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DESCRIPTION
DRUGS USED IN ANGINA AND MITRANSCRIPT
TREATMENT OF ANGINA AND MYOCARDIAL INFARCTION
ZHIYAR MUHAMMADNAZIF IBRAHIM
PARWEEN DLOVAN MUHAMMAD
TABAN FADHIL NABI
BASNA KAMAL MUHAMMADSUPERVISED BY :
Dr. chro
Dr. suzan
Prepared by: Supervised by
What is angina pectoris??
Types of angina?
Myocardial infarctionMyocardial cell death due to prolonged ischemia
Antianginal Drugs
Principle of action:• Angina can be viewed as a problem of
oxygen supply and demand , so these drugs will either increase supply of oxygen and nutrients of reduce myocardial oxygen demand or both.
Supply can be increased by :1*dilating coronary artery2*slowing the heart (coronary flow, uniquely occurs in diastole, which lengthens as heart rate falls).Demand can be reduced by :1*reducing afterload (i.e. reducing peripheral resistance) Reducing the work of heart in perfusing the tissues.2*reducing preload( i.e. venous filling pressure ) according to starling's law of the heart, workload and oxygen demand varies with stretch of cardiac muscle fibers3*slowing the heart
Classification:1- NITRATES:
a)Short acting: glyceryl trinitrate( GTN, nitrogylerine)
b)Long acting : isosorbide dinitrate (if given sublingually its short acting),
isosorbide mononitrate,erythrityl tetranitrate, pentaerythritol tertanitrate.
2- B BLOCKERS: propranolol, metoprolol, atenolol , carvidelol and others
3- CALCIUM CHANNEL BLOCKERS:
a)Dihydropyridines : nefidepine, nicardepine, felodepine, amlodepine,
nitrendepine, lercanidepine, benidepine.
b)Non dihydropyridines: verapamil, diltiazem
4-POTASSIUM CHANNEL OPENER: nicorandil
5-Antiplatelet Drugs: Aspirin , Warfarin (Coumadin
Clopidogrel
6- OTHERS:
Dipyridamole,trimetazidine,ranolazine,oxyphedrine
1-NITRATES AND NITRITES
Are simple nitric and nitrous acid esters of glycerol
Classification of nitrates:1. Rapidly acting nitrates
* used to terminate acute attack of angina
* e.g.- Nitroglycerin and Amyl nitrate
* usually administered sublingually
2. Long acting nitrates
* used to prevent an attack of angina
* e.g. -Erythrytyl tetranitrate, Isosorbide dinitrate, Pentaerythrytol tetranitrate
* administered orally or topically
pharmacokinetics
• The onset of action varies from 1 minute as in
nitroglycerine to one hour as in isosorbide mononitrate
• Nitroglycerine undergoes significant first pass
metabolism in the liver so its given sublingually or as
transdermal patches
• The stability of isosorbide mononitrate against liver
break down gives it its long duration of action and high
bioavailability
• Isosorbide dinitrate gives 2 molecules of isosorbide
mononitrate in the body
• The onset of action varies from 1 minute as in
nitroglycerine to one hour as in isosorbide mononitrate
• Nitroglycerine undergoes significant first pass
metabolism in the liver so its given sublingually or as
transdermal patches
• The stability of isosorbide mononitrate against liver
break down gives it its long duration of action and high
bioavailability
• Isosorbide dinitrate gives 2 molecules of isosorbide
mononitrate in the body
EFFECTS
Coronary artery dilatation
Decrease coronary bed resistance
( Relieved coronary vasospasm)
Increase coronary blood flow
Increase oxygen supply
Reduction on peripheral resistance
(Secondary to dilatation of aorta)
Decrease blood pressure
Decrease after load
Decrease workload
Decrease oxygen consumption
Reduced venous return(Due to dilatation of the veins)
Decrease left ventricular volume
Decrease preload
Decrease workload
Decrease oxygen consumption
ADVERSE EFFECT
1. Throbbing headache
2. Flushing of the face
3. Dizziness – especially at the beginning
of treatment
4. Postural Hypotension – due to pooling of
blood in the dependent portion of the
body
Tolerance
• Tolerance to the action of nitrates develop rapidly in
which blood
• vessels will be desensitized to the vasodilatory effect of
the drug.
