ANS Parasympathetic Drugs Flashcards
1
Q
Acetylcholine
(Miochol)
A
- Agent Type: Cholinoceptor Agonist
- Therapeutic Use (↑↓ Use): Ocular use for pupil constriction (miosis). Limited clinical use due to widespread action.
- Actions: Full agonist on muscarinic & nicotinic receptors. Endogenous NT, doesn’t circulate. Has many sites of action (ANS & NMJ). Brief action due to action of AchE & pseudoAchE (plasma). No reuptake of ACh.
- Adverse: SLUDGE or DUMBBELS; _S_weating, _S_alivation, Lacrimation, Urination, GI Issues (Diarrhea, Abdominal cramps), Emesis, Hypotension, Bradycardia, Miosis/ Cyclopegia, Bronchospasm.
- CV: ↓ BP & Bradycardia, ↓ CO
2
Q
Bethanechol
(Urecholine)
A
- Agent Type: M-receptor agonists: Limited clinical use, wide-action.
- Therapeutic Use (↑↓ Use): Post-operative urinary retention, gut atony
- Actions: M2, M3 > M1. Resistant to AchE. Doesn’t cross BBB. Given SC or IM but not IV (Very Potent).
- Adverse: SLUDGE; Sweating, salivation, lacrimation, urination, diarrhea, abdominal cramps, vomiting, hypotension, bradycardia, miosis, bronchospasm.
3
Q
Pilocarpine (Ocusert-Pilo)
Carbachol (Carbacel)
Methacholine (Provocholine)
A
- Agent Type: M-receptor agonists: Limited clinical use, wide-action.
-
Pilocarpine:
- Therapeutic Use (↑↓ Use): DOC-Acute emergency glaucoma
- Actions: Muscarinic activity; Resistant to AchE. Alkaloid, high lipid solubility, cross BBB. ↑outflow.
-
Carbachol:
- Therapeutic Use (↑↓ Use): Glaucoma, if pilocarpine ineffective
- Actions: Muscarinic & some nicotinic activity; Resistant to AchE.
-
Methacholine
- Therapeutic Use (↑↓ Use): Ocular procedures
- Actions: Resistant to AchE. Does not cross BBB.
- Other Therapeutic Use (↑↓ Use): dry mouth (xerostomia), bronchial challenge.
- Adverse: SLUDGE; Sweating, salivation, lacrimation, urination, diarrhea, abdominal cramps, vomiting, hypotension, bradycardia, miosis, bronchospasm.
4
Q
Edrophonium
(Tensilon)
A
- Agent Type: Reversible Cholinesterase Inhibitors
- Therapeutic Use (↑↓ Use): Diagnostic for myasthenia gravis, Ileus (hypomotility of GI), Arrhythmias
- Actions: Reversible inhibitors AchE→ ↑Ach
- Adverse: SLUDGE; Sweating, salivation, lacrimation, urination, diarrhea, abdominal cramps, vomiting, miosis, hypertension/hypotension, bradycardia, bronchospasm. Muscle weakness (depolarizing block on N-receptors, not reversible).
- Toxicity treatment: Atropine (no 2-PAM).
- Note: Short-acting (5-10 min), no CNS action.
5
Q
Physostigmine
(Eserine)
A
- Agent Type: Reversible Cholinesterase Inhibitors
- Therapeutic Use (↑↓ Use): Reverse atropine toxicity; glaucoma
- Actions: Reversible inhibitors AchE→ ↑Ach
- Adverse: SLUDGE; Sweating, salivation, lacrimation, urination, diarrhea, abdominal cramps, vomiting, miosis, hypertension/hypotension, bradycardia, bronchospasm. Muscle weakness (depolarizing block on N-receptors, not reversible).
- Toxicity treatment: Atropine (no 2-PAM).
- Note: Reversible, CNS action (Alkaloid, high lipid solubility → cross CNS)
6
Q
Neostigmine (Prostigmin)
Pyridostigmine (Mestinon)
Ambenonium
A
- Agent Type: Reversible Cholinesterase Inhibitors
-
Neostigmine:
- Therapeutic Use (↑↓ Use): Myasthenia gravis, reverse NMJ block (used during surgery)
- Actions: Reversible inhibitors AChE→ ↑ACh
-
Pyridostigmine/ Ambenonium: 3-6 hrs action, toxicity is same as for ↑ACh
- Therapeutic Use (↑↓ Use): Myasthenia gravis
- Adverse: SLUDGE; Sweating, salivation, lacrimation, urination, diarrhea, abdominal cramps, vomiting, miosis, hypertension/hypotension, bradycardia, bronchospasm. Muscle weakness (depolarizing block on N-receptors, not reversible).
