vasodilators by hiren patel

8/3/2019 Vasodilators by Hiren Patel

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Pharmacology of Vasodilator

Hiral A. Patel Roll no 62

Sem 5th


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Introductionwhat are vasodilators?

Vasodilation(Vasodilator) refers to the widening ofblood vesselsresulting from relaxation ofsmooth muscle cells within the vessel walls,particularly in the large arteries, smaller arterioles and largeveins

The process is essentially the opposite ofvasoconstriction, or thenarrowing of blood vessels.

When vessels dilate, the flow of blood is increased due to a decrease in

vascular resistance Therefore, dilation of arterial blood vessels (mainlyarterioles) leads to a decrease inblood pressure
http://en.wikipedia.org/wiki/Blood_vesselshttp://en.wikipedia.org/wiki/Smooth_musclehttp://en.wikipedia.org/wiki/Arterieshttp://en.wikipedia.org/wiki/Arterioleshttp://en.wikipedia.org/wiki/Veinshttp://en.wikipedia.org/wiki/Vasoconstrictionhttp://en.wikipedia.org/wiki/Vascular_resistancehttp://en.wikipedia.org/wiki/Blood_pressurehttp://en.wikipedia.org/wiki/Blood_pressurehttp://en.wikipedia.org/wiki/Vascular_resistancehttp://en.wikipedia.org/wiki/Vasoconstrictionhttp://en.wikipedia.org/wiki/Veinshttp://en.wikipedia.org/wiki/Arterioleshttp://en.wikipedia.org/wiki/Arterieshttp://en.wikipedia.org/wiki/Smooth_musclehttp://en.wikipedia.org/wiki/Blood_vessels


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Introduction

The response may be intrinsic (due to local processes in thesurrounding tissue) or extrinsic (due to hormones or thenervous system).

Additionally, the response may either be localized to aspecific organ (depending on the metabolic needs of aparticular tissue, as during strenuous exercise), or systemic

(seen throughout the entire systemic circulation). Factorsthat result in vasodilation are termedvasodilators.
http://en.wikipedia.org/wiki/Hormoneshttp://en.wikipedia.org/wiki/Nervous_systemhttp://en.wikipedia.org/wiki/Systemic_circulationhttp://en.wikipedia.org/wiki/Systemic_circulationhttp://en.wikipedia.org/wiki/Nervous_systemhttp://en.wikipedia.org/wiki/Hormones


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Vasodilators

Why we use vasodilators?Primary use for cardiac disease

To improve haemodynamics, improvecardiac output, and improve tissueperfusion.

Vasodilators do this by dilating arterioles

(decreases resistance) and/or venules

(decreases circulating blood volume)


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Classification of VD

Classification based on chemical nature of drug:

Hydrazinopthalazine: (Direct-acting)

eg:HydralazineOrganic nitrates : eg:Nitroglycerin

Nitric oxide donors : eg:Nitroprusside

Alpha blocker: eg:PrazocinCalcium channel blockers: eg:amlodipine,diltiazem,verapamil.ACEI: eg:captopril,enalapril,fosinopril etc.Potassium channel openers: eg:minoxidil,dizoxide.


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Vasodilators

Classification based on Site of action

Types of vasodilators

Arteriodilators

reduce afterload

Venodilators

reduce preload

Mixed vasodilators


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Vasodilators

Arteriodilators

Hydralazine:

It acts on arteries & arterioles

It is a synthetic drug.


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Mechanism of action

Hydralazine increases cGMP levels, decreasing the action of thesecond messengerIP3, limiting calcium release from thesarcoplasmic reticulum of smooth muscle.

This results in an vessel relaxation. It dilates arterioles more thanveins.

It recently has been identified as a nitric oxide donor.

PK: well absorbed orally.

Undergoes extensive first pass hepatic metabolism.

85%bound to plasma protein.

Duration of effect is 6-8 h.
http://en.wikipedia.org/wiki/Second_messengerhttp://en.wikipedia.org/wiki/Inositol_triphosphatehttp://en.wikipedia.org/w/index.php?title=Calcium_release&action=edit&redlink=1http://en.wikipedia.org/wiki/Second_messengerhttp://en.wikipedia.org/wiki/Inositol_triphosphatehttp://en.wikipedia.org/w/index.php?title=Calcium_release&action=edit&redlink=1http://en.wikipedia.org/wiki/Sarcoplasmic_reticulumhttp://en.wikipedia.org/wiki/Nitric_oxidehttp://en.wikipedia.org/wiki/Nitric_oxidehttp://en.wikipedia.org/wiki/Sarcoplasmic_reticulumhttp://en.wikipedia.org/w/index.php?title=Calcium_release&action=edit&redlink=1http://en.wikipedia.org/wiki/Inositol_triphosphatehttp://en.wikipedia.org/wiki/Second_messenger


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Side effects

Common side-effects include:

