PHARMACOTHERAPY OF

ISCHEMIC HEART DISEASE

DR. SANJAY KUMAR

ASST. PROFESSOR
DEPT. OF PHARMACOLOGY
LCMC&H
 OBJECTIVES
• INTRODUCTION
• MANIFESTATIONS OF ISCHEMIC HEART
DISEASE
• PATHOPHYSIOLOGY OF ISCHEMIC HEART
DISEASE
• DRUGS USED IN ANGINA
• RECENT ADVANCES IN ANGINA
• DRUGS USED IN MI
• DRUG ELUTING STENTS
 INTRODUCTION
• Ischemic heart disease is the one of the most
common cardio-vascular disease in the developed
countries.

• It is caused by localized calcification causing

progressive constrictions of coronary arteries &
exercise induced angina.

• Angina pectoris is a symptom of myocardial

ischemia.
• It is a result of imbalance
between the oxygen supply
and the oxygen demand of the
myocardium.

• Anginal attacks may

precipitate with hypertension,
thyrotoxicosis, anaemia,
obesity, heart failure, cardiac
arrhythmias, acute emotional
stress.
Atherosclerosis manifestations:
1. Endothelial dysfunction
2. No production
3. Vasodilatation
4. Risk of platelet aggregation
5. Influx of lipid scavenger cells
6. Necrosis, sterile inflammation
7. Proliferation of smooth cells
8. Calcification & narrowing of blood vessel
plaque formation
• The manifestations of IHD
1. Effort / classic / asymptomatic angina
2. variant angina (vasospastic)
3. Unstable angina
4. MI
5. Peripheral vascular disease
1. Effort/stable/asymptomatic angina:
• Inadequate blood flow in the presence of CAD
results to effort angina.
• Exercise induced angina.

• Oxygen demand reduced by decreasing cardiac

work.

• Diagnosis by history & stress testing.

• It can be relieved by taking rest (5-15min).

 2. Variant/ vasospastic angina:
• Transient spasm of localized portions of the vessels,
usually associated with underlying atheromas, can
also cause significant ischemia & pain.
• Occurs mostly in the mornings.

• Diagnosis by history.

• Spasm of coronary vessels can be reversed by

nitrates/ CCB.
 3. Unstable angina/ ACS:
• Episodes of angina at rest
• severity of chest pain with previous
• frequency stable angina.
• duration

• It is caused by episodes of increased epicardial

coronary artery resistance / small platelet clots
occuring in the vicinity of the atherosclerotic
plaque.
 Contd..

• Reduction in the flow caused by occlusive thrombi

at site of fissured / ulcerated plaque.

• Inflammation may be risk factor because patient on

TNF will have low risk for MI.

• ACS associated with high risk of MI & death

-medical emergency.
Contd…

• Decrease O2 demand/ increase O2 delivery

( medical/ physical interventions).

• Lipid lowering drugs have become extremely

important in the long term treatment of
atherosclerotic disease.
 PATHOPHYSIOLOGY
•Heart rate •Coronary blood flow
•Contractility •O2 carrying capacity
•Ventricular wall tension
DRUGS USED IN ANGINA
NITRATES
• Prodrugs, donors of exogenous NO.
• Iso forms of NO
nNOS/ NOS-1- central & peripheral neurons
i NOS/NOS-2- vascular smooth muscle, macrophages,
kuffer cells, fibroblasts, neutrophils and endothelial
cells.
e NOS/NOS-3 -vascular endothelium, brain, heart
They are involved in
➢ neurotransmission,
➢ vasomotion
➢ immunomodulation.
Pharmacological actions:
• Nitrates causes Venodilation as well as arterial
relaxation thus it causes reduction in preload
& afterload respectively.
• Thus ventricular work load & oxygen demand
will decrease.
• Coronary circulation- dilates the large
epicardial coronary arteries without affecting
the resistance of the arterioles.
• Dilates the collaterals.
Contd…

