ADRENERGIC DRUGS

Pharmacological Department
Medical School UNPAD
Ike Husen

ADRENERGIC DRUGS
Affect receptors which are stimulated by
NE (noradrenalin) & E (adrenalin)

Adrenergic drugs

Agonist
(sympathomimetic agents)

Antagonists
(sympatholytic agents)

SYNTHESIS OF NE
Tyr
Tirosin hidroksilase

DOPA

Tyr
Inactive
metabolite

Inhibitor:
1= reserpine
2= guanethidine
bretylium

METABOLISM

Dopamine
1

uptake
VESICLES:
Dopamine
dopamine--hydroxylase

REMOVAL OF NE
Inhibitor: cocaine &
imipramine

NE
2

release

BINDING TO
RECEPTOR

Intracellular
response

Adrenoreceptor

Vasoconst.

(+) Inotropic

Periph. resist.

(+) Chronotropic

BP

lipolysis

Mydriasis
Closure internal
sphincter bladder

Vasodilatation

Slightly periph.
Resist.

Inhibition of NE
release

Bronchodilatation

Inhibition of
insulin release

release of glucagon

Glycogenolysis
Relaxed uterine
smooth musc.

DIRECT- ACTING ADRENERGIC AGONISTS

Drug

Receptor
Specificit
y

Drug

Receptor
Specificit
y

Epinephrine*

1, 2
1, 2

Phenylephrin
e

Norepinephrin
e*

1, 2
1

Methoxamin
e

Isoproterenol*

1, 2

Clonidine

Dopamine*

Dopaminergi
c

1, 2

Dobutamine*

* : Cathecolamine

Metaproteren
ol
Turbetaline
Ritodrin
Albuterol

2> 1

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

EPINEPHRINE ACTION; cvs:

1 : (+) inotropic & chronotropic

CO
O2 consumption

: constrict arteriole (skin, mucous memb. viscera)

2 : vasodilator (skeletal m.)

Syst. BP - Diast. BP slightly

EPINEPHRINE ACTION
Respiratory ( 2 ) :

bronchodilator; dyspnea (-) and tidal vol.

Hyperglycemia:

glycogenolysis and release glucagon ( 2 ),

release insulin ( )
Lipolysis: 1

( 3 ?)

Biotransformations
COMT (catechol-O-methyl transferase) MAO
Metabolites

in urine : metanephrine and

vanillylmandelic acid

THERAPEUTIC USES
Bronchospasm:

Acute asthma attack and anaphylactic shock

Glaucoma : topical

glaucoma
In anesthetics : local

IO pressure in open angle

DOA

PHARMACOKINETICS
Rapid OOA
Brief DOA
Administration :
Sc.
Inhalation
Topical

ADVERSE EFFECTS
CNS

disturbances: anxiety, fear, tension,

headache, tremor

Hemorrhage:cerebral
Cardiac

arrhytmias

Pulmonary

edema

hemorrhages

NOREPINEPHRINE

and 1 ; is the most affected in

therapeutic doses
CVS:

syst. (1)- diast. BP: (1)

Bradycardia (baroreflex: )
Therapeutic

uses: (levarterenol)
Shock (RBF: )

ISOPROTERENOL ( 1 and 2 )
CVS:

CO: - syst. BP: slightly (1)

Diast. BP: (2 )
Mean arterial BP:
Pulmo: Bronchodilator (2 )
Th/ uses:
AV block / cardiac arrest
Asthma
Adverse reactions = epinephrine

DOPAMINE
1 and

dopamine receptor ; high doses :

Cardiac

stimulant (1 ) Th/ uses: CHF

(dopaminergic rec. dilates renal

& visceral arterioles )
DOC : shock
RBF:

AR:

Overdose: sympathetic stimulation

Nausea, hypertension, arrhythmias:
short-lived (=DOA) rapidly metabolized

ADRENERGIC ANTAGONISTS
(SYMPATHOLYTICS)
Antagonists

= blockers bind to adrenoceptors

BUT do not
trigger the usual receptor- mediated
intracellular effects.
preventing their activation by
endogenous catecholamines

