cholinergics

Question 1

Muscarinic receptor agonists (parasympathomimetics)

Answer 1

direct agonists of muscarinic receptors

produce effects similar to those observed during stimulation of post ganglionic parasympathetic nerves

Question 2

Muscarinic receptor antagonists (parasympathlytics, antimuscarinic agents)

Answer 2

completely block muscarinic receptors, interfere with responses that result from parasympathetics stimulation

Question 3

Acetylcholinesterase inhibitors (Anticholinesterase

Answer 3

agents that enhance the effects of endogenously produced Ach by blocking its natural breakdown by the enzyme acetylcholinesterase
effective at any site where Ach is the NT

Question 4

Ganglionic blocking agents

Answer 4

neural nicotinic receptor antagonist

competitve antagonists for nicotinic receptors at autonomic ganglia

interfere with ganglionic transmission of both parasympathetic and sympathetic nerves

Question 5

where are muscarinic receptors located

Answer 5

autonomic effector cells innervated by post gang Parasymp

also located on some cells that have no cholinergic innervation (vascular endothelial cells)

located within CNS

actions are blocked by atropine

Question 6

properties and subtypes of muscarinic receptors

Answer 6

5 subtypes (all are GPCRs), widely distributed most cells express a few subtypes but one usually predominates

M2s: functionally dominant subtype in heart
M3s: functionally dominant subtype in smooth muscle, secretory glands, eyes and vascular endothelium

Question 7

effects of muscarinic receptor activation on CV, pulm, UT, GI, misc peripheral effects, CNS effects

Answer 7

CV: Vasodilation (M3 endothelial, M2 decrease HR, M2 decrease AV node)

pulm: bronchoconstriction M3, tracheobronchial secretion M3

UT: detruser muscle contraction M3

GI: increased tone, amp contractions, secretion M3

misc peripheral effects: increase secretion glands M3, miosis and accommodation M3

CNS effects: cortical arousal, all 5 receptors

Question 8

Choline esters

Answer 8

bethanechol, resistant to hydrolysis by cholinesterases, thus T1/2 is increased compared to Ach

Quaternary amines, low F, does not cross BBB

non-selective

Question 9

Naturally occuring alkaloids

Answer 9

pilocarpine is a tertiary amine, therefore readily absorbed after oral admin penetrates CNS

non selective

Question 10

Bethanecole

Answer 10

primary effect: on UT and GI tracts

orally or subQ for urinary retention (post op, diabetic neuropathy, hypoactive bladder)

Question 11

Pilocarpine

Answer 11

used for treatment of xerostomia (due to head and neck radiation Sjörgren syndrome)

Topically in opthalmology for treatment of glaucoma and as mitotic agent

Question 12

side effects and contraindications of muscarinic receptor activations

Answer 12

common side effects: diaphoresis, diarrhea, nausea, difficulty with accommodation, and hypotension
contraindications: asthma and COPD, UT or GI obstruction, acid peptic disease, CV disease accompanied by brady cardia or hypotenstion

Question 13

Toxicology of muscarinic agonists (parasympathomimetics, pilocarpine, bethanecole)

Answer 13

poisoning by ingestion of muscarinic agonists:
SLUDGE (salivation, lacrimation, urination, defecation, gastrointestinal upset, emesis) also hypertension, and bradycardia, and difficulty with accommodation

reversal with atropine

Question 14

muscarinic receptor antagonists (parasympatholytics, or antimuscarinics) and their effects (CV, resp, eye, GI, smooth muscle, sweat glands, CNS)

Answer 14

competitve inhibitors of muscarinic receptors

CV- tachycardia, Av nodal conduction (M2), block reflex vagal slowing of HR and AV node, no effect on vascular tone or BP

Resp- bronchodilation, dec. tracheobronchial secretions (M3 receptor), dries mucous membranes of resp tract

eyes- dilate pupils (mydriasis) and paralyze accommodation by blocking cholinergic response of the pupillary sphincter muscle and ciliary muscle (M3 - photophbia)

GI: decrease secretions, decrease motility (M3)

sm muscl: decrease in tone of ureter and bladder (M3)

sw gland: inhibit activity of sweat, increases body temp

CNs: depression and drowsiness

Question 15

naturally occuring alkaloids of muscarinic antagonist

Answer 15

from belladonna plants (atropine, and scopolamine)

Question 16

semisynthetic of muscarinic antagonist

Answer 16

ipratropium

Question 17

synthetics of muscarinic antagonist

Answer 17

tropicamide, oxybutynin, darifenacin, glycopyrrolate

Question 18

atropine

Answer 18

prototypical antagonist
non-subtype selective muscarinic receptor antagonistss, absorbed orally by the GI tract
Therapeutic uses: bradyarrythmias due to high vagal tone
ophthalmic uses (to produce mydriasis and cycloplegia/paralysis of accommodation)
long acting, treats chronic inflammatory disorders
uses during anesthesia (blocks responses to vagal reflexes and reduces tracheobronchial secretions)

anticholinesterase or muscarinic toxicity

Question 19

scopolamine

Answer 19

non-subtype selective muscarinic receptro antagonist,

greater CNS penetration

major use is to treat motion sickness and vestibular disease

available as a transdermal patch

Question 20

ipratropium

Answer 20

non-subtype selective muscarinic receptor antagonist

Quaternary ammonium compund used exclusively for respiratory tract (inhalation)

