Report in Pharma

8/6/2019 Report in Pharma

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ADRENERGICPHARMACOLOGY


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Phyllis Schweitz

1960s


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230/160mm hg

headache

nausea


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PHENTOLAMINE


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SYMPATHETIC TRANSMISSION


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Dopa decarboxylase

Dopamine hydroxylase

MAO

MAO


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SYMPATHETIC STIMULATION

` stimulates heartbeat

` raises bloodpressure

` dilates the pupils

` dilates the tracheaandbronchi

` stimulates the conversion ofliver glycogen intoglucose

` shunts bloodaway from the skin and viscera to theskeletal muscles, brain, and heart

` inhibits peristalsis in the gastrointestinal (GI) tract

` inhibits contraction ofthe bladderandrectum


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SYMPATHOMIMETIC DRUGS

Substances that mimic the effects ofthe sympathetic

nervous system

Mimic the effects ofits neurotransmitters

Norepinephrine

Epinephrine Dopamine


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CLASSIFICATION OF


DIRECT ACTING

Act on one ormore ofthe adrenergic receptors

INDIRECT ACTING

Increase availability ofepinephrine or norepinephrine

Releasingordisplacing NE from the storage vesicle(amphetamine)

Blocking the entry ofNE back into the sympathetic

neurons (cocaine) Blocking the metabolizing enzymes MAO and COMT

MIXED ACTING

Indirectly release norepinephrine anddirectly act on thereceptor (ephedrine)


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CLASSIFICATION OF


DIRECT ACTING

Act on one ormore ofthe adrenergic receptors

INDIRECT ACTING

Increase availability ofepinephrine or norepinephrine

Releasingordisplacing NE from the storage vesicle(amphetamine)

Blocking the entry ofNE back into the sympathetic

neurons (cocaine) Blocking the metabolizing enzymes MAO and COMT

MIXED ACTING

Indirectly release norepinephrine anddirectly act on thereceptor (ephedrine)


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Dopa decarboxylase

Dopamine hydroxylase

MAO

MAO


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HYPERTENSIVE CRISIS

Monoamine Oxidase

Involved in oxidative deamination of

monoamines (catecholamines) rendering themunable to exert theirfunction

Monoamine oxidase inhibitors (MAOIs)

Prevent deamination followingreuptake of

catecholamines intopresynaptic terminals.

Therefore, more catecholamine accumulates in

presynaptic vesicles forrelease during each

action potential.


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MECHANISM OF HYPERTENSIVE CRISIS

tyramine

Adrenergic nerve terminals

Neural cytoplasm

Displace transmitters from their storage

Via bloodstream and BBB

If MAO is inhibited by MAOI

Via NET

Via VMAT

The mass transfer of norepinephrine from its vesicular storage space

into the extracellular space can precipitate the hypertensive crisis.


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MAOI + TYRAMINE

MAOi intensifies the effect ofTyramine Increase

in bloodpressure

This occurs because ofincreasedbioavailability

oftyramine and increasedavailability of

cathecholamines at the synaptic cleft


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PHENTOLAMINE

Phentolamine is areversible, nonselective a-

adrenoceptor antagonist.

Competitive antagonist at both 1 and 2

receptors

Reduces TPR (total peripheral resistance)

Phentolamine was the ideal agent foruse inintroductory case, because it blocked the a-

adrenergicmediated vasoconstriction that

caused hypertension.


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PHENTOLAMINE ADVERSE

EFFECTS

postural hypotension, flushing, headache

reflex tachycardia

baroreflex mechanism

presynaptic 2 receptorantagonismmay lead to enhanced NE release from

sympathetic nerves

triggers arrythmias andanginal pain in patientsw/ decreased coronary perfusion


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BETA ADRENERGIC BLOCKERSBETA ADRENERGIC BLOCKERS


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DRUGS USED INDRUGS USED IN

HYPERTENSIVE CRISISHYPERTENSIVE CRISIS


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DRUGS USED TO MANAGE

HYPERTENSIVE

Enalaprilat

ACE-inhibitor with arapidonset ofaction and longduration ofaction.

Onset/duration:W

ithin 15 to 30minutes/12-24 hr


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Esmolol

Beta-1 selective blocker. Rapidly

metabolizedby blood esterases (short half-life ~ 9 minutes) and total duration ofaction

~ 30 minutes. Its effects begin almost

immediately.

Onset/duration:1-5 min/15-30 min.


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Fenoldopam mesylate

Fenoldopam is arapid-acting vasodilator.

It is an agonist forD1-like dopamine receptorsandbinds with moderate affinity to 2-

adrenoceptors.


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Hydralazine

Direct arteriolar vasodilator with

little or no effect on the venous

circulation.


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Labetalol

Combinedbeta-adrenergic (B1and B2) andalpha-adrenergic

blocker.


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Nicardipine

Dihydropyridine calcium channelblocker.


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Nitroglycerin

Primarily a venous dilator (lesser

degree - arteriolardilator). It may be most

useful in patients with symptomatic

coronary disease and in those with

hypertension following coronary bypass.Drugofchoice for hypertensive

emergencies with coronary ischemia.


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Sodium nitroprusside

Arteriolarand venous dilator.Considered tobe the most effective

parenteral drugformost hypertensive

emergencies (except myocardial ischemia

orrenal impairment). It dilates both

arteries and veins, and it reduces

afterloadandpreload.


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RESERPINE

Adrenergic Neuron Blocker

Inhibits the function ofpostganglionic adrenergic

neurons

an alkaloid extractedfrom the roots ofan Indian

plant, Rauwolfia serpentina

Effect: Lowers bloodpressure by a combinationofdecreased cardiac output anddecreased

peripheral vascularresistance


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MECHANISM OF ACTION


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GUANFACINE

Centrally Acting Sympathoplegic Drugs

orally active antihypertensive agent

whose principal mechanismofactionappears tobe stimulation ofcentral 2 -

adrenergic receptors.

Effect: This results in adecrease inperipheral vascularresistance anda

reduction in heart rate.


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