This document discusses adrenergic agonists and antagonists. It begins by classifying adrenergic agonists as direct acting, mixed acting, or indirect acting. It then discusses specific alpha-1, alpha-2, beta-1, and beta-2 adrenergic receptor agonists like phenylephrine, clonidine, dobutamine, and terbutaline. It details their mechanisms of action and clinical indications. The document concludes by discussing classes of adrenergic antagonists including alpha receptor antagonists, beta receptor antagonists, and specific drugs like propranolol, prazocin, and yohimbine.

1. ADRENERGIC AGONISTS &
ANTAGONISTS
DR S I N D H U K
MV S C S C H O L A R ,
D E P T O F V P T ,
C OVAS , P O O KO D E .

2. AGONISTS CLASSIFICATION
 DIRECT ACTING  Selective (phenylephrine, dobutamine)
 Non-selective (oxymetazoline, NE, Isoproterenol)
 MIXED ACTING  ephedrine
 INDIRECT ACTING  Releasing agents ( amphetamine)
 Uptake inhibitors (cocaine)
 MAO & COMT inhibitors (entacapone)

3. Alpha -1 adrenergic
receptor agonists
1. phenylephrine
2. methoxamine
3. midodrine

4. Phenylephrine
 direct acting non-catecholamine  powerful alpha 1 agonist/CNS
 MOA : activation of alpha1 adrenoceptors vascular smooth M = VC
 peripheral VC = systolic & diastolic BP
 blood supply renal, splanchnic & skin but coronary blood flow
 I/O pressure  mydriasis

5. Clinical indications
Critical care unit  spinal/epidural anesthesia
 elevates BP (reflux bradycardia negligable) =
beneficial  tachycardic condition/ cardiomyopathy
 as pressor agent  maintenance of blood presso
As midriatic agent  pupil dilation

6. Doses
Pressor agent
Dogs @ 1-3 microgram/kg/min
Cats @ 0.1mg/kg SC
Horses @ 5mg (total) IV
 2.5% ophthalmic solution
 as mydriatic agent 10% solution

7. Methoxamine
 selective alpha1 receptor agonist & similar in
structure/action to phenylephrine
 causes dose related systolic & diastolic BP
 peripheral vascular resistance & VC
 hypertension associated with bradycardia +
activation of vagus

8. Clinical indications
1. pressor agent treatment of hypotension
2. to relieve attacks of paroxysmal
supraventricular tachycardia
Dogs & cats @ 0.04 – 0.08 mg/kg IV
Cattle & horses @ 0.1 - 0.2 mg/kg IM, once day

9. Midodrine
 orally effective prodrug  desglymidodrine
 selectively stimulates alpha adrenoceptors of vascular smooth M &
causes vasoconstriction.
 treatment of autonomic insufficiency & postural hypotension.

10. Alpha -2
adrenergic
receptor
agonists
1. clonidine
2. xylazine
3. guanfacine &
guanabenz

11. Clonidine
 Imidazoline derivative predominantly utilized
in human medicine for hypertension &
tachycardia
 before the research & development, it was
given with out the prescription to cure diseases

12. MOA: (prototype of alpha-2)
 Direct acting  rapid IV inj  transient raise BP  activation of
post-junctional alpha 2 receptors
 Brain alpha 2 receptors especially medulla oblongata  inhibits NE
 central sympathetic outflow
 In periphery  activation of pre-junctional alpha 2 receptors 
suppress release of NE  peripheral vasodilation.
 On Central I-R of brain  activation pre-synaptic alpha2 receptors
 hypotensive effect (no transient hypertensive effect)

14. Clinical indications + doses
In human medicine = Antihypertensive drug
De-addiction therapy for narcotics, tobacco & chronic
alchoholism
In Veterinary medicine
As Sedative & Analgesic
1. sheep @ 0.006 mg/kg IV
2. horses @ 0.025 mg/kg IV

15. Xylazine
Alpha 2 adrenoceptor agonist structurally
similar clonidine
Used as Central sedative analgesic + muscle
relaxant property
 MOA : stimulation action on central alpha 2
receptors  sedation+analgesia
: on CVS  peripheral alpha2 action
 initial peripheral resistance +
BP followed by long duration of
lowered BP(central action)

16. Clinical indications
 sedation in dogs, cats & horses.
 preanesthetic sedative prior to inhalant anesthesia, injectable.
 as sedative prior to local, regional & epidural anesthesia.
 As general anesthesia with ketamine.

