Physiology of ANS Adrenergic drug Antiadrenergic drug Cholinergic drug Anticholinergic drug

1. Do you have
common-sense?

2. Sujit Karpe
Principal
SOJAR COLLEGE OF PHARMACY,
Khandvi
Autonomic Nervous System

4. Voluntary movements

5. Involuntary movements

6. Involuntary movements

9. Nervous animation

15. Overview of the ANS
 Consists of the sympathetic and parasympathetic nervous
system.
 Drugs that stimulate the sympathetic nervous system are
called adrenergic.
 Adrenergic are also called adrenergic agonists or
Sympathomimetics.
 Drugs that stimulate the parasympathetic nervous system
are called cholinergic
 Cholinergic are also called cholinergic agonists or
parasympathomimetics

16. Adrenergic Receptors
 Adrenergic receptors are the sites where
adrenergic drugs bind and produce their
effects.
 Adrenergic receptors are divided into alpha-
adrenergic and beta-adrenergic receptors
depending on whether they respond to
norepinephrine or epinephrine.
 Both alpha- and beta-adrenergic receptors
have subtypes designated 1 and 2.

17. Alpha Receptors
 Alpha1-adrenergic receptors are located
on the postsynaptic effector cells.
 Alpha2-adrenergic receptors are located
on the presynaptic nerve terminals.

18. Beta Receptors
 Both beta-adrenergic receptors are
located on the postsynaptic effector cells.
 Beta1-adrenergic receptors are primarily
located in the heart.
 Beta2-adrenergic receptors are primarily
located in the smooth muscle of
bronchioles, arterioles, and visceral
organs.

19. Dopaminergic Receptors
 Dopaminergic receptors are only
stimulated by dopamine which causes the
vessels of renal, mesenteric, coronary,
and cerebral arteries to dilate and the flow
of blood to increase.

20. Adrenergic Receptor Specificity
Drug α1 α2 β1 β2
Dopaminergic
Epinephrine
Ephedrine
Norepinephrine
Phenylephrine
Isoproterenol
Dopamine
Dobutamine
terbutaline

23. Adrenergic Drugs
Sympathomimetics/adrenomimetics

24. Classification
A. Catecholamines
Adrenaline
Noradrenaline
Isoprenaline
B. Non catecholamines
Ephedrine
Amphetamine

25. Catecholamine – Adrenaline
Mechanism of action on heart

26. Pharmacological action:
On heart:
heart rate and force of contraction
Positive Inotropic and chronotropic effect
beta1 receptor action
On blood vessel:
At low dose
Catecholamine - Adrenaline

27. At high dose
Dale’s vasomotor reversal

28. On Smooth muscle:
Relaxation of bronchial smooth muscle
Relaxation of gut and reduces motility
Relaxation of uterine smooth muscle
On Eye ball:
Mydriasis
On respiration:
Weak stimulation

29. Metabolic effect:
Oxygen consumption
Sugar level by glycogenolysis

31. Pharmacokinetic parameter
Given by IV route
metabolized by MAO and COMT
Oxidized product excreted through urine
Side Effect
Given IV sudden rise in BP
Fear, anxiety, restlessness, headache, tremor, palpitation
Accidental overdose – cardiac arrhythmia, hypertension,
hemorrhage

32. Therapeutic uses:
 Drug of choice in anaphylactic shock (life saving)
 Drug of choice in bronchial asthma
 Life saving in sudden heart block and cardiac arrest
 To stop nasal and gum bleeding topically
 Along with local anesthetics
Contraindications:
Thyrotoxicosis, hypertension, arteriosclerosis, coronary
insufficiency, spinal anesthesia, diabetes.

33. Non catecholamines – Ephedrine
 Alkaloid obtained from genus Ephedra
 Sympathomimetic amine devoid of catechol nucleus
 Indirect acting – releasing nor adrenaline
 Potent CNS stimulant activity
 Produce tachyphylaxis (rapidly diminishing response to successive doses of a drug)
 Tachycardia, premature systole, insomnia and emotional
disturbances are common side effect with ephedrine
 used in bronchial asthma, Mydriatics in elderly patient and as a
nasal decongestant.

