Autonomic Nervous System Pharmacology

1. AUTONOMIC NERVOUS
SYSTEM
The autonomic nervous system (ANS)
controls involuntary activity.

2. AUTONOMIC NERVOUS
SYSTEM
It regulates the functions of:
• glands,
•muscle,
•viscera.
It controls the respiratory system,
cardiovascular system, gastrointestinal
systems, etc.

3. AUTONOMIC NERVOUS
SYSTEM
Classically, there are two major divisions of the
ANS based on structure and function:
a) the sympathetic nervous system, or
adrenergic system; and
b) the parasympathetic nervous
system, or cholinergic system.
Subdivisions of the adrenergic system into alpha
and beta receptors and further sub-types exist.

4. AUTONOMIC NERVOUS
SYSTEM
The somatic nervous system controls voluntary
activity.
This system contains long axons that originate in
the spinal cord and directly innervate skeletal
striated muscle.

5. AUTONOMIC NERVOUS
SYSTEM
GENERALIZATIONS
Sympathetic Parasympathetic
Thoracolumbar
Chain near spinal cord
Preganglionic fibers short
Postganglionic fibers long
Up to 20 post: 1 pregang. Fiber
Fright/fight/frolic
Vasomotor tone
Widespread effects
Craniosacral
Ganglia near effector organ
Preganglionic fiber long
Postganglionic fiber short
1 or 2 post: 1 Preganglionic fiber
Visceral actions, digestion
Heart, eye
Local effects

7. Peripheral transmitters
Transmission of nerve impulses across the
ganglionic synapse or at the effector organs
requires a chemical transmitter - a neurohumoral
transmitter.
The effect on the effector cell is a function of the
receptor site, not the transmitter substance.
There are several neurotransmitters in the
periphery, including acetylcholine, noradrenaline,
dopamine, and purines.

8. Peripheral transmitters
The purinergic system was discovered by blocking
both cholinergic and adrenergic receptors using
ADP and ATP.
However, our focus is only on the cholinergic and
adrenergic systems.

9. Acetylcholine (ACh)
Acetylcholine is the neurohumoral transmitter of:-
•Pre- and postganglionic junctions in the
parasympathetic N.S.
Pre-ganglionic
ACh
Post-ganglionic
Nicotinic receptor
Muscarinic
receptor
ACh
PARASYMPATHETIC
Effector
Organ

10. Acetylcholine (ACh)
Acetylcholine is the neurohumoral transmitter of:-
•Preganglionic junctions in the sympathetic N.S.
Pre-ganglionic
ACh
Post-ganglionic
Nicotinic receptor
Adrenergic
receptor
Noradrenaline
SYMPATHETIC
Effector
Organ

11. Acetylcholine (ACh)
Acetylcholine is the neurohumoral transmitter of:-
•Somatic efferent (Neuromuscular junction, NMJ)
ACh
Nicotinic
receptor
SOMATIC
Skeletal
muscle

12. Acetylcholine (ACh)
ACh is synthesized within cholinergic nerves and
stored within axonal vesicular structures or bound
to membranes or both. It is released by exocytosis
on arrival of a nerve impulse. ACh is a quaternary
ammonium compound.
There are two types of receptors – Muscarinic and
nicotinic.

13. Acetylcholine (ACh)
Muscarinic Receptors
• These are cholinoceptors that are activated by
the alkaloid muscarine.
• They are present on all parasympathetic
postsynaptic effector cells, including:
• smooth muscle,
• heart muscle, and conduction tissue
• exocrine glands and
• CNS cells.

14. Acetylcholine (ACh)
Muscarinic Receptors
• G-protein coupled
• Also pre synaptically
• All blood vessels, though most lack cholinergic
innervations
• Activation releases EDRF

15. Acetylcholine (ACh)
Muscarinic Receptors
Muscarinic receptors consist of several functional
receptor subtypes (M1-M5).
M1 – CNS, gastric parietal cells
M2 – Heart
M3 – Gland secretion, visceral smooth
muscle.
M4
M5

16. Muscarinic Receptors
• 5 subtypes: M1-M5
• M1, M3, M5 fall in one class. Act via IP3 DAG
cascade
• M2 & M4 in another (- cAMP production,
activate K+ channels)
• M4 & M5 are present on nerve endings
certain areas of the brain. Regulate release
of other neurotransmitters.
16

17. M1 M2
Heart Hyperpolarization,
velocity of
conduction,
contractility
Gastric glands Hist. release,
acid secretion,
relaxation of
lower
oesophageal
sphincter
Visceral smooth
muscle
Contraction
CNS Learning,
memory, motor
fn.
Tremor, analgesia
Ach release from
nerve endings
Agonist Oxotremorine Methacholine
Antagonist Pirenzepine
Telenzepine
Methoctramine
Tripitramine
17

18. Muscarinic Receptors
 M3:
◦ Visceral sm. Muscle contraction
◦ Iris: constriction of pupil
◦ Ciliary muscle: contraction
◦ Exocrine glands: secretion
◦ Vascular endothelium: Release of NO
vasodilatation
 Agonist: Bethanechol
 Antagonist: Hexahydrosiladifenidol
Darifenacin
18

19. Acetylcholine (ACh)
Nicotinic Receptors
These are cholinoceptors that are activated by the
alkaloid nicotine. They are present in autonomic
ganglia, adrenal medulla, and neuromuscular junction
(NMJ).
Nicotinic receptors consist of five protein subunits in
skeletal muscle (e.g. α (2), β, γ, δ) and two protein
subunits in ganglia (α and β) that form ligand-gated
(i.e., regulated) ion channel pores in the cell
membranes.

