Drugs of the Cholinergic System Flashcards
Bethanechol
Cholinomimetic
Choline Ester:
_Direct Acting
_Selective
_Agonist
@ GI and Bladder Smooth Muscle
(Relatively Selective)
Use:
1) Constipation due to Lack of Tone
2) Urinary Retention
Methacholine
Cholinomimetic
Choline Ester:
_Direct Acting
_Selective
_Agonist
@ Heart
Predominantly Muscarinic
Use:
1) Bronchial Inhalation Challenge Test
(Triggers Bronchoconstriction)
2) Slows Heart Rate
Adverse Effects:
Arrhythmias
Heart Blocks
Pilocarpine
Alkaloid
Tertiary Amine
Lipid-Soluble
@ Sweat and Salivary Glands
Muscarinic Mostly
Uses:
1) Xerostomia (oral)
2) Glaucoma (eye drops) (not first line)
Muscarine
Alkaloid.
Mushroom.
Muscarinic
Poisoning is treated with Atropine
Nicotinic
Alkaloid.
Tobacco.
Nicotinic
Ganglion Stimulant
Highly Toxic
Edrophonium
Truly Reversible, Truly Competitive Anticholinesterase
Diagnostic for Myasthenia Gravis
Short-acting
Physostigmine
Reversible Anticholinesterase
Tertiary Amine
Lipid-Soluble
Enters CNS
False Substrate; Hydrolyzed by Enzyme
Use:
1) Antimuscarinic Toxicity
Neostigmine
Reversible Anticholinesterase
Quaternary Amine
Ionized
No CNS
False Substrates
Hydrolyzed by Enzyme
Uses:
1) Antimuscarinic Toxicity
2) Atony in Post-operative Ileus
Donepezil
Centrally Acting Reversible Anticholinesterase
-Used to Treat Alzheimer’s
-Lipid-Soluble; Enter CNS.
(Not quaternary)
-Patch administration.
*Donepezil,
*Rivastigmine,
*Galantamine
*Tacrine
Rivastigmine
Centrally Acting Reversible Anticholinesterase
-Used to Treat Alzheimer’s
-Lipid-Soluble; Enter CNS.
(Not quaternary)
-Patch administration.
*Donepezil,
*Rivastigmine,
*Galantamine
*Tacrine
Galantamine
Centrally Acting Reversible Anticholinesterase
-Used to Treat Alzheimer’s
-Lipid-Soluble; Enter CNS.
(Not quaternary)
-Patch administration.
*Donepezil,
*Rivastigmine,
*Galantamine
*Tacrine
Tacrine
Centrally Acting Reversible Anticholinesterase
-Used to Treat Alzheimer’s
-Lipid-Soluble; Enter CNS.
(Not quaternary)
-Patch administration.
*Donepezil,
*Rivastigmine,
*Galantamine
*Tacrine
Pyridostigmine
Reversible Anticholinesterase
@ Peripheral Nervous System
(Doesn’t readily enter CNS)
Was used to treat Organophosphate Poisoning
Adverse Effects:
Gulf War Syndrome with Repeated Doses:
Muscle Aches and Weakness, Diarrhea, Fatigue, Cognitive Problems.
Echothiophate
Irreversible Anticholinesterase
Organophosphate
Long-Acting
Causes Miosis
Malathion
Irreversible Anticholinesterase
Organophosphate
Insecticide
Sarin
Irreversible Anticholinesterase
Organophosphate
Nerve Gas
Atropine
Anti-Muscarinic
Tertiary Alkaloid
Lipid-Soluble
Cross BBB
Enter CNS
Found in _Belladonna (Deadly Nightshade) _Datura Stramonium (stinkweed)
Uses:
_Bradycardia or Heart Block due to Excess Vagal Tone
_Cholinergic Poisoning by Muscarine and/or Anticholinesterase Organophosphates
_Excessive Salivation (Hyperhidrosis)
Effects Vary with Dose:
1) *Small Doses:
* Decreased Salivation and
* Decreased Sweating
2) Larger Doses:
Dilated Pupils,
Blurring of Near Vision,
Tachycardia (Palpitations)
3) Even Larger Doses: Difficulty Speaking and Swallowing, Restlessness and Fatigue, Headache, Hot Dry skin, Difficulty Urinating, Reduced GI Motility
**At Low Therapeutic doses, Atropine has almost no detectable CNS effects.
CNS Stimulation is prominent with *Toxic doses:
_Restlessness,
_Irritability,
_Disorientation, _Hallucinations.
(Secretions are very, very sensitive to small doses of Atropine.)
