CLINICAL PHARMACY IN CARDIOLOGY

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CLINICAL PHARMACY IN CARDIOLOGY
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ISCHEMIC HEART DISEASE

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

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Angina, or angina pectoris, is the medical term
used to describe the temporary chest discomfort
that occurs when the heart is not getting enough
blood

• The heart is a muscle (myocardium) and gets its
  blood supply from the coronary arteries.
• Blood carries the oxygen and nutrients the heart
  muscle needs to keep pumping.
• When the heart does not get enough blood, it can
  no longer function at its full capacity.
• When physical exertion, strong emotions, extreme
  temperatures, or eating increase the demand on
  the heart, a person with angina feels temporary
  pain, pressure, fullness, or squeezing in the
  center of the chest or in the neck, shoulder,
  jaw, upper arm, or upper back. This is angina,
  especially if the discomfort is relieved by
  removing the stressor and/or taking sublingual
  (under the tongue) nitroglycerin.
• The discomfort of angina is temporary, meaning a
  few seconds or minutes, not lasting hours or all
  day.

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• An episode of angina is not a heart attack.
  Having angina means the patient have an increased
  risk of having a heart attack.
• A heart attack is when the blood supply to part
  of the heart is cut off and that part of the
  muscle dies (infarction).
• Angina can be a helpful warning sign if it makes
  the patient seek timely medical help and avoid a
  heart attack.
• Prolonged or unchecked angina can lead to a heart
  attack or increase the risk of having a heart
  rhythm abnormality. Either of those could lead to
  sudden death.

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Not all chest pain is angina. Pain in the chest
can come from a number of causes, which range
from not serious to very serious

• Chest pain can be caused by
• acid reflux (gastroesophageal reflux disease,
  GERD),
• upper respiratory infection,
• asthma, or
• sore muscles and ligaments in the chest (chest
  wall pain)
• If chest pain is severe and/or recurrent, the
  patient should see a healthcare provider.

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Life-threatning symptoms chest pain

• sweating,
• weakness,
• faintness,
• numbness or tingling,
• nausea
• Pain that does not go away after a few minutes
• Pain that is of concern in any way

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Angina is classified as one of the following two
types

• Stable angina
• People with stable angina usually have angina
  symptoms on a regular basis. The episodes occur
  in a pattern and are predictable.
• For most people, angina symptoms occur after
  short bursts of exertion.
• Stable angina symptoms usually last less than
  five minutes.
• They are usually relieved by rest or medication,
  such as nitroglycerin under the tongue.

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Unstable angina

• Angina symptoms are unpredictable and often occur
  at rest.
• This may indicate a worsening of stable angina,
  but sometimes the first time a person has angina
  it is already unstable.
• The symptoms are worse in unstable angina - the
  pains are more frequent, more severe, last
  longer, occur at rest, and are not relieved by
  nitroglycerin under the tongue.
• Unstable angina is not the same as a heart
  attack, but it warrants an immediate visit to the
  healthcare provider or a hospital emergency
  department. The patient may need to be
  hospitalized to prevent a heart attack.

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Most cases of coronary heart disease are caused
by atherosclerosis (hardening of the arteries).

• Atherosclerosis is a condition in which a fatty
  substance/cholesterol builds up inside the blood
  vessels. These buildups are called plaques, and
  they can block blood flow through the vessels
  partially or completely.
• Multiple risk factors
• diabetes,
• high blood pressure,
• smoking,
• high cholesterol, and
• genetic predisposition may accelerate this build
  up.

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Coronary Artery Spasm

• Another cause of unstable angina is coronary
  artery spasm.
• Spasm of the muscles surrounding the coronary
  arteries causes them to narrow or close off
  temporarily. This blocks the flow of blood to the
  heart muscle for a brief time, causing angina
  symptoms.
• This is called variant angina or Prinzmetal
  angina.
• This is not the same as atherosclerosis, although
  some people have both conditions.
• The symptoms often come on at rest (or during
  sleep) and without apparent cause.
• Cocaine use/abuse can cause significant spasm of
  the coronary arteries and lead to a heart attack.
  

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Angina Pectoris Symptoms

• Angina itself is a symptom (or set of symptoms),
  not a disease. Any of the following may signal
  angina
• An uncomfortable pressure, fullness, squeezing,
  or pain in the center of the chest
• It may also feel like tightness, burning, or a
  heavy weight.
• The pain may spread to the shoulders, neck, or
  arms.
• It may be located in the upper abdomen, back, or
  jaw.
• The pain may be of any intensity from mild to
  severe.