• Tolerance can be overcome by a daily nitrate free
interval which is typically of 8 to 12 hours.
• Nitrate free interval is usually at night as the oxygen
demand increase
• But in variant angina which worsen during early morning
due to the circadian catecholamin attack the nitrate free
interval should be at late afternoon.
Tolerance to the Antianginal and
hemodynamic effects of nitrates develops:
higher doses
Drugs have longer half-lives.
It is common in patients being treated with
topical, transdermal or continuous i.v.
infusions
MECHANISM OF ACTION
1. Sublingual route 2. Oral route 3. Intravenous Route 4. Topical route
ROUTES OF ADMINISTRATION
NITROGYLECERINE
-Prototypical nitrate
-Large first-pass effect with PO forms
-Used for symptomatic treatment of ischemic heart conditions (angina)
-IV form used for
• BP control in perioperative hypertension.
• treatment of CHF.
• ischemic pain.
• pulmonary edema associated with acute MI.
Drug interaction
with cGMP-dependent phosphodiesterase
inhibitors (e.g., sildenafil ).
The reason for this adverse reaction is that
nitrodilators stimulate cGMP production and drugs
like sildenafil inhibit cGMP degradation. When
combined, these two drug classes greatly
potentiate cGMP levels, which can lead to
hypotension and impaired coronary perfusion.
CONTRAINDICATION
1. Renal ischemia
2. Acute myocardial infarction
3. Patients receiving other antihypertensive agent
2-B BLOCKERS
atenolol (Tenormin)metoprolol (Lopressor)propranolol (Inderal)nadolol (Corgard)
2 types : non selective and cardioselective
pharmacokinetics
B blockers are orally active.
Propranolol undergoes significant first pass
metabolism
They may take several weeks to develop
full effect
B-BlockersDecrease heart rate & Contractility
Increase duration of diastole
Increase coronary blood flow
Increase oxygen supply
Decrease workload
Decrease O2 consumption
Side effects
Bradycardia
CNS side effects as fatigue, lethargy, insomnia and hallucination.
Hypotension
Decrease in libido
Decreases serum HDL and increases TG
Withdrawal syndrome : rebound hypertension
CONTRAINDICATION
1. Congestive heart failure
2. Asthma and COPD
3. Complete heart block
4. Patients with bradycardia
5. patients with history of cocaine use or in cocaine-induced tachycardia or MI.
ATENOLOL (TENORMIN)
Atenolol is a selective β1 receptor antagonist
PHARMAKOKINETICS
tcmax = 2 to 4 hours after oral
The mean elimination half-life is 6 hours. However, the action of the usual oral dose of 25 to 100 mg lasts over a period of 24 hours.
Atenolol is a hydrophilic drug. The concentration found in brain tissue is approximately 15% of the plasma concentration only. The drug crosses the placenta barrier freely. In the milk of breastfeeding mothers, approximately 3 times the plasma concentrations are measured.
Atenolol is almost exclusively eliminated renally and is well removable by dialysis. A compromised liver function does not lead to higher peak-activity and/or a longer half-life with possible accumulation.
Ca - Channel Blockers
a)Dihydropyridines : nefidepine, nicardepine, felodepine, amlodepine, nitrendepine, lercanidepine, benidepine.
b)Non dihydropyridines: verapamil, diltiazem
Effects1. Coronary artery
dilatation
2. Reduction on peripheral arterial resistance – decrease after load
Coronary artery dilatation
Decrease coronary bed resistance
( Relieved coronary vasospasm)
Increase coronary blood flow
Increase oxygen supply
Reduction on peripheral resistance
(Secondary to dilatation of aorta)
Decrease blood pressure
Decrease after load
Decrease workload
Decrease oxygen consumption
Pharmacokinetics:
Calcium channel blockers are well absorbed form GIT and their bioavailability depends on the extent of first pass metabolism in the gut wall and liver which varies between the drugs.