20. Nicotinic Receptors
 NM & NN two types on basis of location
 Ligand- gated cation channel
 Nm:
 Nm: contains four distinct sub-units in a pentameric
complex (αβγδ or αβγє) in different configurations.
◦ NMJ: Depolarization of muscle end plate
Contraction of skeletal muscle
◦ Agonist: Phenyl trimethyl ammonium,
Nicotine
◦ Antagonist: Tubocurarine, α- Bungarotoxin
20

21. Nicotinic Receptors
 NN:
◦ Autonomic ganglia: depolarization –
postganglionic impulse
◦ Adrenal medulla: catecholamine release
◦ CNS: site specific excitation or inhibition
◦ Agonist: DMPP (Dimethyphenylpiperazinium),
Nicotine
◦ Antagonist: Hexamethonium,
Trimethaphan
21

22. `
Acetyl-cholinester
ase
(True)
Butyrylcholinesterase
(Pseudo)
1. Distribution
All cholinergic sites, RBC,
gray matter
Plasma, Liver, Intestines,
white matter
2. Hydrolysis
ACh Very fast Slow
Methacholine Slower than ACh Not hydrolysed
Benzoylcholine Not hydrolysed Hydrolysed
Butyrylcholine Not hydrolysed Hydrolysed
3. Inhibition More sensitive to
physostigmine
More sensitive to
organophosphates
4. Function Termination of ACh action Hydrolysis of ingested
esters 22

23. Acetylcholine (ACh)
Termination of transmitter action
Termination of transmitter action (ACh) is by
enzymatic degradation (Acetylcholinesterase; AChE)
in the junctional space.
ACh
AChE Acetic acid
+ Choline
[Present in cholinergic nerves, autonomic
ganglia, NMJ, & neuroeffector junctions]

24. Acetylcholine (ACh)

25. Acetylcholine (ACh)
• Choline is present in the
synapse, and is absorbed by a
presynaptic sodium-dependent
transporter (CHT1). This is the
rate-limiting step of Ach
synthesis.
• Once inside, choline is
combined with acetate by
choline acetyltransferase.
• The finished acetylcholine is
stored in vesicles by Vesicular
Acetylcholine Transporter,
VAchT. thus released

26. Acetylcholine (ACh)
• There is up to 50,000 molecules
per vesicle, and about 300,000
vesicles per nerve terminal.
• Arrival of the action potential
opens voltage-gated calcium
channels, which activates
Synaptosome-associated
proteins (SNAPs) and vesicle-
associated membrane proteins
(VAMPs).
• This causes fusion of the vesicle
with the membrane.
• Acetylcholine is thus released

27. Acetylcholinesterase inhibitors
Reversible
Physostigmine
Neostigmine
Edrophonium
Carbamates
Irreversible
Organophosphates

28. Clinical uses of
acetylcholinesterase inhibitors
•Constriction of pupil and sphincter of eye
(physostigmine)
•Myasthenia gravis
•Used to reverse non-depolarizing
neuromuscular blockers
•Used against insecticide or organophosphate
poisoning.

29. Noradrenaline (NA)
Noradrenaline, as well as adrenaline and
dopamine are endogenous catecholamines and
are the sympathetic neurohumoral transmitter
substances in most mammalian species.

30. Noradrenaline (NA)
Noradrenaline is the transmitter at
postganglionic effector junctions of the
sympathetic N.S.
Pre-ganglionic
ACh
Post-ganglionic
Nicotinic receptor
Adrenergic
receptor
Noradrenaline
SYMPATHETIC
Effector
Organ

31. Noradrenaline (NA)
It is stored in minute granular vesicles in nerve
terminals.
Adrenaline (and also Noradrenaline) is stored
in chromaffin granules in the adrenal medulla.
Release is by arrival of a nerve impulse.

32. Noradrenaline (NA)
Termination of action
1. Re-uptake – reuptake into sympathetic
nerve endings (Uptake 1) and uptake at
the effector tissue/surrounding tissue
(Uptake 2).
2. Enzymatic degradation: extraneuronal
degradation by catechol-o-methyl
transferase (COMT); Intraneuronal
degradation by monoamine oxidase
(MAO).
3. Diffusion away from the site.

33. Noradrenaline (NA)
Adrenergic receptors (Adrenoceptors) are
generally divided into α1, α2, β1 and β2
receptors, respectively.
α1 – occur on postsynaptic effector cells
(especially smooth muscle).
blood vessels, bronchi, sphincters, liver.
α2 – occur both pre- and post synaptically.
blood vessels, nerve terminals, fat cells,
blood platelets

34. Noradrenaline (NA)
β1 – occur on postsynaptic effector cells
(especially smooth muscle).
Heart, fat cells, urinary bladder, GIT smooth
muscle.
β2– occur postsynaptically on effector cells
(especially smooth muscle).
Bronchi, blood vessels of skeletal muscle,
uterus.

35. Dopernergic receptors occur pre- and post
synaptically and may be either inhibitory
(e.g., basal ganglia) or excitatory (e.g.
chemo-emetic trigger zone).
Dopamine receptors occur in the smooth
muscle of the renal, mesenteric coronary
and cerebral arteries.

36. Effector Sympathetic Parasympathetic
Heart
Rate
Conduction
Atria,
Ventricles,
Coronary blood vessels
Excitation
1 increased
1 increased
1 force increased
1 force increased
 dilatation/  constriction
Inhibition
Reduced
Slowed
Weakened
None in mammals
Varied
Blood vessels
Cutaneous
Abdominal/
Pelvic viscera
Skeletal muscle
Salivary glands
Pancrease
Lungs
External genitalia
Cerebral
 constriction
 constriction
2 dilatation
 constriction/2 dilatation
 constriction
 constriction
slight
 constriction
 constriction/ dilatation
Dilatation
Dilatation
Dilatation
Slight Dilatation
Dilatation (erection not Ach)
Dilatation
Blood pressure
BP
Blood flow
Raised
Widespread redistribution
Lowered
Local changes
Gastrointestinal tract
Smooth muscle
Sphincters
Secretions
 &  relaxation
 contraction
Decreased
Increased motility & tone
Relaxation
Increased
Bronchi 2 relaxation

37. Effector Sympathetic Parasympathetic
Eye
Pupil
Radial iris muscles
Circular iris muscles
Ciliary muscle
Nictating membrane
dilatation
 (mydriasis)
 contraction
 contraction
 relaxation
 contraction
myosis
-
contraction
constriction
-
Bladder
Detrusor muscle
Sphincter muscle
Retention of urine
 relaxation
 contraction
Voiding of urine
Contraction
relaxation
Genitalia
Uterus
Male
Retracter penis muscle
Female
 contraction (rabbit, dog, pregnant
cat)
 relaxation (cow, sheep, non-
pregnant cat)
 ejaculation
contraction
Contraction
Erection
Relaxation
Erection
Adrenal Adrenaline secretion No innervation
Liver 2 glycogenolysis
2 gluconeogenesis
Fat 1 lipolysis
Salivary glands  scant viscous saliva Watery, profuse saliva
Lachrymal glands - secretion
Nasal  inhibition secretion
Piloerector  retraction

38. Noradrenaline (NA)

39. GANGLIONIC PHARMACOLOGY
Ganglionic blocking drugs inhibit the effect
of Ach at nicotinic receptors by acting
competitively (nondepolarizing blockade) at
both sympathetic and parasympathetic
autonomic ganglia.
Because of lack of selectivity and
numerous adverse effects they are seldom
used clinically.