34. Non catecholamines – Amphetamine
 Indirect acting Sympathomimetic amine devoid of catechol nucleus
 Potent CNS stimulant activity
 Potent anorexient effect (loss of appetite)
 As analeptic to overcome narcolepsy
 As anorexient in management of obesity

35. Adrenergic Blockers
Adrenergic antagonists or sympatholytics,

36. Classification
α- receptor blocker
Phentolamine, Phenoxybenzamine,
Ergot alkaloids
β- receptor blocker
Propranolol, Atenolol, Timolol
Ganglionic blocker
Pentolinium, Mecamylamine

37. α- receptor blocker
 Competitively blocks alpha adrenergic receptor.
 Blocks actions of adrenaline and noradrenaline
 Many drugs interact producing synergistic effects such as
orthostatic hypotension, severe hypotension and vascular
collapse
 Used in management of Pheochromocytoma
 Used in hypertension
 Used in treatment of peripheral vascular diseases

38. β- receptor blocker
 Frequently used
 Lower Blood Pressure
 Negative chronotropes & inotropes
Beta1 Selective Blockade
• atenolol (Tenormin®)
• esmolol (Brevibloc®)
• metoprolol (Lopressor®)
Nonselective
• propranolol (Inderal®)
• labetalol (Normodyne®,
Trandate®)
• sotalol (Betapace®)

39.  Prevent stimulation of the sympathetic nervous system by inhibiting the
action of catecholamines at the beta-adrenergic receptors (beta-
blockers).
 Are selective or nonselective.
 Nonselective beta-blockers affect beta1 receptor sites located mainly in
the heart and beta2 receptor sites located in the bronchi, blood vessels,
and uterus.
β- receptor blocker

40. Pharmacokinetics:
 Absorbed rapidly and are protein-bound; the onset of action is primarily
dose and drug-dependent; distributed widely with the highest
concentrations in the heart, lungs, and liver; metabolized primarily in the
liver; excreted primarily in the urine.
β- receptor blocker

41. Pharmacodynamics:
 Effect adrenergic nerve endings as well as the adrenal medulla.
 Effects on the heart include: decreased peripheral vascular
resistance; decreased blood pressure; decreased force of heart
contractions; decreased oxygen consumption; slowed impulse
conduction; and decreased cardiac output.
 Selective beta1-blockers reduce stimulation of the heart (also called
cardioselective beta-adrenergic blockers).
 Nonselective beta1 and beta2-blockers not only reduce stimulation of
the heart but can also cause the bronchioles of the lungs to constrict.
β- receptor blocker

42. Therapeutic uses:
 Clinical usefulness is based largely upon how they affect the heart.
 Used to treat heart attacks, angina, hypertension, hypertrophic
cardiomyopathy, and supraventricular arrhythmias.
 Also used to treat anxiety, cardiovascular symptoms associated with
thyrotoxicosis, essential tremor, migraine headaches, open-angle
glaucoma, and pheochromocytoma.
Drug interactions/adverse reactions:
 Many causing cardiac and respiratory depression, arrhythmia,
severe bronchospasm, and severe hypotension.
β- receptor blocker

43. β- receptor blocker
Contraindications:
 Congestive heart failure
 Hypotension
 Bronchial asthma
 Diabetes mellitus

44. Ganglionic blocker
 Competitively blocks cholinergic ganglia
 Occupy nicotinic receptor on post synaptic membrane
 Mainly used in treatment of hypertension.

45. Neuromuscular blocking agent /
skeletal muscle relaxant
 Blocks transmission of nerve impulses at skeletal neuromuscular
junction.

46.  Blocks transmission of nerve impulses at skeletal neuromuscular
junction.
 Relaxation of skeletal muscle
 Used as adjuvant to anesthesia to promote skeletal muscle
relaxation during abdominal surgery, orthopedic work, laryngoscopy,
bronchoscopy etc.
 Used in electroconvulsive therapy.
 Used to relieve the spasm of tetanus, athetosis, status epilepticus.
 E.g. – d-tubocurarine, Pancurorium, Gallamine, succinyl choline etc.

47. Myasthenia gravis
• Disease of uncertain
etiology.
• Profound weakness of
skeletal muscle, easy
fatigability.
• Autoimmune disease,
deficiency of postsynaptic
neuromuscular acetyl
choline receptor complex.

48. Myasthenia gravis

49.  MG is rare and only affects 14 to 20 people out of every 100,000.
 MG typically occurs in individuals over the age of 40.
 Diagnosed by administration of edrophonium
 Treated by using Neostigmine, ephedrine sulphate, potassium
chloride, prednisolone.
Myasthenia gravis
Drug
Contraindicated in
Myasthenia gravis

50. Cholinergics
 Drugs that stimulate the parasympathetic
nervous system are called cholinergics.
 Sometimes called cholinergic agonists or
parasympathomimetics, these drugs mimic
the effect of acetylcholine, which is the
neurotransmitter responsible for the
transmission of nerve impulses to effector
cells in the PSNS.

51. Cholinergic Receptors
 The receptors that bind the acetylcholine
and mediate its actions are called
cholinergic receptors.
 These receptors consist of nicotinic
receptors and muscarinic receptors.
 Nicotinic receptors are located in the
ganglia of the PSNS and SNS and are
stimulated by nicotine.

52. Muscarinic Receptors
 Muscarinic receptors are located postsynaptically in the smooth
muscle, cardiac muscle, and glands.
 These receptors are stimulated by muscarine (found in mushrooms).