Interaction:
- Both diltiazem and verapamil cause increase to exposure to carbamazepine ,quinidine and metoprolol. -Verapamil increase plasma concentration of digoxin.
Most commonly used Ca Channel Blockers:
verapamil (Calan)diltiazem (Cardizem)nifedipine (Procardia
NEFIDEPINE
• Nifedipine, a dihydropyridine derivative, functions mainly as an arteriolar vasodilator. This drug has minimal effect on cardiac conduction or heart rate.
• Other members of this class, amlodipine, nicardipine, and felodipine, have similar cardiovascular characteristics except for amlodipine, which does not affect heart rate or cardiac output.
• Nifedipine is administered orally, usually as extended-release tablets.
• It undergoes hepatic metabolism to products that are eliminated in both urine and the feces.
• The vasodilation effect of nifedipine is useful in the treatment of variant angina caused by spontaneous coronary spasm.
verapamil
The diphenylalkylamine verapamil slows cardiac atrioventricular (AV) conduction directly, and decreases heart rate, contractility, blood pressure, and oxygen demand.
Verapamil causes greater negative inotropic effects than nifedipine, but it is a weaker vasodilator.
_The drug is extensively metabolized by the liver; therefore, care must be taken to adjust the dose in patients with liver dysfunction.
ADVERSE EFFECT
Contraindication
Cardiogenic shock. Recent myocardial infarction. Heart failure. Atrioventricular block. in patients with preexisting
depressed cardiac function or AV conduction abnormalities.
In hypotensive patients.
Combination Therapy
Nitrates and b blockers : to prevent the reflex tachycardia produced by nitrates
Ca channel blockers with b blockers for same reason
Ca channel blockers and Nitrates
Nitrates reduce preload and after load
Ca channels reduces the after load
Net effect is on reduction of oxygen demand
STABLE ANGINA
NITRATES , CALCIUM CHANNEL BLOCKER AND B BLOCKERSUNSTABLE ANGINA
NITRATES & CALCIUM CHANNEL BLOCKERVARIANT ANGINA
NITRATES & CALCIUM CHANNEL BLOCKER
4 -POTASSIUM CHANNEL OPENER
NICORANDIL : an effective vasodilator through 2 actions:
1-it acts as nitrates by activating cGMP.
2- opens ATP dependent potassium channels. Leading to hyperpolarization and relaxation of vascular smooth muscle.
Its given orally as an alternative to nitrates incase of tolerance .
Adverse effect : similar to those of nitrates with headache in 35% of patients.
contraindication
People with low blood pressure.
People with cardiogenic shock.
People with heart failure with low filling pressure.
People using drugs for impotence such as sildenafil & tadalafil.
In pregnancy.
In breastfeeding.
PharmacokineticNicorandil is well absorbed with no significant first pass metabolism, metabolism is mainly by denitration into nicotinamide pathway and less than 20% is excreted into urine.
5-ANTIPLATELETS
1-Aspirin-inhibits synthesis of prostacyclin and thromboxane A2- prevent platelet aggregation- decrease thrombosisIndications- several. For angina- primarily used to prevent MI in patients with unstable angina
2-Other agentsClopidogrel (Plavix)- in place of aspirin
Warfarin (Coumadin)
ASPIRIN
WARFARIN
Myocardial infarction
Goals of treatmentThe most important goal of drug therapy early in the course of acute myocardial infarction is to improve the oxygen supply/demand ratio for the heart. The reduction in this ratio that occurs when coronary flow is compromised is the primary reason cardiac function is impaired, which leads to the clinical signs associated with myocardial infarction. There are two strategies to improve the coronary supply/demand ratio, 1) restore normal coronary blood flow.2) decrease myocardial oxygen consumption.