Atropine Poisoning Symptoms:
_Dry Mouth, Thirst
_Blurred Vision (Cycloplegia), Photophobia (Mydriasis)
_Hot, Dry, Flushed Skin
_Increased Body Temperature
_Palpitations
_Restlessness, Excitement, Hallucinations
Red as a Beet Hot as a Hare Dry as a Bone Blind as a Bat Mad as a Hatter
Atropine is Contra-indicated in Narrow Angle Glaucoma (Angle Closure Glaucoma).
_B/c this occurs when the iris blocks the outflow canal of aqueous humor from the eye.
(Atropine would cause the Ciliary muscle to block the flow.)
Contraindicated in Prostatic Hypertrophy.
Atropine causes Urinary Retention, especially in Elderly Males
_B/c of Enlarged Prostate
Lomotil (used to treat Diarrhea)
_Contains Atropine
_May be source of Atropine poisoning, especially in Children
Scopolamine
Anti-Muscarinic
Tertiary Alkaloid
Lipid-Soluble
Cross BBB
Enter CNS
CNS Depressant in Clinical Dosage
- -Drowsiness
- -Amnesia
Use: Anti-Emetic
(Motion Sickness)
In people with Severe Pain:
_Causes CNS Excitation and Hallucinations
Dicyclomine
Anti-Muscarinic
Tertiary Synthetic
Lipid-Soluble
Cross BBB
Enter CNS
Use: Bowel Spasms
(Gastric disorder; GI Tract)
Tropicamide
Anti-Muscarinic
Tertiary Synthetic
Lipid-Soluble
Cross BBB
Enter CNS
Use: Mydriasis and Cycloplegia for Eye Exams
(Cycloplegia = paralysis of Ciliary muscle)
Benztropin
Anti-Muscarinic
Tertiary Synthetic
Lipid-Soluble
Cross BBB
Enter CNS
Use: Parkinson’s
Trihexyphenidyl
Anti-Muscarinic
Tertiary Synthetic
Lipid-Soluble
Cross BBB
Enter CNS
Use: Parkinson’s
Ipratropium
Anti-Muscarinic
Quaternary
Ionized
Can’t cross BBB
Use: COPD
Tiotropium
Anti-Muscarinic
Quaternary
Ionized
Can’t cross BBB
Use: COPD
Oxybutynin
Antimuscarinic
Some M3 Selectivity
Use: Urinary Frequency
Solifenacin
Antimuscarinic
Better M3 Selectivity (than Oxybutynin)
Use: Urinary Frequency
Darifenacin
Antimuscarinic
Better M3 Selectivity (than Oxybutynin)
Use: Urinary Frequency
Tolteridine
M3 Selective Antimuscarinic
Use: Urinary Frequency
Trospium
Non-Selective Antimuscarinic
Use: Urinary Frequency
Curare
Non-Depolarizing (Competitive Antagonist) Neuromuscular (Nicotinic) Blocker
1) Quaternary Alkaloid
2) No CNS effects @ Therapeutic doses
3) Not well Absorbed after Oral administration
(which is why they were able to eat the meat of the animals they had killed with Curare)
South American Arrow Poison
Active Compound is D-Tubocurarine
D-Tubocurarine
Prototype Non-Depolarizing (Competitive Antagonist) Neuromuscular (Nicotinic) Blocker
Active compound in Curare
1) Quaternary Alkaloid
2) Not well absorbed with Oral administration
3) No CNS effects @ Therapeutic doses
4) Weak Ganglionic Blocker
=> Hypotension
5) Liberates Histamine
=> Hypotension
=> Bronchospasm
(These adverse effects are why we no longer use this)
Atracurium
Non-Depolarizing (Competitive Antagonist) Neuromuscular (Nicotinic) Blocker
**Broken Down by Hoffman Elimination!
=> **Temperature and pH Dependent
_Not Enzymatic breakdown
(Not patient dependent)
**Does NOT Depend on Hepatic or Renal Function for its breakdown.
_Thus, will last just as long in elderly and healthy younger person.
Also Broken Down by Ester Hydrolysis
Cisatracurium
Non-Depolarizing (Competitive Antagonist) Neuromuscular (Nicotinic) Blocker
Stereoisomer of Atracurium
Produces Less Histamine than Atracurium
(Now widely used)
Rocuronium
Non-Depolarizing (Competitive Antagonist) Neuromuscular (Nicotinic) Blocker
Has Steroid structure.
Rapid Onset
Intermediate Duration
May be used to Facilitate Intubation.
