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  ½ ;
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 ¼ 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