Cholinergic Drugs Flashcards
M1
Location:
R type:
Mechanism:
Location: nerves
R type: Gq
Mechanism: IP3, DAG
M2
Location:
R type:
Mechanism:
Location: heart, nerves, SM
R type: Gi
Mechanism: - AC/cAMP
M3
Location:
R type:
Mechanism:
Location: glands, SM, endothelium
R type: Gq
Mechanism: IP3, DAG
M4
Location:
R type:
Mechanism:
Location: CNS
R type: Gi
Mechanism: - AC/cAMP
NN
Location:
R type:
Mechanism:
Location: postganglionic cell body, dendrites, CNS
R type: alpha and beta only
Mechanism: depolarize Na/K channel
In most organs, what mAChR dominates?
M3
What mAChR dominates in the heart?
M2
What mAChRs are found in SM?
M2
M3
What are the 4 choline esters?
ACh
Methacholine
Carbachol
Bethanechol
MOA of choline esters
Agonists at cholinergic receptors
How are choline esters charged?
Where is the absorption/distribution subpar?
They are permanently charged.
There is poor absorption and distribution to the CNS.
Which 2 choline esters are negligably affected by cholinesterase?
Carbachol
Bethanechol
Which 2 choline esters have nicotinic actions?
ACh
Carbachol
MOA of alkaloids
Agonists at cholinergic receptors
What 4 major alkaloids and which Rs do they bind?
mAChR: muscarine, pilocarpine
nAChR: nicotine, lobeline
What is the structure of alkaloids?
What is the exception?
They are uncharged tertiary amines, which allows them to be easily absorbed (nicotine patch).
Muscarine, which can cross the BBB and is highly toxic (mushrooms). This is unusual.
Which 2 drug classes are direct-acting drugs?
Choline esters
Alkaloids
What are the 3 groups of AChE inhibitors?
Are they reversible?
Alcohols: reversible.
Carbamic acid esters: reversible, but longer lasting than -OHs.
Organophosphates: irreversible (covalent).
Which AChE inhibitors are lipid soluble: charged or neutral?
Which cross the BBB?
Which are readily absorbed?
Neutral are lipid-soluble.
Neutral can cross the BBB.
Neutral are readily absorbed.
What is ACh approved for use for?
Intraocular use during surgery and causes miosis (pupillary constriction).
What does bethanechol target? What is it used for? (2)
What is a possible S/E?
Targets urinary and GU tracts.
Treats pts. w/ urinary retention and heartburn.
UTI if sphincter fails to relax.
What is carbachol used for? (2)
TTM of glaucoma
To produce miosis during surgery/exam
What is cevimeline used for? (1)
It is an oral tablet used to treat xerostomia (dry mouth).
What is pilocarpine used for? (3)
Xerostomia in pts. w/ Sjogrens or head/neck cancer
Miosis during ophthalmic procedures (topical)
Glaucoma
What kind of agonist is Varenicline? What does it bind to?
What is the MOA?
What is the most common and most serious S/E?
Partial agonist that binds w/ high affinity and selectivity to NN.
Stimulate and moderate release of mesolimbic DA, which is believed to decrease craving and withdrawal SX.
Nausea is most common. Neuropsychiatric SX are most serious.
What 2 groups of disease are the major uses of direct-acting cholinergic agonists?
DZs of the eye (glaucoma, esotropia, etc.)
GI/GU disorders
Muscarinic stimulants have what “predictable” toxicities/side-effects?
Salivation, Lacrimation, Urination, Defecation, Gastrointestinal Distress and Emesis
Which patients are contraindicated for muscarinic stimulants? (4)
Pts. w/ asthma, hyperthyroidism, coronary insufficiency, acid-peptic DZ.
Nicotine poisoning comes from:
Acute nicotine toxicities include:
What is used to treat pts. w/ nicotine toxicity? (2)
Cigarettes and insecticides.
CNS+, skeletal muscle depolarization, respiratory paralysis, HTN, arryhthmias.
Atropine and parenteral anticonvulsants.
How does a mAChR stimulant treat glaucoma?
Generally
Stimulates ciliary body to improves aqueous humor outflow and lower intraocular pressure.
Can be done direct or indirect.
6 common clinical uses of indirect-acting cholinergic agonists
Glaucoma Dementia Antidote to anticholinergis poisoning Reversal of neuromuscular paralysis Myasthenia gravis AChE inhibitor toxicity
What are 3 common CNS disorders that anti-cholinergics are used to treat? (include drug names)
Parkinson DZ: mAChR antagonists can reduce tremors. Tertiary amines benztropine, trihexyphenidyl and procyclidine.
Motion sickness: Scopolamine.
Anesthesia: atropine most often.
Why would mAChR antagonists be used ophthalmic disorders? (2 disorders)
Cycloplegia or prolonged mydriasis (LASIK surgery, etc.)
To prevent synechia formation (when iris adheres to lens or cornea) in uveitis and iritis.
What respiratory syndromes are anticholinergics used for?
Asthma/COPD
-ex: ipratropium bromide and tiotropium (long acting - once daily type)
What can mAChR antagonists be used to treat in GI?
Traveler’s diarrhea. It slows bowel hypermobility.
Anticholinergics for GI disorders are often used in tandem w/…
An opioid antidiarrheal drug to discourage abuse of the opioid.
What is Oxybutynin?
What 3 drugs are preferred to it?
An anticholinergic that is a selective M3 antagonist, but has many S/E (dry mouth, dizziness, constipation, blurred vision, etc).
Darifenacin, Solifenacin and Tolterodine are advantageous because of their longer half-life and reduced incidence of xerostomia and constipation.
What is a common treatment in for mushroom poisoning?
Atropine (antimuscarinic). However, it does not help in delayed-onset mushroom poisoning.
SX of delayed-onset mushroom poisoning
Nausea and vomiting 6-12 hrs post ingestion
Renal/hepatic injury due to amatoxins inhibition of RNA pol.
3 major contraindications for anticholinergics
Glaucoma
Prostatic hyperplasia
Acid-peptic DZ
