Ph18-Direct-Acting Cholinergics

Front 1

What type of receptors does Ach act on?

Back 1

Cholinergic: Muscarinic (M1-5) & Nicotinic (Nm, Nn)

Front 2

Where is Ach the promary neurotransmitter?

Back 2

Parasym/Symp ganglia (N), Parasym postgang jcns (M), Symp sweat glands (M), & NMJ (N)

Front 3

What terminates the action of Ach?

Back 3

Acetylcholinesterase in the synaptic cleft

Front 4

What is the mech of M1, M3, &M5 receptors?

Back 4

Gq-PLC-IP3/DAG->inc Ca

Front 5

What is the mech of M2 & M4 receptors?

Back 5

Gi/Go to inhibit adenyl cyclase-> dec cAMP. Activates specific K+ channels

Front 6

What is the mech of Nn & Nm receptors?

Back 6

Ion channels (Na influx)

Front 7

Where are Nn & Nm receptors located? Blocked by?

Back 7

Nn located in ganglia & blocked by trimethapan. Nm located @ NMJ & blocked by Tubocurarine

Front 8

What are Cholinomeimetics?

Back 8

agents that produce effects similar to those of Ach

Front 9

What the direct-acting cholinomimetics?

Back 9

Primarily muscarinic agonists but can elicit nicotinic effects at higher doses

Front 10

What are the indirect-acting cholinomimetics?

Back 10

Cholinesterase inhibitors= amplify endogenous Ach by effect by inhibiting AChE. Affects both Mus & Nic receptors

Front 11

What are parasympatholytic agents?

Back 11

Anticholinergics= inhibit the action of Ach (reduce parasym effects)

Front 12

Where are M1-5 receptors located?

Back 12

M1=nerves, M2=heart, nerves, sm, M3=glands, sm, endothelium, M4=CNS, M5=CNS

Front 13

*How does muscarinic activation effect the CV system?

Back 13

Vasodilation (M3) & bradycardia (M2)

Front 14

How does muscarinic activation effect blood vessels?

Back 14

affected @lower doses produces NO-> Dec TPR, SBP, & DBP. Accom by reflex tachycardia

Front 15

How does muscarinic activation generally effect the heart?

Back 15

Affected @ higher doses. Dec cAMP & Ca current. Activates K+ channels

Front 16

What are the 3 specific effects of muscarinic activation on the heart?

Back 16

Neg chronotropic: dec pacemaker, inc repolarizing current K+->dec HR. Neg dromotropic: dec AV velocity. Neg inotropic: dec atrial contractility

Front 17

*How does muscarinic activation effect the respiratory system?

Back 17

Sympathetic: Bronchoconstriction (M2/M3) & Inc Secretion (M3)

Front 18

*How does muscarinic activation effect the urinary bladder?

Back 18

Inc voiding: contracts detrusor & relaxes sphincter (M3>M2)

Front 19

*How does muscarinic activation effect the GI tract?

Back 19

Inc movement via myenteric plexus (M1). Inc resting tone & force of contraction, gastric secretion. May cause nausea, vomiting, & diarrhea

Front 20

*How does muscarinic activation effect exocrine glands?

Back 20

Inc secretion of lacrimal , salivary, & sweat glands (M3)

Front 21

*How does muscarinic activation effect the eye?

Back 21

Miosis (iris sphincter) & accomodation (ciliary m)- M3/M2. Facilitate draining of the ant chamber to lower pressure

Front 22

*How does muscarinic activation effect the CNS?

Back 22

Pilocarpin & muscarine cause cortical arousal. M1=epileptogenesis, M2= in SC, M3=food intake (hypothal), M4= like M2, M5= reward circuitry

Front 23

What are the 2 main groups of direct-acting cholinomimetics?

Back 23

Choline esters & natural/synthetic alkaloids

Front 24

What are the 3 clinically utilized choline esters? Importance?

Back 24

Methacholine, Carbachol, & Bethanechol. Less suseptible to degradation & more selective

Front 25

Decscribe the chemistry, absorption, distribution, & elimination of choline esters?

Back 25

Quad amine (hydrophilic), poorly absorbed in GI, doesn't cross BBB easily, & metabolized by AChE

Front 26

Decscribe the chemistry, absorption, distribution, & elimination of natural alkaloids?

Back 26

Muscarine=quad amine absorbed less in GI & pilocarpine= tert amine well absorbed in GI. Can cross BBB, elimin by kidney, excretion accel by acid urine

Front 27

What is the action of methacholine?

Back 27

similar to Ach given iv. No nicotinic effects

Front 28

What are the dosage considerations of methacholine?

Back 28

Somewhat resistant to cholinesterase; longer duration of action

Front 29

What is the clinical use of methacholine?

Back 29

Inhalation spray for bronchial provocation (asthma). Limited use due to side effects

Front 30

What is the action of carbachol?

Back 30

Given iv.greater nicotinic effects than Ach. More effect on GI, bladder, & iris. Less effect on CV system

Front 31

What are the dosage considerations of carbachol?

Back 31

Available only in opthalmic soln (wide angle glaucoma). Resistant to ChE

Front 32

What is the clinical use of carbachol?

Back 32

Not used systemically (due to nicotinic actions). Treat wide angle glaucome & produce miosis during surgery

Front 33

What are the side effects of carbachol?

Back 33

Rare system effects w/ local use, pupillary constriction, accomodative spasm (cyclospasm) & headache, red eye

Front 34

What is the action of bethanochol?

Back 34

Muscarinic effects similar to carbachol. No nicotinic activity

Front 35

What are the dosage considerations of bethanochol?

Back 35

Given po & sc. Totally resistant to ChE

Front 36

What is the clinical use of bethanochol?

Back 36

Treat urinary retention, postoperative abdominal distension, intoxication os rare

Front 37

What are the side effects of bethanochol?

Back 37

Flushing, sweating, bronchoconstriction, abdominal cramps, salivation, diarrhea, headache, difficult visual accomodation. Overdose can cause cardiac arrest

Front 38

What are the contraindications of bethanochol?

Back 38

Peptic ulcer, asthma, coronary insufficiency, caution w/ bradycardia or hypotension.

Front 39

What are the drug interactions of bethanochol?

Back 39

Antagonized by quinidine & procainamide.When combined w/ serotonin (reserpine) can cause hyperthermia

Front 40

What is the action of muscarine?

Back 40

Only muscarinic

Front 41

What is the absorption & inactivation of muscarine?

Back 41

Absorbed from GI. Crosses BBB. Resistant to ChE

Front 42

What is the clinical significance of muscarine?

Back 42

Not used as a drug. Mushroom poisoning

Front 43

How is muscarine poisoning treated?

Back 43

atropine

Front 44

What are the actions of pilocarpine?

Back 44

Predominately muscarinic (M3) when applied topically. CV is less sensitive than othe organs

Front 45

What are the dosage considerations for pilocarpine?

Back 45

Only as opthalmic useor oral for dry mouth

Front 46

What is the clinical use of pilocarpine?

Back 46

Intraocular pressure in wide angle glaucoma

Front 47

What are the side effects of pilocarpine?

Back 47

Ciliary spasm, eye vascular congestion, headache, reduced visual acuity