• Redistribution- Ischemic areas

• Chronic administration will leads to
interarterial anastamoses within the
myocardium.
• Increase exercise tolerance.
• Prevent ECG changes of cardiac ischemia
during exercise.
GTN:
• Peak plama level: 4min; S/L.
• T1/2: 1-3min.
ISOSORBIDE DI NITRATE
• Peak plasma 6mins.
• T1/2 : 45min.
• Isosorbide 2 mono nitrate, isosorbide mono nitrate
are the metabolites and their T1/2: 3-6 hrs.
• Suitable to treat angina.
IS0SORBIDE 5 MONO NITRATE
• First pass metabolism
• High bioavailability
• Onset of action slow
INHALED NO
• Used in pulmonary hypertension.
USES:
• All types of angina
• MI
• Acute LVF
• Chronic heart failure
• Achalasia cardia- inhalation test
• Acute anal fissure
• Cyanide poisoning
• Biliary colic
• Esophageal spasm
Adverse effects:
• Headache
• Hypotension
• Palpitations
• Dizziness
• Monday disease- due to tolerance
• Sudden stoppage- may precipitate angina
Calcium channel blockers
• Calcium channel blockers/Ca+2 entry blockers/
Ca+2 channel antagonist.

• Inhibit the Ca+2 influx.

• Calcium channel blockers ({L-type/slow}) mediate

the entry of extracellular Ca+2 into smooth muscle
and cardiac myocytes and SA node and AV nodal
cell in response to electrical depolarization.
Contd…
• In smooth muscle and cardiac myocytes Ca+2 is
trigger for contraction by different mechanisms.

• In vascular smooth muscle, this leads to relaxation,

especially in arterial beds, in cardiac myocytes to
negative inotropic effects.

• All Ca+2 channel blockers excert these two

principal actions i.e, chronotropic & dromotropic
effects.
TYPES OF Ca+2 CHANNELS:

4 types of channels have been described

1. Voltage sensitive Ca+2 channels.

2. Receptor operated Ca+2 channels
3. Leak channels/ stretch operated channels.
4. Na+-Ca+2 exchange channel
1. Voltage sensitive Ca+2 channels:
• These are influenced by depolarising stimuli,
Activated when membrane potential
drops -40mv/less.

• 5 types of voltage gated Ca+2 channels

(L,T,N,P,Q) have been identified.
Classification of calcium channel blockers

1. Dihydropyridines (DHPs)
a.Ultra short acting: CLEVIDIPINE
b.Short acting: NIFEDIPINE, NICARDIPINE,
NIMODIPINE
c.Intermediate acting: NISLODPINE, NITRENDIPINE,
ISRADIPINE, LACIDIPINE, CILNIDIPINE,
LERCANIDIPINE
d.Long acting: FELODIPINE, BENIDIPINE,
AMLODIPINE
Contd…
2. Non dihydropyridines(Non DHPs)
Short acting: verapamil, diltiazem
Long acting: bepridil
MOA : Ca+2 channel blockers

blocks L type Ca+2 channels

Ca+2 current &Ca+2 entry into cardiac

&vascular smooth muscle

HR, cardiac contractility,

Conduction velocity,
vascular smooth muscle relaxation.
DHP GROUP OF CCBs

NIFEDIPINE
• The short acting capsular form of nifedipine was the
first CCB of this group that was introduced to treat
hypertension & angina.

• Poor out come with unstable angina, risk of

myocardial ischemia, left ventricular dysfunction
because of its short acting & vasodilatory action.
 Contd…
• Extended release formulation of nifedipine or
truly long acting DHPs(AMLODIPINE) which are
free of danger.

• These drugs now using in the treatment of

hypertension & exertional angina.

• In addition it has an intrinsic natriuretic effect

and hence dose not needed an addition of a
diuretic.
Contd…
Contraindications:
• Unstable angina ( unless combined with beta
blocker)
• LV failure
• Aortic stenosis
• Obstructive cardiomyopathy.

Drug interactions:
• Liver disease enzyme inhibitors & grape fruit juice
increase the plasma levels.
Amlodipine:
• Slow but complete oral absorption.
• T1/2: 35-48 hrs.
• Day time fluctuations in blood level are minimal.

USES: hypertension & effort angina .

Adverse effects:
Tachycardia, headache, flushing.
Dose: 5-10mg once daily oral.
Drug interactions: virtually nil.
• Isradipine, nitrendipine, nislodipine, cilnidipine ,
lercandipine, lacidipine & benidipine are
vaso-selective & nifedipine derivatives.