- Toxicity treatment: Atropine (no 2-PAM).
- Note: reversible, No CNS, some direct action
7
Q
Donepezil (Atricept)
Galantamine
Rivastigmine
A
- Agent Type: Reversible Cholinesterase Inhibitors
- Therapeutic Use (↑↓ Use): Alzheimer’s Disease (Do not cure or prevent)
- Actions: Reversible inhibitors AChE→ ↑ACh
- Adverse: SLUDGE; Sweating, salivation, lacrimation, urination, diarrhea, abdominal cramps, vomiting, miosis, hypertension/hypotension, bradycardia, bronchospasm. Muscle weakness (depolarizing block on N-receptors, not reversible). Nausea.
- Toxicity treatment: Atropine (no 2-PAM).
- Note: Reversible, CNS action (Can cross BBB; more effective than Physostigmine)
8
Q
Organophosphate
Echothiophate(Phospholine)
DFP (Isoflurophate)
Vx, Sarin, Soman (Nerve Gases)
A
- Agent Type: Irreversible Cholinesterase Inhibitors, Organophosphates, OGs
-
Echothiophate & DFP
- Therapeutic Use (↑↓ Use): Glaucoma (miosis, cycloplegia)
-
Nerve Gases
- Use (↑↓ Use): Military, classified many 1000s
- Actions: High lipid solubility, readily cross BBB, CNS actions.
- Adverse: SLUDGE; Sweating, salivation, lacrimation,urination, diarrhea, abdominal cramps, vomiting, miosis, hypertension/hypotension, bradycardia, bronchospasm.
- Toxicity treatment before aging: atropine + pralidoxime (2-PAM). AchE aging (DFP: 30-40 min, nerve g: sec/min)
- Note: Muscle weakness (due to depolarizing block on N-receptors, this action is not reversible).
9
Q
Organophosphate
- *Malathion** (Chemathion)
- *Parathion** (Folidol)
A
- Agent Type: Irreversible Cholinesterase Inhibitors, Organophosphates, OGs
-
Malathion
- Therapeutic Use (↑↓ Use): Pesticide, lice/scabies
-
Parathion (higher toxicity)
- Use (↑↓ Use): Pesticide
- Actions: Prodrugs, inactive. Absorbed and converted to active organophosphate (S → O). Irreversible AchE inhibition. Vertebrates and humans quickly inactivate them but not insects (nor fish). Parathion more toxic than malathion. High lipid solubility, Cross BBB, CNS actions.
- Adverse: SLUDGE; Sweating, salivation, lacrimation, urination, diarrhea, abdominal cramps, vomiting, miosis, hypertension/hypotension, bradycardia, bronchospasm. Muscle weakness (depolarizing block on N-receptors).
- Toxicity treatment before aging: atropine + pralidoxime (2-PAM). AchE aging: 2-6 hrs
10
Q
Atropine (Jimsonweed, Deadly Nightshade, Datura)
(Isopto-Atropine, Belladonna Alkaloid)
A
- Agent Type: Competitive, Muscarinic Receptor Antagonists
- Therapeutic Use (↑↓ Use): Reverse AChE inhibition (muscarine poisoning or combined c 2-Pam for nerve gases); Reverse Bradycardia; GI-Disorders; Ocular Iritis; Vagolysis (inhibit action of vagus n. on heart, GI & etc)
- Actions: Alkaloid, CNS action. long-lasting (7 day)
-
Adverse: ↓ Secretions, dry mouth, mydriasis, cycloplegia, constipation (↓ GI Activity), tachycardia, urine retention, hallucinations & excitation. Elderly more sensitive. Toxicity treatment c physostigmine (AchE inhibitor).
- Hot as hell (thermoregulation). Blind as a bat (cycloplegia). Dry as a bone (↓ Secretions). Mad as a hatter (unresponsive, CNS delirium). Red as a beet (erythematous; direct vasodilation).
- Note: Teenage abuse potential for hallucinogen effect.
