An interesting ppt on antianginal drugs and drug therapy of myocardial infarction with illustrations for better understanding of concepts and grasping facts...
5. HEART FACTS
The average adult heart beats
72 times a minute;
100,000 times a day;
3,600,000 times a year;
and 2.5 billion times during a lifetime.
6. HEART FACTS
Though weighing only 11 ounces on average,
a healthy heart pumps
2,000 gallons of blood through
60,000 miles of blood vessels
each day.
7. HEART FACTS
5% of blood supplies the heart,
15-20% goes to the brain and central nervous system,
and 22% goes to the kidneys.
8. ANGINA PECTORIS
Is a pain syndrome due to an adverse
oxygen supply/demand situation in a
portion of myocardium
16. TYPES OF ANGINA
Classical angina
common form
due to fixed coronary obstruction
Ischemic pain is felt
Subside when the increased energy demand is withdrawn
attacks are provoked by
exercise,
emotion,
eating or
coitus
21. Variant angina
Prinzmetal’s angina
Attacks occur at rest or during sleep
Unpredictable
Due to localized coronary vasospasm
23. Unstable angina
Rapid increase in duration and
severity of attacks
Due to rupture of an atheromatous plaque
platelet deposition
progressive occlusion of coronary artery
27. HEART FACTS
The human heart begins to beat as
early as
four weeks after conception
28. HEART FACTS
Grab a tennis ball and squeeze it tightly:
that’s how hard the beating heart works to pump blood.
A woman’s heart typically beats faster than a man’s.
29. HEART FACTS
Every day, the heart creates enough energy to
drive a truck 20 miles.
In a lifetime, that is equivalent to
driving to the moon and back.
30. HEART FACTS
During an average lifetime,
the heart will pump nearly 1.5 million gallons of blood—
enough to fill 200 train tank cars.
32. ANTIANGINAL DRUGS
Prevent, abort or terminate
attacks of angina pectoris
Do not alter the
course of coronary artery
pathology
50. MECHANISM OF ACTION
Denitrated in smooth muscle
release Nitric Oxide
activates cytosolic guanylyl cyclase
increase cGMP
dephosphorylation of MLCK
reduced availability of active MLCK
interferes with the activation of Myosin
fails to interact with actin relaxation
cGMP decrease ca entry relaxation
54. PHARMACOKINETICS
Well absorbed from buccal mucosa, skin,
intestine
Lipid soluble
Undergo extensive 1st
pass metabolism
except isosorbide mononitrate
Rapidly denitrated produce less active
metabolites with longer t1/2
57. ADR
Headache, fullness in head
Flushing,
weakness
Palpitation,
sweating,
dizziness, fainting
Methemoglobinemia – a problem in severe
anemia
Rashes – particularly with pentaerythritol
tetranitrate
65. TOLERANCE
Decreased effectiveness of nitrates on repeated
administration
Seen with GTN used orally, i.v, transdermally
With long acting agents
Cross tolerance also seen
Prevented by keeping nitrate free
interval everyday
66. DEPENDENCE
Seen after sudden withdrawal after
prolonged exposure
Myocardial infarction,
sudden deaths,
increase episodes of angina on record
Add a drug of another class
Withdrawal must be gradual
69. Sex and cardiovascular system
CHANGES DURING ORGASM……
Tachycardia upto 180 beats/ minute
BP 230/130 mmHg even in
normotensives
ECG abnormalities may occur
RESPIRATORY RATE 60 / min
SUDDEN DEATHS
CAUTION – older patients with CAD
74. GLYCERYL TRINITRATE
Volatile liquid
Stored in tight glass container
Taken sublingually terminate an anginal
attack
Acts within 1-2 minutes
Also administered as
sublingual spray,
S.R. capsule,
transdermal patch,
i.v infusion,
transmucosal dosage form
Given as i.v infusion in unstable angina, LVF in MI, during
cardiac surgeries
84. DOCTOR….. DOCTOR…..
Patient: It's been one month since my last visit
and I still feel miserable.
Doctor: Did you follow the instructions on the
medicine I gave you?
Patient: I sure did - the bottle said 'keep
tightly closed.'