Isradipine:
• T1/2: 8 hrs.
• Dose: 2.5-5mg BD orally – for hypertension.

Nitrendipine
• T1/2: 8-12 hrs.
• Dose :20mg OD orally- for hypertension & angina.
 Contd…
Nislodipine :
• T1/2: 8-12 hrs.
• Dose 20mg OD orally- for hypertension.
Lecarnidipine:
• T1/2: 8-10hrs
• Dose 10-20mg OD orally –for hypertension.
Benidipine :
• Newer CCB approved for hypertension & angina.
• Dose : 2-4mg OD/BD orally.
• It is claimed to inhibit cardiac remodelling.
 Contd…
Lacidipine :
• A longer acting newer CCB.

• Slows down the progression of carotid

atherosclerosis, limits the development of new
metabolic syndrome & new diabetes, besides
providing good vasoprotection.

• It cause least ankle oedema.

• Dose 2-6mg od orally – for hypertension.

Contd….
Cilnidipine :
• Renoprotective CCB.
• Approved for hypertension.

Nicardipine :
• T1/2 4hrs.
• It has more pronounced coronary dilatation effect
with lesser effect on cardiac contractility as
compared to nifedipine.
• Dose : 60mg BD oral –for angina & hypertension.
 Contd…
Nimodipine :
• T1/2: 2hrs highly lipid soluble & crosses BBB.
• It shows higher affinity & selectivity for cerebral
blood vessels and appear to reduce morbidity
following a subarachnoid haemorrhage .
• Nimodipine can be used in migraine/ haemorrhagic
stroke.
• Dose :60mg 6hrly for 21 days
• Therapy to be started within 96hrs of the stroke
 Contd…
Clevidipine : ultra short acting CCB
• T1/2: <15min.
• Severe hypertension (pre& post opearative).
• It is more effective than sodium nitroprusside &
glyceryl trinitrate.
Adverse effects:
• Headache, nausea, vomiting
• Tachycardia
• Heart failure.
 NON DHP CCBs
Verapamil :
• Peripheral vasodilator.
• Cardiac depressant – decrease in HR, conduction
velocity, contractility.
• It possesses a non specific alpha adrenergic
blocking – vasodilatation.
Contd….
Uses:
• angina( effort, vasospastic, unstable)
• Supra ventricular tachyarrhythmias
• Post infarction protection
• Mild –moderate hypertension
Dose :120mg BD/80mg TID orally
Adverse effects:
• Constipation very common
• GERD
• Headache
Contd….
• Dizziness
• Worsen MI
• Hypotension – (quinidine + verapamil)
Contraindications :
• Sick sinus syndrome
• AV conduction defects
• Heart failure
 Contd…
Drug interactions:
• Inhibits P- glycoprotein( digoxin transporter)
Thus increases its levels in blood.

• Inhibits CYP3A4 increases statin levels in

blood.
• With beta blockers additive sinus depression

• Disopyramide & quinidine enhances negative

inotropic effect.
Diltiazem :
• less potent coronary as well as peripheral
vasodilator
• Supression of automaticity at SA node and
conductivity at AV node same magnitude as
verapamil.
• Decrease contractility lesser than verapamil.

Adverse effects: low(no constipation)

Bepridil:
• Blocks the Ca+2 channels like verapamil.
• Reduces the HR & BP patient with exertional
angina.
• Also reported to improve left ventricular
performance.
Uses:
• Except who are refractory to all other therapy.
Adverse effects:
• Qtc prolongation
• Agranulocytosis
Contd….
Adverse effects:
• Headache
• Flushing
• Ankle edema
• Tachycardia
• Reversible gingival hyperplasia
 Contd….

Contraindications & drug interactions

• Women are more sensitive than men to its BP
lowering effect.
• Dose : 60-120 mg BD oral;
max 360mg/day.
BETA BLOCKERS
• Beta blockers are the only drugs that are
effective in reducing the severity and frequency
of attacks of exertional angina and in improving
survival in patients who had an MI.

• They are therefore recommended as first line

treatment of patients with stable CAD &
Unstable angina/ACS

• Beta blockers are not useful in vasospastic

angina.
Rationale for their use in angina
• Beta blockers provide relief in angina by reduction in
HR & myocardial contractility due to blockade of
cardiac beta1 receptors.