11
Q
Scopolamine(Isopto-Hyosine)
Propantheline (Probanthine)
- Glycopyrolate* (Robinul, Glycate)
- Pirenzepine* (Gastrozepin)
A
-
Agent Type: Competitive, Muscarinic Receptor Antagonists
- Scopolamine: 3-7 days action; Use: Motion sickness, diarrhea, ↓ Secretions
- Propantheline: Probanthine, Quaternary Amine; Use: GI disorders ie, mild diarrhea, [peptic ulcer]
- Glycopyrolate: GI disorders ie, mild diarrhea, [peptic ulcer]
- Pirenzepine: Peptic Ulcer; M1 Selective
-
Adverse: ↓ Secretions, dry mouth, mydriasis, cycloplegia, constipation (↓ GI Activity), tachycardia, urine retention, hallucinations & excitation. Elderly more sensitive. Toxicity treatment c physostigmine (AchE inhibitor).
- Hot as hell (thermoregulation). Blind as a bat (cycloplegia). Dry as a bone (↓ Secretions). Mad as a hatter (unresponsive, CNS delirium). Red as a beet (erythematous; direct vasodilation).
12
Q
Benztropine
(Cogentin)
A
- Agent Type: Competitive, Muscarinic Receptor Antagonists
- Therapeutic Use (↑↓ Use): Parkinson’s Disease, esp drug induced (improve tremor & rigidity but not bradykinesia)
- Actions: Crosses BBB
-
Adverse: ↓ Secretions, dry mouth, mydriasis, cycloplegia, constipation (↓ GI Activity), tachycardia, urine retention, hallucinations & excitation. Elderly more sensitive. Toxicity treatment c physostigmine (AchE inhibitor).
- Hot as hell (thermoregulation). Blind as a bat (cycloplegia). Dry as a bone (↓ Secretions). Mad as a hatter (unresponsive, CNS delirium). Red as a beet (erythematous; direct vasodilation).
13
Q
- *Ipratropium** (Atrovent)
- *Tiotropium** (Spirival)
A
- Agent Type: Quaternary Amine, Competitive, Muscarinic Receptor Antagonists
- Therapeutic Use (↑↓ Use): COPD (inc bronchitis & emphysema), Asthma–Bronchodilator
- Actions: Competitive, muscarinic antagonists, Do not cross BBB, no CNS action. (Tiotropium: newer agent, better M3-blocker). Hot as hell. Blind as a bat. Dry as a bone. Mad as a hatter. Red as a beet.
- Adverse: ↓ Secretions, dry mouth, mydriasis, cycloplegia, constipation, tachycardia, urine retention, hallucinations & excitation. Elderly more sensitive to adverse effects.
- Note: Duration: Ipratropium 4-6 hr; Tiotropium longer, 1 day
14
Q
Hemicholinium
A
- Agent Type: Inhibitor of Choline Uptake
- Therapeutic Use (↑↓ Use): No clinical use (except for exam question.)
- Actions: inhibits the uptake of choline by cholinergic neuron (Rate-Limiting Step in Synthesis of ACh) & thus inhibition leads to a ↓ in ACh stores. Remember, unlike NE, there is no reuptake of ACh.
- Note: Widespread action since ACh synthesis occurs at many sites- parasympathetic junction, sympathetic junction (sweat glands), autonomic ganglia (PNS & SNS), adrenal glands & NMJ.
15
Q
Nicotine
(Cigarettes, Patches, Gum, Insecticides)
A
- Agent Type: Nicotinic Receptor Agonist
- Therapeutic Use (↑↓ Use): Social (cigarettes), smoking cessation (patches, gum), insecticides
- Actions: Agonist nicotinic receptors (ANS & NMJ). Alkaloid, not endogenous, high lipid solubility. Readily crosses BBB. Widespread body action. Activates stimulatory & reward pathways. Prolonged stimulation (high toxic) causes depolarizing block similar to succinylcholine.
- Adverse: Cancer, lung & CV disease, addiction, withdrawal, paralysis (depolarizing block), headache
- Acute CV: ↑BP, ↑HR, ↑respiration, ↓appetite
- Note: Metabolized & excreted rapidly
16
Q
Botulinum Toxin
(Botox)
A
- Agent Type: Large Peptide, Inhibitor of ACh Release.
- Therapeutic Use (↑↓ Use): Facial or eye spasms (blepharospasm), strabismus, cosmetic (wrinkles, major use), hyperhidrosis (ANS, excess sweating), migraine.
- Actions: Taken up into neuron via endocytosis. Inhibits ACh release by cleaving SNAP-25 docking protein. Acts at all sites of ACh release. Most clinical benefit due to action at NMJ.
- Adverse: Muscle weakness & paralysis, injection soreness, flu syndrome.
- Note: Can come from contamination of improperly prepared food. Long-lasting 3-4 months. Can not reverse action. An antitoxin is available for immediate overdose.