19. Doses
dogs & cats @ 1-3 mg/kg IM
 horses @ 0.6 -1 mg/kg IV
 pigs @ 0.5 – 3 mg/kg IM
Sheep & goats @ 0.1 – 0.2 mg/kg IM
 Cattle @ 0.05-0.03 mg/kg IM

21. Selective alpha 2 receptor agonists.
1. guanfacine
2. guanabenz
3. detomidine
4. apraclonidine
5. tizanide
6. lofexidine

23. Beta -1 adrenoceptor
agonists
1. Dobutamine
2. Denopamine
3. Xamoterol
4. Prenalterol

24. Dobutamine
 Synthetic direct acting catecholamine + selective beta1 adrenergic action
 L - isomer  potent alpha 1 agonist  pressor effect
 D – isomer  potent alpha 1 antagonist  blocks l isomer
D isomer  10 times more potent beta 1 agonist than l isomer

25. MOA + clinical application
 DOSE dependant response
 @ 2.5-15 microgram/kg/min IV infusion  significant change in HR, +++
inotropic +++ chronotropic , peripheral resistance.
 @ very high doses > 20 microgram/kg/min  HR increases
 clinically used as inotropic agent in Rx of CHF in Dogs @ 5 – 20
microgram/kg/min IV infusion
 Equine anesthesia to maintain mean BP  prevents hypotension induced
myopathy = (complication of equine anesthesia)
Horses @ 1 – 5 microgram/kg/min, IV infusion

27. Denopamine
 oral cardioselective drug
 MOA : selective binding to the beta1 adrenergic
receptors in heart  cardiac M contractibility
increased  enhanced cardiac output
 in +ion = potential to dilate coronary blood
vessels
 clinically used to Rx angina & CHF

28. Beta-2 adrenoceptor agonists
1. Terbutaline
2. Clenbuterol
3. Salbutamol
4. Salmeterol
5. Pirbuterol
6. Isoetarine
7. Orciprinaline

29. Terbutaline
 selective beta 2 adrenoceptor agonist found in bronchial, vascular &
uterine smooth M  Relaxation.
 effective when taken orally, S/C, inhalation.
 horse  poor oral absorption  resorcinol ring (not substrate MAO)

30. MOA +CLINICAL INDICATION
 stimulates production of cAMP  activation of adenylate cyclase
 inhibit release of inflammatory mediators  mast cells
 stimulation of beta2 receptors  bronchodilation  bronchial
secretion increases + bronchial clearance by ciliary action.
 mucolytic activity applied therapeutically as a fast acting
bronchodilator & relief from profuse nasal secretion.
 cats  limited use Bcoz cardiac stimulant action
Horses  after parenteral inj = sweating & CNS excitation.

32. Doses
Dogs @ 1.25 – 5 mg/kg, PO, TID.
Cats @ 0.1 mg/kg PO BID
Horses @ 0.002 -0.005 mg/kg IV dose may be adjusted as required
@ 2-4 mg/kg by inhalation using nebulizer

33. Clenbuterol
Direct acting beta 2 receptor agonist  stimulation of beta 2 receptors in
respiratory tract + ciliary beating of respiratory mucosal cells increases 
mucolytic action
 its primarily approved for Horses as a BRONCHODILATOR in the
management of airways obstruction  COPD
@ dose rate of 0.8 microgram/kg BID if no response then
@ 0.16 microg/kg
@ 0.24 microg/kg
@ 0.32 microg/kg

34. Salbutamol
 highly selective beta 2 adrenergic agonist B2 >>B1
 pharmacological + therapeutic indication similar to terbutaline
 bronchodilator effect with minimal cardiac stimulation
Used principally in Dogs & Cats bronchial Smooth M  to alleviate
bronchospasm / cough
 Dogs @ 0.02 – 0.05 mg/kg PO 3-4 times daily

37. Salmeterol
Long acting selective beta2 adrenergic agonist
Higher lipophilicity  prolonged pulmonary residence time
Salmeterol 10 folds potent than salbutamol
Horses  improves pulmonary function 55% with in 60 min of
aerosol administration + long duration of action = 8 hours
 horses @ 0.5 – 1 microgram/kg by aerosol inhalation.

38. ANTI-ADRENERGIC
DRUG/
SYMPATHOLYTICS

40. Alpha receptor antagonists.
Non selective
Eg: phenoxybenzamine, phentolamine.
Alpha-1 selective
Eg: prazocin, terazocin, urapidil etc.
Alpha-2 selective
Eg: yohimbine.

