DRUGS AFFECTING THE

ADRENERGIC NERVOUS
SYSTEM
IKE HUSEN
Depart. of Pharmacology & Therapy
Faculty Of Medicine Padjadjaran
University
Affect receptors stimulated by NE &E
(Agonist antagonist)
Act directly : adrenoceptor
(activating blocking)
indirectly : release NE

ADRENERGIC AGONIST
Adrenergic neurons : CNS & Sympathetic NS
SOA : Adrenergic neuron & receptor
(located on the effector organ)

CARACTERISTIC OF ADRENERGIC
AGONISTS
CATHECOLAMINES

High potency
Rapid inactivation:
COMT&MAO brief of
DOA, orally ineffective
Penetration into the
CNS: poor; SE : (+)
NON CATHECOLAMINES

Not metabolized by
COMT, longer ;
poor substrate for MAO
Penetration into the
CNS:good, action(+)
DIRECT- ACTING ADRENERGIC
AGONISTS
Epinephrine* - Metaproterenol
Norepinephrine* - Terbutaline
Isoproterenol* - Ritodrine
Dopamine* - Albuterol
Dobutamine* - Methoxamine
Phenylephrine - Clonidine
*: Cathecolamine
DIRECT- ACTING ADRENERGIC
AGONISTS :EPINEPHRINE
Cathecolamine
Synthesized in the adrenal medulla

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


EPINEPHRINE
ACTION; cvs:

1:
(+) inotropic & chronotropic CO


O
2
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


EPINEPHRINE
Biotransformations
COMT MAO
Metabolites in urine : metanephrine and
vanillylmandelic acid

EPINEPHRINE
THERAPEUTIC USES
Bronchospasm:
DOC in acute asthma and anaphylactic shock
Glaucoma: topical IO pressure in open
angle glaucoma
In anaesthetics: local sol. DOA
EPINEPHRINE
PHARMACOLOGY
Rapid OOA
Brief DOA
Adm. :
Sc.
Inhalation
Topical

EPINEPHRINE
ADVERSE EFFECTS
CNS disturbances: anxiety, fear, tension,
headache, tremor
Hemorrhage:cerebral hemorrhages
Cardiac arrhytmias
Pulmonary edema
EPINEPHRINE
INTERACTIONS
Hyperthyroidism: CVS actions receptor
Dose

Cocaine: CVS actions >< re-uptake cathecol.



NOREPINEPHRINE
and
1
; is the most affected in therapeutic
doses

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

Theapeutic 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
SE = epinephrine
DOPAMINE

1
and receptor dopamine; high doses :
Cardiac stimulant (
1
) Th/ uses: CHF
RBF: (rec. dopaminergic dilates renal & visceral
arterioles ) DOC : shock)
SE:
Overdose: sympathetic stimulation
Nausea, hypertension, arrhythmias: short-lived (=DOA)
rapidly metabolized to homovanillic acid
Asthma; nasal decongestant , , CNS Ephedrine
CNS stimulant , , CNS Amphetamine
Bronchospasm
Premature labor
2
Terbutaline
Ritodrine
Albuterol
Bronchospasm
2
>
1
Metaproterenol
Hypertension
2
Clonidine
SV tachycardia
1

Methoxamine
Nasal decongestant
SV tachycardia

1
Phenylephrine
Congestive Heart failure
1
Dobutamine
THERAPEUTIC USES
REC.
SPESIFICITY
DRUG
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
ADRENERGIC BLOCKERS
-Blockers:
Phenoxybenzamine d. Terazosine
Phentolamine e. Doxazosine
Prazosine
-Blockers:
Propranolol d. Metoprolol
Timolol e. Pindolol
Acebutolol f. Labetalol
g. Carvedilol
Drugs Affecting Neurotransmitter uptake or realese
Reserpine c.Cocaine
Guanethidine
- 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 tachycardia
- ADRENERGIC BLOCKING
AGENTS : PHENOXYBENZAMINE
Irreversible and noncompetitive -blockers
Therapeutic Uses:
Incomplete urinary voiding
Benign prostatic hypertrophy
Adverse reactions:
Postural hypotension
Sexual function: inhibit ejaculation of semen (retrograde)
Nasal stuffiness
Nausea & vomiting
Tachycardia

- ADRENERGIC BLOCKING
AGENTS : PHENTOLAMINE
Competitive -blockers (4hrs)
Th/ uses: frostbite
SE:
Tachycardia
Postural hypotension
GI stimulation
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

- ADRENERGIC BLOCKING
AGENTS
Competitive antagonists:
Non cardioselective
Cardiosective (
1
)
ISA (intrinsic sympathomimetic activity)
ISA (+) or ISA (-)
Orthostatic hypotension : does not occur (the -
adrenoceptor is not blocked)
Therapeutic uses of -
BLOCKERS
Angina
Arrhythmias
Myocardial infarction
Glaucoma
Prophylaxis of migraine headaches
PROPRANOLOL
(Non cardioselective -blocker)
Actions:
CVS: (><
1
) CO and BP; bradycardia,
work and O
2
consumption (Th/ angina)
Peripheral vasoconst.: (><
2
), but hypotension
triggers a reflex vasoconst. blood flow to the
fingers and toe
Bronchoconstriction
Increased Na+ retention
Disturbance in glucose metabolism
Therapeutic effects of
Propranolol
Hypertension ( CO)
Glaucoma: IOP ( the secretion of aqueos
H.)
Migraine: reducing migraine episodes
Hyperthyroidsm (protecting cardiac arrhytmias)
Angina pectoris
Myocardial infarction
Adverse effect of
Propranolol
Bronchoconstriction
Arrhytmias (rapid withdrawal)
Sexual impairment
Disturbances in glucose metabolism
Other : TAG level


Timolol
Nonselective -blocker
the secretion of aqueos 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:
Diabetic hypertensive patients who are receiving
insulin or oral hypoglycemic agents
Pindolol and acebutolol
(Positive ISA/partial agonists)
Actions:
CVS: Diminish effect on cardiac rate and CO (the effect <
epinephrine)
Decreased metabolic effects: minimize the disturbances of
lipid and carbohydrate metabolism
Therapeutic uses in hypertension:
Hypertension with moderate bradycardia
Hypertension patients whom taking hypoglycemic agents
Hypertensive athletes
Labetalol
(-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
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