40. GANGLIONIC PHARMACOLOGY
Agonists:
Acetylcholine, Nicotine (low doses), Coniine
(obtained from Conium maculatum or
Poison Hemlock), and Lobeline (obtained
from Lobelia spp).
The agonists cause depolarization of the
post-synaptic membrane. Effects are
widespread since they will cause release of
ACh and Noradrenaline from post-ganglionic
endings, and adrenaline from the adrenal
medulla.

41. GANGLIONIC PHARMACOLOGY
Agonists:
Results are hypertension, increased gut
activity, release of ADH and other general
autonomic effects. Convulsions.
Other non-agonist, ganglionic stimulants
are: histamine, serotonin (5HT). and
angiotensin II.

42. GANGLIONIC PHARMACOLOGY
Antagonists:
Nicotine (higher doses) – a long lasting
depolarization.
Tetramethylammonium (TMA) – a
depolarising blocker
Tetraethylammonium (TEA) – a competitive
blocker.
Hexamethonium – a competitive blocker
with tachyphylaxis and no GIT absorption.
Mecamylamine - a competitive blocker

43. GANGLIONIC PHARMACOLOGY
Antagonists:
Pempidine – competitive and one of the
safest.
Trimethaphan

44. GANGLIONIC PHARMACOLOGY
Antagonists:
The ganglion blocking drugs are used in
human medicine to control blood pressure.
Sympathetic tone is most affected. Side-
effects include postural hypotension,
impaired eye accommodation, incontinence,
and chronic constipation.

46. CHOLINERGIC DRUGS
(PARASYMPATHOMIMETIC
DRUGS; CHOLINOMIMETICS)
The cholinergic system has nicotinic
receptors at the autonomic ganglia and at
the NMJ, and Muscarinic receptors at the
parasympathetic terminals and a few
sympathetic terminals.

47. CHOLINERGIC DRUGS
(PARASYMPATHOMIMETIC
DRUGS; CHOLINOMIMETICS)
Pre-ganglionic
ACh
Post-ganglionic
Nicotinic receptor
Muscarinic
receptor
Nicotinic
Receptor (NMJ)
ACh
PARASYMPATHETIC
Effector
Organ

48. CHOLINERGIC DRUGS
Cholinergic drugs are substances that act by direct
action on the Muscarinic and nicotinic cholinergic
receptors or by indirect action through inhibition of
acetylcholinesterase (AChE), cause physiological
response similar to acetylcholine release in the body.
Cholinergic effects refer to ACh effects without
distinction as to the anatomical site of action, whereas
parasympathomimetic effects refer to ACh effects on
effector cells innervated by post-ganglionic fibres of
the parasympathetic N.S.

49. CHOLINERGIC DRUGS
CLASSIFICATION
Direct acting
Plant alkaloids e.g. Pilocarpine
Choline esters e.g. Bethanechol
Indirect acting
Reversible AChE inhibitors, e.g. Neostigmine.
Irreversible AChE inhibitors, e.g.
Organophosphorus compounds.

50. DIRECT ACTING MUSCARINIC
CHOLINOCEPTOR AGONISTS
Direct acting parasympathomimetic drugs act at
Muscarinic cholinoceptors to many of the
physiologic effects that result from stimulation of
the parasympathetic N.S.
In general these are esters of Choline (e.g.
bethanechol, carbachol, methacholine,
Furtrethonium) or alkaloids (muscarine, nicotine,
pilocarpine, arecholine).

51. DIRECT ACTING MUSCARINIC
CHOLINOCEPTOR AGONISTS
Esters of Choline generally have low lipid
solubility, are hydrolyzed in the GIT, have poor
oral absorption and poor distribution to the CNS.
Acetylcholine is not very resistant to hydrolysis,
whilst the other esters are more resistant and can
be given subcutaneously. Even large doses of ACh
intravenously only produce a transient effect of 5-
20 seconds. Alkaloids are tertiary amines, are
absorbed orally, excreted via the kidneys, and
acidification of the urine increases their excretion
rate.

52. Pharmacological effects
Eye
– Direct acting Muscarinic cholinoceptor
agonists contract the circular smooth muscle
fibers of the ciliary muscle and iris to
produce, respectively, a spasm of
accommodation and an increased outflow of
aqueous humor into the canal of Schlemm,
resulting in a reduction in intraocular
pressure.
– These drugs contract the smooth muscle of
the iris sphincter to cause miosis.

53. Pharmacological effects
Cardiovascular system
Agonists produce a negative chronotropic effect
(reduced SA node activity). They decrease the
conduction velocity through the AV node.
They cause vasodilation (through release of nitric
oxide by endothelial cells) and a fall in blood
pressure (hypotension).
These drugs have no effect on the force of
contraction because there are no muscarinic
receptors on, or parasympathetic innervation of,
the ventricles.

54. Pharmacological effects
Gastrointestinal tract
Increased contraction and tone of smooth
muscle, with increased peristaltic activity and
motility. Drugs also cause an increase in salivation
and acid secretion.

55. Pharmacological effects
Urinary tract
Increased contraction of the ureter and bladder
smooth muscle; increase sphincter relaxation.
Respiratory system
Bronchoconstriction

56. ACETYLCHOLINE
H3C – N+ - CH2 – CH2 – O – C- CH3
CH3
CH3 O

57. ACETYLCHOLINE
Not used clinically. Low doses tend to result in
Muscarinic effects whilst higher doses tend to
result in nicotinic effects. Generally, the
Muscarinic effects are miosis, salivation, increased
gut motility, and hypotension. Nicotinic effects are
muscle tremors resulting in muscle weakness and
even paralysis. Other effects are generalized due
to depolarization of postsynaptic membranes of
neurons of both sympathetic and parasympathetic
ganglia (including adrenal medulla) and thus
cause release of ACh, Adrenaline, and
Noradrenaline before blocking transmission of
further efferent impulses

58. MUSCARINE
Found in the mushroom Amanita muscaria (the
Fly Agaric). Not used clinically. Resistant to
hydrolysis.
ARECOLINE
From the Betel Nut or areca palm-nut (Piper
betle). Addictive, and has been widely used in
Asia. Has been used as a purgative anthelmintic.

59. CARBACHOL
(Carbamoyl Choline)
An orally active (or injectible) choline ester
(almost completely resistant to hydrolysis). The
subcutaneaous route may lead to less violent
actions than IV. Has mixed Muscarinic and
nicotinic effectsOccasionally used in horses for
some types of colic, but can cause hypermotility
and purgation, Not to be used in obstructive
colics. It will cause uterine contractions. It can
cause hypotension. It used as a laxative in cattle
and relief of urinary retension.

