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.
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
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
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
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
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
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.
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).
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).
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
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