Cholinergic Drugs Flashcards
Carbachol
Synthetic Choline Ester (Has a amide group so not easily degraded)
Cholinergic Agonist
Has both M receptor and N receptor action
Long action (60-90 min)
Used by corneal application for therapy of wide-angle glaucoma (constrict ciliary muscle, to open the meshwork of the canal of Schlemm.)
Bethanechol
Synthetic Choline Ester (both CH3=Muscarinic specific and NH2 (amide is poorly degraded by AchE)
Cholinergic Agonist (Lower HR, BP; Activate GI & Mucosal Cells, Empty Bladder/rectum, Constrict Bronchi, Miosis)
Only M receptor no N receptor Longest DURATION (60-90 min)
Stimulate smooth muscle Post-Op (atony of GI tract following surgery), dysfunction of bladder emptying, and promotion of saliva formation
Methacholine (Carbastat)
Synthetic Choline Ester (Has a CH3 attached so specific for M receptor)
Cholinergic Agonist
Short acting (10-15 min)
Used to test function of muscarinic receptors, to slow heart in severe Tachycardia
Test for bronchial hyperactivity
Edrophonium (Tensilon)
Cholinesterase Inhibitor
Competitive
Simple Alcohol with a quaternary ammonium group (can’t pass lipid bilayer)
Used in the diagnosis of MYASTHENIA GRAVIS
Duration of Action: 5-15 min
Neostigmine
Prostigmin
Cholinesterase inhibitor
Competitive
Carbamate (Carbamic ester of alcohol with quaternary ammonium)
Increases smooth muscle motility and useful for paralytic ileus and atony of the bladder from surgery
Treatment and diagnosis of myasthenia gravis
Reversal of neuromuscular blockade (caused by curare)
Duration of action: .5-2 hr
Physostigmine (Antilirium)
Cholinesterase Inhibitor
Competitive
Carbamate (carbamic acid ester of alcohols with tertiary amine group=can cross lipid bilayer)
Used TOPICALLY to treat wide-angle glaucoma
Duration of action: .5-2 hr
Pyridostigmine (Mestinon)
Cholinesterase Inhibitor
Competitive
Carbamate
Used in treatment of myasthenia gravis
PRETREATMENT to reduce mortality after exposure to nerve gas, reversal of neuromuscular blockade
Duration of Action: 3-6 hour
Ambenonium (Mytelase)
Cholinesterase Inhibitor
Competitive
Treatment for Myasthenia Gravis
Duration of action (4-8 hr)
Muscarine
Natural Alkaloid
Cholinergic Agonist
(Amanita muscaria)
Selective for muscarinic receptor
Pilocarpine
Natural alkaloid
Cholinergic agonist
Pilocarpus leaves
Anomalous cardiovascular responses, sweat glands particularly sensitive
Nicotine
Natural Alkaloid
Cholinergic agonist
Solanceae nightshade
Tobacco
Selectivity for nicotinic receptors
Vareniciline
Natural alkaloid
Nicotinic Selective
Cholinergic agonist
Diisopropylfluorophosphate (DFP)
Cholinesterase Inhibitor
Noncompetitive
Insecticide
Organophosphate derivative
Irreversible, long lasting
Echothiophate
Cholinesterase Inhibitor
Noncompetitive
Organophosphate derivative
Clinically relevant
Treatment of Glaucoma
Duration of Action: 100 hr
Carbaryl (Sevin)
Cholinesterase Inhibitor
Non Competitive
Insecticide
Malathion
Cholinesterase Inhibitor
Non Competitive
Insecticide
Parathion
Cholinesterase Inhibitor
Non Competitive
Insecticide
Tetraethylpyrophosphate (TEPP)
Cholinesterase Inhibitor
Non Competitive
Insecticide
Sarin
Cholinesterase inhibitor
Non Competitive
Nerve Gas
Soman
Cholinesterase inhibitor
Non Competitive
Nerve Gas
Atropine
Cholinergic Antagonist
Muscarinic Selective
- Very low potency for nicotinic sites, but no selectivity amongst M subtypes
STEP 1 THERAPY against O-P intoxication
- Administer Large DOSE >5mg w/ following smaller doses (1-2mg) - Competitively binds M receptor - Does not alleviate NEUROMUSCULAR HYPERACTIVITY and resulting paralysis
Quick Distribution to CNS= limits use due to side effects
- Therapeutic dose only minor vagal stim
- Toxic dose= central excitation w/restlessness, irritability, disorientation, hallucinations, delirium
- Useful adjunct therapy for PARKINSONs disease
- Salivary, bronchial, sweat glands are most sensitive to atropine
- Relieves urinary incontinence
Pralidoxime (2-PAM)
AChE (Cholinesterase Reactivator)
Step 2 Therapy following O-P intoxication
- Releases the phosphoryl moiety to restore AchE activity of esteratic site
- Must be administered before AchE aging occurs
- Nerve Gas: within min
- Insecticide: within 24 hrs
Therapeutic dose: 1-2 g iv,
- Restores skeletal muscle responsiveness, little effects in CNS
Drugs to treat Acute closed angle glaucoma?
Pilocarpine (muscarinic agonist) and
Physostigmine (AChE inhibitor)
Medical emergency not long term treatment
Drugs to treat GI and Urinary Tract problems?
Bethanechol (cholinergic agonist)
Neostigmine (AChE inhibitor)
Pilocarpine may be used to increase salivary secretions
Cevimeline
Used for treating dry mouth in Sjögren’s syndrome
Drugs to treat Neuromuscular junction problems?
