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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_vessels8/3/2019 Vasodilators by Hiren Patel
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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/Hormones8/3/2019 Vasodilators by Hiren Patel
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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_messenger8/3/2019 Vasodilators by Hiren Patel
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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/Diarrhea8/3/2019 Vasodilators by Hiren Patel
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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_system8/3/2019 Vasodilators by Hiren Patel
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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/Angioedema8/3/2019 Vasodilators by Hiren Patel
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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/Metabolite8/3/2019 Vasodilators by Hiren Patel
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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_edema8/3/2019 Vasodilators by Hiren Patel
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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