• This results in decrease in cardiac output and a

decrease in myocardial O2 requirement, at rest and
during exercise.

• They also prevent arrhythmias which may precipitated

by exercise /stress and decrease in magnitude of ST
segment depression in ECG during exercise.
Contd..
• These are considered as basal protective agents for
most of the patients.

• They are used with nitrates for chronic prophylaxis

of effort angina.

• They do not dilate coronaries.

• Total coronary blood flow is rather reduced due to

blockade of dilator beta 2 receptors as well.
Contd…..

• The mechanism responsible for an increase in the

O2 supply to sub-endocardium of ischemic area is
most likely related to the ability of beta blockers to
increase the diastolic perfusion time, because the
sub-endocardial blood flow and the flow distal to
severe coronary artery stenosis occurs primarily
during diastole.

• Finally , there is evidence that beta blockers inhibits

platelet aggregation.
Contd…
• All beta blockers are nearly equally effective in
decreasing the frequency and severity of attack and
increasing exercise tolerance in classical angina,
cardio selective beta1 blockers like metoprolol /
atenolol are more preferred.

• The non selective beta1+ beta2 blockers like

propranolol & nadolol can worsen prinzmetal
angina, because an unopposed alpha- receptor
mediated coronary vasoconstriction may aggrevate
coronary spasm(CCB preferred here).
Contd…
• Higher doses may worsen classical angina by
causing ventricular dilatation and prolonging
systole, both of which tend to increase O2 demand.

• Beta blockers used to treat effort angina are

bisoprolol and celiprolol.

• Dosage of beta blockers for angina &hypertension

are same
CLASSIFICATION
Non selective beta Non selective beta
blockers (1st blockers with
generation) additional
• Nadolol actions(3rd
• Penbutalol generation)
• Pindolol • Cartelol
• Propranolol • Carvedilol
• Timolol • labetolol
Contd…
Beta 1 selective Beta 1 selective
blockers blockers with
( second generation) additional
• Acebutolol actions(3rd
generation)
• Atenolol
• Betaxolol
• Bisoprolol
• Celiprolol
• Esmolol
• Nebivolol
• Metoprolol
PROPRANOLOL
• Equal affinity for beta1 & beta 2 receptors (nadolol)
• Does not block alpha receptors
• Dose 40- 80 mg /day
• Uses : Anxiety related symptoms
Hypertension
Angina
Life threatening arrhythmias
Contd…
Nadolol- longer acting beta blocker
Uses : hypertension, angina,
• Migraine prophylaxis,
• Tremors in parkinsonism,
• Variceal bleeding in portal hypertension.

Timolol – Hypertension, CHF, acute MI,

• Migraine prophylaxis
• Open angle glaucoma,
• intra ocular hypertension
Metoprolol - CYP2D6
USES:
• Hypertension, angina,
• Tachycardia , heart failure,
• Secondary prevention to myocardial infarction
• Migraine prophylaxis.
labetolol:
• Hypertensive emergencies.
• Pregnancy induced hypertension.
Pindolol-
• hypertension, angina
Uses –
cardiac
• Angina pectoris
• MI
• Cardiac arrhythmias
• Hypertension
• Heart failure & depressed ejection fraction
• HOCM
• pheochromocytoma
Non- cardiac
• Chronic open angle glaucoma
• Thyrotoxicosis
• Portal hypertension
• Withdrawl symptoms in alcohol addicts.
• Prevents migraine
• Anxiety associated symptoms.
Contd..

Drug interactions:
• Colestyramine, colestipol increases it’s absorption
• Enzyme inducers decreases it’s plasma
concentration.
• Impair the clearance of lignocaine and thus may
increase it’s bioavailability.
 RECENT ADVANCES IN ANGINA
PHARMACOTHERAPY
Potassium channel openers :
• K+ions controls the resting membrane.

• Intracellular K+ ions concentration much higher

than extra cellular K+.

• Thus K+ channel openers efflux of K+,

hyperpolarisation
 Contd…
• Such an effect indirectly opposes the opening of
voltage gated Ca+ channels which require
depolarization above a certain threshold
membrane potential for activation.