Diarrhea Tachycardia Headache Nausea /vomiting Depression

Drug-Induced Lupus Erythematosus
http://en.wikipedia.org/wiki/Diarrheahttp://en.wikipedia.org/wiki/Tachycardiahttp://en.wikipedia.org/wiki/Headachehttp://en.wikipedia.org/wiki/Nauseahttp://en.wikipedia.org/wiki/Vomitinghttp://en.wikipedia.org/wiki/Depression_%28mood%29http://en.wikipedia.org/wiki/Drug-Induced_Lupus_Erythematosushttp://en.wikipedia.org/wiki/File:Lupus_facial_rash.jpghttp://en.wikipedia.org/wiki/Drug-Induced_Lupus_Erythematosushttp://en.wikipedia.org/wiki/Drug-Induced_Lupus_Erythematosushttp://en.wikipedia.org/wiki/Drug-Induced_Lupus_Erythematosushttp://en.wikipedia.org/wiki/Depression_%28mood%29http://en.wikipedia.org/wiki/Vomitinghttp://en.wikipedia.org/wiki/Nauseahttp://en.wikipedia.org/wiki/Headachehttp://en.wikipedia.org/wiki/Tachycardiahttp://en.wikipedia.org/wiki/Diarrhea


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Clinical Uses

1.Hydralazine is used to treat severe hypertension.

2.Hydralazine is not used as a primary drug for treating hypertensionbecause it elicits a reflex sympathetic stimulation of the heart (thebaroreceptor reflex).

3.The sympathetic stimulation may increase heart rate and cardiacoutput, and may cause angina pectoris or myocardial infarction.

4.Hydralazine may also increase plasmarennin concentration, resultingin fluid retention.
http://en.wikipedia.org/wiki/Sympathetic_nervous_systemhttp://en.wikipedia.org/wiki/Baroreceptor_reflexhttp://en.wikipedia.org/wiki/Cardiac_outputhttp://en.wikipedia.org/wiki/Cardiac_outputhttp://en.wikipedia.org/wiki/Angina_pectorishttp://en.wikipedia.org/wiki/Myocardial_infarctionhttp://en.wikipedia.org/wiki/Blood_plasmahttp://en.wikipedia.org/wiki/Reninhttp://en.wikipedia.org/wiki/Reninhttp://en.wikipedia.org/wiki/Blood_plasmahttp://en.wikipedia.org/wiki/Myocardial_infarctionhttp://en.wikipedia.org/wiki/Angina_pectorishttp://en.wikipedia.org/wiki/Cardiac_outputhttp://en.wikipedia.org/wiki/Cardiac_outputhttp://en.wikipedia.org/wiki/Baroreceptor_reflexhttp://en.wikipedia.org/wiki/Sympathetic_nervous_system


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Vasodilators

Nitroglycerine - nitric oxide mediated vasodilatation (MOA)

1) Drug metabolized into nitric oxide (NO) in vascular smooth muscle.

2) NO molecules activate an enzyme, guanylyl cyclase (GC).

3) GC converts guanosine triphosphate (GTP) to cyclic guanosine

monophosphate (cGMP).

4) cGMP causes calcium ions to enter storage area of the cell. The loweredconcentrations of calcium ions (Ca2+) set off a cascade of cellular reactionsthat cause the cells contractile filaments (myosin and actin) to slide apart.

5) Smooth muscle cells relax.

6) Blood vessel dilates.


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PK&PD

PK:

Well absorbed through sublingual route.

It produce its effects within few min.

Effective duration of action is appro.30 min.

Ultra short acting drug.

PD:

Postural hypotension

methaemoglo-binaemia(patient skin may appear in blue color)

Headache


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Clinical uses

1.Prevention of stable angina.

2.Prevention of unstable angina.

3.Treatment of acute heart failure.

4.Spasmolytic.

5.Treatment of cyanide poisoning.


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Vasodilators

Mixed Arterio/Venodilators

Prazosin:

MOA:

Blocks alpha1 receptors

PK: It is given orally 1mg t.i.d, gradually upto 20-30mg/day.

ADE:1.headache, 2.syncopal attack.

USE: Used for pulmonary & systemic hypertension.


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Vasodilators

Mixed Arterio/VenodilatorsNitroprusside:

NO mediated activity

Another name of drug is sodium nitroferricyanide

Used for hypertensive emergencies (i.e. acute congestive heart

failure)

Side effects = hypotension

= cyanide toxicity


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Vasodilators

*Renin-angiotensin-aldosterone system *A series of reactions designed to help regulate blood

pressure.

1. When blood pressure falls (for systolic, to

100 mm Hg or lower), the kidneys releasethe enzyme renin into the bloodstream.

2. Renin splits angiotensinogen, a large proteinthat circulates in the bloodstream, into

pieces. One piece is angiotensin I.

3. Angiotensin I, which is relatively inactive, issplit into pieces by angiotensin-convertingenzyme (ACE). One piece is angiotensin II,which is very active.