60. METHACHOLINE
Has little nicotinic action. It cannot be given by
mouth as there is some susceptibility to AChE.
Methacholine is more active on the circulation
than on the GIT, and is used in humans for
controlling atrial tachycardia and the pacemaker.
(Carbachol only affects the heart in overdoses.)

61. BETHANECHOL
Resistant to hydrolysis. Similar to carbachol,
except that it is primarily a muscarinic agonist.
More active on the GIT than the heart, so it is
used for paralytic ileus (a condition occurring
particularly after abdominal surgery or trauma) in
humans. Also used in veterinary medicine for
bladder paralysis and paralytic ileus.

62. INDIRECT ACTING
PARASYMPATHETIC AGENTS
Indirect acting agents inhibit AChE and increase
ACh levels at both Muscarinic and nicotinic
cholinoceptors to mimic many of the physiologic
effects that result from the stimulation of the
parasympathetic division of the ANS.

63. INDIRECT ACTING
PARASYMPATHETIC AGENTS
ACh interacts with AChE at two sites: The N+ of
Choline (ionic bond) binds to the anionic site, and
the acetyl ester binds to the esteratic site (serine
residue). As ACh is hydrolyzed, the serine-OH side
chain is acetylated and free Choline is released.
Acetylserine is hydrolyzed to serine and acetate.
The half-life of acetylserine hydrolysis is 100-150
microseconds.

64. INDIRECT ACTING
PARASYMPATHETIC AGENTS
N - CH2 – CH2 – O – C
CH3
CH3 O
CH3
+
CH3
Esteratic site
Anionic site
-

65. INDIRECT ACTING
PARASYMPATHETIC AGENTS
 AChE Structure:
 AChE forms a gorge which contains an aromatic
anionic site (tryptophan 86)
 And esteratic site serine, glutamate & histidine.
 ACh attracted electrostatically to aromatic pocket
thereafter acetylates the serine residue
 Acetylated enzyme H2O Acetic acid + Choline
(150 micro seconds)

66. INDIRECT ACTING
PARASYMPATHETIC AGENTS
Source: https://pubs.rsc.org/en/content/articlelanding/2019/np/c9np00010k/unauth

67. AChE Structure
Ach
Ser
Glu
His
Anionic Esteratic
Acetylcholinesterase 67

68. Reaction
Ach + Cholinesterase Acetylated
Enzyme hydrolysis Acetic acid + Choline +
Free enzyme
68

69. REVERSIBLE INDIRECT ACTING
PARASYMPATHETIC AGENTS
• Carbamates:
o Physostigmine
o Neostigmine
o Pyridostigmine
o Rivastigmine
o Donepezil
Acridine:
o Tacrine
 Quaternary alcohol
o Edrophonium
Physostigmine is lipid soluble

70. REVERSIBLE INDIRECT ACTING
PARASYMPATHETIC AGENTS
Tacrine & Edrophonium bind only to the
aromatic site electro statically
Prevent access of ACh.
Short lived, diffuse in 2-10 mins
Carbamoylated enzyme (reversible inhibitors)
react slowly in 30 mins -6hr
Reactivation time is less than synthesis of fresh
enzyme.

71. REVERSIBLE INDIRECT ACTING
PARASYMPATHETIC AGENTS
• Organophosphates bind only to esteratic site
• Form covalent bond with ‘OH’ group of Serine
• Hydrolysed at a very slow rate
• Phosphorylated enzyme may undergo aging &
become resistant to hydrolyses

72. INDIRECT ACTING
PARASYMPATHETIC AGENTS

73. REVERSIBLE INDIRECT ACTING
PARASYMPATHETIC AGENTS
NEOSTIGMINE
Synthetic product. Neostigmine bromide is
available for oral use and Neostigmine methyl
sulphate for parenteral use. Bioavailability is poor
and must therefore be given in large doses if
given orally. Duration of effect is approximately 30
minutes. It also has a direct cholinomimetic
action. Does not cross the blood-brain barrier to
any major extent.

74. REVERSIBLE INDIRECT ACTING
PARASYMPATHETIC AGENTS
NEOSTIGMINE
Like ACh, Neostigmine as well as physostigmine
and demecarium undergo a two-step hydrolysis.
However, the serine residue of the enzyme is
covalently carbamylated rather than acetylated.
Hydrolysis of the carbamylserine residue is much
slower than that of acetylserine (30 min – 6 h).
Neostigmine, physostigmine and demecarium also
have direct agonist action on skeletal muscle
nicotinic receptors.

75. REVERSIBLE INDIRECT ACTING
PARASYMPATHETIC AGENTS
NEOSTIGMINE
Clinical uses:
•Treatment of Myasthenia gravis
•Treatment of poisoning from overdose of non-
depolarizing muscle relaxants

76. REVERSIBLE INDIRECT ACTING
PARASYMPATHETIC AGENTS
PHYSOSTIGMINE
Natural product. Usually used as a 1 % solution,
topically in the eye. Similar to pilocarpine. It may
cause pain and irritation leading to hyperemia and
blurred vision. The product is too long acting for
parenteral use.

77. REVERSIBLE INDIRECT ACTING
PARASYMPATHETIC AGENTS
EDROPHONIUM
Edrophonium (Tensilon) acts at the same sites of
AChE to competitively inhibit ACh hydrolysis.
Edrophonium has a short duration of action of 5
to 15 minutes.
CARBAMATES
Insecticides

78. IRREVERSIBLE INDIRECT ACTING
PARASYMPATHETIC AGENTS
• Organophosphate
– Dyflos
– Ecothiophate
– Parathion
– Malathion
– Diazinon
– Tabun, Sarin, Soman
(Nerve Gases)
• Carbamates:
– Carbaryl
– Propoxur
All OP except ecothiophate are lipid soluble.
Insecticides
Insecticides

79. IRREVERSIBLE INDIRECT ACTING
PARASYMPATHETIC AGENTS
ORGANOPHOSPHORUS COMPOUNDS
Organophosphors are seldomly used
pharmacologically except as anthelmintics (e.g.
trichlorphon, dichlorvos, haloxon) and pesticides
(e.g. chlorfenphinos, quinthiophos, malathion,
etc).

