ANS Cholinergic

Question 1

parasympathetic effect on the eye

Answer 1

M3 - Miosis (contraction of sphincter muscle)
M3 - accomodation cyclospasm (near vision contraction of ciliary muscle)
used in opthalmic exams/glaucoma
long term use may lead to cataracts/retinal detachment

Question 2

Muscarinic Antagonism effect on the eye

Answer 2

M3 - Mydriasis (dilation)

M3 - accomodation to far vision leading to cycloplegia

Question 3

Hemicholinium

Answer 3

inhibit choline active transport pp to presynaptic nerve endings.

Question 4

Botulinum Toxin

Answer 4

inhibits Ach exocytosis by interaction with
“clostridum botulinum”
bacterial entersthru recycling vessicle reuptake
synaptobrevin. degrades SNAP-25 preventing vessicle fusion to membrane (protease prevents SNARE complex)
Rx. blepharospasm, strabismus, hyperhydrosis, dystonia, and cosmetics

Question 5

Acetylcholinesterase inhibitors

Answer 5

indirect acting cholinomimetics
Reversible: edrophonium, physostigmine, neostigmine
Irreversible: echothiophate, malathion, parathion

Question 6

Muscarinic effect on the heart

Answer 6

M2 - SA node negative chronotropy
M2 - AV node negative dromotrophy
used in supraventricular tachycardia (SA node M2 receptors via vagus nerve)

Question 7

Muscarinic effect on the Lungs

Answer 7

M3 - bronchioles contraction (bronchospasm)

M3 - gland secretions

Question 8

Muscarinic effect on the GI tract

Answer 8

M3 - increased motility and cramping
M1 - increase secretions
M3 - contraction. diarrhea/involuntary defecation

Question 9

Muscarinic effect on the Bladder

Answer 9

M3 - contraction of detrussor
relaxation of the trigone/sphincter
voiding/urinary incontinence

Question 10

muscarinic effect on the sphincters

Answer 10

M3 - relaxation

lower esophageal contracts!

Question 11

muscarinic effect on the glands

Answer 11

M3 - secretion. sweat thermoregulation, salivation, lacrimation

Question 12

muscarinic effect blood vessel endothelium

Answer 12

M3 - dilation (NO/endothelial derived relaxing factor
NO innervation (no effect indirect agonists AchE inhibitors)

Question 13

Cholinergic receptor mechanism

Answer 13

M1 and 3 (Gq) phospholipase C (IP3/Dag/Ca+)
M2 (Gi) decrease adenylyl cyclase, cAMP
Nn and Nm are both ionic Na/K channels

Question 14

AcetylCholine

Answer 14

M and N choline ester direct agonist
short half life, no clinical use
quickly metabolized by AchE
intraoccular use for cataract surgery to stimulate rapid miosis

Question 15

Bethanechol

Answer 15

M choline ester direct agonist
no AchE hydrolysis, no CNS
DoA ~2hrs
Rx. ileus (postop/postpardum/neurogenic), urinary retention

Question 16

Methacholine

Answer 16

M>N direct agonist
some AchE hydrolysis (unpredictable magnitude)
Dx bronchial hyperreactivity (asthma)

Question 17

Pilocarpine

Answer 17

M direct agonist
no AchE hydrolysis. uncharged (CNS)
Doa ~2hrs. less potent than Ach itself.
Rx. glaucoma (topical), xerostomia

Question 18

Edrophonium

Answer 18

indirect cholinomimetic - AChE Inhibitor
short acting
Diagnosis Myasthenia gravis from cholinergic crisis

Question 19

Myasthinia Gravis

Answer 19

“autoimmune HSR type II disease acting on the nicotinic cholinergic Ach Receptors (muscular end plates fast inotropic inhibited by curare).
Muscle weakness with prolonged activity, worsening over the day, ptosis, double vision, difficulting swallowing/chewing/speaking,
Tx. With long DoA AChE inhibitor (…stigmine)
DD. Lambert-Eaton wiich is worse in morning when Ca+ is lowest

