2 Pharm: Cholinergic Agonists, Antagonists

Front 1

Physostigmine gen

Back 1

Physostigmine gen:
- cholinesterase inhibitor
- tertiary amine, hydrolyzed by plasma esterases
- crosses blood-brain barrier
- miosis, salivation, inc GI motility
- large doses: skeletal m fasiculation, followed by paralysis
- not commonly used

Front 2

physostigmine therapeutic use

Back 2

physostigmine therapeutic use:
- topical tx: simple, secondary glaucoma
- IM, SQ or PO: counteract atropine, muscarinic drug intoxication

Front 3

neostigmine gen

Back 3

neostigmine:
- cholinesterase inhibitor
- tertiary amine, hydrolyzed by plasma esterases
- does not cross b-b barrier
-

Front 4

neostigmine action

Back 4

neostigmine action:
- inhibits AChE, inc ACh from nerve endings
- acts directly on skeletal neuromuscular jxn

Front 5

neostigmine therapeutic use

Back 5

neostigmine therapeutic use:
1. reversal of neuromuscular blockers
2. paralytic ileus
3. atony of u bladder
4. myasthenia gravis-like conditions
- contraindication: GI and urinary obstruction
- duration: 0.5- 2 hrs

Front 6

edrophonium

Back 6

edrophonium (tensilon):
- cholinesterase inhibitor
- quaternary ammonium comp'd
- action like neostigmine
- dx of myasthenia gravis-like dz
- antagonize tubocurarine-like drugs

Front 7

pyridostigmine and demercarium

Back 7

pyridostigmine (mestinon) and demercarium:
- cholinesterase inhibitors
- similar to physostigmine and neostigmine
- longer action: 4-6 hrs
- dem: topical glaucoma tx

Front 8

carbaryl and propoxur

Back 8

carbaryl and propoxur:
- carbamate anti-cholinesterase
- flea control (ectoparasiticides)
- overdose similar to organophosphate poisoning, tx atropine

Front 9

ecthiophate

Back 9

ecthiophate:
- quaternary organophosphate
- long action > 12hr
- topically: tx open angel glaucoma
- ectoparasitacides

Front 10

dichlorvos

Back 10

dichlorvos:
- organophosphate
- anti-helmintic and pesticide

Front 11

organophosphates

Back 11

organophosphates:
1. ecthiopate
2. diisopropyl fluorophosphate (DFP)
3. tetraethylpyrophosphate (TEPP)
4. parathion, malathion
5. soman, tabun, sarin: nerve gases
6. dichlorvos

Front 12

organophosphate signs

Back 12

organophosphate signs:
1. salivation, lacrimation
2. urination, defecation
3. dyspnea
4. miosis
5. bradycardia
6. anorexia, vomiting

Front 13

organophosphate neuro signs

Back 13

organophosphate neuro signs:
1. convulsion
2. skeletal m fasiculation
3. respiratory failure: inhibition of respiratory center in medulla, bronchial spasm
- death due to respiratory arrest

Front 14

organophosphate tx

Back 14

organophosphate tx:
1. detox: dermal, oral exposure
2. stabilization: anticonvulsants, respiratory support
- doxapram/ dopram: universal respiratory stim
3. antidote:
- atropine: counteracts symptoms, doesn't reactivate AChE
- pyridine-2-aldoxime methiodide (2-PAM): reactivates AChE

Front 15

PS antagonists/ parasympathetolytic agents

Back 15

PS antagonists/ parasympathetolytic agents:
1. atropine
2. glycopyrrolate
3. scopolamine (hyoscine)
4. propantheline
5. tropicamide
6. pirenzepine
7. aminopentamide (centrine)

Front 16

Atropine gen

Back 16

Atropine gen:
- PS antagonist: anti-muscarinic
- tertiary amine
- competitive, non-selective (acts in heart, lung, etc) of Ach at muscarinic receptors
-

Front 17

atropine effects

Back 17

atropine effects:
1. heart: SA node= tachycardia
2. CNS: toxic dose= excitation followed by depression
3. smooth m: dec GI amplitude and freq of contraction, bronchodilator
4. eye: mydriasis, blocks sphincter of iris, cycloplegia (inability to accomodate for near vision), inhibits cholingeric control of ciliary mm of lens

Front 18

atropine therapy

Back 18

atropine therapy:
1. preanesthetic: dec salivary and resp secretion
- not in horse, R because slows down GI, thickens saliva which can cause choking
2. opthamology
3. renal and biliary colic
4. counter effects of anti-AChE drugs: neostigmine, thysostigmine

Front 19

atropine HL

Back 19

atropine HL:
- 2.5 hrs
- most excreted in urine w/i 12 hrs

Front 20

atropine adverse effects

Back 20

atropine adverse effects:
1. tachycardia
2. photophobia
3. inc body T
4. restlessness
5. disorientation and CNS stim

Front 21

atropine toxicity

Back 21

atropine toxicity:
1. neostigmine. physostigmine
2. control CNS stim with benzodiazepines

Front 22

glycopyrrolate (robinul)

