drugs affecting the parasympathetic and somatic nervous system

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Drugs affecting the parasympathetic and somatic nervous system

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Drugs affecting the parasympathetic and somatic nervous system. Nervous System. CNS. PNS. Brain Spinal Cord. Autonomic NS. Somatic NS. Sympathetic. Parasympathetic. Drugs and Cholinergic Synapses. PRESYNAPTIC. POSTSYNAPTIC. Choline uptake and Ach synthesis. Metabolic Removal. - PowerPoint PPT Presentation

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Page 1: Drugs affecting the  parasympathetic and somatic nervous system

Drugs affecting the parasympathetic

and somatic nervous system

Page 2: Drugs affecting the  parasympathetic and somatic nervous system

BrainSpinal Cord

CNS

SomaticNS

PNS

Nervous System

Autonomic NS

Sympathetic

Parasympathetic

Page 3: Drugs affecting the  parasympathetic and somatic nervous system
Page 4: Drugs affecting the  parasympathetic and somatic nervous system
Page 5: Drugs affecting the  parasympathetic and somatic nervous system
Page 6: Drugs affecting the  parasympathetic and somatic nervous system

Drugs and Cholinergic Synapses

Page 7: Drugs affecting the  parasympathetic and somatic nervous system

PRESYNAPTICPRESYNAPTIC POSTSYNAPTICPOSTSYNAPTIC

ACh

Choline uptake and Ach synthesis

Choline uptake and Ach synthesis

Metabolic RemovalMetabolic Removal

ActionActionS & S

M / N

ReceptorBinding

ReceptorBinding

AChE

Choline

ACh

Page 8: Drugs affecting the  parasympathetic and somatic nervous system

PRESYNAPTICPRESYNAPTIC POSTSYNAPTICPOSTSYNAPTIC

ACh

Choline uptake Choline uptake and Ach synthesisand Ach synthesis

Choline uptake Choline uptake and Ach synthesisand Ach synthesis

Metabolic RemovalMetabolic Removal

ActionActionS & S

M / N

ReceptorBinding

ReceptorBinding

AChE

Choline

ACh

Page 9: Drugs affecting the  parasympathetic and somatic nervous system

PRESYNAPTICPRESYNAPTIC POSTSYNAPTICPOSTSYNAPTIC

ACh

Choline uptake and Ach synthesis

Choline uptake and Ach synthesis

Metabolic RemovalMetabolic Removal

ActionActionS & S

M / N

ReceptorReceptorBindingBinding

ReceptorReceptorBindingBinding

AChE

Choline

ACh

Page 10: Drugs affecting the  parasympathetic and somatic nervous system

PRESYNAPTICPRESYNAPTIC POSTSYNAPTICPOSTSYNAPTIC

ACh

Choline uptake and Ach synthesis

Choline uptake and Ach synthesis

Metabolic RemovalMetabolic RemovalMetabolic RemovalMetabolic Removal

ActionActionS & S

M / N

ReceptorBinding

ReceptorBinding

AChE

Choline

ACh

Page 11: Drugs affecting the  parasympathetic and somatic nervous system
Page 12: Drugs affecting the  parasympathetic and somatic nervous system

PRESYNAPTICPRESYNAPTIC POSTSYNAPTICPOSTSYNAPTIC

ACh

Choline uptake and Ach synthesis

Choline uptake and Ach synthesis

Metabolic RemovalMetabolic Removal

ActionActionS & S

M / N

ReceptorBinding

ReceptorBinding

AChE

Choline

ACh

Page 13: Drugs affecting the  parasympathetic and somatic nervous system

Cholinomimetic Drugs

Direct Acting Indirect Acting

Receptor AgonistsReceptor Agonists Cholinesterase InhibitorsCholinesterase Inhibitors

● choline esters

● alkaloids

● carbamates

● organophosphates

Page 14: Drugs affecting the  parasympathetic and somatic nervous system

ACh

muscarinicnicotinic(M)(N)

Cholinergic Receptors

Page 15: Drugs affecting the  parasympathetic and somatic nervous system

M1: NEURONAL CNS AND ANS M1: NEURONAL CNS AND ANS PRESYNAPTICPRESYNAPTIC

M2: CARDIACM2: CARDIAC

M3: SMOOTH MUSCLE AND GLANDULARM3: SMOOTH MUSCLE AND GLANDULAR

M3: VASCULAR ENDOTHELIUM M3: VASCULAR ENDOTHELIUM (NON-INNERVATED)(NON-INNERVATED)

