TOPIC OF PRESENTATION:

VASODILATORS Presented by: Group 09

VASODILATORS:

Agents that act as blood vessel dilators. These act by producing relaxation of the vascular smooth muscle, which decrease peripheral vascular resistance and therefore blood pressure.

HYDRALAZINE
ORAL

MINOXIDIL

SODIUM
NITROPRUSSIDE

ORAL

FENOLDOPAM

PARENTRAL

DIAZOXIDE
PARENTRAL

PARENTRAL

 VASODILATOR DRUGS
Decreased systemic vascular resistance.

Decreased renal sodium excretion.

Decreased arterial pressure.

Increased renin release.

Increased sympathetic system outflow.

Increased angiotensin II.

Increased aldosterone Increased systemic vascular resistance.

This leads to:

a. Increased heart rate b. Increased cardiac contractility c. Decreased venous capacitance

Sodium retention, increased plasma volume

Increased arterial pressure

Increased cardiac output.

FENOLDOPAM
Agonist of dopamine D1 receptors Commercial product is a racemic mixture (R)-isomer mediate the pharmacologic action Peripheral arteriolar vasodilator

PHARMACOKINETICS OF FENOLDOPAM
Rapidly metabolized by conjugation Half life is 10 mints Administered by IV infusion
Initiated given dose is 0.1mcg/kg/min and then to a maximum dose of 1.6mcg/kg/min

INDICATIONS OF FENOLDOPAM:
Used for hypertensive emergencies Post operative hypertension
CONTRA-INDICATIONS OF FENODOPAM:

Avoided in patients glaucoma because it increases the intraocular pressure Reflex tachycardia ADVERSE EFFECTS Headache Flushing

HYDRALAZINE
The direct-acting vasodilator used clinically is Hydralazine (Apresoline)

PHARMACOKINETICS OF ` HYDRALAZINE
Oral vasodilator but can be given I/V. Well absorbed. Rapidly metabolized by the liver during first pass so bioavailability is o low averaging 25% o variable among individuals. It is also metabolized in part by acetylation.

40 mg/d to 200 mg/d.

Risk of toxicity is increased in slow acetylators. Rapid acetylators require higher doses.

PHARMACODYNAMICS OF HYDRALAZINE
Opens k+ channels and relaxes the smooth muscles of arterioles. It causes reflex stimulation of sympathetic system. This leads to increased heart rate Increased myocardial contractility Increased cardiac output Increased plasma renin activity Increased fluid retention. This leads to increased arterial pressure and thus antagonizes its antihypertensive action. It is thus given with
A Beta blocker A diuretic.

This leads to decrease in peripheral vascular resistances.

Decrease in arterial blood pressure.

INDICATIONS OF HYDRALAZINE:
Moderate to severe hypertension Hypertensive emergency Heart failure. Hydralazine monotherapy is used in treatment of pregnancy induced hypertension.
CONTRA-INDICATIONS OF HYDRALAZINE:

o Ischemic heart disease o Lupus erythematosus

ADVERSE EFFECTS OF HYDRALAZINE

CNS:
GIT:

Headache Dizziness Peripheral neuropathy Palpitation Flushing Reflex tachycardia Angina Ischemic arrhythmias

Anorexia Nausea.

CVS:

SKIN:

Sweating Lupus erythematosus like syndrome characterized by:

Arthralgia Myalgia Skin rashes fever

 It is prodrug. Administered orally but can be applied topically. 90% absorption from gastrointestinal tract. Topical minoxidil is poorly absorbed averaging 2%. It is widely distributed in body tissues. Plasma half life is 4 hrs.

Metabolized in the liver by the process of conjugation forming its sulfates. Action is due to its active metabolite minoxidil sulphate. It is excreted mainly by the kidneys.

5-40mg/d in single or divided doses.

1. Opens k+ channels in smooth muscles of arterioles.

IT CAUSES VASODILATON BY THE FOLLOWING MECHANISM:

2. Hyperpolarization of smooth muscles leading to dilation of blood vessels.

Due to reflex tachycardia it is given along with a diuretic and Beta blocker.

3. Decrease in peripheral vascular resistance.

4. Decrease in blood pressure.

 Severe hypertension Severe hypertension coupled with renal function impairment.

Topical use for correction of baldness in males.

CONTRA-INDICATIONS OF Minoxidil

Contraindicated in pheochromocytoma

 CNS:
Headache.

SKIN:
Sweating Flushing.

CVS:
Tachycardia Palpitation Angina Pericardial effusion.

ENDO:
Hirsuitism (hypertrichosis) in females.

RENAL:
Edema.

 It is an effective and relatively longacting parentral vasodilator. It has thiazide diuretic like action but no diuretic effects. It is a parentral direct acting vasodilator.

 It is administered parentrally. It is bound extensively to serum albumin. Its is both metabolized and excreted unchanged. Its metabolic pathways are not well characterized. Its half life is about 24 hours

The blood pressure lowering effect of diazoxide is established within 5 min and lasts for 4-12 hours.

Treatment should be started with low doses about 50 to 150mg. Dose of 150 mg should be increased after every 5 min until BP is lowered.

1. It causes vasodilation by:

Opening k+ channels in the smooth muscles of arterioles thus relaxing them. This decreases peripheral vascular resistance.

2. It also relaxes smooth muscles other than the vascular ones. 3. It inhibits the release of insulin from beta cells of pancreas thus leading to hyperglycemia.

Decreased arterial blood pressure.

Reflex sympathetic system stimulation.

I/V in hypertensive emergencies. Orally in hypoglycemia caused by hyperinsulinemia.

Diabetes mellitus Congestive cardiac failure.

 CVS:
Severe hypotension resulting in stroke or myocardial infarction. Angina Cardiac failure in pts with ischemic heart disease.

ENDO:
Hyperglycemia

RENAL:
edema

 It is administered parentrally by continuous I/V infusion. It is poisonous if given orally because of hydrolysis into cyanide. It is taken up and metabolized by RBCs with liberation of cyanide. Mitochondrial enzyme rhodanase in the presence of a sulfur donor metabolizes it to less toxic thiocyanate. Thiocyanate is distributed in ECF and eliminated by the kidneys.

Dosage typically begins at 0.5ug/kg/min. It may be increased up to 10ug/kg/min as necessary to control blood pressure.

 It dilates both arterial and venous vessels. Its action is due to nitric oxide.

Nitric oxide of sodium nitroprusside.

Activation of guanylyl cyclase (GC) in smooth muscles of blood vessels.

Increased intracellular cGMP.

Relaxation of vascular smooth muscle.

 CVS:
Directly relaxes both arterial and venous smooth muscles equally Decreases BP in supine and upright position. Decreases myocardial oxygen demand due to increased venous capacitance.

Slight increase in heart rate and decrease in cardiac output except in cardiac failure. In cardiac failure it may decrease heart rate and increase cardiac output.

RENAL:
Renal blood flow is maintained and renin secretion is increased.

Hypertensive crisis Heart failure Cardiac surgery to produce hypotension Cardiogenic shock Aortic dissection Regurgitant valvular disease.

 Cyanide toxicity: Metabolic acidosis Excessive hypotension Arrhythmias death BLOOD: Methemoglobinemia

THIOCYANATE POISONING:
Weakness Disorientation Psychosis Muscle spasms Convulsions.

ENDO:
Delayed hypothyroidism

Thank You