COPD

reduces bronchosecretions and alleviates bronchoconstriction

Question 21

tropicamide

Answer 21

opthalmic solution to produce mydriasis and cycloplegia

fast acting and short duration

Question 22

oxybutynin

Answer 22

Urinary incontinence

high incedents of antimuscarinic side effects

Question 23

darifenacin

Answer 23

urinary incontinence
M3 receptors
less CNS side effects than oxybutinin

Question 24

glycopyrrolate

Answer 24

blocks parasympathomimetic effects during reversal of NMJ blockade with anti cholinesterase agents

quaternary amine-> no CNS penetration

Question 25

side effects of muscarinic antagonists, contraindications and toxicity

Answer 25

xerostomia, blurred vision, dyspepsia, constipation, cognitive impairment contraindications: urniary or GI tract obstruction, uncontrolled glaucoma, benign prostatic hyperplasia, conditions worsened by tachycardia toxicology: belladonna alkaloids, Hot as hare (no sweating), dry as a bone (dry mouth), red as a beet (excessive heat), blind as a bat (mydriasis), mad as a hatter (ataxia etc) treat with physostigmine

Question 26

acetylcholinesterase inhibitors

Answer 26

cause an increase in acetylcholine in the vicinity of cholinergic nerve terminals aka anticholinesterase agents insecticides, pesticides, nerve gases loci: where Ach is released: muscarinic receptors, autonomic ganglia, CNS therapeutic uses for: atony of smooth muscle of GIT, UT, glaucoma, mg, reversal of competitve NMJ blocking drugs

Question 27

enzymatic hydrolysis of Acetylcholine

Answer 27

transiently acetylated at numerous loci on the enzyme

Question 28

non covalent (reverisble) inhibitors of AchE

Answer 28

Edrophonium: quaternary ammonium (no CNS activity), must be IV administered, rapid onset and short durations Used for diagnosis of MG, and the reversal of paralysis by competitive NM blocking drugs

Question 29

Reversible carbamate inhibitors of AchE

Answer 29

hydrolyzed by AchE but at a slow rate Physostigmine: alkaloid from calabar bean, slowly reversible (hrs) tertiary amine (has CNS effects) uses treatment of chronic wide angle glaucoma, treats toxicity of CNS antimuscarinic agents) Neostigmine: slow reversible, quat amine no CNS effects), treatment of MG oral, preventation and treatment of post op atony of gut and bladder, reversal of paralysis by competitive NMJ blocking drugs

Question 30

organophosphorus compounds

Answer 30

phosphorylate the AchE, return of the activity depends on synthesis of new enzymes, lipophilic and penetrate CNS Nerve gases: sarin Insecticides: malathion (rapidly detoxed in higher order organisms) toxicity: SLUDGE +hypotension+bradycardia+difficiuly with eyes reduced respiration, muscle paralysis, death antidotes: atropine and with moderate to severe pralidoximine (reactivates AchE, but not effective with aged)

Question 31

ganglionic blocking drugs

Answer 31

Ach is released from parasympathetics and sympathetic pre ganglionic neurons, activates postganglionic nicotinic receptors (cation influx) neural nicotinic receptor antagonist - specifically block both the parasympathetic and sympathetic systems leads to vasodilation

Question 32

competitive neuromuscular blocking agents

Answer 32

aka non-depolarizing drugs antagonists of nicotinic receptors at the neuromuscular junction (Nm) duration of action: short, medium, long duration side effects: Nn receptor blockade, M receptor blockade, releaase of histamine route of elimination: inactivated by metabolism or removed by renal excretion

Question 33

Rocuronium

Answer 33

intermediate duration of action, but rapid onset of action, can be used to facilitate endotracheal intubation, hepatic elimination, no Nn/receptor blocking or histamine releaseing effects also cisatracurium, vecuronium, pancuronium (long)

Question 34

depolarizing neuromuscular blockers

Answer 34

activate nicotinic receptors at NMJ maintinging motor end plate depolarization Succinylcholine: has a quat ammonium, does not enter the CNS, not orally absorbed, allows tracheal intubation (rapid onset, short duration of action metabolized by pseudocholinesterase

Question 35

side/adverse effects of nmj block

Answer 35

prolonged apnea, CV collapse (due to histamine release anaphylaxis) ``` Malignant hyperthermia (succinylcholine) hyperkalemia ``` toxic effects: (respiratory paralysis, treat with positive pressure, neostigmine.edrophonium) +glycopyrrolate