(Like, need the patient to be paralyzed briefly for just a brief procedure, like intubation)
Gantacurium
Non-Depolarizing (Competitive Antagonist) Neuromuscular (Nicotinic) Blocker
Investigational
New class (chemical structure)
Ultra-Short-Acting
–May be an Alternative to Succinylcholine (which is a Depolarizing blocker and the only other ultra-short-acting blocker available)
Succinylcholine
Prototype Depolarizing (Partial Agonist) Neuromuscular Blockers
1) Very Brief Duration of Action (5-10 min)
2) Hydrolyzed by Plasma Pseudocholinesterase
_____________
May Get Prolonged Action:
1) Severe Malnutrition
(Not synthesizing enough Pseudocholinesterase)
2) Hepatic Disease
(Not synthesizing enough Pseudocholinesterase)
3) Drug Interactions:
_Neostigmine and other Anticholinesterases
_Ester Local Anesthetics
(Esters are Broken down by Pseudocholinesterase; thus, compete with succinylcholine for enzymatic breakdown)
4) Organophosphate Exposure
(Chronic, Sub-Clinical):
e.g. Field workers and Avid Gardeners with Chronic, Low-dose use of Insecticides
5) Succinylcholine Apnea:
Genetic difference in type of Pseudocholinesterase (less effective form)
\_\_\_\_\_\_\_\_\_\_ Diazepam: _Increases Duration of Non-Depolarizing Blockers _Decreases Duration of Succinylcholine (Depolarizing Blocker)
____________
Adverse Effects:
1) Malignant Hyperthermia:
Treat with Dantrolene*
2) Hyperkalemia
=> Results in Cardiac Depression
(More common in Burn, Trauma patients; Dangerous if on Digoxin)
3) Histamine Release
4) Ganglionic Block:
=> Hypotension!
5) Bradycardia: (Muscarinic)
_Cardiac Arrest may result
6) Increased Bronchial Secretions (Muscarinic)
(Both Succinylcholine and Acetylcholine are derived from Choline. So, may act @ Muscarinic receptors too.)
7) Fasciculations of Abdominal Muscles:
Causing Increased IntraGastric Pressure:
=> Increased Risk for Reflux
(Most likely in patients with Delayed Gastric Emptying, e.g. Diabetics, Morbid Obesity
8) Increased IntraOcular Pressure:
- -Transient (Peaks @ 2-4 min)
9) Post-Operative Muscle Pain
__________________
HOW TO REVERSE EFFECTS:
_Give Plasma!!
Need Normal Pseudocholinesterase!!!
_Cannot give Neostigmine b/c will only exacerbate.
_Don’t give Atropine because Atropine is a Muscarinic Blocker.
Trimethaphan
Ganglion Blockers
No longer available in USA
Uses:
_Anti-Hypertensive (Short-term, for Hypertensive Crisis)
Adverse Effects:
_Many; Depend on the predominant tone at the time of the block
_Usually see Decreased Muscarinic Effects:
1) Mydriasis (Dilated Pupils) (Iris)
2) Cycloplegia, Blurred Vision (Ciliary muscle) (Accommodation)
3) Dry Mouth (Xerostomia),
4) Anhidrosis (Sweat Glands)
(Sympathetic)
5) Tachycardia
6) Constipation
7) Urinary Retention
Note:
1) Predominant Tone in Vasculature is Sympathetic.
_Ganglionic Block results in Vasodilation, Hypotension.
(Sweat Glands Sympathetic too)
2) Predominant Tone everywhere else is Parasympathetic.
_Ganglionic Block results in Anti-Muscarinic effects.
Mecamylamine
Ganglion Blockers
No longer available in USA
Uses:
_Anti-Hypertensive (Short-term, for Hypertensive Crisis)
Adverse Effects:
_Many; Depend on the predominant tone at the time of the block
_Usually see Decreased Muscarinic Effects:
1) Mydriasis (Dilated Pupils) (Iris)
2) Cycloplegia, Blurred Vision (Ciliary muscle) (Accommodation)
3) Dry Mouth (Xerostomia),
4) Anhidrosis (Sweat Glands)
(Sympathetic)
5) Tachycardia
6) Constipation
7) Urinary Retention
Note:
1) Predominant Tone in Vasculature is Sympathetic.
Ganglionic Block results in Vasodilation, Hypotension.
(Sweat Glands Sympathetic too)
2) Predominant Tone everywhere else is Parasympathetic.
Ganglionic Block results in Anti-Muscarinic effects.
Botulinum Toxin
Inhibits Release of Acetylcholine
- Uses (Diluted form):
1) Local Muscle Spasms
2) Excessive Sweating
3) Cosmetic (Reduce Wrinkles)
4) Migraines
Extremely Toxic! High Mortality.
Recovery: Weeks to Months
Food Poisoning
=> Progressive Parasympathetic Block
=> Motor Paralysis
1) Dry Mouth,
2) Blurred Vision
3) Difficulty Swallowing
4) Progressive Respiratory Paralysis => Death!
Anti-toxin is used to treat the poison.
