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ADRENERGIC DRUGS

Pharmacological Department
Medical School – UNPAD
Ike Husen
ADRENERGIC DRUGS
Affect receptors which are stimulated by
NE (noradrenalin) & E (adrenalin)

Adrenergic drugs

Agonist Antagonists
(sympathomimetic agents) (sympatholytic agents)
SYNTHESIS OF NE Inhibitor:
Tyr
1= reserpine
Tyr
Tirosin hidroksilase Inactive 2= guanethidine
metabolite bretylium
DOPA
METABOLISM

Dopamine

1 uptake

VESICLES: REMOVAL OF NE
Dopamine
dopamine-β-hydroxylase Inhibitor: cocaine &
imipramine
NE
2
BINDING TO Intracellular
release RECEPTOR response
Adrenoreceptor

1 1
Vasoconst. (+) Inotropic
 Periph. resist. (+) Chronotropic
 BP  lipolysis
Mydriasis 2
 Closure internal Vasodilatation
sphincter bladder
Slightly  periph.
2 Resist.

Inhibition of NE Bronchodilatation
release Glycogenolysis
Inhibition of  release of glucagon
insulin release
Relaxed uterine
smooth musc.
DIRECT- ACTING ADRENERGIC AGONISTS
Drug Receptor Drug Receptor
Specificity Specificity
Epinephrine* ά1, ά2 Phenylephrine ά1
β1, β2
Norepinephrine* ά1, ά2 Methoxamine ά1
β1
Isoproterenol* β1, β2 Clonidine ά2

Dopamine* Dopaminergic Metaproterenol β2> β1


β1, β2
Dobutamine* β1 Turbetaline
Ritodrin β2
Albuterol
* : Cathecolamine
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  IO pressure in open angle


glaucoma

In anesthetics : local DOA


PHARMACOKINETICS
Rapid OOA
Brief DOA
Administration :
Sc.
Inhalation
Topical
ADVERSE EFFECTS
CNS disturbances: anxiety, fear, tension,
headache, tremor

Hemorrhage:cerebral hemorrhages

Cardiac arrhytmias

Pulmonary edema
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

RBF:  (dopaminergic rec. – dilates renal


& visceral arterioles ) DOC : shock

AR:
Overdose: sympathetic stimulation
Nausea, hypertension, arrhythmias:
short-lived (=DOA) – rapidly metabolized
to homovanillic acid
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 Carvedilol


NEUROTRANSMITTER
UPTAKE/RELEASE
-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 ¼ 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
Disturbance in glucose metabolism
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
Nonselective -blocker
 the secretion of aqueous Humor
Therapeutics uses:
Topical: glaucoma
Systemic: Hypertension
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
Receptor Epin./NE/agonists agents
Cell. effect antagonists agents
partial agonists agents
Antagonist

blocked

Partial Agonist

Cell. effect
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 < -blocker’s 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