Parasympathomimetics Flashcards
4 AMINOPYRIDINE
MECHANISM
K+ channel blocker
Research only!!
ACh
MECHANISM
nACh R and MACh R agonists
METACHOLINE
MECHANISM
selective mACh R agonist
INDICATION
Diagnosis of asthma / COPD bronchial hyperactivity. *Bronchial challenge test challenge test via M3 stimulation it constricts the bronchi.
SIDE EFFECTS: People with preexisting bronchial condition will react to lower dose of the drug (measured by spirometry)
CARBACHOL
MECHANISM:
NACh R and mACh R agonists
NO AChEsterase degradation!!
INDICATION:
Glaucoma
SIDE EFFECTS:
BETANECHOL
MECHANISM
mACh R agonist
NO AchEsterase degradation!!
INDICATION
Bladder and GI atonia fater spinal cord injury
SIDE EFFECTS
MUSCARINE
MECHANISM
mACh R agonist
NO CNS!!
INDICATION
none, it’s a mushroom poison!
SIDE EFFECTS
- myosis and blurred vision
- excessive salivation,sweating and lacrimation
- bronchoconstriction and increased bronchial secretion
- bradycardia
PILOCARPINE
MECHANISM
mACh R agonist
weak nACh R agonist in CNS
INDICATION
- Sjogren syndrome (xerastomia)
- Glaucoma : high IOP (in acute phase: 1st drug used)
SIDE EFFECTS
- bronchospasm
- bradycardia
- vasodilation
- diarrhea
ARECOLINE
MECHANISM
mACh R and nACh R agonists
INDICATION
- Alzheimer’s : memory and cognitive improvement
- antihelmintic drug
SIDE EFFECTS
carcinogenic (NOT 1st drug of choice)
NICOTINE
MECHANISM
nACh R agonist
INDICATION smoking cessation (eg. dermal patches, gums)
SIDE EFFECTS
risk of CVD (in long term use)
LOBELINE
MECHANISM
nACh R agonist
INDICATION
- smoking cessation (eg. dermal patches, gums)
- drug addiction treatment (eg. amphetamines,cocaine and alcohol)
SIDE EFFECTS
- nausea, vomiting and diarrhea
- visual and hearing disturbances
- dizziness
OTHERS:
- SERT and DAT reuptake inhibition
- VMAT 2 ligand : stimulate DA release alone, but dimishes DA release caused by metamphetamines
- MDR inhibitor (reduce chemotherapeutic resistance)
- nACh R AG/ATG
VARENICLINE
MECHANISM
partial nACh R agonist
INDICATION
-smoking cessation
SIDE EFFECTS
- nausea, vomiting
- nightmares and sleep disturbances
- headache
- depression
CEVIMELINE
MECHANISM mACh agonist (M1 and M3) stimulate salivary gland secretion (M3)
INDICATION Sjogren syndrome (xerostomia)
SIDE EFFECTS
- nausea, vomiting and diarrhea
- headache and blurred vision
CONTRAINDICATIONS
- asthma
- glaucoma
EDROPHONIUM
MECHANISM
AChEsterase inhibitor
NO CNS
INDICATION
differential diagnosis of myasthenia gravis (Ab against ACh R) and cholinergic crisis (AChE is inactive–>high ACh stimulation–>the muscles stop responding–>flaccid paralysis and respiratory failure
SIDE EFFECTS
- myasthenia gravis: E reduces muscle weakness
- cholinergic crisis: E inhibits more AChE thus worsening the muscle weakness
OTHER:
-15 mins duration
TACRIN
MECHANISM
AChEsterase inhibitor
CNS + !!
INDICATION
-Alzheimer’s (it is obsolete!)
SIDE EFFECTS
-liver damage
DONEPEZIL
MECHANISM
AChEsterase inhibitor
CNS + !!
INDICATION
-palliative treatment of Alzheimer’s: improves cognition
SIDE EFFECTS
- NO liver damage
- loss of appetite
- diarrhea, vomiting
- muscle cramping
PHYSOSTIGMINE
MECHANISM
AChEsterase inhibitor
CNS + !!
INDICATIONS
- Atropine or Scopolamine overdose
- Glaucoma
- Delayed gastric emptying
- Orthostatic hypotension
SIDE EFFECTS
- nausea, vomiting and diarrhea
- tremor
OTHER
2-3 hours duration
NEOSTIGMINE
MECHANISM
AChEsterase inhibitor
NO CNS!!
INDICATIONS
- Gut/bladder atonia
- Myasthenia gravis
- Glaucoma
- Stop muscle relaxant effect (Curare antidote)
SIDE EFFECTS
- bradycardia
- increased salivation
- nausea
OTHER
0.5-2 hours duration
PYRIDOSTIGMINE
MECHANISM
AChEsterase inhibitor
NO CNS !!!
INDICATIONS
- Gut/bladder atonia
- Myasthenia gravis
- Glaucoma
- Stop muscle relaxant effect (Curare antidote)
SIDE EFFECTS
OTHER
3-6 hours duration (P.O. administration)
DEMECARIUM
MECHANISM
AChEsterase inhibitor
NO CNS!!!