85. ISOSORBIDE DINITRATE
Solid
S/L – Slower acting than GTN
Orally given for chronic prophylaxis
High 1st pass effect
t1/2 - 4O min
Leave 6-10 hr nitrate free interval
86. ISOSORBIDE MONO NITRATE
Active metabolite of ISDN
Little 1st
pass effect high BA
Long acting
SR tablet given once daily in morning
87. OTHER NITRATES
• Erythrityl tetranitrate,
Pentaerythritol tetranitrate
are longer acting
• Used for chronic prophylaxis
89. HEART FACTS
When the body is at rest,
it takes only 6 seconds for the blood
to go from the heart to the lungs and back,
only 8 seconds for it
to go the brain and back, and
only 16 seconds for it
to reach the toes and travel all the way
back to the heart.
102. USES
Angina pectoris –effective in classical
angina, variant angina increase exercise tolerance,
given as “as and when required” basis
Acute coronary syndromes
Congestive heart failure
Acute left ventricular failure
Myocardial infarction – of marginal benefit
Interventional cardiac procedures
Biliary colic
Esophageal spasm
Cyanide poisoning
Venipuncture
114. BETABLOCKERS IN ANGINA
Decrease cardiac work, oxygen consumption during
exercise, anxiety
All are Equally effective in preventing angina
Cardio selective beta blockers are preferred
To be taken on regular schedule
Dosage to be individualized
Tolerance does not develop
DO NOT DILATE CORONARY VESSELS
118. BETABLOCKERS IN ANGINA - CAUTION
Sudden withdrawal
precipitates angina, even MI
beta-blockers are Contraindicated in
variant angina
126. SUMMARY
Angina pectoris is a symptom of myocardial ischaemia
Acute attack is treated with GTN 0.5mg sublingually
Affords only symptomatic relief
Nitrates act by reducing pre-load, afterload, dilates
coronary arteries
Cause headache, flushing, palpitation as side effects
Betablockers are useful in the prophylaxis
Withdrawal of these drugs must be gradual
Sildenafil usage during nitrates therapy may be
fatal
131. PHARMACOLOGICAL ACTIONS
Smooth muscle relaxation –
arterioles, bronchi, biliary, intestinal, bladder,
uterine relaxation-
Marked with DHP group ( nifedipine)
Heart –
negative inotropic, chronotropic, dromotropic
action –
marked with verapamil, lesser extent with
diltiazem, not with DHP group
134. VERAPAMIL
Decreases heart rate, A-V conduction,
dilates arterioles, decreases t.p.r
ADR- nausea, constipation, bradycardia
C/I – A-V block, CHF
D/I – Should not be given with
betablockers, quinidine, increases digoxin
level
141. DILTIAZEM
Cause consistent fall in BP, dilate
coronaries
Less potent vasodilator than nifedipine &
verapamil
Modest negative inotropic action
ADR – similar as verapamil
145. NIFEDIPINE
Prototype of DHP
Arteriolar dilatation t.p.r decreases
fall in BP
ADR – palpitation, flushing, ankle edema,
hypotension, headache
ADR can be minimized by low starting
dose, using retard formulation
152. AMLODIPINE
Slow oral absorption
Devoid of vasodilator side effects like
flushing, palpitation, headache, postural
dizziness
Long t1/2
Diurnal fluctuation is small
Action extends over next morning
159. NITRENDIPINE
Release nitric oxide additional
mechanism For vasodilatation
Retard atherosclerosis
Indicated in hypertension, angina
pectoris
164. NIMODIPINE
Short acting DHP
Selectively relaxes cerebral blood vessels
Used in treating neurological deficit due
to cerebral vasospasm following
subarachnoid hemorrhage
168. USES OF CALCIUM CHANNEL
BLOCKERS
•
Can be safely given where beta blockers are
contraindicated ( COPD, PVD )
• Angina pectoris – in both classical angina & variant angina
• reduce afterload, long acting DHP are preferred
• Myocardial Infarction - verapamil/diltiazem given in secondary prophylaxis
where beta blockers are contraindicated
• Hypertension
• Cardiac arrhythmias
176. OTHER USES OF CALCIUM CHANNEL BLOCKERS
Hypertrophic cardiomyopathy – verapamil
Premature labour – nifedipine
Migraine – verapamil
Raynaud’s phenomenon – DHP’s
Nocturnal leg cramps