Further treatment is based on the following:
Restoration of the balance between the oxygen supply and demand to prevent further ischemia
Pain relief
Prevention and treatment of any complications that may arise
Classes of Drugs Used to Treat Myocardial Infarction
1•Vasodilators (dilate arteries and veins)- nitrodilators- angiotensin converting enzyme inhibitors (ACE inhibitors)- angiotensin receptor blockers (ARBs)
2•Cardiac depressant drugs (reduce heart rate and contractility)- beta-blockers
3•Antiarrhythmics (if necessary)
4•Anti-thrombotics (prevent thrombus formation)- anticoagulant- anti-platelet drugs
5•Thrombolytics (dissolve clots - i.e., "clot busters")- plasminogen activators
6•Analgesics (reduce pain)- morphine
ACEI(angiotensin converting enzyme inhibitors)
Cardiorenal Effects of ACE Inhibitors
Vasodilation (arterial & venous)- reduce arterial & venous pressure- reduce ventricular afterload & preload
Decrease blood volume- natriuretic- diuretic
Depress sympathetic activity
Inhibit cardiac and vascular hypertrophy
Specific Drugs
• benazepril• captopril• enalapril• fosinopril• lisinopril• moexipril• quinapril• ramipril
Note that each of the ACE inhibitors named above end with "pril".
captopril
Captopril is a potent, competitive inhibitor of angiotensin-converting enzyme (ACE), the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS).
PharmacokineticsAbout 70% of orally administered
captopril is absorbed. Bioavailability is reduced by presence of food in stomach. It is partly metabolized and partly excreted unchanged in urine.
Adverse reactions
CNS: headache, dizziness, drowsiness, fatigue, weakness, insomnia
CV: angina pectoris, tachycardia, hypotension
EENT: sinusitis
GI: nausea, diarrhea, anorexia
GU: proteinuria, erectile dysfunction, gynecomastia, renal failure
Hematologic: anemia, agranulocytosis, leukopenia, pancytopenia, thrombocytopenia
Metabolic: hyperkalemia
Respiratory: cough, asthma, bronchitis, dyspnea, eosinophilic pneumonitis
Skin: rash, angioedema
Other: altered taste, fever
contraindication
Hypersensitivity to drug or other ACE inhibitors
Angioedema (hereditary or
Idiopathic)
Pregnancy
Angiotensin receptor blockers
Specific Drugs
• candesartan• eprosartan• irbesartan• losartan• olmesartan• telmisartan• valsartan
Note that each of the ARBs named above ends with "sartan."
Losartan
Losartan is an oral medication that belongs to a class of drugs called angiotensin receptor blockers (ARBs)
Losartan (more specifically, the chemical formed when the liver converts the inactive losartan into its active form) blocks the angiotensin receptor. By blocking the action of angiotensin, losartan relaxes muscle cells and dilates blood vessels thereby reducing blood pressure.
Losartan was approved by the FDA in April 1995.
Adverse effect
CNS: dizziness, insomnia, headache, asthenia, fatigue
CV: hypotension
EENT: sinus disorders
GI: nausea, vomiting, diarrhea, dyspepsia, abdominal pain
Metabolic: hyperkalemia
Musculoskeletal: joint pain, back pain, muscle cramps
Respiratory: symptoms of upper respiratory infection, dry cough
Other: hypersensitivity reactions including angioedema
Contraindications• Hypersensitivity to drug or its components
INTERACTION
Drug-drug. Diuretics, other antihypertensives: increased risk of hypotension
Fluconazole: inhibited losartan metabolism, increased antihypertensive effects
Indomethacin: decreased losartan effects
Phenobarbital, rifamycins: enhanced losartan metabolism, decreased antihypertensive effects
Potassium-sparing diuretics, potassium supplements: hyperkalemia
Drug-diagnostic tests. Albumin: increased level
Drug-food. Salt substitutes containing potassium: hyperkalemia
Beta-adrenergic receptor blocking agents (beta-blockers) are drugs with multiple actions on the heart. Blockade of beta-1 receptors results in slowing of heart rate, reduction in myocardial contractility, and lowering of systemic blood pressure. In the context of acute myocardial infarction (AMI), which represents a state of reduced oxygen supply to the affected portion of the heart, these effects may be beneficial as they result in reduced myocardial workload and oxygen demand. Furthermore, beta-blockers may reduce the risk of ventricular arrhythmias, which are an important cause of death following AMI.