INDICATION
(P.O. administration)
-Glaucoma: reduce IOP (via myosis and ciliary muscle constriction–> facilitating aqueous humor outflow)
SIDE EFFECTS
- bradycardia and cardiac disturbance
- nausea and vomiting
- urinary incontinence
AMBENOMIUM
MECHANISM
AChEsterase inhibitor
NO CNS!!
INDICATION
(P.O. administration)
-Myasthenia gravis
SIDE EFFECTS
-nausea and vomiting
OTHER
4-8 hours duration
RIVASTIGMINE
MECHANISM
AChEsterase inhibitor
CNS!!!
INDICATION (administration: P.O. or dermal patches) cognitive,functional and behavioural improvement -Alzheimer's -Parkinson's induced dementia
SIDE EFFECTS
- nausea
- vomiting
Poison, Nerve gases
MECHANISM
AChEsterase inhibitor
NO indication
SIDE EFFECTS (prolonged effect) -convulsions -involuntary urination and defecation -pupil constriction, profuse salivation -death by asphyxiation
OTHER
Oximes can be given to reverse the effect of the poison while the enzyme is still not irreversibly inhibited.
HEMICHOLINUM
MECHANISM
Na/Choline transporter inhibitor (ChT)
INDICATION
No clinical use, only research!
TETRADOTOXIN
MECHANISM
Na channel inhibitor (no AP)
INDICATION
-local anesthetic
SIDE EFFECTS
- paresthesia of lips, tongue and extremities
- hypersalivation, sweating
- respiratory difficulty
OMEGA CONOTOXIN
ZICONOTIDE
MECHANISM
- Ca channel imhibitor
- NT vescicle release inhibitor
INDICATION
-CSF injection for chronic pain, FDA approved
VESAMICOL
MECHANISM
VAT (vesicular ACh Transporter) inhibitor
INDICATION
No clinical use, only research!
BOTULINUM TOXIN
MECHANISM NT vescicle release (SNARE) inhibitor (Clostridium Botulinum, gram + INDICATION -plastic surgery -muscle relaxant
SIDE EFFECTS
- infant (cause: honey):
1. floppy baby syndrome (hypotonia)
2. SIDS (sudden infant death syndrome) due to respiratory insufficiency - adult (cause: unproperly canned food)
1. blurred vision, nausea, vomiting
2. breathing/swallowing problem
3. muscle weakness
4. consitipation
ATROPINE
MECHANISM
mACh R antagonist
CNS: passes BBB!!
INDICATIONS
A.OPHTALMOLOGY
-Pupil dilation, long lasting (8days, not good, can cause glaucoma–> high IOP!!)
B.GASTROENTEROLOGY
-Biliary cramps (decreases SMC in gall bladder)–>always used together with PAPAVERIN (SMC relaxant, also used in erectile dysfunciton)
-Diarrhea: atropine + DIPHENOXYLATE –> centrally acting opioid with local GI effect–>decreases the peristalsis for stool consolidation
C. PULMONOLOGY
-Bronchodilation + inhibition of bronchial secretion
(not used)
D.NEUROLOGY
-Parkinson: Inhibits tremors. Side effect is mental depression.
E.ANESTHESIOLOGY
-Inhibits gastric acid secretion
-Prevents bradycardia and AV block during surgery
F.CARDIOLOGY
-Increases heart rate to normal tone–>inhibits parasympathetic effect on heart!
-2nd/3rd degree AV block treatment
G.NO effect on skeletal muscle (only nACh R!)
H.CHOLINERGIC POISONING: caused by organophosphate (eg.insecticides,nerve gases)–> AChE inhibition: high ACh
I.ANTIEMETIC (antivomiting)
Inhibits the vomiting triggering area of the medulla
SIDE EFFECTS
- Systemic 2-3h
- Local eye drops 7-10d!!!
Dose related effects:
- 0.5mg therapeutic dose
- 2-3mg tachycardia, fever in children (thermoregulation is via sweat glands–>inhibition=no sweating=high T)
- 3-5mg aphonia (speaking disturbance), swallowing difficulty
- 5-10mg confusion, hallucination, epilepsy, CNS extrapyrimidal effect
- > 10mg respiratory depression, vasodilation, hypotension
- 100mg lethal dose
Atropine poisoning:
1. Peripheral effect: dry mouth/skin, wide pupils, constipation, dysuria
2. CNS: hallucinations, restlessness, dyskinesia, epilepsy, coma, death
Therapy:
-Physostigmine IV for CNS
-Neostigmine for pheriphery
OTHER MNEMONIC for indications!!! "DUMBBELSS" Diarrhea Urination Myosis Bradycardia Bronchoconstriction Excitation (CNS: decrease EPSP, used for low tremor) Lacrimation Salivation Sweating (only sympathetic innervation using muscarinic receptors).
SCOPOLAMINE
MECHANISM
mACh R antagonist
CNS: passes BBB!
