –

““big triplebig triple””

hypercholesterolemiahypercholesterolemia arterial hypertensionarterial hypertension

smokingsmoking

95 % of patients with IHD are observed to have atherosclerotic changes in coronary arteries

Atherosclerotic changes Atherosclerotic changes in coronary arteriesin coronary arteries

ANTIANGINALANTIANGINAL ( (CORONARY CORONARY ACTIVEACTIVE) ) DRUGSDRUGS

І. І. Nitrates and sidnonimins Nitrates and sidnonimins

ІІ. ІІ. BetaBeta--adrenoblockersadrenoblockers

ІІІ. ІІІ. Antagonists of calcium ionsAntagonists of calcium ions

ІУ. ІУ. Activators of potassium channelsActivators of potassium channels

• Inhibitors of ACE

• Platelet inhibitors and anticoagulants

• Drugs with metabolic influence on myocardium

NITRATESNITRATES

nitroglycerinnitroglycerin

isosorbidisosorbid dinitratedinitrate

isosorbidisosorbid-5--5-mononitratemononitrate

NITROGLYCERINENITROGLYCERINE

• TabletsTablets (under the tongue)• 1 % alcohol or oil solutionsolution (under the tongue)• aerosolaerosol

OnsetOnset - - 2-3 2-3 minmin

Duration of actionDuration of action - 20-30 - 20-30 minmin• ampoulesampoules 1 % solution – intravenously dropply

0,01% solution• prolongedprolonged forms of nitroglycerine: trinitrolong,

sustak, nitrong, ointment, plaster

NITROGLYCERINNITROGLYCERIN pharmaceutical formspharmaceutical forms

NITROGLYCERINNITROGLYCERIN pill bottlespill bottles

NitroglycerineNitroglycerinetransdermal system in a form of plaster

SIDE EFFECTS OF SIDE EFFECTS OF NITROGLYCERINENITROGLYCERINE

burstingbursting, , pulsating headachepulsating headache

decreasing of arterial pressuredecreasing of arterial pressure

((tachycardiatachycardia, , dizzinessdizziness, , collapsecollapse – – postural hypotensionpostural hypotension))

facial flushingfacial flushing, , feeling of feverfeeling of fever

Contraindications for Contraindications for nitroglycerine administrationnitroglycerine administration

• increasing of intracranial pressure, insult

• acute myocardial infarction (in case of presence of hypotonia and collapse)

PROLONGED FORMS OF PROLONGED FORMS OF NITROGLYCERINENITROGLYCERINE

• Trinitrolong – polymer films (0,001 g or 0,002 g of nitroglycerine) action develops immediately, lasts for 3-5 hours

• Sustac - Sustaс-mite (contains 0,0026 g of nitroglycerine) and Sustac-forte (0,0064 g of nitroglycerine)

onset – after 10 min, maximal action – after 1 hour, duration of action – 4-5 hours

• Nitrong – microcapsule form of nitroglycerine of prolonged action

onset – 30-60 min, maximal effect - after 3-4 hours,

Duration of action - 6-8 hours

Nitroglycerin and Premature BirthNitroglycerin and Premature Birth• The five-year, randomized check

involved 153 women selected at the time they went into pre-term labor (at 24 to 28 weeks).

• Employing nitroglycerin patches for pregnant women prolonged their pregnancy and what's new, the babies were born healthy, with less side effects than those induced by other drugs.

• In Canada, about 7.5 % of all babies are born prematurely (before 37 weeks) and 1 to 2 % are severe cases, before 34 weeks.