MUSCARINIC RECEPTOR SUBTYPESMUSCARINIC RECEPTOR SUBTYPES

Page 16: Drugs affecting the  parasympathetic and somatic nervous system

CNS

AChNEN

1

2

1

N

ACh

MACh

C

T

L

SACh

NESG

AChN

ACh

SMN

Muscarinic Agonists/Antagonists

M

Page 17: Drugs affecting the  parasympathetic and somatic nervous system

AChNEN

1

2

1

N

ACh

MACh

CNS

C

T

L

SACh

NESG

AChN

ACh

SMN

Nicotinic Agonists/Antagonists

M

Page 18: Drugs affecting the  parasympathetic and somatic nervous system

SITE EFFECT

EFFECTS OF STIMULATING MUSCARINIC RECEPTORS (SLUDE)

BRONCHOSPASM

BRADYCARDIA

VASODILATION

MIOSIS

INCREASED URINATION

INCREASED GI MOTILITY

INCREASED SALIVATION

INCREASED TEARSLACRIMAL GLANDS

SALIVARY GLANDS

GI TRACT

BLADDER

IRIS

AIRWAYS

VASCULATURE

HEART

SWEAT GLANDS INCREASED SWEATNG

Page 19: Drugs affecting the  parasympathetic and somatic nervous system

MUSCARINIC AGONISTS MUSCARINIC AGONISTS MUSCARINIC AGONISTS MUSCARINIC AGONISTS

AChACh - - no clinical useno clinical use AChACh - - no clinical useno clinical use

Choline EstersCholine Esters

carbacholcarbachol – muscarinic and nicotinic agonist – muscarinic and nicotinic agonist

bethanecholbethanechol – muscarinic agonist– muscarinic agonist

• • used to prevent urinary retentionused to prevent urinary retention

• • effects mostly on GI and urinary system effects mostly on GI and urinary system when administered p.o. or s.c.when administered p.o. or s.c.

• • used to produce miosis during ocular surgeryused to produce miosis during ocular surgery

•• adverse effects – overstimulation of adverse effects – overstimulation of muscarinic receptorsmuscarinic receptors

Page 20: Drugs affecting the  parasympathetic and somatic nervous system

MUSCARINIC AGONISTS: MUSCARINIC AGONISTS: MUSCARINIC AGONISTS: MUSCARINIC AGONISTS:

AlkaloidsAlkaloids AlkaloidsAlkaloids

•• No nicotinic effectsNo nicotinic effects

•• Somewhat selective for salivary glandsSomewhat selective for salivary glands

• • Orally for the treatment of xerostomiaOrally for the treatment of xerostomia

•• Used topically to treat glaucomaUsed topically to treat glaucoma

Adverse Effects:Adverse Effects: ‘‘over stimulation’ of muscarinic receptorsover stimulation’ of muscarinic receptors

pilocarpinepilocarpine – muscarinic agonist – muscarinic agonist

• • Used for Sjorgren’s SyndromeUsed for Sjorgren’s Syndrome

Page 21: Drugs affecting the  parasympathetic and somatic nervous system

GlaucomaGlaucoma

Chronic open-angle glaucoma (most common): The drainage angle of the eye becomes less efficient with time causing inefficient drainage of aqueous humour and increased pressure within the eye. Gradually produces optic nerve damage.

Closed (or narrow)-angle glaucoma: The drainage angle of the eye becomes physically blocked by a narrow angle, preventing drainage of aqueous humour slowly or suddenly.

Page 22: Drugs affecting the  parasympathetic and somatic nervous system

Treatment – Increase outflow of aqueous humour

• • mitotic agents (parasympathomimetics; e.g. pilocarpine)mitotic agents (parasympathomimetics; e.g. pilocarpine)

Management of Glaucoma:Lower intraocular pressureManagement of Glaucoma:Lower intraocular pressure

• • Cholinesterase Inhibitors (physostigmine)Cholinesterase Inhibitors (physostigmine)

Treatment – Decrease ciliary body production of aqueous humour

• • Carbonic anydrase inhibitors; e.g. acetazolamide)Carbonic anydrase inhibitors; e.g. acetazolamide)

• • Other: prostaglandin analogs (latanoprost), alpha-2 Other: prostaglandin analogs (latanoprost), alpha-2 agonists (brimonidine)agonists (brimonidine)

