3. Autonomic drugs
Drugs that exerts pharmacological effects simulating activation,
intensification or inhibition of either the sympathetic/parasympathetic
nervous system have been historically referred to as autonomic drugs.
classification
sympathomimetic
sympatholytic
parasympathomimetic
parasympatholytic
7. ADRENERGIC/SYMPATHOMIMETIC DRUGS
Amine substances that causes physiologic response similar to those
evoked by the endogenous adrenergic mediators viz Epinephrine &
Norepinephrine are known as ADRENERGIC DRUGS
SYMPATHOMIMETIC = pharmacologic effect mimic sympathetic nervous
system
clinically relevant adrenergic agonist
pharmacological action.
receptor activation.
9. Adrenoceptors / adrenergic receptors
• adrenoceptors are macro molecular structure localized on/within the
surface membrane of cells innervated by adrenergic neurons
• basic physiological function is to recognize & interact with
endogenous adrenergic mediators viz : Adr, Noradr.
• adrenergic receptors are membrane bound G protein coupled
receptors which functions primarily by increasing / decreasing the
intracellular production of secondary messengers cAMP, IP3, DAG.
10.
11.
12.
13. Organs Alpha action Beta action
Arterioles & veins Vasoconstriction = rise in BP Vasodilation = fall in BP
Heart Arrhythmia @ higher dose Positive inotropic, positive
chronotropic
Radial muscle of iris Mydriasis
aqueous secretion
Relaxation of ciliary muscles
aqueous secretion
Urinary bladder contraction relaxation
Uterus contraction Relaxation
Splenic capsule Contraction Relaxation
Insulin Secretion inhibited Augumented insulin
Glucagon Secretion
21. Metabolic effects
Carbohydrate metabolism glycogenolysis in liver
release of glucagon
& release of insulin
Lipid metabolism -> raises concentration of free fatty acids in blood
-> stimulates beta receptors of adipose tissues
-> activates adenylate cyclase
-> cAMP stimulates lipase for hydrolysis of triacylglycerols
-> free fatty acids & glycerol
22. Pharmacokinetics
orally not effective -> rapid metabolism by MAO & COMT
rapidly absorbed after IM injection
for immediate effects I/V
on inhalation action restricted to respiratory tract (local action)
23. Clinical indications
Drug of choice for treatment of Type 1
hypersensitivity reaction
In critical conditions = drowning, suffocation,
shock, electrocution
Bcoz of vasoconstriction property used in
combination with local anesthetics
Severe respiratory distress like acute asthma &
anaphylactic shock (B.dilator)
In opthalmology as 2% epinephrine solution
24.
25. Doses
for hypersensitivity reaction
Small animals @ 5-20 microg/kg, IV, SC, IM
@ 50 microg/kg endotracheally (feline asthma)
Large animals @ 20 micrig/kg IM & 5-10 microg/kg IV
for cardiac resucscitation (asystole/cardiac arrest)
Small animals @ 10-20 microg/kg IV
@ 100 – 200 microg/kg endotracheally
Large animals @ 20 microg/kg SC, IV, I/tracheally.
26. Norepinephrine
Noradrenaline released by the mammalian post ganglionic sympathetic NS
NA constitutes 10-20% of catecholamine content adrenal medulla
NA affects large area of brain -> mainly Alertness & Arosal.
Levo form >> dextro form
NE differs from Epi only by lacking the methyl substitution in amino group
chemically 1-B (3,4 – dihydroxy phenyl) alpha - aminoethanol
27.
28. Pharmacological effects
Blood vessel -> Vasoconstriction
BP -> dose related increase in systolic & diastolic BP
heart -> potent myocardial stimulant
Smooth Muscles -> Relaxation of intestinal SM = retention of ingesta
Metabolic effect -> hyperglycemia
30. Clinical indications
I. NE has limited use but therapeutically
important in INTENSIVE CARE UNIT
II. in patients with critical hypotension
(vasodilatory shock viz septic shock &
neurogenic shock )
III. in the treatment of BP, NE is administered by
I/V infusion dose titrated to pressor response.
IV. Major limitation in clinical application = NE
reduces blood supply to kidneys
31. Doses
All species @ 0.1 – 0.2
microgram/kg/min IV infusion in
5% dextrose or 5% dextrose saline
solution but never use NS solution
alone.
infusion of NE should be
reduced gradually, avoiding abrupt
withdrawl.
32. Isoprenaline/isoproterenol
Direct acting synthetic CA’s with chemical name d, 1- B(3,4-
dihydroxyphenyl)-alpha-isopropyl aminoethanol Hcl.
It was commonly used to treat ASTHMA before the clinical
applications of beta receptors were discovered.
Iso predominantly stimulates B1 & B2
adrenoceptors and has no alpha activity
@ therapeutic levels.
33. Pharmacological effects
1. CARDIOVASCULAR SYSTEM
>decreased pheripheral resistance (relaxation
of skeletal muscles)
>markedly decreases diastolic pressure
with moderately increase in systolic pressure
>most potent cardiac stimulant
+++chronotropic +++inotropic
34. GIT
Potent INHIBITORY effect
RESPIRATORY EFFECTS
>potent BRONCHODILATOR.
>inhibits the antigen mediated
release of histamine & other
mediators of inflammation.
>often used clinically to dilate
bronchiolar airways during
episode of allergic reactions.
35. Clinical indications + Doses
for Sinoatrial arrest, Sinus Bradycardia, Complete AV block
Dogs & Cats @ 0.4 mg (total dose) in 250 ml of 5% dextrose slow IV infusion.
for bronchoconstriction/feline asthma
Dogs @ 0.1 – 0.2 mg (total dose) IM or SC 4 times a day.
