synthesis, storage, release, metabolism, physiological function, receptors of sympathetic hormones and their modulator.

1. SYMPATHOMIMETIC DRUGS

2.  These drugs stimulate the sympathetic nervous system.
 They mimic the action of endogenous catecholamines.
 Major endogenous catecholamines are:-
 Norepinephrine: is the major neurotransmitter in the
sympathetic nervous system.
 Adrenaline: Secreted by adrenal medulla,
 Dopamine: major transmitter in basal ganglion, limbic system,
CTZ,

4. Phenylalanine
Hepatic
hydoxylas
e
tyrosine
hydoxylase
dopa
decarboxylase
dopamine B-
hydoxylase

6. RECEPTORS

7.  blood vessels, salivary glands, bronchi, uterus,
bladder neck, radial muscles of iris, liver cells,
intestine (inhibitory effect - relaxation).
 Alpha1A- urinary bladder neck & prostate, liver,
blood vessels
 Alpha1B- blood vessels, lungs, kidney, spleen
 Alpha1D- platelets, prostate, bladder, aorta, coronary
arteries.
 Alpha1L- blood vessels, smooth muscles, lower urinary
tract, prostate.

8.  Located presynaptically in postganglionic
sympathetic neurons.
 decreases the release of NE - Homotropic
presynaptic receptor activation.

9.  Presynaptic alpha2 receptors on cholinergic
nerve terminal in gut , when activated will
decrease the release of Ach ( relaxation)-
Heterotropic presynaptic receptor activation.

10.  Supersensitivity can also result after
denervation or after continued blockade of the
receptor by an antagonist.
 e.g.- rebound hypertension observed after
sudden withdrawal of beta-1 receptor blockers.

11.  Continued receptor stimulation by an
agonist causes desensitization i.e. receptor
becomes less responsive to the agonist.
 E.g. desensitization of beta 2 receptors in
bronchial asthma pts. treated with beta2
agonists.

12. Sympathomimetics
Directly
acting
Indirectly
acting
Mixed

15. HEART
 β1 receptors in heart.
 ↑ in HR – activation of of beta1 receptors on SA
node.
 Force of cardiac contraction is ↑ed – beta1
receptor stimulation in ventricular myocardium.
 Cardiac output & oxygen consumption of the
heart are markedly ↑ed.
 Enhanced conduction

16.  BLOOD VESSELS ( Alpha1 & Beta2 receptors)
 Alpha1 receptors ( vasoconstriction)- skin, mucosal,
splanchnic, renal blood vessels .
 D1 receptor – vasodilatation of renal blood vessels.
 Coronaries – beta2 predominantly- vasodilatation.
 Pulmonary blood vessels- alpha1- vasoconstriction-
decongestion.
 Skeletal muscle blood vessels- beta2- vasodilatation

17.  Alpha1- radial muscles of iris-
active mydriasis.
 Alpha1 receptors – ciliary
blood vessels- constriction-
reduced aqueous production-
adrenaline, dipivefrine
 Alpha2 receptors- ciliary
epithelium- reduce aqueous
secretion- apraclonidine,
brimonidine
 Beta2 receptors on ciliary
epithelium- enhance aqueous
secretion – their blockade by
timolol/ betaxolol reduces
secretion.

18. LUNGS
 Bronchial smooth
muscles – beta2
receptors-
bronchodilation
 Pulmonary blood
vessels- alpha1
receptor-
vasoconstriction-
decongestion
GIT
 Smooth muscles of
stomach n intestine- beta2
receptors & alpha1-
relaxation- decrease in
tone n motility.
 Alpha2 receptors located
presynaptically in
cholinergic neurons-
stimulation decreases
Ach release- reduced
tone n motility.
 Sphincters – alpha1-
contracted- closure of
sphincters

19. BLADDER
 Detrusor muscles-beta2- relaxation
 Trigone & sphincter- alpha1a- contraction.
UTERUS
 Non pregnant- alpha1- Contraction
 Pregnant uterus- beta2- relaxation.
 Ejaculation is facilitated by alpha1 receptors
present on vas deferens, seminal vesicles,
prostrate.