• • Topical beta-blockers (timolol, levobunolol)Topical beta-blockers (timolol, levobunolol)

Page 23: Drugs affecting the  parasympathetic and somatic nervous system

Antimuscarinic Drugs

● atropine

● ipratropium (quaternary)

● scopolamine

● glycopyrrolate

● oxybutynin

Natural Alkaloids

Semi-synthetic Derivatives

● tiotropium (quaternary; 24h duration)

Page 24: Drugs affecting the  parasympathetic and somatic nervous system

AChNEN

1

2

1

N

ACh

MACh

CNS

C

T

L

SACh

NESG

AChM

N

ACh

SMN

Muscarinic Antagonists

XX

XX

Page 25: Drugs affecting the  parasympathetic and somatic nervous system

ANTIMUSCARINIC AGENTSANTIMUSCARINIC AGENTS

BELLADONNA BELLADONNA ALKALOIDSALKALOIDS

• • ATROPINEATROPINE

• • SCOPOLAMINESCOPOLAMINE

TX: USED WHEN A REDUCTION OF PARASYMATHETIC TONE IS DESIRABLETX: USED WHEN A REDUCTION OF PARASYMATHETIC TONE IS DESIRABLE

• • Preop to reduce salivations / bronchial secretionsPreop to reduce salivations / bronchial secretions

• • Reduce intestinal motilityReduce intestinal motility

• • Treat overactive bladderTreat overactive bladder

• • Ophthalmological examinationsOphthalmological examinations

• • Prevent motion sicknessPrevent motion sickness

• • Treat asthmaTreat asthma

• • Treat AChE inhibitor poisoningTreat AChE inhibitor poisoning

• • Prevent vagal stimulation during anesthesia and surgeryPrevent vagal stimulation during anesthesia and surgery

Page 26: Drugs affecting the  parasympathetic and somatic nervous system

ATROPINE: OVERVIEW OF TOXIC ACTIONSATROPINE: OVERVIEW OF TOXIC ACTIONS

DRY AS A BONEDRY AS A BONE DRY AS A BONEDRY AS A BONE

HOT AS A PISTOLHOT AS A PISTOL HOT AS A PISTOLHOT AS A PISTOL

REDRED AS A BEETAS A BEET REDRED AS A BEETAS A BEET

BLIND AS A BATBLIND AS A BAT BLIND AS A BATBLIND AS A BAT

MAD AS A HATTERMAD AS A HATTER MAD AS A HATTERMAD AS A HATTER

Page 27: Drugs affecting the  parasympathetic and somatic nervous system

ATROPINE: OVERVIEW OF ACTIONS

0.5 mg: Paradoxical bradycardia; Some dryness of mouth; Inhibition of sweating

1.0 mg: Increased xerostomia; Thirst; Mild tachycardia; Mild mydriasis

2.0 mg: Marked tachycardia; Xerostomia; Pupilary dilation; Some blurring of vision and decrease in gastric acid secretion

Page 28: Drugs affecting the  parasympathetic and somatic nervous system

ATROPINE: OVERVIEW OF ACTIONS

5.0 mg: Difficulty in speaking, swallowing and urination; Decreased intestinal motility; Restlessness; Headache; Dry hot skin

10 mg & UP: Rapid and weak pulse; Fixed, maximally dilated pupils; Blurred vision; Ataxia; Excitement; Hallucinations and delirium; Coma.

Page 29: Drugs affecting the  parasympathetic and somatic nervous system

ATROPINE OVERDOSE: ANTIDOTE - Physostigmine

ATROPINE OVERDOSE: ANTIDOTE - Physostigmine

ACh ActionActionS & S

M Atro

pine

Atropin

e

AChE

Choline

ACh

Page 30: Drugs affecting the  parasympathetic and somatic nervous system

ATROPINE OVERDOSE: ANTIDOTE - Physostigmine

ATROPINE OVERDOSE: ANTIDOTE - Physostigmine

ACh ActionActionS & S

M

Atropin

e

Atropin

e

AChE

Choline

ACh

Physostigmine

X

Page 31: Drugs affecting the  parasympathetic and somatic nervous system

CHOLINESTERASE (AChE) CHOLINESTERASE (AChE) INHIBITORSINHIBITORS

AGENTS USED TO ENHANCE TRANSMISSIONAGENTS USED TO ENHANCE TRANSMISSION AT CHOLINERGIC JUNCTIONSAT CHOLINERGIC JUNCTIONS

•• Short-acting (noncovalent inhibitors)