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Other symptoms may occur with an angina attack

• Shortness of breath
• Lightheadedness
• Fainting
• Anxiety or nervousness
• Sweating or cold, sweaty skin
• Nausea
• Rapid or irregular heart beat
• Pallor (pale skin)
• Feeling of impending doom
• These symptoms are identical to the signs of an
  impending heart attack described by the American
  Heart Association. It is not always easy to tell
  the difference between angina and a heart attack,
  except angina only lasts a few minutes and heart
  attack pain does not go away.

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Antianginal (coronary active) drugs

• a group of drugs which using different
  mechanisms even out irregularities between
  myocardium need in oxygen and its blood supply
  by coronary arteries
• clinically it is manifested by removal or
  prevention of angina attacks (improvement of
  disease current) and increasing of patients
  tolerance to physical load

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ANTIANGINAL (CORONARY ACTIVE) DRUGS

• ?. Nitrates and sidnonims which are close to the
  first ones
• ??. Beta-blockers
• ???. Calcium channel blockers (CCBs)
• ??. Activators of potassium channels
• Hypercholesterolemia drugs
• Antiplatelets and anticoagulants
• Drugs with metabolic influence on miocardium

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NITRATES

• nitroglycerin
• isosorbid dinitrate
• isosorbid-5-mononitrate

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MECHANISM OF ACTION OF NITRATES

• Interaction with sulfhydryl (SH-) groups
  (nitrate receptors) inside cells of vascular
  smooth muscles
• Stimulation of formation of endothelial factor of
  relaxation of vessels (?RF) nitrogen oxide (NO)
  
• Decreasing of ionized ??2 contents
• Relaxation, dilation of vessels, including
  coronary vessels

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MECHANISM OF ACTION OF NITRATES

• Decreasing of tone of venules decreasing of
  preloading (income of blood into heart during
  diastole) decreasing of work of left ventricle
  and heart output
• Decreasing of tone of arterioles decreasing of
  afterloading (decreasing of arterial pressure,
  end diastolic pressure in left ventricle and its
  volume, decreasing of tension of myocardium wall
• decreasing of heart need in oxygen
• improvement of blood float in ischemic zone of
  myocardium redistribution of coronary blood
  circulation with increasing of perfusion of
  subendocardial areas
• dilation of large coronary vessels if they are
  in spasm or narrowed with aterosclerotic mass
• development of anastomoses between arteries in
  myocardium (in case of prolonged administration)

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NITROGLYCERINE

• Tablets (under the tongue)
• 1 alcohol or oil solution (under the tongue)
• aerosol
• Latent period - 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 is taken only when the patient
  actually has symptoms or expect to have them.
  Slow - or long-acting nitroglycerin can be used
  as a preventative treatment for angina but not
  until beta blockers are tried first.

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NitroglycerineUnique transdermal system in a
form of plaster
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SIDE EFFECTS OF NITROGLYCERINE

• bursting, pulsating headache
• decreasing of arterial pressure
• (heartbeat, dizziness, collapse)
• skin redness, feeling of fever

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Contraindications for nitroglycerine use

• Close-angled form of glaucoma
• increasing of intracranial pressure, stroke
• acute myocardium infarction (in case of presence
  of hypotension 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)
• beginning of action after 10 min,
• maximal action after 1 hour,
• duration of action 4-5 hours
• Nitrong microcapsule form of nitroglycerine of
  prolonged action
• latent period 30-60 min,
• maximal effect - after 3-4 hours,
• action duration - 6-8 hours

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Other nitrates

• Nitrosorbid isosorbid dinitrate
• latent period 30-50 min,
• duration of action 4-6 hours and more
• With sublingual administration of the drug latent
  period grows short to 3-5 min
• buccal form (Dinitrolslrbilong)
• 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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Iso Mak Retard 20mgIso Mak Retard 40mg Isomak
Retard 60mg(isosorbid dinitrate)
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IsoketIsosorbid dinitrate
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SYDNONIMINS

• Molsidomine corvaton - sydnopharm
• is metabolized in liver forming a substance
  SIN-1a which contains free N? group (doesnt
  need previous interaction with SH-groups)
• nitrogen oxide stimulates guanilatecyclase that
  activates synthesis of cGMP
• cGMP causes dilation of vessels
• 2 mg of molsidomine 0,5 mg of nitroglycerine

