Pharmacology: Block 2: Neuroeffector Systems 3, Muscarinic Receptor Agonists/antagonists

Front 1

Cholinesterase is ineffective against what type of choline esters?

Two examples?

Back 1

Against choline esters that are CARBAMIC ACID ESTERS.

Ex: Carbachol, bethanechol

Front 2

What types of choline esters do NOT bind well to nicotinic receptors?

Back 2

Those that have methyl groups

Ex: Methacholine, bethanechol.

Front 3

c/c the properties of acetylcholine and bethanechol.

Back 3

Acetylcholine: Doesn't have a methyl group OR a carbamic acid group so it binds both the muscarinic and nicotinic receptor AND it is degradeable by cholinesterase.

Bethanechol has BOTH a methyl group AND a carbamic acid group, so it does NOT bind to the nicotinic receptor AND is NOT degraded by cholinesterase.

Front 4

Cholinesterase is ineffective against what type of choline esters?

Two examples?

Back 4

Against choline esters that are CARBAMIC ACID ESTERS.

Ex: Carbachol, bethanechol

Front 5

What types of choline esters do NOT bind well to nicotinic receptors?

Back 5

Those that have methyl groups

Ex: Methacholine, bethanechol.

Front 6

c/c the properties of acetylcholine and bethanechol.

Back 6

Acetylcholine: Doesn't have a methyl group OR a carbamic acid group so it binds both the muscarinic and nicotinic receptor AND it is degradeable by cholinesterase.

Bethanechol has BOTH a methyl group AND a carbamic acid group, so it does NOT bind to the nicotinic receptor AND is NOT degraded by cholinesterase.

Front 7

Muscarine

Back 7

Quartenary amine
Isolated from mushrooms
Not used theraputically

Front 8

Pilocarpine

Back 8

Not susceptible to cholinesterases (because it's not an ester).
Teritary amine.
Better lipid solubility, absorption, and longer half-life than choline esters. (Penetrates CNS)
Shows selectivity for postsynaptic M1 receptors in sympathetic ganglia --> inc in BP (via the direct muscarinic pathway --> EPSP).

Front 9

What are two examples of naturally occuring alkaloids that are muscarinic agonists?

Back 9

Muscarine and pilocarpine.

Front 10

Muscarinic agoinists are ______omimetic.

Back 10

Muscarinic agoinists are PARASYMPATHomimetic.

Front 11

What is a good example of accentuated antagonism?

Back 11

During exercise S activity is high, so introducing a drug such as a choline ester that will stimulate PS activity will bring HR down

Front 12

Muscarinic agonists are used to treat diseases of what two organ systems?

Back 12

GI and the eye.

Front 13

What is the main action of muscarinic receptor agonists in treating the diseases of the eye?

Back 13

To relieve intraocular pressure. (Methacholine, carbachol, and pilocarpine)

Front 14

What is the main action of muscarinic receptor agonists in treating the diseases of the GI tract?

Back 14

To correct conditions where smooth muscle activity is depressed. (Bethanechol)

Front 15

What is inhaled methacholine used for?

Back 15

For provocative testing for bronichial hyperreactivity. Methacholine challenge test.

Front 16

What are adverse effects of muscarinic agonists treated with?

Back 16

Muscarinic antagonists (atropine).

Front 17

Muscarinic antagonists generally have the opposite effect as muscarinic agonists except at what receptor?

Back 17

At the non-innervated receptors (e.g. endothelial cells). Remember, for an antagonist to work, an agonist has to be present.

Front 18

Atropine

Back 18

Highly selective for the muscarinic receptor.

Tertiary amine alkaloid ester of tropic acid. Is absorbed in the gut and across the conjunctival membrane. Has access to the CNS (stimulant).

Has a blood half-life of 2 hrs.

l-isomer is the active form

Found in deadly nightshade and jimsonweed.

(Atropen®)

Front 19

Scopolamine

Back 19

Muscarinic antagonist

CNS depressant (amnesia, sleep) at low doses. Is a CNS stimulant at high doses.

Absorbed through the skin (because it is a tertiary amine)

Used for motion sickness. Also used to improve tremor and rigidity in Parkinson's disease.

Has effects on the CNS, not the PNS

(Transderm Scop®)

Front 20

Ipratropium

Back 20

Muscarinic antagonist

Quartenary charged molecule, thus decreased uptake from oral route, reduced CNS access.

Used for inhalation treatment of asthma and COPD. Produces bronchodilation, but lacks the CNS actions of atropine.

Triotropium is a newer agent that has a longer half-life than ipratropium.

(Atrovent®)

Front 21

Dicyclomine

Back 21

Muscarinic antagonist

Used to treat intestinal hypermotility.

(Bentyl®)

Front 22

Does ipratropium inhibit bronchial secretions?

Back 22

No. (Atropine does).

Front 23

True or false: atropine is only effective at binding the M3 receptor.

Back 23

False. Atropine does not distinguish between muscarinic receptor subgroups.

Front 24

What is muscarinic antagonist that shows selectivity for the M3 subtype? (Extra credit) What are two others?

Back 24

1. Tolterodine

2. Oxybutynin
3. Darifenacin

Front 25

What is tolterodine used to treat?

Back 25

Urinary incontinence (muscarinic antagonist)

Front 26

What is a risk associated with using muscarinic antagonists in the eye?

Back 26

Muscarinic antagonists relax the ciliary muscle, putting pressure on the Canal of Schlemm and increasing the risk of acute glaucoma.

Front 27

What affect will a muscarinic antagonist have on the heart?

Back 27

It will increase HR by removing the PS block.

Front 28

What is "Atropine fever"?

Back 28

Atropine blocks sweating by blocking cholenergic sympathetic neurons --> hyperthermia in children.

Front 29

What are the three most serious adverse effects of muscarinic antagonists?

Back 29

1. Atropine fever
2. Acute-angle glaucoma
3. Urinary retention and constipation.

Front 30

What is the saying that is used to describe muscarinic antagonist toxicity?

Back 30

"Dry as a bone, blind as a bat, red as a beet, and mad as a hatter."

Usually don't find people "mad as a hatter," rather, you find them to be lethargic and spacy.

Front 31

What is the treatment for muscarinic antagonist overdose?

Back 31

Cholinesterase inhibitors and anticonvulsant drugs.