Cholinergics

Question 1

Acetylcholine

Answer 1

Cholinergic Agonist

Quaternary amine, vulnerable to cholinesterase

Question 2

Methacholine

Answer 2

Direct Muscarinic Agonists
Quaternary amines so do not cross blood brain barrier
Muscarinic actions greater than nicotinic actions. Used mainly for local drug action to avoid cardiovascular effects
Tx: Topical for miosis during ophthalmologic surgery, diagnosis of bronchial hyper reactivity
Adverse: Parasympathetic excess with systemic activity (nausea, diarrhea, mitosis, vision disruption and headaches, urinary urgency, breathing difficulty), diaphoresis (sweating)

Contraindications: Bladder or gastrointestinal obstruction, asthma patients, ulcer patients, coronary artery disease, hyperthyroidism, parkinsonism, seizure disorders

Question 3

Bethanechol

Answer 3

Direct Muscarinic Agonists
Quaternary amines so do not cross blood brain barrier
Inhalation for diagnosis of bronchial airway hyper reactivity
Tx: Urine retention
Adverse: Parasympathetic excess with systemic activity (nausea, diarrhea, mitosis, vision disruption and headaches, urinary urgency, breathing difficulty), diaphoresis (sweating)

Contraindications: Bladder or gastrointestinal obstruction, asthma patients, ulcer patients, coronary artery disease, hyperthyroidism, parkinsonism, seizure disorders

Question 4

Carbachol

Answer 4

Direct Muscarinic Agonists
Quaternary amines so do not cross blood brain barrier.
Topically for treatment of glaucoma and induction of miosis during ophthalmologic surgery.
Tx: glaucoma, primary open angle
Adverse: Parasympathetic excess with systemic activity (nausea, diarrhea, mitosis, vision disruption and headaches, urinary urgency, breathing difficulty), diaphoresis (sweating)

Contraindications: Bladder or gastrointestinal obstruction, asthma patients, ulcer patients, coronary artery disease, hyperthyroidism, parkinsonism, seizure disorders

Question 5

Cevimeline

Answer 5

Direct Muscarinic Agonists
Both are tertiary amines and cross into central nervous system
Enhances lacrimal secretions in Sjögren’s syndrome.
Tx: dry mouth in sjogren’s syndrome,
Adverse: Parasympathetic excess with systemic activity (nausea, diarrhea, mitosis, vision disruption and headaches, urinary urgency, breathing difficulty), diaphoresis (sweating)

Contraindications: Bladder or gastrointestinal obstruction, asthma patients, ulcer patients, coronary artery disease, hyperthyroidism, parkinsonism, seizure disorders

Question 6

Pilocarpine

Answer 6

Direct Muscarinic Agonist
Both are tertiary amines and cross into central nervous system
Enhances lacrimal secretions in xerostomia related to cancer therapy or Sjögren’s syndrome and topically for treatment of glaucoma and induction of mitosis
Tx: Glaucoma, dry mouth in sjogren’s syndrome
Adverse: Parasympathetic excess with systemic activity (nausea, diarrhea, mitosis, vision disruption and headaches, urinary urgency, breathing difficulty), diaphoresis (sweating)

Contraindications: Bladder or gastrointestinal obstruction, asthma patients, ulcer patients, coronary artery disease, hyperthyroidism, parkinsonism, seizure disorders

Question 7

Cholinesterase Inhibitors

Answer 7

Carbamates, Organophosphates, Centrally acting agents
Stimulation of muscarinic response in autonomic effectors
Stimulation, followed by depression or paralysis, of autonomic ganglia (including adrenal medulla) and neuromuscular junction (nicotinic)
Stimulation, and occasional depression, of central nervous system cholinergic receptors

Question 8

Pyridostigmine

Answer 8

Peripherally-Acting Cholinesterase Inhibitors
Carbamate, quaternary amine
Tx: myasthenia gravis treatment, reversal of neuromuscular blockade by non-depolarizing muscle relaxants, glaucoma, atony of GI and bladder

Toxicity: Diarrhea, Urination, Miosis, Bronchoconstriction, Excitation (muscles and central nervous system), Lacrimation, and Salivation/Sweating