Question 20

Cholinergic crisis

Answer 20

Organophosphates/carbamates etc.
Rx. with atropine (effects) and pralidoxime (AchE regenerator)
DUMBBELSS
diarrhea, urination, miosis, bradycardia, bronchoconstriction, excitation (CNS/ nicotinic muscle excitation then paralysis), lacrimation, salivation, sweating.
nicotinic effects: skeletal excitation followed by paralysis, CNS stimulation

Question 21

lambert-Eaton

Answer 21

autoimmune disease HSR type II acting on the presynaptic voltage-gated Ca+2 channels preventing excocytosis of Ach to act on nAchR of the motor end plate.
Muscle weakness worst in the morning when Ca+ is lowest.
dd. Myasthenia Gravis that acts on the AchR themselves and worsens at night with use.”

Question 22

Physostigmine

Answer 22

indirect cholinomimetic- AchE inhibitor
enters CNS
DoA ~3hrs (intermediate)
Rx. Glaucoma
Rx. Atropine overdose +/- symptomatic (and antidepressant OD)

Question 23

Neostigmine

Answer 23

indirect cholinomimetic- AchE inhibitor
NO CNS
DoA short acting more potent than physostigmine. Contraction before paralysis.
Rx. Ileus
Rx. urinary retention
Rx. myasthenia
Rx. reversal of nondepolarizing NMJ blockers (curare)

Question 24

pyridostigmine

Answer 24

indirect cholinomimetic- AchE inhibitor
NO CNS
DoA ~4hrs 
Rx. Ileus
Rx. urinary retention
Rx. myasthenia
Rx. reversal of nondepolarizing NMJ blockers (curare)

Question 25

Indirect acting cholinomimetics

Answer 25

``` AChE inhibitors: -endrophonium (short acting diagnostic) -physostigmine (CNS - atropine antidote) -neostigmine and pyridostigmine (rx ileus, urine ret, myast, reverse NMJ blockes) -donepezil (CNS -Alz) -tacrine (CN - Als with hepatic effects) Irreversible: organophosphates ( toxin rx glaucoma detox with paralidoxime) - echothiophate, parathion, malathion ```

Question 26

Alzheimers

Answer 26

late onset dementia with progressive memory loss ad cognitive decline. Neurropathology includes neurofibrillary tangles, amylid plaques, and loss of Ach neurons in the Meynert's necleus rational for clinical use of AchE inhibitors. degeneration of neurons in specific regions of cerebral cortex and hippocampus. Most common cause of dementia, incraease with age. Sporatic/ rarely familial. Increased risk in patients with Downs syndrome (ch21) often by 40YOA 4 genes are associated: 9amyloid precursor protein) APP encoding betaAPP, PSEN1 and 2 coding for presenilin. APOE is not associated with monogenic alzhymers but increases susceptability to nonfamilial (most common form) and influences the age of onset of some monogenetic forms. * Deposition of two fibrillary proteins (intracellular): Beta-amyloid and Tau (neurofibrillay tangles extracellular) [hirano bodies] - amyloid/senile plaques which contain amyloid and APOE lipoproteins form in the extracellular spaces - Tau proteins are microtubule-associated axon structural support proteins abundant in the brain, hyperphosphorylations of which compose the intracellular neurofibrillary tangles found within neurons. Although accumulation of tau fibrillary tangles is one cause of neuro degeneration in alheimers, the actual Tau protein mutations are associated with other neurodegenative deseases such as AD demenia, frontotemporal dimentia. - The beta-APP amyloid presursor protein (21q21.3) proteolytically cleaved by Alpha, beta, (both cell surface) and gamma (atypical) secretases. 90% betaAPP are cleaved by alpha protease which cleaves within the beta-amyloid (Abeta) domain precluding its formation. The remaining 10% cleaved by beta and gamma protease into Abeta40 and very little Abeta42. Mutations are seen to increase the production of Abeta42 a neurotoxin. Diagnostically Abeta42 elevated in plasma serum. Presenilin 1 and 2 also increase production of Abeta42 as they are critical cofactors for gamma protease. Mutation in PSE1 has earlier onset of symptons than mutations in PSEN2. APOE is a component of the alzhymer amyloid plaques by binding to the Abeta proteins. Three common allleles for APOE gene Echo2,3 and 4. APOEecho4 homozygots have onset before 70yrs, heterozygots after 70yrs. Those with APOEecho2 are shown to have later onset. Carriers of the APOE echo4 allele are also shown to have poorer outcomes of head injury. * final stages are primive reflexs and death by malnutrition, secondary infections, heart disease.

Question 27

Parathion

Answer 27

indirect cholinomimetic - irreversible AChE inhibitor Organophospates insecticide/military weapons DUMBBELSS diarrhea, urination, miosis, bradycardia, bronchoconstriction, excitation (CNS/ nicotinic muscle excitation then paralysis), lacrimation, salivation, sweating. RX. atropine/pralidoxime

Question 28

Malathion

Answer 28

indirect cholinomimetic - irreversible AChE inhibitor Organophospates - degraded by UV light. tx head lice DUMBBELSS diarrhea, urination, miosis, bradycardia, bronchoconstriction, excitation (CNS/ nicotinic muscle excitation then paralysis muscle), lacrimation, salivation, sweating. RX. atropine/pralidoxime

Question 29

Pralidoxime

Answer 29

regeneration of AchE rx in cholinergic crisis due to AChE Inhibitor overdose functions by reversing the phosphorylation of AchE and by aging of the organophosphate by cleaving it. Atropine used for muscarinic management effect.

Question 30

Atropine

Answer 30