80. IRREVERSIBLE INDIRECT ACTING
PARASYMPATHETIC AGENTS
ORGANOPHOSPHORUS COMPOUNDS
Cholinesterase reactivators i.e. oximes, react
directly with alkylphosphate compounds and free
the enzyme. Pralidoxime methiodide (PAM) and
obidoxime (Toxogonin) are effective in
reactivating phosphorylated enzyme and may be
used as an antidote for the treatment of poisoning
with organic phosphates.

81. IRREVERSIBLE INDIRECT ACTING
PARASYMPATHETIC AGENTS
ORGANOPHOSPHORUS COMPOUNDS
Pralidoxime and obidoxime are more active at the
NMJ than the CNS and not effective at the
muscarinic sites. Obidoxime can pass the blood-
brain barrier. Dose of obidoxime is 4-8 mg/kg, IV.
If the animal responds, give every 2 hrs, 2 – 3
times. Only effective up to 36 - 48 hours after
poisoning. Start with atropine and 5 minutes later
give obidoxime.

82. CHOLINERGIC ANTAGONISTS
(PARASYMPATHOLYTICS)
Parasympatholytics are competitive
pharmacological antagonists of the muscarinic
receptors. These products are also known as
muscarinic blockers or antimuscarinics.
CLASSIFICATION
– Belladonna alkaloids – natural/synthetic
– Synthetic antimuscarinic compounds

83. CHOLINERGIC ANTAGONISTS
(PARASYMPATHOLYTICS)
NATURAL BELLADONNA ALKALOIDS
The are widely distributed in nature, especially in
solanaceae plants e.g. Deadly Night Shade
(Atropa belladonna), Jimson weed (Datura
stramonium) and Hembane (Hyoscyamus niger).

84. ATROPINE (DL-Hyoscyamine)
Originally obtained from the Deadly Nightshade
plant. It is racemic (DL or +/-) hyoscyamine. It is
a tertiary amine alkaloid that is a competitive
antagonist for muscarinic receptors. Used as the
sulphate.
It causes:
•Decreased secretory activity in the respiratory
tract and GI tracts (but gastric secretions need
very high doses to be inhibited).
•Bronchial dilatation
•Increased heart rate (due to decreased vagal
modulation of the pacemaker)

85. ATROPINE (DL-Hyoscyamine)
It causes:
Decreased GIT activity (less sensitive than the heart)
Pupillary dilatation (which is sometimes too long
lasting, so other drugs are preferred)
Decreased urine flow (although atropine is not very
effective clinically for this).
Cycloplegia (long-lasting and can lead to blockage of
the Canals of Schlemm).
Peripheral vasodilatation (non-muscarinic) leading to
raised skin temperature.

86. ATROPINE (DL-Hyoscyamine)
It causes:
Overdose can produce the above plus CNS
stimulation followed by CNS depression and death
from respiratory depression.
Use physostigmine (“Eserine”) as the antidote.

87. ATROPINE (DL-Hyoscyamine)
Uses:
•Antispasmodic (spasmolytic); but can excessively
slow a normal gut. Usually used in hypermotile
states. Is a constituent of “Lomotil”.
•In horses to protect the heart from the heart-
blocking actions of xylazine.
•As an adjunct to anaesthesia – antisecretory and
bronchodilatory.
•Ophthalmologically to view the eye.
•Antidote to organophosphates.

88. HYOSCYAMINE
The L form is the active form so equal weight
dose with atropine is more potent (atropine being
diluted with the D form). Similar to atropine.
Occurs in plants, but on extraction forms atropine
by racemization.
HYOSCINE-N-BUTYLBROMIDE
(Buscopan)
Used in calf antidiarrhoeal preparations.

89. SCOPOLAMINE (L-hyoscyamine)
Present in plants of the Solanaceae. Slight
sedative effect on the CNS. Produces sedation and
sleep in dogs at small doses. May cause
excitement in the horse. Similar to atropine.
Stimulates, rather than depresses the respiratory
system.

90. SYNTHETIC AND SEMI-SYNTHETIC
BELLADONNA ALKALOIDS
The synthetic substitutes have been introduced
for clinical use in ophthalmology (mydriatics and
cycloplegics) and in gastroenterology (anti-ulcer
and spasmolytic agents). Only a few of these are
used to any appreciable extent in veterinary
medicine.
Some of these compounds are:
• Atropine methylnitrate
• Homotropine
• Eucatropine.

91. SYNTHETIC ANTIMUSCARINIC
COMPOUNDS
»Methylscopolamine
»Methantheline
»Probantheline
»Dicyclomine
»Glycopyrrolate

92. SYNTHETIC ANTIMUSCARINIC
COMPOUNDS
Glycopyrrolate (“Robinul-V”) is a long-acting
quaternary ammonium compound with 5 times
the potency of atropine as an antisialogogue.

93. ADRENERGIC DRUGS
(SYMPATHOMIMETIC DRUGS)
The adrenergic system has nicotinic cholinergic
receptors in sympathetic ganglia and alpha (α)
and beta (β) receptors at the sympathetic effector
tissues.
Pre-ganglionic
ACh
Post-ganglionic
Nicotinic receptor
α1 & α2
β1 & β2
Noradrenaline
SYMPATHETIC
Effector
Organ

94. ADRENERGIC DRUGS
(SYMPATHOMIMETIC DRUGS)
The two principle adrenergic chemical messengers
are adrenaline from chromaffin cells in the adrenal
medulla and noradrenaline from postganglionic
neuronal endings. These two chemicals are
catecholamines.

95. ADRENERGIC DRUGS
(SYMPATHOMIMETIC DRUGS)

96. Biosynthesis of catecholamines
The enzymes occur in the neuronal cytoplasm
except dopamine β-hydroxylase which is in the
neuronal vesicles. Dopamine is a CNS transmitter
and there are dopamine receptors in the
mesenteric and renal blood vessels.

97. Biosynthesis of catecholamines
PNMT=Phenethanolamine-N-methyl transferase

98. Storage and release
Noradrenaline within the storage granule is bound with
calcium, ATP and chromagrannin. This noradrenaline is
in equilibrium with a ‘free pool’ of noradrenaline in the
cytoplasm. With the arrival of an action potential and the
entry of calcium into the cell, noradrenaline is released by
exocytosis.
1. Some drugs (“Indirect sympathomimetics” e.g.
tyramine, amphetamine) cause release of
noradrenaline from the granules, and thus cause
sympathetic effects.

99. Storage and release
2. Some drugs (“depleters”) cause release of
noradrenaline and depletion of stores, thereby
decreasing subsequent action of the neurone.
Guanethidine (and the related guanadrel) and
bethanidine cause depletion without first causing
release, or only release in non-clinical amounts.
Guanethidine has a structure that precludes entry into
the CNS so its action is peripheral. Tyramine and
amphetamine will cause release of guanethidine,
showing its uptake into the stores.
3. Some drugs interfer with release e.g. bretylium.
4. Reserpine blocks incorporation of noradrenaline into
the granules.