•• Medium-duration (‘reversible’ carbamate inhibitors)

•• Irreversible (organophosphates)

Page 32: Drugs affecting the  parasympathetic and somatic nervous system

AChNEN

1

2

1

N

ACh

MACh

CNS

C

T

L

SACh

NESG

AChM

N

ACh

SMN

CholinesteraseInhibitors

Page 33: Drugs affecting the  parasympathetic and somatic nervous system

Cholinesterase Inhibitors - ActionCholinesterase Inhibitors - Action

ACh

Ach - normally removed from synapse via AChEAch - normally removed from synapse via AChE

ActionActionS & S

M / NM / N

ReceptorBinding

ReceptorBinding

AChEAChEXAChE Inhibitor

ACh

Page 34: Drugs affecting the  parasympathetic and somatic nervous system

- DRUG OF CHOICE TO TREAT POISONING - DRUG OF CHOICE TO TREAT POISONING WITH ATROPINIC AGENTSWITH ATROPINIC AGENTS

• • PHYSOSTIGMINEPHYSOSTIGMINE

Cholinesterase Inhibitors (reversible)

- READILY PENETRATES CNS- READILY PENETRATES CNS

• • NEOSTIGMINE and PYRIDOSTIGMINENEOSTIGMINE and PYRIDOSTIGMINE

- DO - DO NOTNOT PENETRATE CNS PENETRATE CNS

- USED TO TREAT MYASTHENIA GRAVIS- USED TO TREAT MYASTHENIA GRAVIS

Carbamates; BIND TOCarbamates; BIND TO THE ESTERATIC SITE OF AChE THE ESTERATIC SITE OF AChE

- NEOSTIGMINE USED AS ANTIDOTE FOR - NEOSTIGMINE USED AS ANTIDOTE FOR OVERDOSE OF “CURARE-LIKE” DRUGSOVERDOSE OF “CURARE-LIKE” DRUGS

- USED TO TREAT ALZHEIMER’S AND DEMENTIA- USED TO TREAT ALZHEIMER’S AND DEMENTIA

- USED TO TREAT GLAUCOMA- USED TO TREAT GLAUCOMA

Page 35: Drugs affecting the  parasympathetic and somatic nervous system

- Diagnostic agent used to test for - Diagnostic agent used to test for myasthenia gravismyasthenia gravis

• • EDROPHONIUMEDROPHONIUM

Cholinesterase Inhibitors

- Very short acting- Very short acting

Page 36: Drugs affecting the  parasympathetic and somatic nervous system

CHOLINESTERASE INHIBITORS: ACUTE TOXICITYCHOLINESTERASE INHIBITORS: ACUTE TOXICITY

SYMPTOMS DUE TO EXCESS OF SYMPTOMS DUE TO EXCESS OF ACh AT SYNAPSEACh AT SYNAPSE

• • MUSCARINIC RECEPTORSMUSCARINIC RECEPTORS

- SLUDE- SLUDE

• • NICOTINIC RECEPTORSNICOTINIC RECEPTORS

- FASCICULATION, MUSCLE CRAMPS, - FASCICULATION, MUSCLE CRAMPS, WEAKNESS, RESPIRATORY PARALYSISWEAKNESS, RESPIRATORY PARALYSIS

Page 37: Drugs affecting the  parasympathetic and somatic nervous system

Cholinesterase Inhibitors - Action and ReversalCholinesterase Inhibitors - Action and Reversal

ACh

Ach - normally removed from synapse via AChEAch - normally removed from synapse via AChE

ActionActionM / NM / N

ReceptorBinding

ReceptorBinding

AChEAChEXAChE Inhibitor

ACh

Page 38: Drugs affecting the  parasympathetic and somatic nervous system

Antidote for Overdose of Carbamate Cholinesterase Inhibitors: AtropineAntidote for Overdose of Carbamate Cholinesterase Inhibitors: Atropine