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Molsidomine

• latent period - 20 min (5-10 min if
  administered sublingually), action duration - 6
  hours.
• can be used for prophylaxis and releasing angina
  attacks in patients with glaucoma
  (doesnt increase intraocular pressure)
• indicated for patients who make breaks in using
  nitrates to decrease tolerance towards them
• doesnt lead to development of tolerance (doesnt
  need previous combining with drugs containing SH-
  groups)
• absence of withdrawal syndrome

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BETA-BLOCKERS

• Using in Angina
• blockade of b1-adrenoreceptors of heart
  decreasing of power and frequency of heart
  contractions and as follows cardiac need in
  oxygen
• decreasing of thrombocyte aggregation and
  prevention of clotts formation
• increasing of diastole duration 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 seat,
  prevention of development of cardiac arrhythmias

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Anaprilin ß1- ß 2 adrenoblocker
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Vasocardin 100 mgMethoprolol tartrate
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Nebivololbeta-blocker that also causes
vasodilation by stimulating the release of nitric
oxide
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• Beta blockers are taken every day, regardless of
  whether the patient is having symptoms, because
  they are proven to prevent heart attacks and
  sudden death.

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Calcium channel blockers

• 1. Derivatives of difenilalkilamin (verapamil)
• 2. Derivatives of benzothiazepine (dylthiazem)
• 3. Derivatives of dyhydropyridine (nifedipin,
  amlodipin, nimodipin)
• Drugs of 1 and 2 groups dominantly influence on
  heart (depress automatism of sinus node,
  conductivity through conductive heart system),
  show antiarrhythmic, antianginal and hypotensive
  action.
• Derivatives of dyhydropyridine (group of
  nifedipin) decrease blood pressure and cause
  dilation of coronary vessels, cause reflective
  tachycardia

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Calcium channel blockers classification
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Nifedipin - corinfar - fenigidin - adalate

• Doesnt depress conductivity in myocardium,
• has a weak antiarrhythmic action
• Maximal concentration of the drug in blood
  occurs after 45-60 min after administration
  orally and after 2-3 min if administered
  sublingually
• Effect lasts for 4-6 hours

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

• almost dont cause tachycardia
• are indicated for prolonged treatment of patients
  with stable angina
• arent indicated in case of non stable angina
  (long lasting latent period)
•  

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Indications
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Nifedipin (??2 ions antagonist of
dyhydropyrydine series)
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Nifedipin (
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• Calcium channel blockers are used primarily when
  beta blockers cannot be used and/or the patient
  is still having angina with beta blockers.
  Calcium channel blockers also lower blood
  pressure and certain ones slow heart rate.
  Calcium channel blockers have to be taken every
  day.

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Common side effects of calcium channel blockers
include

• headache,
• constipation,
• rash,
• nausea,
• flushing,
• edema (fluid accumulation in tissues),
• drowsiness,
• low blood pressure, and
• dizziness.
• Sexual dysfunction, overgrowth of gums, and liver
  dysfunction also have been associated with
  calcium channel blockers. Verapamil (Covera-HS,
  Verelan PM, Calan) and diltiazem (Cardizem LA,
  Tiazac) worsen heart failure because they reduce
  the ability of the heart to contract and pump
  blood.

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POTASSIUM-CHANNEL ACTIVATORS

• NICORANDIL Ikorel
• activates ??2-depending potassium channels
• causes relaxation of smooth muscles of vessels
• coronary, arteriolar and venous vasodilation
  
• improvement of blood supply of myocardium,
  decreasing of pre- and afterloads of heart,
  decreasing of myocardial need in oxygen,
  separation of ischemic damage zone

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Antiplatelet agents

• Commonly prescribed include
• Aspirin
• Ticlopidine
• Clopidogrel
• Dipyridamole

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Acetylsalicylic acid

• 80-100 mg per day as antiplatelet drug,
  decreases risk of development of acute myocardial
  infarction and decreases mortality of patients
  with IHD
• Helps prevent clotting in patients who have had a
  heart attack, unstable angina, ischemic strokes,
  TIA (transient ischemic attacks, or "little
  strokes") and other forms of cardiovascular
  disease.
• Usually prescribed preventively when plaque
  buildup is evident but there is not yet a large
  obstruction in the artery.

