Adrenergic DrugsI (Dr.ike)

8/11/2019 Adrenergic DrugsI (Dr.ike)

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DRUGS AFFECTING THE

ADRENERGIC NERVOUS

SYSTEM

IKE HUSEN

Depart. of Pharmacology & TherapyFaculty Of MedicinePadjadjaran

University


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DRENERGIC DRUGS

Affect receptors stimulated by NE &E

(Agonistantagonist)

Act directly : adrenoceptor

(activatingblocking)

indirectly : release NE


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ADRENERGIC AGONIST

Adrenergic neurons : CNS & Sympathetic NS

SOA : Adrenergic neuron & receptor

(located on the effector organ)


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DIRECT- ACTING ADRENERGIC

AGONISTS

Epinephrine* - Metaproterenol

Norepinephrine* - Terbutaline

Isoproterenol* - Ritodrine

Dopamine* - Albuterol

Dobutamine* - MethoxaminePhenylephrine - Clonidine

*: Cathecolamine


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DIRECT- ACTING ADRENERGIC

AGONISTS :EPINEPHRINE

Cathecolamine

Synthesized in the adrenal medulla

and Low doses : - predominant on vasc. syst.High doses : - predominant on vasc. syst.


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EPINEPHRINE

ACTION; cvs:

1:(+) inotropic & chronotropic CO

O2 consumption

: constrict arteriole (skin, mucous memb.viscera)

2 : vasodilator (skeletal m.)

Syst. BP - Diast. BP slightly


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EPINEPHRINEACTION

Respiratory (2 ) :bronchodilator; dyspnea (-) and tidal vol.

Hyperglycemia:glycogenolysis and release glucagon (2 ),

release insulin ()Lipolysis: 1


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EPINEPHRINEBiotransformations

COMTMAO

Metabolites in urine : metanephrine and

vanillylmandelic acid


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EPINEPHRINETHERAPEUTIC USES

Bronchospasm:

DOC in acute asthma and anaphylactic shock

Glaucoma: topical IO pressure in openangle glaucoma

In anaesthetics: local sol. DOA


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EPINEPHRINEPHARMACOLOGY

Rapid OOA

Brief DOA

Adm. :

Sc.

Inhalation

Topical


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EPINEPHRINEADVERSE EFFECTS

CNS disturbances: anxiety, fear, tension,

headache, tremor

Hemorrhage:cerebral hemorrhages

Cardiac arrhytmias

Pulmonary edema


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EPINEPHRINEINTERACTIONS

Hyperthyroidism: CVS actionsreceptor Dose

Cocaine: CVS actions>< re-uptake cathecol.


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NOREPINEPHRINE

and 1 ; is the most affected in therapeuticdoses

CVS: syst.- diast. BP: (1)Bradycardia (baroreflex: )

Theapeutic uses: (levarterenol)Shock (RBF: )


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DOPAMINE

1 and receptor dopamine; high doses :

Cardiac stimulant (1 )Th/ uses: CHF

RBF: (rec. dopaminergicdilates renal & visceralarterioles ) DOC : shock)

SE:

Overdose: sympathetic stimulationNausea, hypertension, arrhythmias: short-lived (=DOA)

rapidly metabolized to homovanillic acid


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Asthma; nasal decongestant, , CNSEphedrine

CNS stimulant, , CNSAmphetamine

Bronchospasm

Premature labor2

Terbutaline

Ritodrine

Albuterol

Bronchospasm2> 1Metaproterenol

Hypertension2Clonidine

SV tachycardia1Methoxamine

Nasal decongestant

SV tachycardia

1Phenylephrine

Congestive Heart failure1Dobutamine

THERAPEUTIC USESREC.SPESIFICITY

DRUG


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ADRENERGIC ANTAGONISTS

(ADRENERGIC BLOCKERS)

Antagonists = blockers bind to adrenoceptors

BUT do not

trigger the usual receptor- mediated intracellular

effects.

preventing their activation by

endogenous catecholamines


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ADRENERGIC BLOCKERS

-Blockers:Phenoxybenzamine d. Terazosine

Phentolamine e. Doxazosine

Prazosine

-Blockers:Propranolol d. MetoprololTimolol e. Pindolol

Acebutolol f. Labetalol

g. Carvedilol Drugs Affecting Neurotransmitter uptake or realese

Reserpine c.Cocaine

Guanethidine


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- ADRENERGIC BLOCKING

AGENTS

Main effects: BP

(normally main effect of -adrenoceptor :controlof the vasculature)

Reduces sympathetic tone of blood vessels:

decreases peripheral vasc. resistance

BPreflex tachycardia


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AGENTS: PHENOXYBENZAMINE

Irreversible and noncompetitive -blockers Therapeutic Uses:

Incomplete urinary voidingBenign prostatic hypertrophy

Adverse reactions:Postural hypotension

Sexual function: inhibit ejaculation of semen (retrograde)Nasal stuffiness

Nausea & vomiting

Tachycardia


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AGENTS: PHENTOLAMINE

Competitive -blockers (4hrs)

Th/ uses: frostbite

SE:

Tachycardia

Postural hypotension

GI stimulation


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PRAZOSIN and TERAZOSIN

(1

blockers)

Action: CVS: peripheral resist. and BP

Th/ uses: hypertension

SE:

Syncope (first pass effect), may be minimized by

adjusting the first dose to 1/3 or of normal dose

Nasal congestion, GI hypermotility, fluid retention,orthostatic hypotension


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AGENTS

Competitive antagonists:

Non cardioselective

Cardiosective (1)

ISA (intrinsic sympathomimetic activity)

ISA (+) or ISA (-)

Orthostatic hypotension : does not occur (the -adrenoceptor is not blocked)


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Therapeutic uses of -

BLOCKERS

Angina

Arrhythmias

Myocardial infarction

Glaucoma

Prophylaxis of migraine headaches


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PROPRANOLOL

(Non cardioselective -blocker)

Actions:

CVS: (>< 2), but hypotensiontriggers a reflex vasoconst. blood flow to thefingers and toe

BronchoconstrictionIncreased Na+ retention

Disturbance in glucose metabolism


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Therapeutic effects of

Propranolol

Hypertension (CO)

Glaucoma: IOP (the secretion of aqueosH.)

Migraine: reducing migraine episodes

Hyperthyroidsm (protecting cardiac arrhytmias)

Angina pectoris

Myocardial infarction


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Adverse effect of

Propranolol

Bronchoconstriction

Arrhytmias (rapid withdrawal)

Sexual impairment

Disturbances in glucose metabolism

Other : TAG level


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Timolol

Nonselective -blocker

the secretion of aqueos Humor

Therapeutics uses:

Topical: glaucoma

Systemic: Hypertension


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Acebutolol, atenolol,and metoprolol

(Cardioselective in low drugs

doses)

Action:

Decrease BP

Increase exercise tolerance in angina

Therapeutic use in hypertension:

Diabetic hypertensive patients who are receiving

insulin or oral hypoglycemic agents


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Pindolol and acebutolol(Positive ISA/partial agonists)

Actions:

CVS: Diminish effect on cardiac rate and CO (the effect

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Adrenergic DrugsI (Dr.ike)