Iso Mak Retard 20mgIso Mak Retard 40mg Isomak Retard 60mg(isosorbid dinitrate)

IsoketIsoketIsosorbid dinitrateIsosorbid dinitrate

Mechanism of tolerance to nitratesMechanism of tolerance to nitrates

Other nitratesOther nitratesNitrosorbid Nitrosorbid – – isosorbid dinitrateisosorbid dinitrate

onset - 30-50 min, duration of action – 4-6 hours and more

With sublingual administration of the drug onset decreases to 3-5 min

• buccal form (Dinitrosorbilong)• tablets of prolonged action (Isoket-retard)

• ointment• aerosol

• drugs for intravenous introduction

IsosorbidIsosorbid-5--5-mononitratemononitrate - pharmacologically active metabolite of isosorbid dinitrate

duration of action - from 6 till 24 hours

SYDNONIMINSSYDNONIMINSMolsydomineMolsydomine – – corvatoncorvaton - - sydnopharmsydnopharm

• is metabolized by the liver forming a substance – SIN-1a which contains free NО group (doesn’t need

previous interaction with SH-groups) • nitric oxide stimulates guanylate cyclase that

activates synthesis of cGMP• cGMP causes dilation of vessels

2 2 mg of molsydominemg of molsydomine == 0,5 0,5 mg of nitroglycerinmg of nitroglycerin

Molsidomine metabolismMolsidomine metabolism

BETA-ADRENOBLOCKERSBETA-ADRENOBLOCKERSMechanism of action during ischemic attackMechanism of action during ischemic attack

• blockade of 1-adrenoreceptors of heart: decrease of cardiac output and frequency of heart contractions and as follows cardiac need in oxygen

• decreasing of platelets aggregation and prevention of plug formation

• increasing duration of diastole – improvement of coronary vessels saturation with blood – improvement of perfusion of ischemic areas of myocardium

• Decreasing of calcium ions accumulation – releasing of cardiac muscle tension, improvement of metabolic processes, increasing of ATP synthesis

• in case of acute myocardium infarction – increasing of blood supply of ischemic areas of heart, decreasing of size of infarction area, prevention of development of cardiac arrhythmias

Beta-adrenoblockersBeta-adrenoblockers

AnaprilinAnaprilin β1- β 2 adrenoblocker

Vasocardin Vasocardin 100 100 mgmg

Methoprolol tartrateMethoprolol tartrate

NadololNadolol (( β1, β 2- β1, β 2- adrenoblockeradrenoblocker ))

NebivololNebivolol

CALCIUM IONS ANTAGONISTSCALCIUM IONS ANTAGONISTS

1. Derivatives of difenilalkilamin (verapamil)2. Derivatives of benzothiazepine (dylthiazem)

3. Derivatives of dihydropyridine (nifedipin, amlodipin, nimodipin)

Drugs of 1 and 2 groups dominantly influence on heart (depress automatism of sinus node, slow cardiac conduction, decrease heart rate and oxygen demand), show antiarrhythmic, antianginal and hypotensive action

Derivatives of dihydropyridine (group of nifedipin) – decrease blood pressure and cause dilation of coronary vessels, cause reflective tachycardia

Antagonists of calcium ionsAntagonists of calcium ions – derivatives of dihydropyridine of ІІ ІІ generationgeneration (amlodipinamlodipin,

isradipin, nicardipin)

• don’t cause tachycardiadon’t cause tachycardia

• areare indicated for prolonged treatment of indicated for prolonged treatment of patients with stable anginapatients with stable angina

• Are not indicatedAre not indicated in case of unstable anginain case of unstable angina ((long onsetlong onset))

  

Hypertension Verapamil Dylthiazem Nifedipin Felodipin Amlodipin

Stenocardia Dylthiazem

Nifedipin Amlodipin Verapamil

Supraventricular tachy-arrhythmia

Verapamil Dylthiazem

Possible combination with β-blockers

Dylthiazem Nifedipin Amlodipin

-recommended drug --should be used carefully

Usage of calcium ions antagonistsUsage of calcium ions antagonists

Illness Drugs

Felodipin

Nifedipin (Са2+ ions antagonist of dihydropyridine group)

Nifedipin (Са2+ ions antagonist of dihydropyridine group)

Nifedipin (Са2+ ions antagonist of dihydropyridine group)