100. Storage and release
1. Some drugs (“Indirect
sympathomimetics” e.g.
tyramine, amphetamine) cause
release of noradrenaline from the
granules, and thus cause
sympathetic effects.

101. Storage and release
2. Some drugs (“depleters”) cause
release of noradrenaline and
depletion of stores

102. Storage and release
3. Some drugs interfer with release
e.g. bretylium.

103. Storage and release
4. Reserpine blocks incorporation of
noradrenaline into the granules.

104. Fate of transmitter
1. Passage across the synapse to bind to receptors
2. Uptake I back into the neurone
3. Uptake II at the effector site
4. Diffusion away from the site.

105. Fate of transmitter
Uptake I into the neurone (which can be blocked
by cocaine) leads to noradrenaline (NA) joining
the neurone pool for re-use or to the noradrenaline
being metabolized by monoamine oxidase
(MAO). Ninety (90) % of released NA undergoes
uptake I. Uptake I is energy dependent, can take
up low concentrations and is saturisable.

106. Fate of transmitter
Uptake II is less important, takes place in
sympathetically-innervated effector tissues and leads to
metabolism of NA by catechol-O-methyl transferase
(COMT). Uptake II occurs mainly at high concentrations,
occurs mainly in sympathetically-innervated tissues and
is not blocked by cocaine. Catechol-O-methyl transferase
occurs extracellularly in liver, kidney, brain and
sympathetically-innervated tissues (but not the neurone).
Related substances can “fool” the system. For instance, 6-
hydroxy dopamine undergoes Uptake I and displaces
neuronal stores leading to degeneration of the neurons (a
chemical sympathectomy). Guanethidine also undergoes
Uptake I and its action is blocked by cocaine.

107. Drugs interfering with adrenergic
neurone function
Depleters: Bethanedine, guanethidine replace
noradrenaline in stores.
Release inhibitor: Bretylium accumulates in sympathetic
neurons and inhibits release of NA. Used in human
intensive care to treat arrhythmias.

108. Drugs interfering with adrenergic
neurone function
Reserpine: A rauwolffian alkaloid used as a sedative in
man and to decrease blood pressure. Has been used in
turkeys to reduce blood danger from aortic aneurysm.
Blocks incorporation of NA into granules.
Alpha methyl dopa: Used for hypertension in man.
Cocaine: Blocks Uptake I and therefore potentiates NA at
the synapse.

109. Adrenergic Receptors
There are two main sub-types of adrenergic receptor,
alpha (α) and beta (β), subdivided into α1, α2, β1 and β2.
Alpha 1 (α1) are mainly on postsynaptic receptors
(smooth muscle and glands), while α2 have a presynaptic
function on the periphery and postsynaptic action
centrally and in the uterus. There are further subdivisions:
α1a, α1b, α2a, α2b, α2c). Another classification of α2
receptors names them after the chromosomal location of
their genes: α2 c2, α2 c4, α2 c10.

110. Adrenergic Receptors
The extent of whether the effect produced is alpha or beta
depends on distribution of the receptors and also the
affinity of the transmitter for the receptors. Endogenous
noradrenaline has alpha and beta effects whilst
exogenous noradrenaline has higher alpha than beta
(physiological dose versus pharmacological). In
comparison of noradrenaline, adrenaline and isoprenaline
(isoproterenol in USA) the following orders have been
found:

111. Adrenergic Receptors
Potency, alpha receptors: adrenaline> noradrenaline>>
isoprenaline
Beta receptors: isoprenaline> adrenaline>
noradrenaline
Selectivity alpha receptors: noradrenaline> adrenaline>>
isoprenaline
Beta receptors: isoprenaline> adrenaline>
noradrenaline
Isoprenaline is a synthetic agonist.

112. Adrenergic Receptors
α1 and α2 } - Generally excitatory
β1 and β 2 } - Generally inhibitory

113. Adrenergic Receptors
Noradrenaline α + β1
Adrenaline α + β1 β2
Dopamine α1 (High dose) + β1 (High dose)
Isoprenaline β1 + β2
Dobutamine α1 (High Dose) + β1(Low dose)
Phenylphrine α1
Clenbuterol β2

114. CLASSIFICATION OF
SYMPATHOMIMETIC DRUGS
Direct acting.
Natural occurring catecholamines, e.g. Noradrenaline,
adrenaline, dopamine.
Synthetic catecholamines, e.g. Isoproterenol, dobutamine.
Non-catecholamines, e.g. ephedrine, clenbuterol,
phenylephrine.
Indirect acting.
Amphetamine.

115. NORADRENALINE (“LEVOPHED”)
(USA = NOREPINEPHRINE)
Must be given parenterally as it is inactivated in the gut.
Endogenous NA can be released by indirect-acting
sympathomimetics. At pharmacological doses the main effects are
alpha 1 and 2 (alpha 1 > alpha 2), but even physiologically it has
relatively little beta 2 activity.
The main alpha effect is to raise blood pressure (α1). There is also
some β1 action to cause positive inotropism and chronotropism
(unless vagal reflex action negates the chronotropic effect).
Be careful in shock as in hypovolaemic shock it may not cause a
rise in blood pressure and in fact it may decrease perfusion of
potentially hypoxic tissues due to the alpha vasoconstrictor effect.

116. ADRENALINE
(USA = EPINEPHRINE)
Has to be given parenterally. It has alpha and beta effects (beta at
small doses; alpha predominate at larger doses). It is more selective
for receptors at the periphery (alpha 1>2).
Pharmacological actions

117. ADRENALINE
(USA = EPINEPHRINE)
CVS.
Heart. Adrenaline has positive inotropic and chronotropic
effects due to stimulation of beta 1 receptors with an increase in
cardiac output. Also positive dromotropic effect. The overall
effect is pressor (alpha) and depressor (beta).
-Coronary vasodilation
- reflex slowing at high doses (remember – alpha effects
predominate at higher doses)
-increases the irritabibility of the myocardium. Occurs particulary
during anaesthesia with certain agents e.g. halothane, thiopentone.
Blood vessels
-viscerocutaneous vasoconstriction through α1-receptor
stimulation.