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Common types of cholesterol-lowering drugs
include

• statins
• resins
• nicotinic acid (niacin)
• gemfibrozil
• clofibrate
• Various medications can lower blood cholesterol
  levels. They may be prescribed individually or in
  combination with other drugs. They work in the
  body in different ways. Some affect the liver,
  some work in the intestines and some interrupt
  the formation of cholesterol from circulating in
  the blood. 
• Reason for Medication
• Used to lower LDL ("bad") cholesterol, raise HDL
  ("good") cholesterol and lower triglyceride levels

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Choose good nutrition Reduce blood cholesterol
Lower high blood pressure Be physically active
every day Aim for a healthy weight Manage
diabetes Reduce stress Limit alcohol Stop
smoking
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ACUTE MYOCARDIAL INFARCTION

• one of the main reasons of disablement and
  mortality of people of employed age in many world
  countries, including Ukraine
• men suffer from MI almost 5 times more often than
  women
• Mortality of patients with MI during first two
  hours starting from the beginning of the process
  makes around 50 of all mortal cases connected
  with MI
• the most often death causes acute
  cardiac-vascular insufficiency (angina pectoris,
  lung edema, cardiogenic shock), heart rupture,
  heavy cardiac arrhythmia
• other complications of MI thrombosis and
  emboli, acute and chronic heart aneurisms,
  Dreslers syndrome, chronic cardiac insufficiency

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TREATMENT OF MYOCARDIAL INFARCTION

• three stages
• Immediate treatment decreasing pain and
  treatment of heart beats arrest
• Early treatment separation of zone of
  infarction seat and prevention of early life
  threatening complications (cardiac arrhythmias,
  acute cardiac insufficiency)
• Further treatment prevention and therapy of
  late complications of MI, prophylaxis of
  recurrent MI and death of the patients

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TREATMENT OF ACUTE MYOCARDIAL INFARCTION

• Releasing of pain and
• cardiogenic shock prophylaxis
• nitroglycerin (1 tablet under the tongue every
  7-10 min.)
• Neuroleptanalgesia (fentanil with droperidol),
  morphine, omnopon, promedol (in combination with
  atropine, dimedrol, aminasine)
• nitrous oxide in combination with neuroleptics
• in case of remaining pain non narcotic
  analgesics in combination with antihistamine and
  neuroleptic drugs
• to increase arterial pressure during cardiogenic
  shock intravenously dropply dopamine (drugs of
  choice), noradrenalin, mesaton
• sometimes glucocorticosteroids are used

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TREATMENT OF ACUTE MIOCARDIAL INFARCTION (contd)

• Size limitation
• of infarction seat
• Intravenous dropply introduction of
• 0,01 nitroglycerin solution
• Administration of b-blockers

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TREATMENT OF ACUTE MYOCARDIAL INFARCTION (contd)

• Treatment and prophylaxis of heart arrhythmias
• Treatment of ventricular arrhythmias i.v.
  slowly 0,2 solution of xycain, novocainamid
  intramuscularly
• Prophylaxis of ventricular extrasystole and
  tachycardia magnesium sulfate (intravenous
  dropping introduction of 4-5 solution),
• ?-adrenoblockers
• Arrhythmias of atrial origin heart glycosides,
  antagonists of calcium channels
• Bradycardia - isadrin, atropine sulfate, alupent
  (i.v.)

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TREATMENT OF ACUTE MYOCARDIAL INFARCTION (contd)

• CORRECTION OF BLOOD CLOTTING
• thrombolytic drugs
• streptokinase (1,5 mln OD), urokinase (2 mln
  OD), aktilise recombinant tissue activator of
  plasminogen (100 mg) intravenous
• after performing of thrombolytic therapy
  intravenous introduction of heparin, at first 10
  000 OD, after 1000 OD per hour during 24-48
  hours
• anticoagulants of indirect action
• acetylsalicylic acid
• (80-100-300 mg per day)

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• Treatment of heart insufficiency
• i.v. furosemid (40-120 mg) i.v. dropply
  nitroglycerine (12-20 hours), morphine
• i.v. dropply dopamin and dobutamin
• heart glycosides in tachysystolic form of
  scintillating arrhythmia or fluttering of atria
  with moderate left-ventricular insufficiency
• General measures
• oxygen inhalation
• correction of acid-base balance

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ANTIARRHYTHMIC DRUGS CLASS Mechanism
of Action Drug name IA NaChannel
blocker Disopyramide, procainamide,
quinidine IB NaChannel blocker Lidocaine,
mexiletine, tocainide IC NaChannel
blocker Flecainide, propafenone II ?
Adrenoreceptor blocker Esmolol, metoprolol,
pindolol, propranolol III KChannel
blocker Amiodarone, bretylium, sotalol IV Ca
Channel blocker Diltiazem, verapamil Other
antiarrhythmic drugs Adenosine, digoxin
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