Cholinergic Drugs

Question 1

M1

Location:
R type:
Mechanism:

Answer 1

Location: nerves
R type: Gq
Mechanism: IP3, DAG

Question 2

M2

Location:
R type:
Mechanism:

Answer 2

Location: heart, nerves, SM
R type: Gi
Mechanism: - AC/cAMP

Question 3

M3

Location:
R type:
Mechanism:

Answer 3

Location: glands, SM, endothelium
R type: Gq
Mechanism: IP3, DAG

Question 4

M4

Location:
R type:
Mechanism:

Answer 4

Location: CNS
R type: Gi
Mechanism: - AC/cAMP

Question 5

NN

Location:
R type:
Mechanism:

Answer 5

Location: postganglionic cell body, dendrites, CNS
R type: alpha and beta only
Mechanism: depolarize Na/K channel

Question 6

In most organs, what mAChR dominates?

Answer 6

M3

Question 7

What mAChR dominates in the heart?

Answer 7

M2

Question 8

What mAChRs are found in SM?

Answer 8

M2

M3

Question 9

What are the 4 choline esters?

Answer 9

ACh
Methacholine
Carbachol
Bethanechol

Question 10

MOA of choline esters

Answer 10

Agonists at cholinergic receptors

Question 11

How are choline esters charged?

Where is the absorption/distribution subpar?

Answer 11

They are permanently charged.

There is poor absorption and distribution to the CNS.

Question 12

Which 2 choline esters are negligably affected by cholinesterase?

Answer 12

Carbachol

Bethanechol

Question 13

Which 2 choline esters have nicotinic actions?

Answer 13

ACh

Carbachol

Question 14

MOA of alkaloids

Answer 14

Agonists at cholinergic receptors

Question 15

What 4 major alkaloids and which Rs do they bind?

Answer 15

mAChR: muscarine, pilocarpine

nAChR: nicotine, lobeline

Question 16

What is the structure of alkaloids?

What is the exception?

Answer 16

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.

Question 17

Which 2 drug classes are direct-acting drugs?

Answer 17

Choline esters

Alkaloids

Question 18

What are the 3 groups of AChE inhibitors?

Are they reversible?

Answer 18

Alcohols: reversible.

Carbamic acid esters: reversible, but longer lasting than -OHs.

Organophosphates: irreversible (covalent).

Question 19

Which AChE inhibitors are lipid soluble: charged or neutral?

Which cross the BBB?

Which are readily absorbed?

Answer 19

Neutral are lipid-soluble.

Neutral can cross the BBB.

Neutral are readily absorbed.

Question 20

What is ACh approved for use for?

Answer 20

Intraocular use during surgery and causes miosis (pupillary constriction).

Question 21

What does bethanechol target? What is it used for? (2)

What is a possible S/E?

Answer 21

Targets urinary and GU tracts.

Treats pts. w/ urinary retention and heartburn.

UTI if sphincter fails to relax.

Question 22

What is carbachol used for? (2)

Answer 22

TTM of glaucoma

To produce miosis during surgery/exam

Question 23

What is cevimeline used for? (1)

Answer 23

It is an oral tablet used to treat xerostomia (dry mouth).

Question 24

What is pilocarpine used for? (3)

Answer 24

Xerostomia in pts. w/ Sjogrens or head/neck cancer
Miosis during ophthalmic procedures (topical)
Glaucoma

Question 25

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?

Answer 25

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.

Question 26

What 2 groups of disease are the major uses of direct-acting cholinergic agonists?

Answer 26

DZs of the eye (glaucoma, esotropia, etc.) GI/GU disorders

Question 27

Muscarinic stimulants have what "predictable" toxicities/side-effects?

Answer 27

Salivation, Lacrimation, Urination, Defecation, Gastrointestinal Distress and Emesis

Question 28

Which patients are contraindicated for muscarinic stimulants? (4)

Answer 28

Pts. w/ asthma, hyperthyroidism, coronary insufficiency, acid-peptic DZ.

Question 29

Nicotine poisoning comes from: Acute nicotine toxicities include: What is used to treat pts. w/ nicotine toxicity? (2)

Answer 29

Cigarettes and insecticides. CNS+, skeletal muscle depolarization, respiratory paralysis, HTN, arryhthmias. Atropine and parenteral anticonvulsants.

Question 30

How does a mAChR stimulant treat glaucoma? Generally

Answer 30

Stimulates ciliary body to improves aqueous humor outflow and lower intraocular pressure. Can be done direct or indirect.

Question 31

6 common clinical uses of indirect-acting cholinergic agonists

Answer 31

``` Glaucoma Dementia Antidote to anticholinergis poisoning Reversal of neuromuscular paralysis Myasthenia gravis AChE inhibitor toxicity ```

Question 32

What are 3 common CNS disorders that anti-cholinergics are used to treat? (include drug names)

Answer 32

Parkinson DZ: mAChR antagonists can reduce tremors. Tertiary amines benztropine, trihexyphenidyl and procyclidine. Motion sickness: Scopolamine. Anesthesia: atropine most often.

Question 33

Why would mAChR antagonists be used ophthalmic disorders? (2 disorders)

Answer 33

Cycloplegia or prolonged mydriasis (LASIK surgery, etc.) To prevent synechia formation (when iris adheres to lens or cornea) in uveitis and iritis.

Question 34

What respiratory syndromes are anticholinergics used for?

Answer 34

Asthma/COPD | -ex: ipratropium bromide and tiotropium (long acting - once daily type)

Question 35

What can mAChR antagonists be used to treat in GI?

Answer 35

Traveler's diarrhea. It slows bowel hypermobility.

Question 36

Anticholinergics for GI disorders are often used in tandem w/...

Answer 36

An opioid antidiarrheal drug to discourage abuse of the opioid.

Question 37

What is Oxybutynin? What 3 drugs are preferred to it?

Answer 37

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.

Question 38

What is a common treatment in for mushroom poisoning?

Answer 38

Atropine (antimuscarinic). However, it does not help in delayed-onset mushroom poisoning.

Question 39

SX of delayed-onset mushroom poisoning

Answer 39

Nausea and vomiting 6-12 hrs post ingestion | Renal/hepatic injury due to amatoxins inhibition of RNA pol.

Question 40

3 major contraindications for anticholinergics

Answer 40

Glaucoma Prostatic hyperplasia Acid-peptic DZ