• This results fall of cytosolic Ca+2

concentration, with a reduction of cellular
contractile activity at the myocardial &vascular
level.
TYPES OF K+CHANNELS

1. Voltage gated K+ channel.

2. Calcium activated K+ channel
3. ATP sensitive K+ channel
4. Several other types of K+ channels also identified
– receptor operated,
Na+ activated,
Cell volume sensitive K+ channels
Voltage gated K+ channel:
• Opens when depolarization occurs & therefore
helps in repolarization

• Present in vascular & other smooth muscles-

produces relaxant effects

• Other muscles like tracheal, broncheal,

intestinal, uterine, urinary bladder & corpus
luteum.
Contd…
• EXAMPLE :
Diazoxide,
Pinancidil,
minoxidil,
cromokalim
• Voltage gated K+ channel openers for blood
vessels& cause membrane hyperpolarization,
leading to vasodilatation & fall in BP
• These are primary used as anti hypertensive drugs.
Calcium-activated K+ channel:
• Intracellular Ca+2 concentration

K+ Channel opens

efflux of K+

Repolarisation of the cell

• These are sensitive to number of neurotransmitter

actions such as 5HT, Ach,NE
ATP sensitive K+ channel :
• Present in cardiac muscle, beta cells of the islets.

• Closes intracellular ATP increases

• Opens intracellular ATP drops

• Such K+ channel openers act by antagonizing the

actions of intracellular ATP on these channels.
Contd…
• Opening of these channels blocked by
SULFONYLUREAS (glibenclamide).

• Blockade Depolarization of beta cells

which stimulates insulin.

EXAMPLE :
• Nicorandil
 NICORANDIL:
• Newer anti anginal drug.

• It activates ATP sensitive K+ channels &

hyperpolarizes vascular smooth muscle.

• Reduces pre & afterload & produces coronary

vasodilation.

• Nicorandil carries nitrate like moiety, also exerts

nitrate like effect.
Contd…
• Its arterio vasodilator effects are due to K+ channel
opening, whereas venodilator effects are due to
nitrate like moeity.
• Nicorandil coronary blood flow without producing
significant effects on contractility, conduction, heart
rate& BP.

USES :
1. Vasospastic angina
2. Chronic stable angina @ dose 10-20 mg BD / orally
Adverse effects:
• Flushing
• hypotension
• Palpitations
• Dizziness
• Headache
• Oral , GI ulcers
• perforation
• Nausea
• vomiting
Contd..
Contraindications:
• Cardiogenic shock
• LVF with low filling pressure & hypotension.

Drug interactions:
• It shouldn’t be used with sildenafil as the
hypotensive effects of nicorandil are
potentiated by sildenafil.
CYTO PROTECTIVE DRUGS
TRIMETAZIDINE:
• New Ca+2 channel blocker belongs to piperazine group.

• It is a type of cellular anti ischemic drug that has

cyto protective effects.

• Inhibits the long chain 3 keto acyl co-enzyme A Thiolase in

fatty acid beta oxidation.

• This leads to partial shift from FFA to glucose oxidation in

the heart, which provides less ATP but requires less
O2( beneficial in ischemia)
 contd
• In the presence of ischemia it maintains
LV functions without affecting haemodynamics.

• It acts on BP reduction independently, trials are

underway to use it in place of nitrate to allow free
use of sildenafil in patients of angina with erectile
dysfunction.
Contd…
USES :
a. stable/ effort angina.
b. Infarction sequelae
c. Ischemia of labyrinths as in meniere’s disease.
d. DM+ HF

Adverse effects:
Parkinson’s disease
GI symptoms
Thrombocytopenia,
Agranulocytosis
RANOLAZINE :
• FDA & EMA approved second line drug for chronic
angina.
MOA
1. Inhibits the several ions fluxes I k, I Na
• Preferential I Na
• Late I Na causes Ca+2 overload, arrhythmias,
diastolic relaxation.
2. Reduces fatty acid oxidation & stimulate glucose
metabolism without inhibiting carnitine palmityl
transferase 1
 Contd….
• Weak beta receptor blocking activity.
• Metabolism by CYP3A4

USES:
• Relieves angina & decreases the incidence of
serious ventricular arrhythmias in patients with post
acute coronary syndrome
• Decreases nitrates use & decreases frequency of
anginal attacks.
Contd..
Adverse effects :
• Qtc prolongation concurrent use of quinidine,
dofetilide, sotalol should be avoided.