``` muscarinic receptor antagonist (prototype) CNS activity management of AchE inhibitor overdose antisecretory mydriasis/cycloplegia (short acting) hyperthermia (vasodilate) tachycardia sedation urinary retention and antidiarrheal behavioral excitation and hallucinations (antispasmolitic) C/I narrow anlge glaucoma, ```

Question 31

Drugs with antimuscarinic effects

Answer 31

``` antihistamines tricyclic antidepressants quinidine amantadine meperidine C/I narrow anlge glaucoma, ```

Question 32

Tropicamide

Answer 32

direct muscarinic blocker | opthalmology (topical)

Question 33

scopolamine

Answer 33

direct muscarinic blocker rx motion sickness sedation short term memory block

Question 34

Benztropine

Answer 34

direct muscarinic blocker lipid soluble (CNS) Rx Parkinsonism Rx acute extra pyramidal symptoms induced by antipsychotics

Question 35

trihexyphenidyl

Answer 35

direct muscarinic blocker lipid soluble (CNS) Rx Parkinsonism Rx acute extra pyramidal symptoms induced by antipsychotics

Question 36

ipratropium

Answer 36

direct muscarinic blocker asthma and COPD (inhalation) NO CNS no change in mucus viscosity

Question 37

Donepezil

Answer 37

``` indirect cholinomimetic- AchE inhibitor lipid soluble (CNS) Rx. alzheimers (oral bioavail 100% long DoA) ```

Question 38

Tacrine

Answer 38

indirect cholinomimetic- AchE inhibitor lipid soluble (CNS) Rx. alzheimers no longer used due to liver toxic