Question 9

Physostigmine

Answer 9

Peripherally-Acting Cholinesterase Inhibitors
Carbamate, Tertiary amine - CNS
Tx: myasthenia gravis treatment, reversal of neuromuscular blockade by non-depolarizing muscle relaxants, glaucoma, atony of GI and bladder

Toxicity: Diarrhea, Urination, Miosis, Bronchoconstriction, Excitation (muscles and central nervous system), Lacrimation, and Salivation/Sweating

Question 10

Ambenonium

Answer 10

Peripherally-Acting Cholinesterase Inhibitors
Carbamate, quaternary amine
Tx: myasthenia gravis treatment, reversal of neuromuscular blockade by non-depolarizing muscle relaxants, glaucoma, atony of GI and bladder

Toxicity: Diarrhea, Urination, Miosis, Bronchoconstriction, Excitation (muscles and central nervous system), Lacrimation, and Salivation/Sweating

Question 11

Demecarium

Answer 11

Peripherally-Acting Cholinesterase Inhibitors
Carbamate, quaternary amine
Tx: myasthenia gravis treatment, reversal of neuromuscular blockade by non-depolarizing muscle relaxants, glaucoma, atony of GI and bladder

Toxicity: Diarrhea, Urination, Miosis, Bronchoconstriction, Excitation (muscles and central nervous system), Lacrimation, and Salivation/Sweating

Question 12

Edrophonium

Answer 12

Peripherally-Acting Cholinesterase Inhibitors
Quaternary and highly water soluble
Short duration, rapid renal elimination
Tx: diagnosis of myasthenia gravis and treatment, reversal of neuromuscular blockade by non-depolarizing muscle relaxants

Toxicity: Diarrhea, Urination, Miosis, Bronchoconstriction, Excitation (muscles and central nervous system), Lacrimation, and Salivation/Sweating

Question 13

Neostigmine

Answer 13

Peripherally-Acting Cholinesterase Inhibitors
Carbamate, Quaternary amine
Tx: myasthenia gravis treatment, reversal of neuromuscular blockade by non-depolarizing muscle relaxants, glaucoma, atony of GI and bladder

Toxicity: Diarrhea, Urination, Miosis, Bronchoconstriction, Excitation (muscles and central nervous system), Lacrimation, and Salivation/Sweating

Question 14

Echothiophate

Answer 14

Organophosphates
Treatment of open-angle glaucoma

Related to demyelination and results in flaccid and spastic paralysis. Toxicity independent of cholinesterase inhibitory activity. Recovery expected in only the mildest of cases

Question 15

Parathion, Malathion

Answer 15

Organophosphates
Pro-drug insecticides converted to active paraoxon and malaoxon
Malathion less toxic in mammals as partially detoxify and do not absorb well through skin
Onset begins about two weeks following acute exposure

Related to demyelination and results in flaccid and spastic paralysis. Toxicity independent of cholinesterase inhibitory activity. Recovery expected in only the mildest of cases

Question 16

Soman

Answer 16

Organophosphates
Nerve toxins, agents of chemical warfare

Related to demyelination and results in flaccid and spastic paralysis. Toxicity independent of cholinesterase inhibitory activity. Recovery expected in only the mildest of cases

Question 17

Pralidoxime chloride or 2-PAM

Answer 17

Quaternary compound
Binds to anionic site and promotes dephosphorylation of enzyme - treats cholinesterase overdose
restores cholinesterase activity regeneration must begin within minutes to hours of phosphorylation

Question 18

Donepezil

Answer 18

Centrally-Acting Cholinesterase Inhibitors

Tx: dementia

Question 19

Rivastigmine

Answer 19

Centrally-Acting Cholinesterase Inhibitors

Tx: dementia

Question 20

Galantamine

Answer 20

Centrally-Acting Cholinesterase Inhibitors

Tx: dementia

Question 21

Atropine

Answer 21

Muscarinic Antagonists
Effects = inhibition of sweating, flushing, cycloplegia, mydriasis, decreased salivation, reduced GI secretions & motility, urinary retention, bronchial dilations & decreased secretions, bradycardia (low dose) & tachycardia (high dose), cognitive dysfunction, drowsiness, sedation, ataxia, delirium, hallucinations, coma;