Drug interactions :
• Safely combined with Ca channel blockers, beta
blockers, nitrates (but not with verapamil,
diltiazem)
• Metabolism by CYP3A4 drugs like anti fungals, anti
virals increase its concentration. It may leads to Qtc
prolongation.
DIRECT BRADYCARDIAC AGENTS
IVABRADINE:
MOA:
• Blocks hyperpolaristion- activated cyclic nucleotide
channel through Na+ channels present in SA node.

• Inhibition of these channels by ivabradine

decreases myocardial O2 demand thus decreases
HR & doesn’t effect the contractile force like beta
blockers.
• IVABRADINE= BETA BLOCKER/CCB
Contd…
• There is no negative inotropic effects/ reduction in
BP nor any rebound on cessation of therapy( like
beta blocker)
• Chances of marked SA node depression are also less
because If current is only one the several
pacemaker current at SA node (beta blockers &
CCBs like verapamil effect all).

Uses
• FDA- Only heart failure
• EMA- stable angina & HF
Contd….
ADVERSE EFFECTS : Rare
• Except unusual disturbances in nocturnal vision
with flashing lights which may impair driving @
night

contraindications:
• Ivabradine + beta blocker= Bradycardia,
Atrial fibrillation,
Qtc prolongation
• Ivabradine + CCB
ANTI PLATELET AGENTS
Contd…
ASPIRIN :
• TXA2 inhibitor
• TXA2 is potent vasoconstrictor & platelet
aggregator
• Aspirin 75-325mg daily
• Effective in decreasing the incidence of ischemia,
CAD
• Recent reports suggested that vasodilatory effects
of ACE inhibitors are blunted by concomitant aspirin
therapy.
 Contd…
• Ticlopidine -thienopyridine derivatives
• Clopidogrel -they do not interfere with
• Prasugrel prostaglandin synthesis.

MOA:
• Inhibits ADP pathway of thrombocytes
• ADP RECEPTORS(irreversible) platelet
• (P2Y1)(P2Y12) aggregation
Contd…
• Clopidogrel safer toxicity profile compared to
ticlopidine.

• Clopidogrel= aspirin (secondary prevention of

stroke) .

• Exhibits supra additive synergism when used with

aspirin.

• All these drugs prophylactically alone / adjuvant

drugs for unstable angina & prevent thrombosis(Sx)
 Contd….
• Ticlopidine 250mg BD

• Clopidogrel initially loading dose 300-600mg

F/B
75mg OD

• Prasugrel initially loading dose 60mg

F/B
5-10mg OD
PHOSPHODIESTERASE-3 INHIBITOR
CILASTAZOLE :
• It promotes vasodilatation,
• Inhibition of platelet aggregation( C-AMP in vessel
wall).

USES:
• An adjuvant in anti anginal therapy.
• Intermittent claudication
Contd…

• Metabolism by CYP3A4 – Anti Fungals, Verapamil,

diltiazem should be avoided.
• Dose : 100mg BD orally (30 min before/2hrs after
food).
DIPYRIDAMOLE :
• Phosphodiesterase-3 inhibitor accumulation
• Inhibits adenosine deaminase of adenosine
& Cyclic-AMP

Inhibits platelet aggregation &

stimulate release of PGI2
Contd…

USES:
• Decreases the incidence of thrombo-embolic events
in prosthetic valves.
• As a vasodilator : myocardial perfusion imaging
(thallium scanning) .
• It has minimal effect on BP , cardiac work, as venous
return is not decreased.
• Not useful in angina.
HMG -CO A INHIBITORS
STATINS :
• Absorption 30-85% by oral.
• Beta hydroxy form Inhibits the HMG CO -A
Reductase
• Except simvastatin & lovastatin inactive
lactones liver beta hydroxy form

• Atorvastatin, lovastatin, simvastatin undergo

extensive first pass metabolism by CYP3A4
Contd….
• Acts by improving endothelial function
• Stabilizes platelets.
• Inhibits inflammatory response associated with
atherogenesis.