41. NON SELECTIVE ALPHA ADRENERGIC
RECEPTORS ANTAGONISTS
1. HALOALKYLAMINE DERIVATIVES/ ALKYLATING AGENTS
– phenoxybenzamine , dibenamine
2. IMIDAZOLINE DERIVATIVES – tolazoline, phentolamine
3. ERGOT DERIVATIVES – ergotamine ,
dihydroxyergotamine

42. Phenoxybenzamine
Haloalkylamine derivative  binds to a1/a2 R 
inhibits activation mediated by endogenous
catecholamines.
blocks both alpha 1 & alpha 2 adrenoceptors  non
competitive block  irreversible block.
Progressive decrease in peripheral resistance,
tachycardia, relaxation of nictating membrane, blocks
pupillary dilatation, relaxation of urinary sphincter,
increases insulin secreation.
Used in the treatment of hypertension caused by
pheochromocytoma

43. DALE’S EPINEPHRINE REVERSAL PHENOMENA

44. DOSES
 For Rx of reflux dyssinergia in Dogs @ 0.25
– 0.5 mg/kg, PO, BID
For hypertension associated with
phaeochromocytoma Dogs @ 0.2 – 1.5
mg/kg PO BID

45. TOLAZOLINE
Imidazole derivative
Direct vasodilator & cardiac stimulant action
Also blocks 5HT receptors + histamine like action
In veterinary medicine used primarily as Antidote to xylazine overdose
in dogs & cats @ 4 mg/kg slow IV

46. ERGOT ALKALOIDS
 Are the 1st adrenergic blocking drugs
discovered with which Henry Dale
demonstrated the vasomotor reversal
phenomenon.
Therapeutic use  mainly to
stimulate contraction of uterus post –
partum & to relieve the pain of
migraine in human medicine.

49. SELECTIVE ALPHA-1 ADRENERGIC
RECEPTOR ANTAGONISTS.
1. QUINALZOLINE DERIVATIVES – prazosin, terazocin
2. INDOLE DERIVATIVES – indoramin
3. MISCELLANEOUS – urapidil, ketanserin

50. Prazocin Hcl
Prototype of selective Alpha-1 adrenergic R antagonists
Extremly potent & highly selective alph-1 receptor blocking drug
Alpha-1 Receptor (1000folds) >>>> Alpha-2 Receptor
Pharmacological effect peripheral vascular resistance & BP
In dogs for Rx systemic hypertension/pulmonary hypertension
< 15 kg BW @ 1 mg total dose, PO, TID
> 15 kg BW @ 2 mg total dose, PO, TID

52. Therapeutic application in human
medicine
 Terazocin  structural analogue of prazocin mainly used for the Rx
of BPH-Benign Prostatic Hyperplasia ( BP by peripheral vasodilation)
It is often considered the drug of choice for men with hypertension &
prostate enlargement.
 Indoramin  indole derivative & competitive alpha1 R antagonist
occasionally used in human beings for the Rx of hypertension & BPH.
 Prazocin  primarily used in humans for the management of
hypertension.

55. Miscellaneous drugs
Urapidil  acts both as an alpha1 adrenoceptor antagonist & an
5HT1A receptor agonist
Ketanserin  blocks alpha1 adrenoceptors, serotonin 5HT2A &
5HT2C receptors & histamine H1 receptors.
The exact role of these drugs in Rx of hypertension & other
conditions remains to be determined.

56. SELECTIVE ALPHA-2
ADRENRGIC
RECEPTOR
ANTAGONISTS.

57. YOHIMBINE
Indolealkylamine alkaloid obtained naturally from west
African evergreen tree = Pausinystalia yohimbe
 Rx of xylazine & medetomedine reversal
Dogs & Cats @ 0.1 mg/kg, slow IV.
 Rx of xylazine induced emesis
Dogs & Cats @ 0.25 – 0.5 mg/kg IM SC BID

58. Atipamezole
Synthetic selective alpha-2 adrenoceptor blocking drug primarily used as
a reversal drug for Medetomidine & dexmedetomidine induced adverse
effects.
Acts by competitively blocking alpha2 receptors in CNS & periphery.
Clinical indications:
I. For Amitraz poisoning all species @ dose rate 0.05mg/kg, IV
II. For medetomidine & other alpha2 agonist reversal
Dogs @ 5 times the previous asministered dose of medetomidine,IM.
Cats @ 2.5 times the previously administered dose of medetomididne , IM.