Question 39

Organophophates and carbamates

Answer 39

``` indirect cholinomimetic- AchE inhibitor irreversible toxin, lipid soluble (CNS) rx glaucoma detox with paralidoxime DUMBBELSS diarrhea, urination, miosis, bradycardia, bronchoconstriction, excitation (CNS/ nicotinic muscle excitation then paralysis), lacrimation, salivation, sweating. ```

Question 40

echothiophate

Answer 40

indirect cholinomimetic- AchE inhibitor irreversible toxin, lipid soluble (CNS) rx glaucoma detox with paralidoxime

Question 41

Chronic AchE inhibitor toxicity

Answer 41

peripheral neuropathy causing muscle weakness and sensory loss. demyelination not due to AchE inhibition

Question 42

Parkinsons

Answer 42

loss of pigmented dopamine secreting dopaminergic neuronal cells of the substantia nigra. Associated with somatic deletion of mtDNA and subsequent clonal expansion of the deletions in each cell. Treat with L-dopa (but acts globaly acting on the affect, motivation,and reward center of the brain which can lead to psychosys) Lewy Bodies

Question 43

ANS pharm on dually innervated tissue

Answer 43

``` PANS dominates in dual innervation SA and AV nodes- bradycardia pupil (miosis constriction/accomodation near vision cyclospasm) salivation GI and GU muscles sphincters ``` SANS is only dominant in vascular tone (veins and arterioles) and thermoreg sweat glands.

Question 44

hexamethonium

Answer 44

Nn nicotinic receptor antagonist (ganglion block SANS or PANS) reduce predominant autonomic tone (basal) prevent baroreceptor reflex in HR toxicity - rarely used

Question 45

mecamylamine

Answer 45

Nn nicotinic receptor antagonist (ganglion block SANS or PANS) reduce predominant autonomic tone (basal) prevent baroreceptor reflex in HR toxicity - rarely used

Question 46

Baroreflex

Answer 46

increase MAP - increase APs (rate of change) * Aortic arch thru Vagus (X) * Carotid Sinuses thru glossopharyngeal (IX) nucleus tractus solitarius of the medulla * efferent PANS vagus X to SA node (M2) * efferent SANS to SA, AV, muscle, Artierioles, Veins. (B1 and a2) vasodilate (B2)

Question 47

Charbachol

Answer 47

M choline ester direct agonist doa ~1 hr, poor AchE substrate tx glaucoma

Question 48

Muscarine

Answer 48

M direct agonist Toxic mushroom DUMBBELSS diarrhea, urination, miosis, bradycardia, bronchoconstriction, excitation (CNS/ nicotinic muscle excitation then paralysis), lacrimation, salivation, sweating.

Question 49

Cevimeline

Answer 49

M natural alkaloid direct agonist M1/M3 agonist (M2 is cardio) tx xerostomia (used with pilocarpine)

Question 50

Rivastigmine

Answer 50

indirect cholinomimetic- AchE inhibitor transdermal patch tx Alzheimers, dimentia, parkinsons

Question 51

Galantamine

Answer 51

indirect cholinomimetic- AchE inhibitor | tx alzeimers. natural OTC sleep aid.

Question 52

propantheline

Answer 52

direct muscarinic blocker | rx urge incontinence

Question 53

terodiline

Answer 53

direct muscarinic blocker | rx urge incontinence

Question 54

darifenacin

Answer 54

direct muscarinic blocker M3 selective rx urge incontinence

Question 55

solifenacin

Answer 55

direct muscarinic blocker M3 selective rx urge incontinence

Question 56

fesoterodine

Answer 56

direct muscarinic blocker | rx urge incontinence

Question 57

tolterodine

Answer 57

direct muscarinic blocker | rx urge incontinence

Question 58

trospium

Answer 58

direct muscarinic blocker | rx urge incontinence

Question 59

cyclopentolate

Answer 59

direct muscarinic blocker | opthalmologic produce myadriasis and cycloplegia prior to refraction

Question 60

tiotropium

Answer 60

direct muscarinic blocker NO CNS DoA long, inhaled solutions Tx Asthma/COPD, xerostomia nasal spray

Question 61

trimethaphan

Answer 61

Nn nicotinic receptor antagonist (ganglion block SANS or PANS) reduce predominant autonomic tone (basal) prevent baroreceptor reflex in HR toxicity - rarely used Oral, CNS, DoA ~10hrs Tx Aortic dissection decrease BP in emergency