Toxicity = blurred vision, dry mouth and skin, confusion, big pupils (mydriasis), constipation, urinary retention, sedation, mega-ileus, mega-colon, hyperthermia in midgets

Indications: Bradycardia, muscarinic over activation, cycloplegia or mydriasis induction, aspiration prophylaxis
contraindications: glaucoma, prostatic hyperplasia, cardiac disease, infants hyperthermia

Question 22

Scopolamine

Answer 22

Muscarinic Antagonists
Effects = inhibition of sweating, flushing, cycloplegia, mydriasis, decreased salivation, reduced GI secretions & motility, urinary retention, bronchial dilations & decreased secretions, bradycardia (low dose) & tachycardia (high dose), cognitive dysfunction, drowsiness, sedation, ataxia, delirium, hallucinations, coma;

Toxicity = blurred vision, dry mouth and skin, confusion, big pupils (mydriasis), constipation, urinary retention, sedation, mega-ileus, mega-colon, hyperthermia in midgets

Indication: amnesia induction, motion sickness, mania, sedation induction, parkinson’s disease.
contraindications: glaucoma, prostatic hyperplasia, cardiac disease, infants hyperthermia

Question 23

Dicyclomine

Answer 23

Muscarinic Antagonists
Effects = inhibition of sweating, flushing, cycloplegia, mydriasis, decreased salivation, reduced GI secretions & motility, urinary retention, bronchial dilations & decreased secretions, bradycardia (low dose) & tachycardia (high dose), cognitive dysfunction, drowsiness, sedation, ataxia, delirium, hallucinations, coma;

Toxicity = blurred vision, dry mouth and skin, confusion, big pupils (mydriasis), constipation, urinary retention, sedation, mega-ileus, mega-colon, hyperthermia in midgets

Indications: Overactive bladder, urinary incontinence
contraindications: glaucoma, prostatic hyperplasia, cardiac disease, infants hyperthermia

Question 24

Oxybutynin

Answer 24

Muscarinic Antagonists
competitive blockers of acetylcholine binding Effects = inhibition of sweating, flushing, cycloplegia, mydriasis, decreased salivation, reduced GI secretions & motility, urinary retention, bronchial dilations & decreased secretions, bradycardia (low dose) & tachycardia (high dose), cognitive dysfunction, drowsiness, sedation, ataxia, delirium, hallucinations, coma;

Toxicity = blurred vision, dry mouth and skin, confusion, big pupils (mydriasis), constipation, urinary retention, sedation, mega-ileus, mega-colon, hyperthermia in midgets

Treatment: Overactive bladders, neurogenic bladder, urinary urgency
contraindications: glaucoma, prostatic hyperplasia, cardiac disease, infants hyperthermia

Question 25

Darifenacin

Answer 25

Muscarinic Antagonists
competitive blockers of acetylcholine binding Effects = inhibition of sweating, flushing, cycloplegia, mydriasis, decreased salivation, reduced GI secretions & motility, urinary retention, bronchial dilations & decreased secretions, bradycardia (low dose) & tachycardia (high dose), cognitive dysfunction, drowsiness, sedation, ataxia, delirium, hallucinations, coma;

Toxicity = blurred vision, dry mouth and skin, confusion, big pupils (mydriasis), constipation, urinary retention, sedation, mega-ileus, mega-colon, hyperthermia in midgets

Indications: Overactive bladder, urinary incontinence
contraindications: glaucoma, prostatic hyperplasia, cardiac disease, infants hyperthermia

Question 26

Tolterodine

Answer 26

Muscarinic Antagonists
competitive blockers of acetylcholine binding Effects = inhibition of sweating, flushing, cycloplegia, mydriasis, decreased salivation, reduced GI secretions & motility, urinary retention, bronchial dilations & decreased secretions, bradycardia (low dose) & tachycardia (high dose), cognitive dysfunction, drowsiness, sedation, ataxia, delirium, hallucinations, coma;

Toxicity = blurred vision, dry mouth and skin, confusion, big pupils (mydriasis), constipation, urinary retention, sedation, mega-ileus, mega-colon, hyperthermia in midgets

