DRUGS USED IN ANGINA AND MI

1. Supervised by
ZHIYAR MUHAMMADNAZIF IBRAHIM
PARWEEN DLOVAN MUHAMMAD Dr. chro
TABAN FADHIL NABI
SUPERVISED BY :
Dr. suzan
BASNA KAMAL MUHAMMAD

2. What is angina pectoris??

3. Types of angina?

4. Myocardial infarction
Myocardial cell death due to prolonged ischemia

5. 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.

6. Supply can be increased by :
1*dilating coronary artery
2*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 fibers
3*slowing the heart

7. 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

8. 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

9. • 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

11. Coronary artery dilatation
Decrease coronary bed
resistance
(Relieved coronary
vasospasm)
Increase coronary blood
flow
Increase oxygen supply

12. Reduction on peripheral
resistance
(Secondary to dilatation of aorta)
Decrease blood pressure
Decrease after load
Decrease workload
Decrease oxygen
consumption

13. Reduced venous return
(Due to dilatation of the veins)
Decrease left ventricular
volume
Decrease preload
Decrease workload
Decrease oxygen
consumption

14. 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

15. 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.

16. 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

17. MECHANISM OF ACTION

18. ROUTES OF ADMINISTRATION
1. Sublingual route
2. Oral route
3. Intravenous Route
4. Topical route

20. 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.

21. 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.

22. CONTRAINDICATION
1. Renal ischemia
2. Acute myocardial infarction
3. Patients receiving other
antihypertensive agent

23. 2-B BLOCKERS
2 types : non selective and cardioselective
atenolol (Tenormin)
metoprolol (Lopressor)
propranolol (Inderal)
nadolol (Corgard)

24. pharmacokinetics
 B blockers are orally active.
 Propranolol undergoes significant first
pass metabolism
 They may take several weeks to develop
full effect

25. B-Blockers
Decrease heart rate & Contractility
Increase duration of diastole Decrease workload
Increase coronary blood flow Decrease O2 consumption
Increase oxygen supply

26. 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

27. 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.

28. ATENOLOL (TENORMIN)
Atenolol is a selective β1 receptor antagonist

29. 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.

30. Ca - Channel Blockers
a)Dihydropyridines : nefidepine,
nicardepine, felodepine,
amlodepine, nitrendepine,
lercanidepine, benidepine.
b)Non dihydropyridines: verapamil,
diltiazem

31. Effects
1. Coronary artery
dilatation
2. Reduction on peripheral
arterial resistance –
decrease after load

32. Coronary artery
dilatation
Decrease coronary bed
resistance
(Relieved
coronary vasospasm)
Increase coronary blood
flow
Increase oxygen supply

33. Reduction on peripheral
resistance
(Secondary to dilatation of
aorta)
Decrease blood pressure
Decrease after load
Decrease workload
Decrease oxygen
consumption

34. 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.

35. Most commonly used Ca Channel
Blockers:
verapamil (Calan)
diltiazem (Cardizem)
nifedipine (Procardia

36. 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, nicardipin
e, and felodipine, have
similar cardiovascular
characteristics except for
amlodipine, which does not
affect heart rate or cardiac
output.

37. • 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.

38. 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.

39. _The drug is extensively metabolized by
the liver; therefore, care must be taken
to adjust the dose in patients with liver
dysfunction.

40. ADVERSE
EFFECT

41. Contraindication
 Cardiogenic shock.
 Recent myocardial infarction.
 Heart failure.
 Atrioventricular block.
 in patients with preexisting
depressed cardiac function or AV
conduction abnormalities.
In hypotensive patients.

42. 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

43. STABLE ANGINA
NITRATES , CALCIUM CHANNEL BLOCKER AND B BLOCKERS
UNSTABLE ANGINA
NITRATES & CALCIUM CHANNEL BLOCKER
VARIANT ANGINA
NITRATES & CALCIUM CHANNEL BLOCKER

44. 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.

45. Pharmacokinetic
Nicorandil 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.
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.

46. 5-ANTIPLATELETS
1-Aspirin-
inhibits synthesis of
prostacyclin and
ASPIRIN
thromboxane A2-
prevent platelet aggregation-
decrease thrombosis
Indications- several. For angina-
primarily used to prevent MI in
patients with unstable angina
2-Other agents
Clopidogrel (Plavix)- in place of WARFARIN
aspirin
Warfarin (Coumadin)

47. Myocardial infarction
Goals of treatment
The 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.

48. 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

49. 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

50. 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

52. Specific Drugs
• benazepril
• captopril
• enalapril
• fosinopril
• lisinopril
• moexipril
• quinapril
• ramipril
Note that each of the ACE inhibitors named above end with
"pril."

53. 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).

54. Pharmacokinetics
About 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.

55. 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

56. contraindication
 Hypersensitivity to drug or other ACE inhibitors
 Angioedema (hereditary or
 Idiopathic)
 Pregnancy

57. Angiotensin receptor blockers

58. Specific Drugs
• candesartan
• eprosartan
• irbesartan
• losartan
• olmesartan
• telmisartan
• valsartan
Note that each of the ARBs
named above ends with
"sartan."

59. 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.

60. 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

61.  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

62. B BLOCKERS IN MI
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.

63. nadolol
propranolol
timolol
atenolol
Metoprolol
carvidelol

64. carvidelol
Reduces morbidity and mortalility rate
due to myocardial infarction its called
third generation b locker because of
its effects:
Inhibits lipid peroxidation
Inhibits release of free radicals from
neutrophils
Scavenger of free radicals

65. 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...

66. 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.

67. 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.

68. Given:
Orally
Side Effects:
• Vomiting
• Headache
• Dizziness
• Chest Pain
Drug Interactions:
Saquinavir
Increase Quinidine levels by inhibiting
removal of Quinidine by liver.
Contraindications:
Patients with Heart Failure

69. 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)

70. Streptokinase & Mechanism
of Action

71. • Given by: Injection
• Side Effects
• Low Blood Pressure
• Nausea
• Headache
• Easy Bruising
Drug Interaction:
• Aprotinin
• Reverses effect of Streptokinase
Contraindications:
• Injury & Trauma

72. Analgesics
Used to reduce pain.

73. CLASSES:
 Paracetamol and NSAIDs
 COX-2 inhibitors
 Opiates and morphinomimetics
 Flupirtine
 Combinations

74. Morphine
Powerful Narcotic Analgesic.
Mechanism of Action:
 Acts on Opioid receptors in brain.
 Binds to & inhibits GABA inhibitory interneurons.
 Inhibits pain.

75. 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.

77. 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.h
tm
 http://www.cvpharmacology.com/vasodilator/ACE.ht
 m

78. http://www.cvpharmacology.com/antiarrhy/antiarrhythmic.htm
http://www.medicinenet.com/quinidine/article.htm
http://www.medicinenet.com/streptokinase-
injection/article.htm
http://www.cvpharmacology.com/thrombolytic/thrombolytic.ht
m
http://www.medterms.com/script/main/art.asp?articlekey=102
23
http://www.everydayhealth.com/drugs/morphine
http://www.rochester.edu/uhs/healthtopics/Alcohol/interactions
.html
http:/drugs.webmd.boots.com/drugs/drug-328-nicorandil.aspx?