ACh ActionActionM / NM / N

AChEAChEXAChE Inhibitor

Atropi

ne

ACh

Page 39: Drugs affecting the  parasympathetic and somatic nervous system

• ORGANOPHOSPHATES: ORGANOPHOSPHATES: IRREVERSIBLY PHOSPHORYLATE IRREVERSIBLY PHOSPHORYLATE

SERINE HYDROXYL AT ACTIVE SITE OF AChESERINE HYDROXYL AT ACTIVE SITE OF AChE

Cholinesterase Inhibitors

• • Malathion, Parathion, DiazinonMalathion, Parathion, Diazinon

INSECTICIDESINSECTICIDES

NERVE GASESNERVE GASES

• • Sarin, Soman, TabunSarin, Soman, Tabun

Page 40: Drugs affecting the  parasympathetic and somatic nervous system

Antidote for Overdose of Organophosphate Cholinesterase Inhibitors: 2-Pralidoxime (2-PAM)

Page 41: Drugs affecting the  parasympathetic and somatic nervous system

GANGLIONIC BLOCKING AGENTSGANGLIONIC BLOCKING AGENTS

• • TRIMETHAPHANTRIMETHAPHAN

• • HEXAMETHONIUMHEXAMETHONIUM

- Used to produce controlled hypotension- Used to produce controlled hypotension

GANGLIONIC STIMULATING AGENTSGANGLIONIC STIMULATING AGENTS

• • NICOTINENICOTINE

Page 42: Drugs affecting the  parasympathetic and somatic nervous system

NEUROMUSCULAR (NMJ)NEUROMUSCULAR (NMJ)BLOCKING AGENTSBLOCKING AGENTS

Page 43: Drugs affecting the  parasympathetic and somatic nervous system

AChNEN

1

2

1

N

ACh

MACh

CNS

C

T

L

SACh

NESG

AChM

N

ACh

SMN

NMJ Blocking Agents

Page 44: Drugs affecting the  parasympathetic and somatic nervous system

NMJ BLOCKING AGENTS USED IN SURGERY TO NMJ BLOCKING AGENTS USED IN SURGERY TO PROMOTE SKELETAL MUSCLE RELAXATIONPROMOTE SKELETAL MUSCLE RELAXATION

NMJ Blocking Agents

- Intubation- Intubation

- Maintain controlled ventilation- Maintain controlled ventilation

- Paralysis of skeletal muscle in area - Paralysis of skeletal muscle in area

of surgeryof surgery

Page 45: Drugs affecting the  parasympathetic and somatic nervous system

NMJ BLOCKING DRUGSNMJ BLOCKING DRUGS

DEPOLARIZINGDEPOLARIZING

(non-competative)(non-competative)

•• SUCCINYLCHOLINESUCCINYLCHOLINE

NONDEPOLARIZINGNONDEPOLARIZING(competative)(competative)

• • TUBOCURARINETUBOCURARINE

Long DurationLong Duration

Short DurationShort Duration

• • MIVACURIUMMIVACURIUM

• • PANCURONIUMPANCURONIUM

Intermediate DurationIntermediate Duration

Page 46: Drugs affecting the  parasympathetic and somatic nervous system

Nondepolarizing NMJ Blocking Agents:Mechanism of Action

Nondepolarizing NMJ Blocking Agents:Mechanism of Action

SMparalysis

SMparalysis

NN

AChEAChE

Tubo

cura

rine

ACh SM

ACh

Page 47: Drugs affecting the  parasympathetic and somatic nervous system

Antidote for Overdose of nondepolarizing NMJ Blocking Agents: NeostigmineAntidote for Overdose of nondepolarizing NMJ Blocking Agents: Neostigmine

recovery from

SM paralysis

recovery from

SM paralysis

NN

AChEAChE

Tubocurarine

ACh SM

Neostigmine

ACh

X

Page 48: Drugs affecting the  parasympathetic and somatic nervous system

NN

AChEAChE

Succi

nylc

holin

e

ACh SM

ACh SMparalysis

SMparalysis

Caution: Succinylcholine may produce hyperkalemia

Depolarizing NMJ Blocking Agents:Mechanism of Action

Depolarizing NMJ Blocking Agents:Mechanism of Action

Page 49: Drugs affecting the  parasympathetic and somatic nervous system

Antidote for overdose of Succinylcholine: ‘no pharmacological approach’; ventilationAntidote for overdose of Succinylcholine: ‘no pharmacological approach’; ventilation

NN

AChEAChE

Succi

nylc

holin

e

ACh SM

ACh

butyrlcholinesterase

recovery from

SM paralysis

recovery from

SM paralysis