53. Nicotinic Receptors

54. Cholinergic Drugs
 Cholinergic drugs can be direct-acting
(bind to and activate cholinergic receptors)
or indirect-acting (inhibit cholinesterase
which is the enzyme responsible for
breaking down acetylcholine).

55. Classification
Esters of choline
Acetyl choline, Methacholine, Carbacol, Bethanecol
Cholinomimetic alkaloids
Pilocarpine, Muscarine, Arecholine
Cholinesterase inhibitors/ anticholinesterase
Reversible synthetic – Neostigmine
Reversible Natural – Physostigmine
Irreversible – Organophosporus compounds (OPC)

56. Esters of choline – Acetyl choline
Pharmacological action
A. Muscarinic action
Heart
 Depresses SA node, AV node
 Reduces conductivity, contractility, automaticity
 Stopping of heart
Blood vessel and blood pressure
 Vasodilation
 Decrease in peripheral resistance and output
 hypotension

57. Eye ball
 Contraction of ciliary muscle and
circular fibre
 Reduction in size of pupil – Miosis
 Spasm of accommodation (short site)
 Decreases intra ocular tension (used in treatment of glaucoma)
Smooth muscle
 Increases tone, rhythmic activity of smooth muscle of GI tract
 Increases peristalsis
 Contraction of smooth muscle of gall bladder, urinary bladder
 Relaxation of smooth muscle of trigonal sphincter

58. Exocrine glands and secretions
 Increases gastric, intestinal, pancreatic, bronchial, salivary, lacrimal,
nasopharyngeal secretions
 Enhances sweating
B. Nicotinic actions
 Stimulate adrenal medulla to release adrenaline and noradrenaline
 Induces contraction of skeletal muscles
Salivation
Lacrimation
Urination
Defecation
Gastric motility
Emesis
Cholinergic agents
cause SLUDGE!

59. Therapeutic uses
 Destroyed by pseudo cholinesterase present in blood serum,
intestine, skin and many other tissue
 Also destroyed by true cholinesterase present in nervous tissue,
human placenta and erythrocytes
Hence cannot be used for
any therapeutic purpose

60. Esters of choline – Metha choline
 Parasympathomimetic agent
 Acts only on muscarinic receptors
 Actions similar to acetyl choline
 Resistance to pseudo and true cholinesterase
 Can be given orally but poorly absorbed
 Used to treat paroxysmal atrial tachycardia
 Used to treat glaucoma

61. Esters of choline – Carbacol
 Parasympathomimetic agent
 Potent muscarinic actions
 Actions similar to acetyl choline
 Resistance to pseudo and true cholinesterase
 Used to treat post operative intestinal atony and retention of urine
 Used to treat glaucoma
 Used to treat paroxysmal atrial tachycardia

62. Esters of choline – Bethanecol
 Parasympathomimetic agent
 More selective muscarinic actions on GI tract and urinary bladder
 Has negligible nicotinic action
 Resistance to pseudo and true cholinesterase
 Used to treat post operative urinary retention
 Used to treat abdominal distention
 Used to treat paralytic ileus

63. Cholinomimetic alkaloids – Pilocarpine
 Obtained from leaves of Pilocarpus microphyllus
 Potent stimulant of glandular tissue of salivary gland and sweat
gland
 Has marked diaphoretic effect and produce profuse sweating
 Act as sialagogue and increases salivary secretion
 On eye produces miosis and spasm of accommodation and effect
last for 2-3 days
 Mainly used in treatment of glaucoma

64. Anticholinesterase – Physostigmine
 An alkaloid obtained from dried
ripe seeds of Physostigma
venenosum
 Blocks true and pseudo
cholinesterase
 Rarely used for systemic
purpose
 Used in treatment of glaucoma
 Used in treatment of atropine
poisoning

65. Anticholinesterase – Neostigmine
 Synthetic quaternary ammonium compound
 Blocks both true and pseudo cholinesterase
 On GI tract increases tone, motility of gut and
promotes propulsion of intestinal contents

66. Anticholinesterase – Neostigmine
 Neostigmine improve power of skeletal muscle by:-
i. By its anticholinesterase activity causing greater
accumulation of acetyl choline at motor end plates
ii. By increasing the amount of acetyl choline
released during each nerve impulse
iii. As it structurally resembles acetyl choline it
directly stimulates cholinergic receptor on motor
end plate
 Drug of choice in treatment of Myasthenia gravis

67. OPC poisoning

68. OPC poisoning
Cause:
occupational – person engaged in spraying insecticide
Accidental – by consumption of agricultural products sprayed with insecticide
Suicidal – due to intentional ingestion

69. Symptoms:
Miosis, headache, bronchospasm,
hypotension, respiratory depression,
convulsions, nausea, vomiting,
abdominal cramps
Diagnosis
If administration of 0.6mg of atropine
the symptoms improve, case belongs
to OPC poisoning
OPC poisoning

