brief description of Autonomic drugs & detailed note on catecholamines & noncatecholamines

1. CATECHOLAMINES &
NON CATECHOLAMINES.
.PRESENTED BY
DR SINDHU K
MVSC SCHOLAR,
DEPT OF VPT, COVAS.

2. `

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

4. Classifications
 sympathomimetic  adrenergic
 adrenomimetic
 sympatholytic  receptor blocking effects
 neuronal blocking effects
 parasympathomimetic  cholinergic
 cholinomimetic
 parasympatholytic  receptor blocking effects
 neuronal blocking effects

5. Adrenergic
nerves are
not
required for
their effect.
CATECHOLAMINES
Activate
receptor
of
effector
cells
catecholamines
Direct acting
sympatho
mimetic
amines
catecholamines

6. CATECHOLAMINES
 Norepinephrine – alpha agonist property
 Epinephrine – mixed acting (alpha & beta agonist)
 Isoproterenol – selective beta agonist
 Dopamine – immediate precursor of NE

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.

8. `

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.

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

15. Epinephrine
secreted by adrenal
medulla & neuro -
effector transmitter of
adrenergic drugs.

16. `

17. Pharmacological effect
cardiovascular system
 vascular smooth muscle : alpha = vasoconstriction -> mesenteric arteries
-> mucus membrane
-> renal beds
-> cutaneous
: beta = vasodilation -> skeletal muscle
-> coronary blood vessel
-> liver

18. Blood pressure
Norepinephrine -> dose related increase in systolic & diastolic BP
Epinephrine -> potent vasopressor agent

19. Heart
Iso >>> Epi > Norepi

20. Smooth muscles & uterus
Alpha receptors causes contraction -> release of intracellular Ca++
activation of IP3
Contraction
Beta receptors -> Relaxation

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

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

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

29. Pharmacokinetics
Ineffective when given orally
poorly absorbed from S/C site
inactivated by MAO & COMT
4-16 % administered drug excreted
in urine

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

37. Pharmacological effect
MOA  mixed adrenergic action
-> direct (alpha & beta)
-> indirect (release of NE)
 dopaminergic actions (D1, D2
receptors)

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.

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

48. .
.

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

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.

57. Clinical
indications
Topically as
decongestant
 Rhinitis &
conjunctivitis

58. Discussion

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
 google images