INDICATION
- Vomiting (kinetosis, motion sickness)
- Enhance anaesthesia effect
SIDE EFFECTS
- sedation
- amnesia (memory loss)
OTHER 2-3h shorter local effect! Dosage: -0.4mg therapeutic dose -500mg lethal dose
HOMATROPINE
MECHANISM
mACh R antagonist
CNS: psses BBB!
INDICATION
- Eye examination
- Mydriasis (pupil dilation=mAchR on sphincter pupil muscle)
SIDE EFFECTS
- 2-3d local effect
- less potent than atropine
- blurred vision, photosensitivity
TROPICAMIDE
MECHANISM mACh R antagonist CNS: passes BBB! INDICATION -Eye examination -Mydriasis (pupil dilation=mAchR on sphincter pupil muscle)
SIDE EFFECTS
- high IOP
- blurred vision
- photosensitivity
CYCLOPENTOLATE
MECHANISM mACh R antagonist CNS: passes BBB! INDICATION -Eye examination -Mydriasis (pupil dilation=mAchR on sphincter pupil muscle)
SIDE EFFECTS
- high IOP
- blurred vision
- photosensitivity
BENZATROPINE
MECHANISM
mACh R antagonist
CNS: passes BBB!
INDICATION
Tremor dominant Parkinson’s patients:
-improves tremor and rigidity
-alleviates bradykinesia (slow movements)
SIDE EFFECTS
- Dry mouth
- Blurred vision
- Cognitive changes
- Constipation and urinary retention
- Tachycardia
- Anorexia
BIPERIDEN
MECHANISM
mACh R antagonist
INDICATION
Tremor dominant Parkinson’s patients:
-improves tremor and rigidity
-alleviates bradykinesia (slow movements)
SIDE EFFECTS
- blurred vision
- dry mouth
- sleepiness
- constipation
- confusion
PROCYCLIDINE
MECHANISM
mACh R antagonist
CNS: passes BBB!
INDICATION
Tremor dominant Parkinson’s patients:
-improves tremor and rigidity
-alleviates bradykinesia (slow movements)
SIDE EFFECTS
- tachycardia
- hallucinantions
OXYBUTYNIN
MECHANISM
mACh R antagonist
CNS: passes BBB!
INDICATION
-hyperactive bladder syndrome
SIDE EFFECTS
- dry mouth
- difficulty in urination
- constipation
- blurred vision
- drowsiness
- dizziness.
TROSPIUM
MECHANISM
mACh R antagonist
NO BBB!
INDICATION
-hyperactive bladder syndrome: relaxation of the smooth muscle in the urinary bladder (detrusor muscle)
SIDE EFFECTS
- dry mouth
- indigestion
- constipation
PIRENZEPINE
MECHANISM
mACh R antagonist (M1)
NO BBB!
INDICATION
- High dose is needed, not good for therapeutic use
- ->PPI and H2 blockers are used instead
- peptic ulcer: reduces the gastric acid secretions and muscle spasm
SIDE EFFECTS
- delayed gastric emptying
- constipation
TELEZEPINE
MECHANISM
mACh R antagonist (M1)
CNS: passes BBB!
INDICATION
it’s 25 more potent than Pirenzepine!!
-peptic ulcer
SIDE EFFECTS
- delayed gastric emptying
- constipation
BUTYL-SCOPOLAMINE
MECHANISM
mACh R antagonist
NO BBB! (medulla oblongata: weak BBB, thus has little effect against nausea)
INDICATION
- SMC spasm (GI/bladder/biliary)
- antiemetic: chemoreceptor triggering zone inhibition
SIDE EFFECTS (minimal) -somnolence
IPRATROPIUM
MECHANISM
mACh R antagonist
NO BBB!
INDICATION Administration: Inhalation (local effect only!) -COPD -Bronchodilation -Anti bronchial secretion
SIDE EFFECTS (minimal)
- nausea, dry mouth
- sedation
TIOTROPIUM
MECHANISM
mACh R antagonist (M3)
NO BBB!
INDICATION
Long acting: 24 hours! Not used for acute state!
-Asthma treatment: bronchodilation effect
-Anti brochial secretion
SIDE EFFECTS (minimal)
- dry mouth
- throat irritation
HEXAMETHONIUM
MECHANISM
nACh R antagonist (Nneural)
it’s a ganglion blocker!! NO BBB!
INDICATION
poorly absorbed by GI
-chronic HTN (not used)
TRIMETAPHAN
MECHANISM
nACh R antagonist (Nneural)
it’s a ganglion blocker!!
INDICATION
- Hypertensive crisis (not used)
- Aortic dissection (not used)
MECAMYLAMINE
MECHANISM
nACh R antagonist (Nneural)
it’s a ganglion blocker!!
INDICATION
research!!
-anti HTN (not used)
-smoking cessation: lowers nicotine cravings
SIDE EFFECTS
- nausea, decreased appetite and vomiting
- orthostatic hypotension
- dry mouth
