ADREGERNIC DRUGS

- Stimulated by norepinephrine
- SYMPATHOMIMETICS: activate adrenergic receptors
- SYMPHATOLYTICS: bock the activation of adrenergic receptors
ADRENERGIC NEURON
Where? CNS and periphery of sympathetic NS
Function? Link between ganglia and the effector organ

ADRENERGIC RECEPTOR MECHANISMS OF ACTION OF SYMPATHOMIMETICS

Alpha; based on their affinities for agonists and antagonist

DIRECT ACTING INDIRECT ACTING MIXED ACTING
ALPHA 1 ALPHA 2 AGONIST AGONIST AGONIST
post synaptic membrane of sympathetic presynaptic Act directly on a or b Block the Stimulate
the effector nerve endings receptors reuptake of adrenoreceptors,
Constriction of vascular Control the release of Release of norepinephrine norepinephrine or enhance release
smooth muscle norepinephrine from sympathetic nerve, cause the release of
Vasoconstriction, increased Inhibition of norepi, release of epinephrine of norepinephrine norepinephrine
bp, mydriasis acethylcoline, insulin release from adrenal medulla from the
Beta; by strong response to isoproterenol cytoplasmic pools
dopamine Cocaine, Ephedrine
amphetamine
BETA 1 BETA 2
Epi = norepi Epi>norepi
Heart, kidney Vasculature of skeletal
muscle, bronchial smooth THREAPEUTIC USE
muscle Raise bp in shock – dopamine, norepinephrine, ephedrine, phenylephrine
Tachycardia, increased Vasodilation, relaed uterine anorexiant- dextroamp,phentermine,sibutramine
myocardial contractility, smooth muscle Bronchodilator- salbutamol,bambuterol,salmeterol,formoterol uterine relaxant- salbutamol
release of rennin, increase Cardiac stimulant- epi,isoprenaline,dobutamine mydriatic – ephedrine,
bp phenylephrine
CNS Stimulant- amphetamine,dextroamp,methamp
CLASSIFICATION OF SYMPATHOMIMETICS Local vasoconstrictor- epi
Nasal decongestant- xylometazoline,oxyme,naphazoline
CATECHOLAMINES NON-CATECHOLAMINES
+ catechol nucleus Lack catechol nucleus
Epnephrines, Amphetamine,
norepinephrines, salbutamol,phenylephrine,tyramine
dopamine,ispretenol,
High potency, rapid Longer half lives, not inactivated by
inactivation, brief period of COMT, prolonged duration of
action, ineffective when action, increased lipid solubility,
administered orally, poor
can penetrate CNS
penetration to CNS
 EPINEPHRINE (ADRENALINE) NOREPINEPHRINE ISOPROTENOL
PHARMACOLOGICA Acts on a1,a2, B1,B2,B3 1. CNS Nonselective B- rreceptor agonist
L ACTION 1. CNS Direct stimulant effect (B1), constricts all bv (a1) inc skin,
B1 receptor mucous memb,etc
HEART + sys,dias,pulse pressure Intense stimulation of the heart (B1), increasing
heart rate contractility, cardiac output
+ heart rate - + rate of spontaneous depolarization of SAnode GREATER VASOCONSTRICTION THE EPINEPHRINE
+ myocardial contractility BCOS X INCLUDE VSODILATION (B2)
+ conduction velocity Dilates the arterioles of skeletal muscle (B2),
+ cardiac output decreased peripheral resistance.
2. REFLEC BRADYCHARDIA
+ excitability cause cardiac arrhythmias
High doses : headaches, tremor, restlessness Baroreceptor reflex: NE + bp , stimulate BR , induce
rise in vagal activity, vagal activity produces reflex Cardiac stimulatory action, increase systolic blood
BLOOD VESSELS , BP
B1 receptor kidney – renin release bradycardia, pressure slightly, reduces mean arterial and
NOT AFFECT POSITIVE INOTROPIC EFFECTS OF THE diastolic blood pressures.
Renin production of angiotensin III (vasoconstrictor)
Constricts renal, mesenteric, pulmonary and splanchnic DRUGS
vessels but dilates the blood vessels of skeletal muscles, Potent bronchodilator
vessels going to liver and coronary vessels (B2) weak b2 activity is why NE not useful in treatment of
IV in moderate causes biphasic bronchospasm and anaphylaxis
( initial rise BP due to a1 (bv)and heart (b1) followed by fall in
BP vasodilation in skeletal muscle (B2)
USED TO RAISE BP IN HYPOTENSIVE STATES BUT IT
MAY BE DECREASE BLOOD FLOW TO VITAL
2. RS ORGANS BY CAUSING WIDESPREAD
Relaxes bronchial smooth muscle (b2) VASOCONSCTRICTION
Bronchodilator but short doa
Inhibit inflammatory mediator frm mast cells (b2)
Reduces secretions and relieves mucosal congestion by
vasoconstrictor effect
3. GIT
Relaxes smooth muscle (a2 b2)
Reduces intestinal tone and peristaltic movement
4. Bladder
Relaxes destructor muscle (B2) contracts the spinchter (a1)
results: difficulty in urination
5. Eye
Administered as prodrug, used for induction and
maintenance of mydriasis during intraocular surgery
6. Metabolic effects
Increases bg by;
Stimulating hepatic glycogenolysis (b2)
+ glucagon (b2) - insulin (a2) - glucose

