ANTIANGINAL (CORONARY ACTIVE) DRUGS

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ANTIANGINAL (CORONARY ACTIVE) DRUGS
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ISCHEMIC HEART DISEASE

• 2,4 mln. people die from IHD annually

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ISCHEMIC HEART DISEASE

• There are 35 risk factors for development of IHD
• 3 the most important ones are
• big triple
• hypercholesterolemia
• arterial hypertension
• smoking
• 95 of patients with IHD are observed to have
  atherosclerotic changes in coronary arteries

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Atherosclerotic changes in coronary arteries
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ANTIANGINAL (CORONARY ACTIVE) DRUGS

• ?. Nitrates and sidnonimins
• ??. Beta-adrenoblockers
• ???. Antagonists of calcium ions
• ??. Activators of potassium channels
• Inhibitors of ACE
• Platelet inhibitors and anticoagulants
• Drugs with metabolic influence on myocardium

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NITRATES

• nitroglycerin
• isosorbid dinitrate
• isosorbid-5-mononitrate

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NITROGLYCERINE

• Tablets (under the tongue)
• 1 alcohol or oil solution (under the tongue)
• aerosol
• Onset - 2-3 min
• Duration of action - 20-30 min
• ampoules 1 solution intravenously dropply
  0,01 solution
• prolonged forms of nitroglycerine trinitrolong,
  sustak, nitrong, ointment, plaster

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NITROGLYCERIN pharmaceutical forms
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NITROGLYCERIN pill bottles
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Nitroglycerinetransdermal system in a form of
plaster
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SIDE EFFECTS OF NITROGLYCERINE

• bursting, pulsating headache
• decreasing of arterial pressure
• (tachycardia, dizziness, collapse postural
  hypotension)
• facial flushing, feeling of fever

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Contraindications for nitroglycerine
administration

• increasing of intracranial pressure, insult
• acute myocardial infarction (in case of presence
  of hypotonia and collapse)

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PROLONGED FORMS OF NITROGLYCERINE

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

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Nitroglycerin 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.

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Iso Mak Retard 20mgIso Mak Retard 40mg Isomak
Retard 60mg(isosorbid dinitrate)
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IsoketIsosorbid dinitrate
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Mechanism of tolerance to nitrates
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Other nitrates

• Nitrosorbid isosorbid 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
• Isosorbid-5-mononitrate
• - pharmacologically active metabolite of
  isosorbid dinitrate
• duration of action - from 6 till 24 hours

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SYDNONIMINS

• Molsydomine corvaton - sydnopharm
• is metabolized by the liver forming a
  substance SIN-1a which contains free N? group
  (doesnt need previous interaction with
  SH-groups)
• nitric oxide stimulates guanylate cyclase that
  activates synthesis of cGMP
• cGMP causes dilation of vessels
• 2 mg of molsydomine 0,5 mg of nitroglycerin

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Molsidomine metabolism
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BETA-ADRENOBLOCKERS

• Mechanism of action during ischemic attack
• blockade of b1-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

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• Beta-adrenoblockers

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Anaprilin ß1- ß 2 adrenoblocker
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Vasocardin 100 mgMethoprolol tartrate
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Nadolol ( ß1, ß 2- adrenoblocker )
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Nebivolol
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CALCIUM 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

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Antagonists of calcium ions derivatives of
dihydropyridine of ?? generation (amlodipin,
isradipin, nicardipin)

• dont cause tachycardia
• are indicated for prolonged treatment of patients
  with stable angina
• Are not indicated in case of unstable angina
  (long onset)
•  

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Usage of calcium ions antagonists
Illness
Drugs
Hypertension
Verapamil
Dylthiazem
Nifedipin
Felodipin
Amlodipin
Stenocardia
Dylthiazem
Nifedipin
Amlodipin
Verapamil
Supraventricular tachy-arrhythmia
Verapamil
Dylthiazem
Possible combination with ß-blockers
Dylthiazem
Nifedipin
Amlodipin
Felodipin
-recommended drug


--should be used carefully
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Nifedipin (??2 ions antagonist of
dihydropyridine group)
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Nifedipin (??2 ions antagonist of
dihydropyridine group)
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Nifedipin (??2 ions antagonist of
dihydropyridine group)
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AMLODIPIN
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ACTIVATORS OF POTASSIUM CANALS

• NICORANDIL
• activates ??2-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

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Acetylsalicylic acid 80-100 mg daily

• against platelets aggregation, decreases risk of
  development of acute myocardium infarction and
  decreases mortality of patients with IHD
• Throughout the world it is also used as a drug
  for basic treatment of IHD (can be used for
  years)
• Main complication gastric bleeding

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ACUTE MYOCARDIAL INFARCTION

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

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cholesterol lowering drugs

• Statins - HMG-CoA reductase inhibitors
• Fibrates

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Statins - HMG-CoA reductase inhibitors

• block the enzyme in the liver that is responsible
  for making Cholesterol hydroxy-methylglutaryl-c
  oenzyme reductase
• Statins lower Bad Cholesterol Levels, raise Good
  Cholesterol Levels, and can slow down the
  formation of plaques in arteries.
• lower the chances of a heart attack and death in
  a group who have an elevated risk of developing
  Heart Disease or who already have Heart Disease

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Mechanism of statins action
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Benefits of Statins

• improving on the whole vascular function
• reduce the size of plaques in the arteries
• stabilize plaques there by reducing the chance of
  rupture and reduce chance of acute heart attacks
• reduce inflammation, believed to be an important
  component of plaque formation and rupture.
• Statin reduces CRP levels

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Statins
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Statins
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Cholesterol-lowering statin drugs side 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

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Fibrates entering the market over 40 years
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Fibrates
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Fibrates complications

• Nausea, diarrhea and abdominal pain
• Renal insufficiency
• Rhabdomyolysis
• Hypersensitivity, rash
• formation of gallstones

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Nicotinic 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