20. SWEAT GLANDS
 innervation is
sympathetic in origin
but cholinergic in
character- sweating.
CNS
 Activation of
presynaptic α2
receptors, decrease in
central sympathetic
outflow.
 Other effects- inhibit
histamine release
from mast cells (
beta2 effect).

21.  ADIPOCYTES- beta3- lipolysis- increase in free fatty acids.
 Pancreas – alpha2 on pancreatic beta cells- decreased insulin
release, beta2- alpha cells- increase glucagon release.
 In liver
glycogenolysis, gluconeogenesis- hyperglycemia.

22. EPINEHRINE
 Receptor affinity beta2 >beta1>
alpha1&2.
 Low doses- action predominantly on
beta2 receptors.
 High dose- alpha effect.
 Weak beta3 activity.
 B.P. – biphasic response
 Beta1 stimulation-increase in co & HR-
increase in BP
 Alpha1- vasoconstriction- increase in
BP.
 As plasma conc. falls- beta2-
vasodilatation- fall in BP.
 Dale’s vasomotor reversal
phenomenon- pretreatment with
alpha blocking drugs( Priscoline)- fall
in BP due to beta2 effect become
more apparent.

23.  A- anaphylactic shock- 0.3-0.5ml of
1:1000 solution of epinephrine i/m -
relieve angioneurotic oedema of
larynx, bronchospasm, prevents
release of histamine from mast
cells, maintains B.P.
 B- bronchial asthma
 C- cardiac resuscitation- 0.1 mg/ml
intracardiac injection- revive from
cardiac arrest from drowning, elec
trocution
 D- prolong duration of LA.
 E- Epitaxsis

24.  ADR-
 Increase in BP-
cerebral
hemorrhage.
 Ppt angina,
palpitation,
arrhythmia.
 Pulmonary oedema
 Tremor , anxiety,
headaches.
 Contraindications
 Hyperthyroidism
 Angina
 HTN
 Ventricular fibrillation.
 Halothane group of GA-
increase the sensitivity of
myocardium towards
catecholamines.

25. NOREPINEPHRINE
 Alpha1&2> beta1>beta3
 Poor beta2 action.
Uses-
 Cardiogeneic shock, surgical shock- increases
vascular resistance, decreased blood flow to vital
organs.

26.  D1 ,D2 ,beta1 action
 Little effect on alpha receptors.
 No effect on beta2 & 3 receptors.
At therapeutic doses ( 2 -5 micro/kg/min iv)
 DA causes vasodilatation by stimulating
 D1 of renal blood vessels.
 Renal blood flow is enhanced & inc. GFR.
Intermediate infusion (5- 10 micro/kg/min)
 DA directly stimulates β1 recep. on the heart → +ve inotropic & +ve
chronotropic effect, but total peripheral resistance remains unchanged.
Higher infusion rates (> than 10 micro/kg/min)
 Peripheral arterial & venous constriction occur mediated by α1 receptor
stimulation.

27.  Cardiogeneic shock from MI, trauma,
surgery.
 CHF, renal & liver failure.
 5-10 microgram/kg/min - dose
USES

28. ISOPRENALINE
 Potent nonselective β receptors agonist
 beta1&2>>beta3.
 No alpha action
 Used in emergency to stimulate HR in pts
with bradycardia or heart block

29. DIPIVEFRINE
 Prodrug of epinephrine.
 Enhanced corneal penetration.
 Used in treatment of glaucoma.
 Adr- photosensitivity, conjuctival
hyperaemia.

30.  Mainly beta1 action, little alpha effect.
 No effect on DA, beta2&3 receptors.
 On heart- positive inotropic & less chronotropic
effect, without any change on peripheral
vascular resistance and BP.
 Used in pts of heart failure (2-5 microgram/kg/min iv)

31.  PHENYLEPHRINE
 alpha1 selective agonist,
noncatecholamine.
 not metabolized by COMT, longer
duration of action.
 Alpha1 receptor activation –
increase in peripheral vascular
resistance and BP.
 Used as a nasal decongestant and
as mydriatic.