PHARMACOKINETI Rapid onset brief doa X oral, S.C or direct IV injection X Oral (extensive first-pass metabolism)
CS X oral anaphylaxis – intramuscular emergency – IV Administered by i.v. infusion Given parentally or as an aerosol
Others: subcutaneously, endotracheal tube, inhalation Metabolized by COMT
THERAPEUTIC USES Anaphylactic shock, bronchial asthma, cardiac To treat shock (septic shock) bcos it + vascular Increase heart rate in heart block
resuscitation, epistaxis,glaucoma resistances and + bp
Raises BP in hypotensive states but it decrease
blood flow to vital organs by causing widespread

ADVERSE EFFECTS Tachycardia, headache, restlessness, tremors, rise bp
Serious: cerebral haemorrhage, cardiac arrhythmias
DOBUTAMINE
PHARMACOLOGICAL ACTION Primarily b1 receptor
agonist with minor b2 and
a1 effects
+ heart rate n cardiac
output
Total peripheral
resistance not affected
(vasoconstriction [a1-
mediated] is balanced by
vasoconstriction [b2])
+ cardiac output in acute
heart failure (i.v. infusion)
As well as inotropic
support after cardiac
surgery
PHARMACOKINETICS + cardiac output , x elevate
O2 demands of the
myocardium as much as
other sympathomimetics
drugs.
THERAPEUTIC USES Used in caution in atrial
fibrillation, as it increases
atrioventricular
conduction
ADVERSE EFFECTS Tachycardia, rise in BP
and tolerance
vasoconstriction
Similar with epinephrine Tachycardia, palpitation, cardiac
arrhythmias
ALBUTEROL, FORMOTEROL NAPHAZOLINE MIRABEGRON AND
LEVALBUTEROL, INDICATEROL, OXYMETAZOLINE, VIBEGRON
METAPROTENOL, OLODATEROL, TETRAHYDROZOLINE
TERBUTALINE SALMETEROL
Selective B2 receptor Long acting B2 receptor A1 a2 B3
As bronchodilators (LABA) Cause local Relax the detrusor smoot
Short acting B2 agonists For management resp vasoconstriction muscle and increase
(SABA) disorders (asthma, chronc bladder capacity
pulmonary obstructive
pulmonary disease) Found in nasal spray
Albuterol and its R isomer decongestants, ophthalmic Mirabegron increase bp .
levalbuterol for the drops for the relief cannot use in patients with
management of acute redness of the eyes uncontrolled hypertension
bronchospasm
Stimulate a receptors on + digoxins by inhibiting p-
blood vessels supplying glycoprotein-mediated
nasal mucosa and elimination, inhibits
conjunctiva CYP2D6 isozyme
Producing Vibegron has minimal
vasoconstriction, interactions with CYP450
decongestion drug interaction less than
mirabegron
Metered dose inhalers NOT RECOMMENDED NOT RECOMMENDED to
FOR MONOTHERAPHY use more than 3 days
FOR ASTHMA
Highly efficacious when
combined with
corticosteroid
Injectable terbutaline- Overactive bladder
reversal of acute
bronchospasm, uterine
relaxant
Tremor (tolerance Local irritation, sneezing
develops) Oxymetazoline produce
Restlessness, nervousness headaches
apprehension, anxiety sleeping disturbances
Rebound congestion and
dependence may occur if
use more than 3 days
INDIRECT ACTING ADREGERNIC AGONIST ADRENERGIC ANTAGONIST
 A1 blocker affect bp, induces reflex tachycardia

AMPHETAMINE COCAINE
+ bp by a1 To block sodium-
(vasculature), b1 chloride
(heart) dependent NE
Mediated by transporter
increase release Causes reuptake
of catecholamines of NE into ad
Complemented by neuron
inhibition of NE accumulate in
reuptake of these syn, enhanced
catecholamines symp activity,
and MAO potebtion of the
action E n NE
DOA NE n E +
PHENOXYBENZAMINE PHENTOLAMINE Selective a1 blocker:
Local anasthesia Prazosin
or PHARMACOLOGY ACTION CARDIOVASCULAR EFFECTS Imidazole derivatives Potent n selective a1
vasoconstriction Prevent a1 receptor Block NA at a1 n a2 (comp) Well absorbed in GIT undergo first pass met
during endoscopic mediated vasoconstriction of Venodilation more than arteriolar Arteriolar dilation more prominent
nasal surgery peripheral bv caused by dilation
endogenous catecholamines- Block 5-HT receptors, K+ channels
decreased peripheral causes histamine releases from
resistance and refle mast cells
MIXED ACTION tachycardia
By blocking a2, + NE, + HR and
EPHEDRINE N PSEUDOEPHEDRINE cardiac output – cardiac
Not only enhance but directly stimulate arrhythmias and anginal pain
Similar to E but less potent Bcos of this not used for
Long DOA hypertension
Oral administration
Ephedrine Produce bronchodilation
Treatment bronchialspasm PHARMACOKINETICS Orally or through slov iv Intravenously Orally (prazosin) at bedtime
infusion Rapid but short DOA ALFUZOSIN: orally
Slow onset but long DOA Tamsulosin: orally
THERAPEUTIC USES pheochromocytoma ALFUZOSIN: Benign prostatic
hyperplasia
TAMSULOSIN: BPH in normotensive
ADVERSE EFFECTS Tachycardia, Prazosin: postural hypotension n
palpitation,arrhythmias, angina n MI syncopal attacks within 30=90 min
may be precipitated Nasal stuffiness, tachycardia impaired
ejaculation and impotence