70. OPC poisoning
Treatment
Symptomatic treatment
 If ingested by oral route, rapid
gastric lavage is advisable
 For removal of secretions and
maintenance of patient’s
airways, place the patient in
prone position
 Clear mouth and pharynx with
finger or suction

71. Treatment
Symptomatic treatment
 If airway obstruction persists,
endotracheal intubation has to be done
 If patient’s body is soiled with
insecticides, remove clothes and
medicated bath is recommended
Drug treatment
 Atropine sulphate – 2- 4 mg initially up
to 50 mg parentally (Selective Antidote)
 Enzyme reactivators – Obidoxime
(250mg), pralidoxime (1 – 2gm IV )

72. Cholinergic Blockers
 Cholinergic blockers, anticholinergics, parasympatholytics, and
antimuscarinic agents are all terms for the class of drugs that block the
actions of acetylcholine in the PSNS.
 Cholinergic blockers allow the SNS to dominate and, therefore, have
many of the same effects as the adrenergic.
 Cholinergic blockers are competitive antagonists that compete with
acetylcholine for binding at the muscarinic receptors of the PSNS,
inhibiting nerve transmission.
 This effect occurs at the neuroeffector junctions of smooth muscle,
cardiac muscle, and exocrine glands.
 Have little effect at the nicotinic receptors.

73. Belladonna Alkaloids - Atropine
 Blocks muscarinic actions of acetylcholine
 Mainly obtained from Atropa belladonna and also from Hyoscymus niger,
Datura stromonium

74. Pharmacological actions:
Exocrine gland and secretions
Reduces all exocrine secretions including lacrimal, salivary, gastric, sweat,
laryngeal, pharyngeal and causes dryness of mouth and intense thirst
GI tract
Reduces tone, motility, peristalsis and cause constipation

75. Urinary tract
Produces reduction in ureteral
peristalsis
Eye ball
Relaxation of circular muscle and
tightening of suspensory ligament
Dilation of pupil Mydriasis
Produce Cycloplegia (long site)
Because of mydriasis and cycloplegia
patient is sensitive to bright light –
Photophobia
Pharmacokinetic effect:
 Well absorbed orally
 Bound to plasma protein
 Eliminated through kidney

76. Therapeutic effect:
 As an anti spasmodic
 As an anti secretary to reduce secretions of peptic ulcer and night sweat
in patient’s with tuberculosis
 As pre anesthetic medication
 In fundoscopic examination of eye
 Along with Neostigmine in treatment of Myasthenia gravis to block the
muscarinic actions of neostigmine
 Drug of choice in treatment of OPC poisoning
 Used in nocturnal enuresis
 In treatment of Parkinsonism
Contraindication:
 Narrow angle glaucoma
 Angina pectoris
 Congestive heart failure
Side effects:
 Dryness of mouth and intense thirst
 Blurring vision
 Urinary retention
 Palpitation, tachycardia
 Constipation
 Hyper pyrexia

77. Belladonna poisoning
Cause
 Overdose during nocturnal enuresis
 Application of belladonna plaster over large surface leads to systemic
absorption
 Ingestion of leave and seeds
Lethal dose
Children: 10 – 20 mg
Adults: 80 – 130 mg
Symptoms
 Dryness of mouth
 Mydriasis/ blurring of vision/ photophobia
 Urinary retention
 Hyper pyrexia
 Mania and delirium

78. Belladonna poisoning
Diagnosis
Add a drop of patient’s urine in cat’s eye, dilation of pupil
Treatment
Symptomatic:
 If poisoning by mouth, gastric lavage is advised
 Keep patient in dark room to alleviate photophobia
 Catheterization is advised as remedy for urinary retention
 Ice cold bag sponging is advised to treat pyrexia
 If respiration is severely hampered, artificial respiration is advised
Drug treatment:
Physostigmine – 1 to 4 mg by slow IV route
Antidote
Physostigmine

79. Atropine substitute used in eye
Atropine is rarely used in eye examination because
 Not specific in action
 Possess long DOA
 May prove to be allergic
Hence atropine substitutes are used
 For selective action
 Shorter DOA
 In case of atropine tolerance
E. g. : -
Homatropine
Eucatropine
Cyclopentolate

80. Spasmolytics - antispasmodics
 Relieve spasm
1. Atropine methonitrate: 0.2 mg to 0.4 mg
2. Methscopolamine bromide : 2mg to 5 mg orally
3. Methantheline : 50 mg – 100mg orally
4. Propanthelline: 30mg – 40 mg orally
5. Dicyclomine: 10 mg/ml

81. Adrenergic
Drugs
Antiadrenergic
Drugs
Cholinergic
Drugs
Anticholinergic
drug
OppositeAction