Download CVS PHARMACOLOGY

CVS PHARMACOLOGY
Drugs to treat myocardial ischemia
Etiology
• 1. Decrease in myocardial oxygen supply
[determined by oxygen-carrying capacity of
blood & coronary blood flow];
• 2. Increase in myocardial oxygen demand
[Determined by heart rate & ventricular
contractility] or both.
Angina Pectoris is a common manifestation of Ischemia
characterized by pressing discomfort ( & pain) radiating to left
shoulder, arm, jaw.
Organic Nitrates
• Examples –Nitroglycerine, Isosorbide dinitrate
and iso-sorbide mononitrate
• Pharmacologic Properties:
• Reduce myocardial oxygen demand
• In low concentration produce dilation of vein
• Nitrates have also relaxing effect on large
coronary vessels
Organic Nitrates
• Do not directly alter inotropic or chronotropic state of
heart rather
• decrease preload and after-load as a result of venous
capacitance and arterial resistance vessels thus reduce
myocardial oxygen demand and relief symptoms of
angina.
• M/A: Leads to formation of reactive free radical NO,
activate guanylyl cyclase, increase synthesis of cyclic
GMP in smooth muscle and other tissues of heart.
Cyclic GMP-dependent protein kinase catalyse
phosphorylation of various proteins and regulates
contractile state in smooth muscle.
Calcium Channel blockers
• Mechanism of vascular smooth muscle contraction due to influx of Ca+2
• i) voltage-sensitive Ca+2 channels open in response to depolarization of
membrane.
• ii) agonist induced contraction result from formation iP3, which acts as a
second messenger to release intracellular Ca+2
• iii) receptor operated
• An increase in cytosolic Ca+2 results in enhanced binding of Ca+2 to
protein calmodulin. This complex in turn activates myosin light-chain
kinase allowing phosphorylation of Myosin. Such phosphorylation
promote interaction between actin and myosin and contraction of smooth
muscle.
• Mechanism of calcium channel blockers [Amlodipine, Nifedipine,
Verapamil]: Inhibit voltage –dependent Ca+2 channels in vascular smooth
muscle
β-adrenergic receptor antagonists
• Efficacious for angina pectoris, acute
myocardial infarction and congestive heart
failure
• Adrenaline is vasoconstrictor. It’s blockage
results in blocking of vasoconstriction.
• Reduce oxidative stress in myocardium and
improve efficiency of myocardium
• Example: propranolol,carvidolol, metoprolol
Drugs to treat heart failure
Consequence of cardiac failure & Drugs used
Reduced cardiac output
Renin
Elevated cardiac
pressure
β blockers,
nitrates
Sympathetic nervous system activation
Angiotensin-I
Vasoconstriction
ACE inhibitor
(enalapril, captopril)
Angiotensin-II
ARBs (Losartan,
Candesartan)
Aldosteron
Spironolactone
Vasodilators like
nitrates
Sodium & water
retention
Diuretics
Role of aldosterone to initiate heart
failure
Mechanism
Increased sodium and water
retention
Pathological effect
Edema, elevated cardiac pressure
Potassium & magnesium loss Arrythmogenesis
Reduced uptake of NE
Arrythmogenesis &
Vasoconstriction
Alteration in sodium channel Incrased excitability & contractility
expression
of cardiac myocytes
Drugs to treat hypertension
•
•
•
•
•
•
Classification
1. Diuretics: thiazides (chlorthalidone), loop diuretics (furosemide),
K+ spearing diuretic (spironolactone)
2. Sympatholytic : α-adrenergic antagonist (prozosin), β -adrenergic
antagonist (metoprolol), Mixed-carvedilol, adrenergic neuron
blocking (reserpine)
3. Vasodilators: Arterial (hydralazine, minoxidil), venous
(nitroprusside)
4. Calcium channel blockers: Verapamil, Diltiazim, nifedipine,
amlodipine
5. ACE inhibitor: Captopril, Ramipril, Enalapril
6. Angiotensin-II receptor blockers (ARBs ): Losartan, Valsartan,
Candesartan
CNS PHARMACOLOGY
Pathophysiology and management of
• Parkinson’s disease
• Alzheimer’s disease
• Stroke
Drugs used in different CNS pathological
conditions
M/A, Clinical use and S/E
•
•
•
•
Antipsychotics
1. Phenothiazines: Fluphenazine, Chlorpromazine
2. Butyrophenons: Haloperidol
3. Clozapine-type : Olanzapine, Loxapine
4. Other heterocyclics: Resperidone
Antiepileptics: Carbamazepine, Valproic Acid,
Phenytoin, Gabapentine
Sedative-hypnotics: Benzodiazepines (Diazepam,
Clonazepam etc. ) & Barbiturates (pentobarbital,
phenobarbital etc.)