B BLOCKERS IN MI
nadololpropranololtimololatenololMetoprololcarvidelol
carvidelol
Reduces morbidity and mortalility rate due to myocardial infarction its called third generation b locker because of its effects:Inhibits lipid peroxidationInhibits release of free radicals from
neutrophilsScavenger of free radicals
Side effects
slow or uneven heartbeats;
feeling light-headed, fainting;
feeling short of breath, even with mild exertion;
swelling of your ankles or feet;
nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing...
Antiarrhythmic Drugs
• The aim is to restore normal rhythm and conduction. And prevent arrhythmias that follow MI
Quinidine
Procainamide
Disopyramide
• Used to:
Decrease/increase conduction velocity.
Alter the excitability of cardiac cells by changing the duration of the effective refractory period.
Suppress abnormal automaticity.
Quinidine
Antiarrythmic drug
Na Channel Blocker
Decreases speed of electrical current that travels through heart muscle.
Prolongs period during which heart muscle cells become electrically stimulated to contract.
Prolongs recovery period after contraction.
Given: Orally
Side Effects: • Vomiting• Headache• Dizziness• Chest Pain
Drug Interactions: SaquinavirIncrease Quinidine levels by inhibiting removal of Quinidine by liver.
Contraindications:Patients with Heart Failure
Thrombolytic Drugs
Used to dissolve blood clots.
The thrombolytic drugs include:
tissue plasminogen activator t-PA:
alteplase (Activase)
reteplase (Retavase)
tenecteplase (TNKase)
anistreplase (Eminase)
streptokinase (Kabikinase, Streptase)
urokinase (Abbokinase)
Streptokinase & Mechanism of Action
• Given by: Injection
• Side Effects• Low Blood Pressure• Nausea• Headache• Easy Bruising
Drug Interaction: • Aprotinin• Reverses effect of Streptokinase
Contraindications: • Injury & Trauma
Analgesics
Used to reduce pain.
CLASSES:
Paracetamol and NSAIDs
COX-2 inhibitors
Opiates and morphinomimetics
Flupirtine
Combinations
Morphine
Powerful Narcotic Analgesic.
Mechanism of Action:
Acts on Opioid receptors in brain.
Binds to & inhibits GABA inhibitory interneurons.
Inhibits pain.
Given: Orally/ Injection
Side Effects:• Slow breathing• Slow heartbeat• Sedation• Confusion
Drug Interactions: Sedatives that make you sleepy and slow your breathing.
Contraindications:In alcoholic patients which can lead to increased sedation & death.
THANK YOU
references
Richard D. howland , Mary J. Mycek.2000. pharmacology.USA. Williams & wilkins.
Rand,Dale,Ritter,Moore.2004. pharmacology.Uk.churchil livingstone, Elsevier limited.
Bertram Katzung.2007.basic and clinical pharmacology.singapore.McGRawHill.
http://www.cvpharmacology.com/clinical%20topics/angina.htm
http://www.cvpharmacology.com/Angina/antianginal.htm
http://www.cvpharmacology.com/vasodilator/vasodilators.htm
http://www.cvpharmacology.com/vasodilator/ACE.ht
m
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http:/drugs.webmd.boots.com/drugs/drug-328-nicorandil.aspx?