184. RATIONAL DRUG COMBINATIONS
• When mono therapy fails to give relief
• Beta blockers + long-acting nitrates –
• tachycardia due to nitrates is blocked,
• ventricular dilatation, reduced coronary blood flow due to
B –blocker is blocked
• Slow acting DHP Ca channel blocker + B-blocker
• Nitrates + CCB Valuable in severe vasospastic angina
• Nitrates + B-blocker + CCB in resistant cases
• (VERAPAMIL/DILTIAZEM should be avoided in such
combinations)
201. POTENTIAL CLINICAL
APPLICATIONS
Angina pectoris when tolerance is a
problem, when others are
contraindicated
Hypertension
CHF
Myocardial salvage in MI
212. DIPYRIDAMOLE
Powerful coronary dilator
Can cause coronary steal phenomenon
Inhibits platelet aggregation
Not useful as an antianginal drug
Used in the prophylaxis in post MI, post
stroke to prevent thrombosis
217. TRIMETAZIDINE
Novel antianginal drug
Improve cellular tolerance to ischemia by
inhibiting LC3CAT
Reduce anginal attacks in patients not
responding to other drugs
ADR- gastric burning, dizziness, fatigue,
parkinsonism
Useful as an add on medication to
conventional therapy in angina, post MI
219. RANOLAZINE
Trimetazidine congener
Spares fatty acid oxidation and shifts ATP
production to more O2 efficient
carbohydrate oxidation
Torsades de pointes is a risk
Recommended only in combination
221. IVABRADINE
Pure hear rate lowering antianginal drug
Recently introduced as an alternative to betablockers
Blocks cardiac pacemaker cell “f” channels
decreases heart rate decreases oxygen demand,
prolongs diastole improves myocardial blood flow
increased oxygen supply
ADR VISUAL DISTURBANCES, headache, dizziness,
nausea
USES chronic stable angina pectoris alternate to
betablockers, inappropriate sinus tachycardia
223. DRUGS FOR PERIPHERAL
VASCULAR DISEASES
CYCLANDELATE
XANTHINOL NICOTINATE
PENTOXIPHYLLINE
CILOSTAZOLE
CCBs
ALPHABLOCKERS
PGI2 severe cases with rest pain
224. PENTOXIPHYLLINE
Analogue of theophylline
Weak PDE inhibitor
Increases blood flow in ischemic areas by
reducing whole blood viscosity,
And by improving flexibility of RBCs
ADR nausea, vomiting, dyspepsia,
bloating
USES intermittent claudication, Trophic
leg ulcers, TIAs
227. CILOSTAZOLE
PDE-3 inhibitor
Increases cyclic AMP vasodilatation, antiplatelet
aggregating activity
More effective than pentoxiphylline for claudication
pain
Not to be used in heart failure
ADR HEADACHE, nausea, dizziness, palpitation,
weakness
USES intermittent claudication with no rest pain or
heart failure
230. MYOCARDIAL INFARCTION
Ischaemic necrosis of a portion of the
myocardium due to sudden occlusion of a
branch of coronary artery
Acute thrombus is the cause
25% die before therapy
Has to be treated in I.C.C.U’S
241. DRUG THERAPY OF
MYOCARDIAL INFARCTION
Parenteral
Morphine/pethidine,
diazepam for pain, anxiety,
fear
Oxygenation
Streptokinase/ urokinase/
alteplase for thrombolysis
249. DRUG THERAPY OF MYOCARDIAL INFARCTION
• Low dose aspirin for the
prevention of thrombi
extension
• Heparin/oral anticoagulants
to prevent DVT
• Dopamine/ dobutamine for
increasing pumping action of
heart
253. DRUG THERAPY OF
MYOCARDIAL INFARCTION
GTN i.v/nitroprusside for vasodilatation
Frusemide I.V if pulmonary edema present
i.v beta blocker to prevent arrhythmias
Lidocaine/procainamide for tachyarrhythmias
Atropine for heart block
263. DRUG THERAPY OF
MYOCARDIAL INFARCTION
• Sodium bicarbonate i.v to correct acidosis
• Slow i.v infusion of saline/LMW dextran
• to maintain blood volume,
• tissue perfusion,
• Microcirculation
• ACE inhibitors/ARB’s to prevent
remodeling, CHF
268. PREVENTION OF FUTURE
ATTACKS
Aspirin low dose/clopidogrel given on
long-term basis
Betablockers to reduce
risk of reinfarction,
CHF,
death
Statins to control hyperlipidaemias
297. Any intelligent fool can make things
bigger, more complex, and more violent.
It takes a touch of genius -- and a lot of
courage -- to move in the opposite
direction."
Albert Einstein