AMLODIPINAMLODIPIN

ACTIVATORS OF POTASSIUM ACTIVATORS OF POTASSIUM CANALS CANALS

NICORANDILNICORANDIL

• activates Са2+-depending potassium channels• causes relaxation of smooth muscles of vessels – coronary, arteriolar and venous vasodilation • improves of blood supply of myocardium,

decreasing of pre- and afterloads of heart, decreasing of myocardial need in oxygen, of ischemic damage zone

Acetylsalicylic acid Acetylsalicylic acid 80-100 80-100 mg dailymg daily

• against platelets aggregationagainst platelets aggregation,, decreases risk of development of acute decreases risk of development of acute myocardium infarction and decreases myocardium infarction and decreases mortality of patients with IHDmortality of patients with IHD

• Throughout the world it is also used as Throughout the world it is also used as a drug for basic treatment of IHD (can a drug for basic treatment of IHD (can be used for years)be used for years)

• Main complication – gastric bleedingMain complication – gastric bleeding

ACUTE MYOCARDIAL ACUTE MYOCARDIAL INFARCTIONINFARCTION

From a 45-year-old man who died of an acute myocardial infarction. Postmortem serum Cholesterol 100 times more than normal.

cholesterol lowering drugscholesterol lowering drugs

Statins - HMG-Statins - HMG-CoA reductase CoA reductase

inhibitorsinhibitors

FibratesFibrates

Statins - HMG-CoA reductase Statins - HMG-CoA reductase inhibitorsinhibitors

• block the enzyme in the liver that is responsible block the enzyme in the liver that is responsible for making Cholesterol – for making Cholesterol – hydroxy-methylglutaryl-coenzyme reductase hydroxy-methylglutaryl-coenzyme reductase

• Statins lower Bad Cholesterol Levels, raise Statins lower Bad Cholesterol Levels, raise Good Cholesterol Levels, and can slow down Good Cholesterol Levels, and can slow down the formation of plaques in arteries. the formation of plaques in arteries.

• lower the chances of a heart attack and death in lower the chances of a heart attack and death in a group who have an elevated risk of a group who have an elevated risk of developing Heart Disease or who already have developing Heart Disease or who already have Heart DiseaseHeart Disease

Mechanism of statins action Mechanism of statins action

Benefits of StatinsBenefits of Statins

• improving on the whole vascular functionimproving on the whole vascular function

• reduce the size of plaques in the arteriesreduce the size of plaques in the arteries

• stabilize plaques there by reducing the stabilize plaques there by reducing the chance of rupture and reduce chance of chance of rupture and reduce chance of acute heart attacksacute heart attacks

• reduce inflammation, believed to be an reduce inflammation, believed to be an important component of plaque formation important component of plaque formation and rupture.and rupture.

• Statin reduces CRP levelsStatin reduces CRP levels

StatinsStatins

StatinsStatins

Cholesterol-lowering “statin” drugs Cholesterol-lowering “statin” drugs side effectsside effects

• fatigue• muscle pain (9 % of patients) • at higher doses and long term administration –

myopathy (rhabdomyolysis) acute damage to muscle tissue - can be very serious

• reduced proliferation• damage to kidneys• increased risk for cataracts• elevated blood sugar• increased risk for prostate and breast cancer

Fibrates entering the market over 40 yearsFibrates entering the market over 40 years

FibratesFibrates

Fibrates complicationsFibrates complications

• Nausea, diarrhea and abdominal pain

• Renal insufficiency

• Rhabdomyolysis

• Hypersensitivity, rash

• formation of gallstones

Nicotinic acid or niacinNicotinic acid or niacin

useful for patients with mixed dyslipidemias

inhibits transport of free fatty acids to the liver from peripheral adipose tissue resulting in decreased triglyceride synthesis

increases in HDL cholesterol and decreases in VLDL and LDL cholesterol

for diabetic dyslipidemia to increase HDL cholesterol