Vasodilators

(direct & indirect)

y
 CARDIAC REMODELLING:
C-R is the determinant of clinical course of heart
failure.def as molecular,cellular,and interstitial
changes and manifested clinically aschange in
size,shape,and function of the heart resulting from
cardiac load or injury .
CR is influenced by hemodynamic
load.nurohormonal activation,and some other
factors .
Beta blockers help in preventing this cardiac
remodelling after an acute MI.
 Contin…..
• Beta blockers and ACE-inhibitors are the
blocking agents on this remodelling
process.they decrease morbidity and
mortality in pts of post MI.
• CR is now recognized as imp aspect of CVS
disease progression and is therefore
emerging as therapeutic target in HF of all
etiologies.
Introduction to vasodilators
hem
Compensatory responses to vasodilators
 Vasodilators (based on mode of action)
• Direct vasodilators.ARTERIOLAR DILATORS:
– Hydralazine
– Minoxidal

– Diazoxide
– Fenoldopam
– Nitroglycerine

– Calcium channel blockers

• Dihydropyridines (nifedipine , nimodipine , isradipine ,
felodipine , amlodipine)
• Benzothiazepines (diltiazem)
• Phenylalkylamine (verapamil)
 CONTIN….
• 2-ARTERIOLOR AND VENODILATORS:

• Sodium nitropruside
• Indirect vasodilators

– Drugs that inhibit renin-angiotensin-aldosterone

– Direct renin inhibitors (aliskiren and beta blockers)
– ACE inhibitors
– ARBs

– Drugs that inhibit sympathetic system

• Alpha antagonists – prazocin , terazocin , phentolamine
• Centrally acting drugs – clonidine , methyldopa

– Nitroglycerine & isosorbide dinitrate

– Brain natriuretic peptide- nesiritide
Vasodilators (upon vessel selectivity)
Direct vasodilators
 VASDODILATORS TEND TO:
• Inc BP back to higher levels by:
• Inc renin release
• Inc sympathetic outflow.
• CAUSE:
• Reflex tachycardia
• Flushing
• Edema
• headacher
 hydralazine
• It is an oral arteriolar dilator.

• Mechanism of action:
– Not clear
– May involve generation of NO and stimulation of
cGMP.
– CLINICAL-USES:
– Hypertension
– CCF
 minoxidil
• It is also an oral and arteriolar dilator.
• But it has an intense action than hydralazine.

• mechanism of action:
– It is a potassium channel opener.
– Resulting in hyperpolarization
– And stabilization of membrane at its RMP
– CLINICAL USES:……
 diazoxide
• It is a parentral arteriolar dilator.
• Structurally similar to thiazide diuretics but
has no diuretic action.

• Mechanism of action:
– Potassium channel opener
 Sodium nitroprusside
• Fastest acting , arterial and venous
dilator.USED IN HYPERTENSIVE EMERGENCIES.
• USED PARENTERAL;
Mechanism of action:
– It releases nitric oxide NO that activates guanylyl
cyclase or
– Directly stimulates the enzyme to increase c GMP
 DISTINCTIVE ADVERSE EFF:
• CYANIDE POISIONING:
• It’s a complex of iron,cyanide,and nitro gp and
is rapidly metabolized by uptake into RBCs with
liberation of CYANIDE.
• RX:
• Sodium thiosulphate to convert into
thiocyanate.
• May cause METHHEMOGLOBINEMIA.give
methylene blue for this.
 fenoldopam
• D1 receptor agonist
• Peripheral Arteriolar dilator.
• Causes natriuresis.