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Cont

4. Angiotensin II, a hormone, causes the muscular walls of small arteries(arterioles) to constrict, increasing blood pressure. Angiotensin II also triggersthe release of the hormone aldosterone from the adrenal glands.

5. Aldosterone causes the kidneys to retain salt (sodium) and excrete potassium.The sodium causes water to be retained, thus increasing blood volume andblood pressure


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Vasodilators

ACE Inhibitors

Arterio & venodilators

Also reduce aldosterone release

Commonly used for heart failure

Commonly used for hypertension, secondary to renal disease

Oral administration


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Vasodilators

ACE Inhibitors

Captopril:

CAPTOPRIL WAS THE FIRST DRUG IN ACEI

(PROTOTYPE)

Thought to improve all stages of heart failure

PK:PO good bioavailability

Metabolized in liver/excreted renally.

Captopril


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Adverse effects

angioedema agranulocytosis proteinuria

hyperkalemia teratogenicity postural hypotension
http://en.wikipedia.org/wiki/Angioedemahttp://en.wikipedia.org/wiki/Agranulocytosishttp://en.wikipedia.org/wiki/Proteinuriahttp://en.wikipedia.org/wiki/Hyperkalemiahttp://en.wikipedia.org/wiki/Teratogenhttp://en.wikipedia.org/wiki/Teratogenhttp://en.wikipedia.org/wiki/Hyperkalemiahttp://en.wikipedia.org/wiki/Proteinuriahttp://en.wikipedia.org/wiki/Agranulocytosishttp://en.wikipedia.org/wiki/Angioedema


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Calcium channel blockers

Voltage-operated slow ca2+ channels of cardiac

and vascular smooth muscle can be blocked by adiverse group of drugs.

Classification of CCB:

Classification based on chemical nature of drug

Dihydropyridine compounds: Amlodipine , nifidipine etc.

Benzothiazapines: Diltiazem

Diphenylalkylamines: Verapamil


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Vasodilators

L- type Calcium channel

blockers MOA: Contraction of vascular smooth muscle is

dependent upon the influx of Ca2+

Ca2+ channel blockers reduce this influx ofCa2+ allowing relaxation of vascular smoothmuscle (especially arterial).


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Vasodilators

Calcium channel blockers

Amlodipine

Drug of choice for hypertension secondary to chronic renaldisease/failure

Amlodipine is almost entirely metabolised to inactive

metabolites. 10% of the parent substance and 60% of themetabolites are excreted in urine
http://en.wikipedia.org/wiki/Metabolitehttp://en.wikipedia.org/wiki/Metabolite


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Adverse effects

Adverse side effects of the use of amlodipine may be

Peripheral edema

Dizziness; palpitations; headache; nausea

Behavior, hepatitis,jaundice

Stevens-Johnson syndrome
http://en.wikipedia.org/wiki/Peripheral_edemahttp://en.wikipedia.org/wiki/Dizzinesshttp://en.wikipedia.org/wiki/Palpitationshttp://en.wikipedia.org/wiki/Headachehttp://en.wikipedia.org/wiki/Nauseahttp://en.wikipedia.org/wiki/Behaviorhttp://en.wikipedia.org/wiki/Hepatitishttp://en.wikipedia.org/wiki/Jaundicehttp://en.wikipedia.org/wiki/Stevens-Johnson_syndromehttp://en.wikipedia.org/wiki/Stevens-Johnson_syndromehttp://en.wikipedia.org/wiki/Stevens-Johnson_syndromehttp://en.wikipedia.org/wiki/Stevens-Johnson_syndromehttp://en.wikipedia.org/wiki/Jaundicehttp://en.wikipedia.org/wiki/Hepatitishttp://en.wikipedia.org/wiki/Behaviorhttp://en.wikipedia.org/wiki/Nauseahttp://en.wikipedia.org/wiki/Headachehttp://en.wikipedia.org/wiki/Palpitationshttp://en.wikipedia.org/wiki/Dizzinesshttp://en.wikipedia.org/wiki/Peripheral_edema


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Therapeutic uses

1.angina pectoris and myocardial ischaemia

2.hypertrophic cardiomyopathy.

3.cardiac arrhythmias.

4.CCF.


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Potassium channel openers

Potassium channel openers: eg:minoxidil,diazoxide.

Minoxidil:MOA: It opens voltage gated k+ channels of BV and causes

membrane hyperpolarization.

It is given orally.

It is a potent long acting vasodilator

ADE: 1)causes reflex tachycardia 2)marked salt and waterretention.3) hirsutism

USES: Topically used to treat male pattern baldness.

Severe hypertension with renal impairment.

Treat moderate hypertension


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Bibliography

1.Good mans and Gilman's.

2.Rang and dale.

3.cvs pharmacology.net.


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Thank you

vasodilators by hiren patel

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