32. Midodrine
 Prodrug, active metabolite
desglymidodrine has a
selective α1 receptor activity.
 Used to treat postural
hypotension
 Main adverse effect is
hypertension in supine
position, hence dosing at bed
time should better be
avoided.

33.  Belongs to imidazoline group of antihypertensive
drugs.
 After IV injection (at higher concentrations) clonidine
produces a transient rise in BP but on oral
administration (low plasma concentration) it
produces only fall in BP.
 clonidine has lesser intrinsic activity on α2 receptors
present postsynaptically on vascular smooth muscle
at lower plasma concentrations

34. ◦ stimulates α2 receptors present at vasomotor
centre leading to reduction in central sympathetic
outflow resulting in fall in BP and heart rate.

35.  Moderate hypertension orally 100 to
300 mcg BD, along with diuretic to
counteract sodium and water
retention.
 To control Diarrhoea in diabetic
patients with Autonomic
Neuropathy
 reduces intestinal motility by
inhibiting the release of Ach.
 Preanesthetic medication
 Management of Nicotine, Alcohol
and Opiate withdrawal
clonidine by decreased central
sympathetic outflow controls the
adverse sympathetic effects
associated with withdrawal of
opioids, alcohol and smoking.

36. ADR
 Major
◦ Rebound hypertension after abrupt withdrawal of drug (due to super
sensitivity of newly formed α1 receptors)
 Other
◦ Dry mouth
◦ Sedation
◦ Nasal stuffiness
◦ Constipation
◦ Impotence
◦ Contact dermatitis with transdermal patch

37.  Selective α2 agonist which are used for treatment
of glaucoma.
 reduce the formation of aqueous humor by their α2
receptor agonist action (present on ciliary
epithelium).
 Potent ocular hypotensives, which does not cross
BBB and hence have least systemic effects (unlike
clonidine which crosses BBB).
 Primarily used to prevent an acute rise in
intraocular pressure after laser trabeculoplasty

38.  Centrally acting antihypertensive
 Used in pregnancy

39.  Sedation
 Dryness of mouth
 Involuntary movements
 Gynaecomastia
 Galactorroea
 Hepatotoxicity
 haemolytic anaemia

40.  Preferential affinity for β2 receptors.
 Inhalation in form of aerosol, leads to effective activation
of β2 receptors in bronchi.
◦ Salbutamol Terbutaline
◦ Remiterol Fenoterol
◦ Salmeterol Formoterol
◦ Bambuterol Pirbuterol

41.  selective β2 agonist with relaxant effects
on smooth muscles of bronchi and uterus.
 Minimal cardiac stimulant effects and is
safer than Isoprenaline.
 Not metabolised by COMT and so exhibit
longer duration of action than
Isoprenaline.
 For immediate relief of asthma is given by
oral inhalation from (100mcg in single
dose, orally 2 to 4 mg TDS, IM or slow IV
injection)
 Sustained release tablets are also
available

42.  Inhalation causes fewer side effects than systemic administration.
 Also used for arrest of uncomplicated premature labour. between
24 to 34 weeks of gestation by giving an IV infusion but associated
with nausea and vomitting with risk of developing pulmonary
edema limits it use for this purpose.
 Isoxsuprine or Ritodrine having more selective β2 action on uterus
is more preferred.
 Common side effects include tremors in hands, palpitations,
headaches and hypokalaemia (after large dose)

43.  Like salbutamol, it is also
β2 selective bronchodilator.
 Effective orally, sc or by
inhalation
 Used to relieve acute
bronchospasm as occurs in
asthma
 Tolerance may develop on
regular use (similar to
other β2 agonists).
 Used in management of
COPD

44.  Also used to arrest uncomplicated premature
labour but side effects do not favour its use
for this purpose.
◦ Dose 2.5 to 5 mg BD or TDS oral; 250 mcg by
inhalation

45. THANK YOU