118. ADRENALINE
(USA = EPINEPHRINE)
CVS.
-vasodilation of the arterioles of skeletal muscle (β2 effect).
-greater vasoconstriction in the splanchnic area
Spleen – contraction of the splenic capsule via α1 stimulation
(especially in the equine).
Blood pressure – initial rise in both systolic and diastolic
pressures, but later return to normal.

119. ADRENALINE
(USA = EPINEPHRINE)
Respiratory system – potent bronchodilator.
Gastrointestinal system. Frequency and amplitude of
peristaltic contractions of GIT is decreased.
Urinary tract. Small doses increase blood flow in the
kidney and therefore also urine production. Larger doses
shut down the capillary bed of the kidney through α1
receptor activation, thereby reducing GFR and urine
production. Relaxation of the bladder.

120. ADRENALINE
(USA = EPINEPHRINE)
Uterus – variable responses of uterine muscle- normally
relaxation.
Eye – mydriatic (α1 receptor effect on radial muscles);
Retraction of nictating membrane via α1 receptors;
Conjuctival and scleral blood vessels are constricted and
a decrease in intra-ocular pressure may occur.
Skin – piloerection; blanching/paling of skin due to
vasoconstriction occurs.

121. ADRENALINE
(USA = EPINEPHRINE)
Skeletal muscle – increased force of contraction.
Metabolic effect. Has an overall calirogenic effect.
Increased glycogenolysis occur in the liver and skeletal
muscle (α and β effects). Fatty acid mobilization is
accelerated resulting in increased lactic acid formation.
Sweat glands. Marked sweating occurs in the horse.

122. ADRENALINE
(USA = EPINEPHRINE)
Clinical uses
1. Combined with local anaesthetics e.g. procaine
usually at concentrations of 1:100,000.
2. Local haemostatic – α1 effect (vasoconstriction)
3. Anaphylactic, anaphylactoid reactions. Due to its
potent bronchodilatory properties (β2 effect). Not to
be used in asthma cases due to arrhythmogenecity.
4. Cardiac arrest (except if halothane is in use).
5. Congestion of the nasal mucosa.

123. XYLAZINE
(“ROMPUN”; “ANASED”)
Has peripheral and central alpha 1 and alpha 2 effects.
The cardiodepressant action is via post-synaptic α2
receptors in the CNS (aided by reflex bradycadia). It also
has some actions on H2 (histamine) receptors, opioid,
5HT receptors and dopaminergic and cholinergic
receptors. The sedation (see CNS notes) is caused by α2
agonism in the CNS. It is reversible by the experimental
drug, yohimbine.
Used in veterinary medicine as a sedative, an anaesthetic
premedicant, and as a joint drug in combinations with
anaesthetics. In small animals (cats and dogs) it causes
vomiting in a proportion of individuals.

124. DETOMIDINE
Similar to xylazine with action on α2 receptors. Used as a
sedative.
MEDETOMIDINE
Similar to xylazine with action on α2 receptors. Used as a
sedative.

125. DOPAMINE
Has alpha, β1 and β2 effects (due to indirect NA release)
as well as acting on dopamine receptors. The alpha effect
occurs mainly at high doses, whilst beta vasodilatation
occurs at normal doses. Inactive by mouth. Passes poorly
to the CNS, therefore L-Dopa is used clinically in
humans with Parkinson’s disease.
The dopaminergic effect , observed at very low doses,
consists of vasodilatation of renal and splanchnic
vasculature. This effect is blocked by Haloperidol, a
butyrophenone tranquilizer.
It has been used to limited extent in dogs.

126. DOPAMINE
USES.
Congestive heart failure; renal shut down; shock to
increase perfusion of tissues; Parkinsonism in man (L-
Dopa).

127. SALBUTAMOL (“Ventolin”)
Beta 2 agonist, which is long-acting as it is resistant to
MAO and COMT. Being specific to beta 2 receptors it
has little cardiac effect. Used in man for
bronchodilatation in asthma – comes in inhalers or as
tablets or syrup. Has been used in veterinary medicine for
uterine relaxation and in navicular disease.

128. CLENBUTEROL (“Planipart”)
Beta 2 agonist. Same uses as for salbutamol but with the
added benefit of veterinary licence. Introduced as a
control method for the timing of parturition, but it is
difficult to use. Used for uterine relaxations, i.e. in
operations and during handling of the uterus. Longer
acting than isoxsuprine (1-2 hours versus 10-25 minutes).

129. ISOXSUPRINE (“Circulon”)
Beta 2 agonist. Has been used for uterine relaxation, but
is only licensed for improving circulation in the hoof in
navicular disease in horses (hence its tradename).
DOBUTAMINE
A beta 1 agonist with some beta 2 and a few alpha 1
effects. It is mainly inotropic and increases cardiac
output.

130. ISOXSUPRINE (“Circulon”)
Beta 2 agonist. Has been used for uterine relaxation, but
is only licensed for improving circulation in the hoof in
navicular disease in horses (hence its tradename).
DOBUTAMINE
A beta 1 agonist with some beta 2 and a few alpha 1
effects. It is mainly inotropic and increases cardiac
output.
FENOTEROL
Used in human medicine for asthma.

131. EPHEDRINE
It is an alkaloid obtained from several plants of the genus
Ephedra but is also produced synthetically. Similar to
noadrenaline but has a slower onset of action and
duration of effect (7-10 times).
Primarily an α1-agonist but also has some β1 action. Has a
CNS stimulant effect as a result of corticomedullary and
respiratory centre stimulation. Tachyphylaxis results after
prolonged use. Used mainly as a decongestant. Used in
hypotension in humans, in asthma, and for overdosage of
phenothiazine tranquilizers in humans.

132. Uses of Ephedrine in dogs
Urinary incontinence caused by urethral
sphincter mechanism incompetence in
ovariohysterectomized (USMI) female dogs.
Treatment of hypotension during
anesthesia.
Nasal congestion.
 N.B. Polyuria should be excluded before treatment is
given for urinary incontinence, as many conditions
that cause polyuria would be exacerbated by
ephedrine.

133. METHOXAMINE (“Vasoxyl”)
Almost exclusively α1 agonist. Used as a pressure agent
and as a nasal decongestant.
PHENYLEPHRINE (“Neosynephrine”)
Similar to methoxamine. Used in human ophthalmology
to cause papillary dilatation. Also a decongestant.
METARAMINOL
Has direct alpha effects and mixed indirect alpha and beta
due to NA release. Resistant to MAO and COMT. A
powerful vasoconstrictor.

134. AMPHETAMINE
Dexamphetamine is lipophilic and passes to the CNS. It
is a CNS stimulant. L-amphetamine is a peripheral
indirect sympathomimetic.

