4. DSA Cholinergic Drugs Flashcards
Receptor Type: M1
Location:
GPCR:
Mechanism:
Receptor Type: M1
Location: Nerves
GPCR: Gq/11
Mechanism: IP3/DAG cascade
Receptor Type: M2
Location: Heart, nerves, smooth muscle
GPCR:
Mechanism:
Receptor Type: M1
Location: Heart, nerves, smooth muscle
GPCR: Gi/o
Mechanism: Inhibit cAMP, activation of K+ channels
Receptor Type: M3
Location: Glands, smooth muscle, endothelium
GPCR:
Mechanism:
Receptor Type: M3
Location: Glands, smooth muscle, endothelium
GPCR: Gq/11
Mechanism: IP3/DAG
Receptor Type: M4
Location: CNS
GPCR:
Mechanism:
Receptor Type: M4
Location: CNS
GPCR: Gi/o
Mechanism: Inhibit cAMP
Receptor Type: M5
Location: CNS
GPCR:
Mechanism:
Receptor Type: M5
Location: CNS
GPCR: Gq/11
Mechanism: IP3/DAG
Receptor Type: NN
Location: postganglionic cell body, dendrites, CNS
GPCR:
Mechanism:
Receptor Type: NN
Location: postganglionic cell body, dendrites, CNS
GPCR: a/b only
Mechanism: Na/K+ depolarizing ion channel
In most organs, M3 is predominant. What predominates in the heart?
M2
List the following's receptor as M3, M2 or M3/M2... Heart SA/AV Nodes Atria Ventricle Eye Blood Vessels Endothelium Glands (lacrimal, salivary, bronchial, sweat) Lung GI/GU
Heart SA/AV Nodes M2 Atria M2 Ventricle M2 (dec) Eye M3/M2 Blood Vessels None Endothelium M3 Glands (lacrimal, salivary, bronchial, sweat) M3/M2 Lung M3/M2 GI/GU M3/M2
Cholinergic agonists mimic the actions of ACh on nAChRs and mAChRs, classified based on their?
mechanism of actions
What direct acting cholinergic agonists do the following? agonists at cholinergic receptors permanently charged poor absorption and distribution to CNS Metabolized by acetylcholinesterase
Choline Esters
All of the following are? Acetylcholine Metacholine Carbachol Bethanechol
Choline Esters
What direct acting cholinergic agonists do the following?
agonist at cholinergic receptors
uncharged tertiary amines, well absorbed
Muscarin charged but can cross the BBB and is high toxic
Alkaloids
Muscarine
Pilocarpine (both mAChR)
Nicotine / Lobeline (nAChR)
Alkaloids
There are 3 groups of AChE inhibitors which are indirect acting cholinergic agonists.
1) alcohols (reversible)
2) carbamic acid esters (reversible but longer lasting)
3) ?
Organophosphates - irreversible (covalent bond)
Charged AChE inhibitors are insoluble in lipids, do not cross the BBB and have poor PO absorption while neutral AChE inhibitors…?
can cross BBB and are readily absorbed- most commonly organophosphates/tertiary agents
Cholinergic agonists help rest and digest, leading to pupillar constrction, salivation, constriction/secretion of bronchi, voiding of urine, slowing of heart and what in the GI tract? (3)
Gastric secretion increased, colic, diarrhea
What is approved for intraocular use during surgery and causes miosis (reduced pupil size)?
Acetylcholine
What is a selective mAChR agonist that primarily effects the urinary and GU tracts and can be used to treat patients with urinary retention and heartburn?
Bethanechol
What is a nonspecific cholinergic agonist that is used for the treatment of glaucoma or to produce miosis during surgery or opthalmic examination?
Carbachol
What is an oral tablet used to treat dry mouth (xerostomia) in patients with Sjogren syndrome?
Cevimeline
What is approved for xerostomia treatment in patients with sjorgren or head and neck cancer treatment related xerostomia (PO), miosis during opthalmic procedures (topical) and for glaucoma (topical)?
Pilocarpine (pure mAChR agonist)
What is FDA approved for smoking cessation, which binds with high affinity and selectivity to a42b2 nAChRs (NN)? MOA = stimulation and moderate sustained release of mesolimbic dopamine, thought to reduce craving and withdrawal symptoms.
Varenicline (Chantix)
SE: nausea, changes behavior, agitation, depressed mood, suicide
Toxicity of direct acting muscarinic stimulants include nausea, vomiting, diarrhea, urinary urgency, slavation, sweating. These drugs are contraidication in people with? 4
asthma, hyperthyroidism, coronary insufficiency, and acid-peptic dz
Toxicity of direct acting nicotonic stimulants includes cns stimulation, skeletal muscle end plate depolarization, respiratory paralysis, hypertension and cardiac arrhythmias. How can one get nicotine poisoning?
cigarettes and insecticides
Some clinical uses of indirect-acting cholinergic agonists include glaucoma, myasthenia gravis, reversal of neuromuscular paralysis, AChE inhibitor toxicity, and what other 2 things?
dementia
Antidote to anticholinergic poisoning
Cholinergic antagonists increase flight or fight, including, pupillary dilation, dry mouth, accelerated heart rate, relaxation of bronchi, and what regarding bladder and GI tract?
retention of urine
gastric secretion reduced, constipation
What anticholinergic agents are used for motion sickness? 1
Scopolamine
What anticholinergic agents are used for GI disorders? 4
Atropine
Dicyclomine
Glycopyrrolate
Hyoscyamine
What anticholinergic agents are used for opthalmology? 5
atropine cyclopentolate homatropine scopolamine tropicamide
What anticholinergic agents are used for respiratory disorders? 2
Ipratropium
Tiotropium
What anticholinergic agents are used for urinary disorders? 5
Darifenacin M3 Oxybutynin M3 Solifenacin M3 Tolterodine M3 Trospium
What anticholinergic agents are used for cholinergic poisoning? 1
Atropine (+ pralidoxime)
What anticholinergic agents are used for movement disorders? 5
Benztropine Biperiden Orphenadrine Procyclidine Trihexyphenidyl
What are the overall effects of anticholinergic drugs?
general increase in sympathetic tone
What are 3 contraindications when prescribing anticholinergic drugs?
glaucoma
Prostatic hyperplasia
Acid-peptic disease
