Cholinergics Flashcards
Acetylcholine
Cholinergic Agonist
Quaternary amine, vulnerable to cholinesterase
Methacholine
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
Bethanechol
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
Carbachol
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
Cevimeline
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
Pilocarpine
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
Cholinesterase Inhibitors
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
Pyridostigmine
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
Physostigmine
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
Ambenonium
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
Demecarium
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
Edrophonium
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
Neostigmine
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
Echothiophate
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
Parathion, Malathion
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
Soman
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
Pralidoxime chloride or 2-PAM
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
Donepezil
Centrally-Acting Cholinesterase Inhibitors
Tx: dementia
Rivastigmine
Centrally-Acting Cholinesterase Inhibitors
Tx: dementia
Galantamine
Centrally-Acting Cholinesterase Inhibitors
Tx: dementia
Atropine
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
Scopolamine
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
Dicyclomine
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
Oxybutynin
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
Darifenacin
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
Tolterodine
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
Nicotine
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)
Varenicline
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
Succinylcholine
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.
Atracurium
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.
Cisatracurium
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
Pancuronium
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
Roburonium
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
Tubocurarine
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
Vecuronium
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