Cats @ 0.2mg (total dose) in 100 ml of 5% dextrose slow IV infusion to effect, TID
Horses @ 0.4 microgram/kg in normal saline, slow IV.
36. DOPAMINE
3,4-dihydroxy phenyl ethylamine
Endogenous CA’s = immediate precursor of NE
as central NT in the basal ganglia & the
adrenal medulla.
PERIPHERY -> synthesized in renal epithelium
diuretic/natriuretic.
is an important adrenergic & dopaminergic
agonist used in ICU = maintain HR/BP
39. Cardiovascular system
@ low I/V dose = 0.5 – 2 microgram/kg/min RENAL DOSE
acts on vascular D1 dopaminergic receptors & dilates renal, mesenteric,
coronary vascular bed.
@ intermediate dose = 2 – 10 microgram/kg/min RENAL&CARDIAC DOSE
Stimulates renal D1 receptors + activates beta adrenergic receptors on heart
-> release of NE ++inotropic effect, systolic BP
@ high dose = > 10 microgram/kg/min PRESSOR DOSE
Activates vascular alpa1 adrenoceptors VC, elevated BP negate the
dopaminergic effect.
40.
41. Clinical indication + doses
Adjunctive therapy of acute cardiac failure
All species @ 1 – 10 microgram/kg/min, IV infusion in NS
Adjunctive therapy for oliguric renal failure
All species @ 2 – 5 microgram/kg/min, IV infusion with diuretics
Treatment of severe hypotension/shock
All species @ 1 – 20 microgram/kg/min, IV infusion
42. NONCATECHOLAMINES
3-4 DIHYDROXYBENZENE max potency
many drugs without catechol nucleus exerts similar effect = noncatecholamines
1. Ephedrine
2. Amfetamine
3. Methyl phenidate
4. Pseudoephedrine
5. Phenyl Propanol Amine
6. oxymetazoline
43. EPHEDRINE
mixed acting alkaloid isolated from Chinese
shrub Ma huang
levo isomer = more active
used as stimulant, nasal decongestant,
bronchodilator, to promote urinary
incontenance in small animals.
44. MOA
sympathomimetic action
= direct activation of alpha/beta receptors
= release of endogenous NE
action in CNS limited bcoz crosses BBB
weakly & not very efficiently.
repeated doses causes TACHYPHYLAXIS
(depletes the neuronal pool of NE)
45. Doses
1. For bronchoconstriction
Dogs @ 1-2 mg/kg, PO, BID
Cats @ 2-5 mg/kg, PO, BID
2. Urinary incontinence
Dogs & Cats @ 2-4mg/kg PO TID
3. As Pressor agent
Dogs @ 0.5-0.75 mg/kg, IV,IM, SC
4. As decongestant 1-1.5% solution.
46. PSEUDO EPHIDRINE
stereo-isomer of ephedrine
pharmacological effect = Ephedrine
in veterinary medicine it is used orally as
decongestant symptomatic relief in URT inf
cats allergic rhinitis
Dogs @ 15-50 mg (total) PO TID
Cats @ 2-4 mg/kg PO BID
49. AMPHETAMINE
synthetic sympathomimetic powerful CNS
stimulant action + alpha/beta adrenergic action
powerful psycho stimulant drug + potent drug of
abuse & drug dependency.
50. Pharmacological effects
Release of several NT’S = NE, Dopamine,
serotonin from storage vesicle @ their
respective nerve terminals.
Peripheral effects
Central effects
{stimulates entire CS axis, cortex, brain stem,
medulla high alertness, decreasd fatigue,
mood elevation, euphoria, decreased appetite}
CNS stimulant = drug of abuse = athletics &
race horses improve physical performance
51. METAMPHETAMINE
In humans causes amphetamine psychosis
resembles paranoid schizophrenic attacks like
hallucinations & paranoid delusions, loss of weight
tolerance to central action toxic effects of
amphetamine
pharmacokinetic+pharmacodynamics
recovery = rapid after withdrawal of drug but
chronic conditions precipitate as psychosis
in veterinary medicine limited use
52. METHYL PHENIDATE
Racemic mixture of a psychostimulant drug with
structural resemblance to amphetamine
MOA - dopamine level & NE in brain through
reuptake inhibition of MAO transporters.
approved clinically for Rx of attention deficient hyper
activity syndrome, psychiatric disorder, obsessive
compulsive disorders in humans
53.
54. PHENYL PROPANOL AMINE
Non catecholamine sympathomimetic agent
Pharmacological action = Ephedrine
In veterinary medicine used as decongestant, mild
bronchodilator
For the treatment of urethral sphincter hypotonus.
Dogs & cats @ 1-2 mg/kg PO TIB
55. OXYMETAZOLINE
Direct acting noncatecholamine
MOA : non selectively agonizes alpha1 & alpha2 adrenergic receptors
: vascular alpha1 adrenergic receptors VasoConstriction.
: local application stimulation of endothelial post synaptic alpha2
receptors VC (on systemic circulation)
: In contrast ~ centrally mediated inhibition of sympathetic tone via
pre-synaptic alpha2 receptors vasodilation.
59. Thank you
References
GOODMAN & GILMAN`S The pharmacological basis of therapeutics,
11th edition
HS SANDHU Essentials of veterinary pharmacology and toxicology,
2nd edition.
H RICHARD ADAMS Veterinary pharmacology and therapeutics, 8th
edition.
Jim E Riviere & Mark G Papich, Veterinary Pharmacology and
Therapeutics, 9th edition
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