- Myasthenia Gravis, neuromuscular blockade reversal
AChE inhibitors
- Edrophonium, pyridostigmine, neostigmine, ambenonium
Homatropine
Cholinergic Antagonist
Muscarinic Selective
Tertiary Semisynthetic derivative of ATROPINE
Elicit Mydriasis (Opening of Pupil) and Cycloplegia (loss of accomodation) TOPICAL TREATMENT
Duration of Action: 2-4 hours
Minor inhibition of Respiratory Tract secretions
Tertiary: Non polar so can cross BBB
Scopolamine
Cholinergic antagonist
Muscarinic Selective
Quick distribution after dose makes it limited use due to CNS side effects
- Tertiary ammonium= crosses BBB (central effects)
- CNS depression with drowsiness, amnesia, fatigue, dreamless sleep, euphoria
- Prevents motion sickness
- HIGH AMNESIA effect used before for pre-anesthetic
- Duration: 5-10 hours
Methscopoloamine
Cholinergic Antagonist
Muscarinic Selective
Quaternary Derivative of scopolamine
- PNS activity only due to charged N
- USED FOR GI Diseases
- Inhibits secretions of respiratory tract
- Does not have CNS effect so no amnesia or anti-Parkinson effects
Duration of action: 5-10 hours
Trihexyphenidyl
Cholinergic Antagonist
Muscarinic Selective
Tertiary amine
Useful adjunct therapy for low uncoordinated movement and excess salivation for parkinsonism
- Extra pyramidal side effects of anti-psychotic drugs
Duration of action: 3-6 hours
Tropicamide
Cholinergic Antagonist
Muscarinic Selective
Tertiary amine
Useful for mydriasis and cycloplegia
ONLY TOPICAL OCULAR TREATMENT
Duration of action: .5-1.5 hours
Cyclopentolate
Cholinergic Antagonism
Muscarinic specific
Duration of action: 1 day
Used in Opthalmology to elicit mydriasis and cycloplegia
Ipratropium
Cholinergic Antagonist
Muscarinic selective
Reduce bronchial secretions as a TOPICAL treatment (target bronchodilation and minimizes mucociliary clearance problems)
Quaternary derivative of Atropine, CANT CROSS BBB
- Bronchodilation, tachycardia, decreased salivation
- Minimize mucociliary clearance effect usually seen so useful for patients with airway problems
- Cannot cross membrane so very specific
- Useful in COPD patients
Tiotropium
Cholinergic antagonist
Muscarinic specific
Target Respiratory tract
Longer acting compared to ipratropium
Reduce bronchial secretions, elicits bronchodilation
Darifenacin
Cholinergic Antagonist
M3 selective
Greater M3 selectivity makes it longer duration of action
May help alleviate bladder spasm, slows micturition
Solifenacin
Cholinergic Antagonist
M3 Specific
Greater M3 selectivity has a longer duration of action at relaxing the smooth muscle wall of genitourinary system (ureters, bladder wall)
Alleviates bladder spasm following urologic surgery
Tolterodine
Cholinergic Antagonist
M3 Selective
Greater M3 selectivity allows a longer duration of action
Helps relax smooth muscle of genitourinary system
- Lower micturition speed
Mecamylamine
Cholinergic Antagonist
Nicotinic Selective
Ganglionic Blocking Agent
Secondary Amine to improve GI absorption following oral admin
Lasts 12 hours
CNS side effects: Tremor, Confusion, seizures, mania, depression
Nondepolarizing COMPETITIVE antagonist
Trimethaphan
Cholinergic Antagonist
Nicotinic Selective
Ganglionic Blocking Agent
- Sulfonium (positive charge sulfur groups) developed for IV infusion (lasts minutes)
NONDEPOLARIZING competitive antagonist
Clinical use: Short acting ganglionic blocker that give through IV during surgery to minimize blood loss in operative area (LOWERS ARTERIAL PRESSURE)
Must monitor excessive hypotension and possible brain anoxia
Succinylcholine
Cholinergic Antagonist
Noncompetitive Depolarizing Agent
Depolarize end plate region to inhibit acetylcholine
- Acts NONCOMPETITIVELY as receptor agonist opening Na channels, mimicking ACh action,
NOT A SUBSTRATE FOR AChE, but is hydrolyzed by plasma ChE
ONLY DEPOLARIZING neuromuscular BLOCKER
Phase I block: Membrane remains depolarized and unresponsive to later pulses,
- ChE inhibitors augment response rather than reverse block
Phase II Block: if allowed to stay in system will repolarize membrane but becomes resistant to depolarization
Do not use if patient:
- Plasma ChE mutations (DIBUCAINE TEST)
- Organophosphate intox
- Patients with CHF, burns, trauma, or neuromusc disease, due to excess release of K as a result of this function
- Patients with glaucoma as extraocular muscles will contract
Curare (d-tubocurarine)
Cholinergic Antagonist
Non-Depolarizing
Benzylisoquinolines (Devoid of vagolytic and ganglionic blocking activity)
- Elicitis some histamine release
Competes with acetylcholine for N2 receptor site
Induces Muscle RELAXATION
Atracurium and cisatracurium
Cholinergic antagonist
Non-depolarizing
Competes with acetylcholine for N2 receptor site
Benzylisoquinolones
Intermediate Acting
Mivacurium
Cholinergic antagonist
non-depolarizing
Benzylisoquinolone (some histamine)
Short Acting
Pancuronium (long lasting) and vecuronium (intermediate lasting)f
Cholinergic antagonist
Non-depolarizing
Long Acting
AMMONIO STEROID
- NO histamine release, some Muscarinc block eliciting vagal blockade and tachycardia