Indications: Overactive bladder, urinary incontinence

contraindications: glaucoma, prostatic hyperplasia, cardiac disease, infants hyperthermia

Question 27

Nicotine

Answer 27

Nicotinic Agonist
activates adrenal release of catecholamines, increase HR, force of contraction, CO & BP (there are no nicotinic receptors on the heart); increased GI tone & motility, nausea, vomiting, & diarrhea; CNS dose dependent (stimulation, seizures, depression)

Question 28

Varenicline

Answer 28

Nicotinic Agonist - partial agonist
activates adrenal release of catecholamines, increase HR, force of contraction, CO & BP (there are no nicotinic receptors on the heart); increased GI tone & motility, nausea, vomiting, & diarrhea; CNS dose dependent (stimulation, seizures, depression)
Used for smokers
Adverse: negative mood and behavioral changes

Question 29

Succinylcholine

Answer 29

Depolarizing neuromuscular blockers
Overstimulates neuromuscular junction first by depolarization block and then desensitization (inactivating channel)
Cholinesterase inhibitors will not reverse a depolarizing blocker but may intensify the blockade
inactivated by pseudocholinesterase very short duration of action.
Causes short lived flaccid paralysis for quick procedures - children are very sensitive.
Adverse effects: myoglobinuria and postoperative pain, hyperkalemia, prolonged contraction in patients with myotonia, malignant hyperthermia.

Question 30

Atracurium

Answer 30

Non-depolarizing Neuromuscular Blockers
At low doses competitive reversible blockers of neuromuscular junction causes brief progressive flaccid paralysis Order: head and neck –> limb muscles –> muscles of respiration.
At higher doses, block the ion channel at the neuromuscular end plate to further weaken. muscular activity.

All used intravenously, actions are terminated by redistribution from site of blockade
Neuromuscular blockers are not anesthetics.

Question 31

Cisatracurium

Answer 31

Non-depolarizing Neuromuscular Blockers
long duration of action, - doesn’t require dosage reduction in renal failure patients.

At low doses competitive reversible blockers of neuromuscular junction causes brief progressive flaccid paralysis Order: head and neck –> limb muscles –> muscles of respiration.
At higher doses, block the ion channel at the neuromuscular end plate to further weaken. muscular activity.

All used intravenously, actions are terminated by redistribution from site of blockade

Question 32

Pancuronium

Answer 32

Non-depolarizing Neuromuscular Blockers
has vagolytic activity that can increase heart rate
At low doses competitive reversible blockers of neuromuscular junction causes brief progressive flaccid paralysis Order: head and neck –> limb muscles –> muscles of respiration.
At higher doses, block the ion channel at the neuromuscular end plate to further weaken. muscular activity.

All used intravenously, actions are terminated by redistribution from site of blockade

Question 33

Roburonium

Answer 33

Non-depolarizing Neuromuscular Blockers
Very fast onset of action useful for intubation of patients with gastric contents

At low doses competitive reversible blockers of neuromuscular junction causes brief progressive flaccid paralysis Order: head and neck –> limb muscles –> muscles of respiration.
At higher doses, block the ion channel at the neuromuscular end plate to further weaken. muscular activity.

All used intravenously, actions are terminated by redistribution from site of blockade

Question 34

Tubocurarine

Answer 34

Non-depolarizing Neuromuscular Blockers
Prototype drug obtained from snakes, triggers histamine release lowering blood pressure.

At low doses competitive reversible blockers of neuromuscular junction causes brief progressive flaccid paralysis Order: head and neck –> limb muscles –> muscles of respiration.
At higher doses, block the ion channel at the neuromuscular end plate to further weaken. muscular activity.

All used intravenously, actions are terminated by redistribution from site of blockade

Question 35

Vecuronium

Answer 35

Non-depolarizing Neuromuscular Blockers
At low doses competitive reversible blockers of neuromuscular junction causes brief progressive flaccid paralysis Order: head and neck –> limb muscles –> muscles of respiration.
At higher doses, block the ion channel at the neuromuscular end plate to further weaken. muscular activity.

All used intravenously, actions are terminated by redistribution from site of blockade