Classification
-BLOCKERS

-BLOCKERS

Phenoxybenzamine

Propanolol

Phentolamine

Timolol

Prazosin

Acebutolol

Terazosin

Metoprolol

Doxazosin

Pindolol
Labetalol

DRUGS AFFECTING
NEUROTRANSMITTER
UPTAKE/RELEASE

Carvedilol

-ADRENERGIC BLOCKING AGENTS

Main effects: BP

(normally main effect of -adrenoceptor :control of the

vasculature)
Reduces sympathetic tone of blood vessels:

decreases peripheral vasc. resistance

BP reflex

Adverse effect:
Orthostatic hypotension
Tachycardia
Fatigue
Sexual disturbances

PHENTOLAMINE
Competitive -blockers (4hrs)
Th/ uses:

Frostbite
Sex. Dysfunction (male)
AR:

Tachycardia
Postural hypotension
GI stimulation

PRAZOSIN, TERAZOSIN and DOXAZOSIN

( 1 blockers)
Action: CVS: peripheral resist. and BP
Th/ uses: hypertension
AR:

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

- ADRENERGIC BLOCKING AGENTS

Competitive antagonists:
Non cardioselective
Cardioselective (1)
ISA (intrinsic sympathomimetic activity)

ISA (+) or ISA (-)

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

Adverse effect of - ADRENERGIC

BLOCKING AGENTS
Hypotension
Bradycardia
Fatigue
Drowsiness

PROPRANOLOL (Non cardiosel. -blocker)

Actions:
CVS: (><1)
CO and BP;
bradycardia, work and O2 consumption
(Th/ angina)
Peripheral vasocons >< 2, but
hypotension triggers a reflex vasoconst.
blood flow to the fingers and
toe
Bronchoconstriction
Increased Na+ retention

Therapeutic uses
Hypertension

( CO)
Glaucoma: IOP ( the secretion of
aqueous H.)
Migraine: reducing migraine episodes
Hyperthyroidsm (protecting cardiac
arrhythmias)
Angina pectoris
Myocardial infarction

Adverse effect
Bronchoconstriction
Arrhythmias

(rapid withdrawal)
Sexual impairment (pathogen. ???)
Disturbances in glucose metabolism
Other : TAG level

Timolol
-blocker
the secretion of aqueous Humor
Therapeutics uses:
Topical: glaucoma
Systemic: Hypertension
Nonselective

Acebutolol, atenolol,and
metoprolol

(Cardioselective in low drugs doses)

Action:

Decrease BP
Increase exercise tolerance in angina
Therapeutic use in hypertension, espec.:
Diabetic hypertensive patients who are
receiving insulin or oral hypoglycemic
agents

Agonist, antagonist and partial agonist of

adrenoceptor
Agonist
Epin./NE/agonists agents

Receptor
Cell. effect

Antagonist

blocked
Partial Agonist

Cell. effect

antagonists agents
partial agonists agents

Pindolol and acebutolol

(Positive ISA (intrinsic sympathomimetic activity/partial agonists)

Actions:

CVS: Diminish effect on cardiac rate

and CO (the effect < epinephrine)
Decreased metabolic effects: the
disturbances of lipid and carbohydrate
metabolism < -blockers effects

Therapeutic

uses in hypertension:
Hypertension with moderate
bradycardia
Hypertension patients whom
taking hypoglycemic agents
Hypertensive athletes

Labetalol and Carvedilol

(-blocker with concurrent 1 blockers)

Actions:

Periph. Vasodilator (!!) and BP

Not alter serum lipid or blood glucose levels
Therapeutic uses:
Elderly hypertensive patient in whom
increased peripheral vasc. Resistance is
undesirable
Adverse effects:
Orthostatic hypotension and Dizziness

Drugs Affecting Neurotransmitter Release or

Uptake
I. Reserpine
Inhibits transport NE into vesicle: Impair
sympathetic function
Actions:
Decrease BP
Increase parasympathetic activity, esp. :GIT
Therapeutic Uses:
Hypertension
Adverse reactions:
Insomnia, nighttime hallucinations,
depression