135. ISOPRENALINE
(USA=ISOPROTERENOL)
A beta 1 and beta 2 agonist. It causes decrease in
peripheral resistance, is inotropic and chronotropic (with
additional reflex tachycardia due to fall in blood
pressure). Used in man, by the systemic route as when
given orally it is liable to COMT in the GIT mucosa and
liver. It is resistant to MAO and does not undergo uptake
1.
USES: Inotropism; bronchodilatation (safer modern
drugs available); with other agents in shock for its
vasodilatory effect.

136. CLONIDINE
Alpha 2 agonist used in human medicine.
OTHERS:
• Prenalterol – mainly beta 1 effects but some beta 2.
• Orciprenaline (Metaproterenol in USA) –
beta 2 agonist
• Terbutaline – beta 2;
• Ritodrine – beta 2;
• Albuterol – beta 2;
• Pirbuterol – beta 2.

137. SUMMARY OF ADRENERGIC
AGONISTS BY RECEPTOR TYPE
Alpha 1: Phenylephrine, Methoxamine
Mainly alpha 1, some beta:
Noradrenaline, Metaraminol
Mixed alpha 1 and beta: Dopamine, adrenaline,
amphetamine, ephedrine, phenylpropanoamine
Mainly beta, some alpha 1: Isoprenaline, isoxsuprine,
dobutamine, mephentermine, nylidrin.

138. SUMMARY OF ADRENERGIC
AGONISTS BY RECEPTOR TYPE
Alpha 2: Clonidine, xylazine, detomidine,
medetomidine, alpha methyl noradrenaline.
Beta 1: Prenalterol
Beta 2: Salbutamol, clenbuterol, albuterol,
orciprenaline, terbutaline, fenoterol, ritodrine,
isoetharine, quinterenol, pirbuterol.

139. ADRENERGIC BLOCKADE
There are four sites at which to block the adrenergic
(sympathomimetic) system. Drugs which do this
specifically are called sympatholytics.
1. Decrease sympathetic tone via the CNS.
2. Ganglionic blockade (not specific)
3. Decrease transmitter (neurone blockade)
4. Adrenoceptor blockade

140. ADRENERGIC BLOCKADE
There are four sites at which to block the adrenergic
(sympathomimetic) system. Drugs which do this
specifically are called sympatholytics.
1. Decrease sympathetic tone via the CNS.
2. Ganglionic blockade (not specific)
3. Decrease transmitter (neurone blockade)
4. Adrenoceptor blockade
Very few of these drugs are used routinely in veterinary
practice. The ergot derivatives are used for their direct
smooth muscle actions rather than alpha blockade. They
are used extensively in human cardiovascular medicine.

141. Alpha receptor blockers
PHENTOLAMINE (“REGITINE”)
An early alpha 1 & 2 antagonist and also smooth muscle
relaxant. Causes lowered blood pressure. A short acting
drug (α1>a2). Noradrenaline increases due to α2
inhibition of negative feedback. Therefore, beta 1 effects
occur such as increased heart rate.

142. Alpha receptor blockers
PHENOXYBENZAMINE
Also an early alpha 1 & 2 blocking agent. No direct
smooth muscle effect. Long-acting due to formation of a
covalent bond at the receptor site. Has some effect on
histaminic, muscarinic and tryptaminergic receptors.
Acts on peripheral and central alpha receptors:
peripherally α1 > α2; Centrally α1 only.
Decreases blood pressure and increases cardiac output
(negative feedback inhibited → NA release).
Uses in humans: To correct anaesthetic arrhythmias.
For urinary retention as it relaxes the bladder sphincter.

143. Alpha receptor blockers
ERGOT ALKALOIDS
There are two main groups, amine and peptide: ergometrine
(=ergonovine, used for the myometrium), LSD and methysergide
(a sedative) are amines and dihydroergotamine and bromocryptine
are peptide derivatives.
These drugs have several effects:
1. Smooth muscle stimulation (causing vasoconstriction and
eventual gangrene of the extremities – seen in rye bread
poisoning in humans. This effect is used to stimulate uterine
contraction.
2. Hallucinations – LSD is Lysergic acid diethylamide.
3. Block 5HT receptors.
4. Alpha blockade (after initial agonist effect).
Veterinary Use: As uterine stimulation at parturition and help to
stem uterine haemorrhage.

144. Alpha receptor blockers
ERGOT ALKALOIDS
BROMOCRYPTINE
-Is used for its agonist activity on dopamine receptors, but it still
has α-antagonist activity.

145. Alpha receptor blockers
PHENOTHIAZINES
These tranquilizers have an alpha blocking side effect.
(see CNS notes)
YOHIMBINE (“REVERZINE”; “YOBINE”)
Peripheral and central α2 blocker. Used to reverse
ketamine and xylazine anaesthesia/sedation (see CNS
notes). It is related to reserpine.
ATIPAMEZOLE (“ANTISEDAN”)
An imidazole derivative which is specific and selective
for α2 receptors. Used to reverse medetomidine sedation.

146. Alpha receptor blockers
IDAZOXAN
Has been used experimentally to reverse xylazine in
calves. It may have greater selectivity for α2 receptors
than yohimbine. It has histaminergic and cholinergic
effects. It is an imidazoline.
PRAZOSIN (“MINIPRESS”)
Peripheral α1 antagonist. Dilates arterioles and decreases
peripheral resistance.
LABETALOL
Has both α and β blocking activity.

147. Beta receptor blockers
PROPRANOLOL (“Inderal”)
One of the early beta receptor blocking agents. Blocks β1
and β2 with no agonism. It is a powerful local anaesthetic
although it is not used as such. The L(-) form is the beta
blocker, the racemic mixture (DL or +/-) is used as an
anti-arrhythmic agent.
It causes negative inotropism, causes hypotension and
decreased cardiac output. There is some increase in
peripheral resistance. Also bronchoconstriction,
inhibition of glycolysis. Decrease in renin secretion.
General side-effects of beta blockade: postural
hypotension, non-ejaculation, nasal congestion.
Used in man for angina, and to treat arrhythmias.

148. Beta receptor blockers
CARAZOLOL (“SUACRON”)
Mixed β-blocker used to prevent tachycardia in pigs
under stress e.g. transport to the abattoir, boars during
mating and sows at partus. Has negative inotropic,
chronotropic, and dromotropic effects also reduces blood
pressure caused by the cardiosympathetic effect.
METOPROLOL
Beta 1 antagonist. Effects as for propranolol but no
bronchoconstriction.
LABETALOL
Both an alpha and beta blocker.