61. BETA ADRENERGIC RECEPTOR
ANTAGONISTS
 NON SELECTIVE
{1st Generation}
propranolol, nadolol, pindolol, timolol, sotalol
{3rd Generation}
carvedilol, carteolol, labetalol, bucindolol
SELECTIVE
{2nd Generation}beta 1 : metoprolol, atenolol, esmolol, acebutolol
{3rd Generation}beta 2 : betaxolol, celiprolol, nebivolol

62. Non-selective beta adrenergic receptor antagonists.

63. Propranolol
Prototype of nonselective B
receptor blockers.
Interacts with both B1 & B2
receptors.
Lacks sympathomimetic activity.
Powerful local anesthetic action.
Partial agonist @ serotonin 5HT1B
receptors.

64. Clinical indication + doses
 Negative inotropic & negative chronotropic effects.
Peripheral vasoconstriction.
 Bronchoconstriction.
Used as Antiarrhythmic drug
Dogs @ 0.1 mg/kg IM TID
Horses @ 175 mg/kg total dose PO
Cats @ 2.5 mg/kg total dose PO

66. Selective beta
adrenergic
receptor
antagonists.

67. METAPROLOL
 prototype of selective B1 adrenergic receptor
(cardioselective)
Potency to block cardiac stimulation action >>>
propranolol.
Effectively used for supraventricular Tachycardia,
premature ventricular contraction & V. hypertrophy.
Dogs @ 5-50 mg total dose PO BID/TID
Cats @ 2 – 15 mg total dose PO TID

68. LABETALOL
 mixed alpha & beta adrenoceptor blocker
Primarily used in Human medicine for Rx of
hypertension
 In veterinary medicine pheochromocytoma
& clonidine withdrawal hypertension
Dogs @ 0.2 – 0.4 mg/kg PO once daily
following titrating dose to twice daily.

69. Atenolol
Devoid of intrinsic sympathomimetic & membrane
stabilizing activity.
It is used mainly as anti-arrhythmic drug.
Clinical indication:
I. For cardiac conditions Dogs @ 6.5-25mg total dose,
PO, BID/TID Cats @ 6.5-12.5mg total dose, PO, SID
II. For hypertension Dogs & Cats @ 2 mg/kg, PO, SID

70. Esmolol
An ultra short acting cardioselective beta1 adrenoceptor blocker.
It is devoid of intrinsic sympathomimetic & membrane stabilizing action.
Esmolol is very useful for the investigation & immediate therapy for
tachycardias.
It is particularly useful in critical ill patients where adverse effects of
bradycardia, heart failure/hypotension which may require rapid withdrawl of
drug.
For investigation, esmolol may be used as a test drug to indicate whether
beta blocker therapy is warranted as an antiarrhythmic agent or not??

71. Dogs & Cats @ 0.5-1 mg/kg, slow IV as loading dose
followed by 0.05 -0.2 mg/kg/min IV infusion.

72. Butaxamine
Selective beta-2 adrenergic receptor antagonist.
Blocks vasodilator & bronchial smooth muscle
inhibitory effect of isoprenaline which are mediated through B2
receptors.
Primarily used in research where B receptor blockade is studied
with other effects of drug.
Butaxamine is not clinically used because blockade of B2 adrenergic
receptor has no therapeutic application.

73. ALPHA & BETA ADRENERGIC RECEPTOR
ANTAGONISTS.
I. LABETALOL
II. CARVEDILOL

74. LABETALOL
Mixed alpha & beta adrenoceptor blocker.
Primarily used in human beings for Rx hypertension &
Phaeochromocytoma , clonidine withdrawl hypertension
and in geriatric patients.

75. Carvedilol
Mixed alpha & beta adrenoceptor antagonist which blocks B1, B2 & A1
receptors also possess antioxidant, antiproliferative & membrane stabilizing
effects.
Undergoes Firstpass metabolism & t1/2 = 1.5 hrs.
Therapeutic indication: Hypertension (A1 antagonism)
Tachyarrhythmias ( B1 antagonism)
MI & CHF (antioxidant/antiproliferative effect).
Dogs @ 0.2-0.4 mg/kg, PO, once daily, followed by titrating dose to twice daily.
Contraindicated in dehydrated/hypotensive/asthmatic animals.
Adverse effect in dogs  bradycardia, hypotension, bronchoconstriction.

78. LETS HAVE RECALL OF
WHAT WE LEARNT TILL
NOW !!!

80. 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.