• Mechanism of action:
– It acts on Dopamine 1 (D1) receptors and cause
arteriolar dilation and natriuresis.
– Causes inc iop so avoid in glaucoma pts.
 Uses of vasodilators (in hypertension)
• Essential hypertension
• Hypertensive emergencies (Na nitroprusside)
• Pulmonary arterial hypertension
• Production of controlled hypotension during
surgery
• Pheochromocytoma
 Other uses of vasodilators
• Peripheral vascular disease
• Angina pectoris
• MI
• Heart failure
• Insulinoma (diazoxide)
 Adverse effects of vasodilators(in
common)
• Postural hypotension
• Headache , flushing , dizziness

• Reflex tachycardia , palpitations , can precipitate

angina and arrythmias

• Expansion of blood volume

• Edema
Distinctive adverse effects of vasodilators

• SLE like syndrome - HYDRALAZINE

• Hypertrichosis - MINOXIDIL
• Hyperglycemia - DIAZOXIDE
• Hyperuricemia - DIAZOXIDE
• Cyanide poisoning – SODIUM NITROPRUSSIDE
• Thiocynate poisoning - SODIUM NITROPRUSSIDE
• Increased intraocular pressure - FENOLDOPAM
 Drug interactions and cautions
• Effect of Vasodilators may be potentiated with
the use of
– Other anti-hypertensives

• Effect of vasodilators like diazoxide can be

decreased with
– oral hypoglycemics and insulin

– Caution: Avoid excessive hypotension with

vasodilators
 Calcium channel blockers
• Mechanism of action on vascular smooth muscle
– L-type calcium channels are common in cardiac and smooth
muscles. They contain several drug receptors like alpha 1 & 2.
gamma , theta.

– Nifedipine Binds to alpha 1 subunit receptor of L-type voltage

dependant Calcium channels and block them and verapamil and
diltiazem to some other nearby receptors.

– They bind to the inner surface of the membrane of the open and
inactivated channels

– So decrease the frequency of opening of channels in response to

depolarization
Calcium channel blockers
• Resulting in
– In vascular smooth muscles : relaxation

– Dihydropyridines have a greater effect on vessels

than heart.
– Diltiazem , verapamil have lesser effects.

– Arterioles are more sensitive to veins

– So afterload is decreased more than preload.
 Adverse effects of calcium channel
blockers
• Flushing
• Dizziness
• Reflex tachycardia
• Nausea
• Constipation
• Peripheral edema
• cardiac depression
Indirect vasodilators
• Indirect vasodilators

– Direct renin inhibitors (aliskiren)

– ACE inhibitors
• Captopril enalapril lisionopril fosinopril ramipril
• Benzapril moexipril perindopril trandopril quinapril

– ARBs
• Losartin valsartin candesartin irbesartan eprosartan
• Telmisartan olmesartan
– Nitroglycerine & isosorbide dinitrate
– Brain natriuretic peptide- nesiritide
– Sympatholytics
• Alpha antagonists – prazocin , terazocin , phentolamine
• Centrally acting drugs – clonidine , methyldopa
mechanism of action of aliskiren, ACE inhibitors , ARBs
 Adverse effects
• Severe hypotension
• Hyperkalemia
• Dry cough , wheeze
• Angioedema

• Interactions:
– Potassium supplements – worsens hyperkalemia
– NSAIDs impair hypotensive effects of ACE inhibitors
 Nitroglycerine &
isosorbide dinitrate-
mechanism of action
 Adverse effetcs of nitrates & nitrites
• Postural hypotension
• Reflex tachycardia
• Headache
 Nesiritide- Brain Natriuretic Peptide
Analog
• Cause both arteriolar and venous dilatation
• Increases c GMP in vascular smooth muscles

• Adverse effects:
– Excessive hypotension
– Renal damage and deaths reported so should be
used with caution
 Learning Resources

• Basic and clinical pharmacology by Katzung , 11th edition

• Nauman’s textbook of pharmacology , 2nd edition

• Lippincott’s pharmacology , 3rd edition

• Internet
Thank you
Direct vasodilators Indirect vasodilators

• Ca antagonists • Drugs that inhibit

– Sympathetic system
– RAAS
• Potassium openers
( nicorandil, minoxidil,
diazoxide)

• Act via cyclic

nucleotides( nitrates,
nitroprusside,nesiritide)

• PDE inhibitors

• Unknown MOA
( hydralazine)