Back 22

glycopyrrolate (robinul):
- PS antagonist (anti-muscarinic)
- synthetic quarternary ammonium compound
- preanesthetic IV, IM, SQ
- doesn't enter CNS or eye
- effects longer than atropine: 2-3 hrs, antisalivation up to 7 hrs
- elimination primarily by kidney, not metabolism

Front 23

scopolamine (hyocine) and N-butylscopolammonium (bucospan)

Back 23

scopolamine (hyocine) and N-butylscopolammonium (bucospan):
- PS antagonists, anti-muscarinic
- resemble atropine
- crosses B-B barrier
- control motion sickness
- Bucospan: Eq IV as anti-spamodic in colic, intestinal impaction
- cause excitation or sedation

Front 24

propantheline

Back 24

propantheline:
- PS antagonist (anti-muscarinic)
- small animal anti-spasmodic, diarrhea tx
- eq: relaxes for rectal exam to prevent injury

Front 25

tropicamide

Back 25

tropicamide:
- PS antagonist (anti-muscarinic)
- shorter duration
- opthalmology

Front 26

pirenzepine

Back 26

pirenzepine:
- PS antagonist (anti-muscarinic)
- dec gastric acid secretion

Front 27

autonomic ganglionic agonists

Back 27

autonomic ganglionic agonists:
1. nicotine: nicotinic receptor
2. anti-nematodal: levamisole, pyrantel, morantel
- activate nicotinic in S and PS ganglia: stimulate post-ganglionic neurons
- mimic ACh action

Front 28

autonomic ganglionic antagonists

Back 28

autonomic ganglionic antagonists:
- act at post-ganglionic nicotinic: blocks S and PS transmission
1. hexamethonium
2. trimethaphan
3. mecamylamine

Front 29

cholinergic agonists

Back 29

cholinergic agonists:
1. choline
2. acetylcholine
3. methacholine: acetyl-b-methylcholine
4. carbachol: carbamylcholine
5. bethanecol
6. plant alkaloids: pilocarpine, aerocholine, muscarine

Front 30

cholinergic smooth m, gland effects

Back 30

cholinergic smooth mm and gland effects:
- stim M3
1. inc GI motility, secretion
2. smooth m contraction: uterus, ureters, bladder, bronchi and sphincter of iris mm
3. bronchial constriction
4. inc salivary, lacrimal gland secretion

Front 31

cholinergic CNS effects

Back 31

cholinergic CNS effects:
- musc and nico in CNS
- ACh in circulation: no effect as lipophobic and poorly penetrates B-B barrier

Front 32

cholinergic cardio effects

Back 32

cholinergic cardio effects:
- similar to vagal stim:
1. - inotropic
2. - chronotropic
3. vasodilation: most peripheral vessels not cholinergically innervated so little control of BP
- some ACh analogs inhibit release of NE from S end nerve terminal by activating M2 receptors on endothelial cells: NO release causing vasodilation

Front 33

ACh effects on other systems

Back 33

ACh effects on other systems:
- little use in therapy except topical to constrict pupil in ocular sx
- atropine: muscarinic antagonist
- somatic NM jxn

Front 34

drug effects of cholinergic agents

Back 34

drug effects of cholinergic agents:
SLUDGE
1. Salivation
2. Lacrimation
3. Urination, urinary incontinence
5. Diarrhea
6. GI cramps
7. Emesis

Front 35

drug effects of cholinergic agents

Back 35

drug effects of cholinergic agents:
1. stim intestine: secretion, motility
2. stim bladder: inc urine freq
3. stim pupil: miosis (constriction), dec intraocular P

Front 36

cholinergic rx

Back 36

cholinergic rx:
synthetic choline ester compounds that act similar to ACh:
1. methacholine
- more active in GI than cardio
2. carbachol
3. bethanecol

Front 37

carbachol

Back 37

carbachol:
- cholinergic agonist
- quarternary N compound with carbamic acid ester bond not hydrolyzed by AChE
- activates M and N

Front 38

carbachol therapy

Back 38

carbachol therapy:
1. topical producing miosis
2. SQ: tx GI, rumen or uterine atony, impaction
- use w/ caution to prevent rupture of tracts

Front 39

bethanechol

Back 39

bethanechol:
- muscarinic agonist
- resembles carbachol: quarternary N compound resistant to AChE hydrolysis

Front 40

bethanechol therapy

Back 40

bethanechol therapy:
1. SQ tx for bladder distention: inc contractility
2. GI and uterine atony: caution as may cause rupture
- no GI abs

Front 41

pilocarpine

Back 41

pilocarpine:
- cholinergic agent: primarly M
- tertiary amine alkaloid
- doesn't cross cell mem
- arecoline similar action

Front 42

pilocarpine therapy

Back 42

pilocarpine therapy:
1. glaucoma: dec intraocular P
2. like ACh: stim exocrine galnds, saliva, mucous, gastric/ dig/ pancreatic secretions

Front 43

anti-cholinesterase agent

Back 43

anti-cholinesterase agents:
1. reversible: physostigmine, edrophonium, pyridostigmine
2. irreversible: organophosphates eg diisopropyl fluorophosphate (DFP)