USES:
• Supportive treatment for coronary artery disease
• LDL Dietary modification + statin therapy
Contd….
• Atorvastatin can be given in renal failure.
• Atorvastatin -can be given 11 yrs & older
Lovastatin
Simvastatin

• Rosuvastatin & atorvastatin- longer half lifes.

• Pravastatin can be given 8yrs & older.

• Contraindicated in pregnancy & lactation.

RHO KINASE INHIBITOR
FASUDIL :
• Inhibitor of smooth muscle Rho kinase

• It causes vascular smooth muscle relaxation

through Rho associated protein kinase pathway .

Uses:
• Angina
• Pulmonary arterial hypertension
MISCELLANEOUS DRUGS

MOLSIDOMINE :
• Vascular smooth muscle relaxant
• Exert its action by donating NO

MILDRONATE & PERHEXILINE:

• They inhibits the fatty acid oxidation
• Shown improvement in tachycardia induced angina
DRUGS USED IN MI
Contd….
Management of MI :
• Relief Of Pain
• Anti platelet therapy
• Thrombolytic therapy
• Maintainance of effective blood volume
• Inotropic drugs
• Prevention of arrhythmias
• Beta blockers
• Anti coagulants
THROMBOLYTICS
MOA:
• Tissue plasminogen activator + fibrin

Plasminogen = Degradation of fibrinogen

Uses:
Acute MI
Ischemic stroke
Pulmonary embolism
ACE INHIBITORS:
• All are prodrugs except (lisinopril, captopril)
• Dose should be reduced in renal insufficiency

MOA :
• It inhibits the conversion of ang I – ang II
• Also inhibits degradation of bradykinin.
• ACE inhibitors increase by 5 fold the circulating
levels of the natural stem cell regulator AcSDKP
which may contribute the cardio-protective effects
of ACE inhibitors.
Classification

• Sulfhydryl- containing ACE inhibitors structurally

related to captopril
• Dicorboxyl -containing ACE inhibitors structurally
related to enalapril (lisinopril perindopril, benzapril,
quinapril, moexipril, trandropril, ramipril)
• Phosphorus- containing ACE inhibitors structurally
related to fosinopril.
Contd….

Uses:
• Hypertension
• Left ventricular systolic dysfunction
• MI
• Prevents renal disease progression diabetes
mellitus .
• Scleroderma renal crisis
Contd….

Adverse effects
• Hypotension
• Cough
• Hyperkalemia
• Acute renal failure
• Angioedema
• Teratogenic effects on foetus
• Skin rash
Contd….

Drug interactions :
• Aspirin decreases the bioavailability.

• ACE Inhibitors + K+ sparing diuretics= hyperkalemia.

• May increase digoxin and lithium plasma levels.

Drug Eluting Endovascular stents

• Intra coronary stents can improve angina and

reduce adverse events in patients with ACS.

• Long term efficacy of intra coronary stents is limited

by sub acute luminal restenosis within the stent,
which in bare metal stents, occurs 20-30% of
patients during first 6-9 months
 Contd…

• Drugs used in intravascular stents are paclitaxel,

sirolimus and it’s derivatives (zatarolimus,
everolimus).

• Dual anti platelet therapy (aspirin typically with

clopidogrel) is recommended for one year after
intracoronary stenting with drug- eluting stents,
similar to bare metal stents.
PERIPHERAL VASCULAR DISEASE
OBSTRUCTIVE VASOSPASTIC
• Atherosclerosis/ • Raynaud syndrome
Thromboangitis with • Rx: CCB- Verapamil,
large vessels/Diabetes diltiazem
with small vessels • Beta adrenergic
involvement. stimulants : isoxsuprine
Rx: Pentoxifylline • Alpha adrenergic
naftidofuryl oxalate blockers : talazoline,
cilostazol prazosin
• Anticoagulants :
heparin, warfarin
 REFERENCES
❖GOODMAN & GILMAN – The Pharmacological
Basis Of Therapeutics , 13th Edition.
❖G.KATZUNG – Basic & Clinical Pharmacology ,
12th Edition.
❖R.S.SATOSKAR – Pharmacology &
Pharmacotherapeutics , 25th Edition.
❖SHARMA & SHARMA’S –Principles of
pharmacology, 3rd edition.
❖RANG & DALE’S –Pharmacology, 9th edition