Cholinergic Flashcards
(21 cards)
List anticholinesterases. (DU-23N)
Indirectly acting
(acetylcholinesterase inhibitors/anticholinesterases)
Reversible
Indirectly acting
(acetylcholinesterase inhibitors/anticholinesterases)
1.Reversible
Tertiary amines
a) Physostigmine
Quaternary amines
a) Neostigmine
b) Pyridostigmine
c) Edrophonium
2.Irreversible
Organophosphorous Compounds (OPC)
a) Soman
b) Malathione
c) Parathione
d) Paraxone
Enlist four cholinergic drugs. (DU-18Nov)
Directly acting cholinergic drugs
(cholinoceptor stimulation)
1.Choline esters
Acetylcholine
Methacholine
Carbachol
Bethanicol
2.Cholinomimetic alkaloids
Chiefly muscarinic
a) Muscarine
b) Pilocarpine
Chiefly nicotinic
a) Nicotine
b) Lobeline
Enumerate the cholinergic receptors. (DU-21M)
Muscarinic
M1 (neural)- cns, peripheral neurons, gastric parietal cells
M2 (cardiac)- heart, presynaptic terminal, smooth muscles
M3 (glandular/ smooth muscle)- cns
M4- cns
M5
Nicotinic-
Nm- neuromuscular junction
Nn- autonomic ganglia, adrenal medulla.
the clinical indications of cholinomimetic drugs. (DU-18M)
1.Eye: (Pilocarpine)
Acute angle closure glaucoma, a medical emergency (Pilocarpine).
Accommodative esotropla (strabismus caused by hypermetropic accommodative error) in young children.
2.GIT: (Bethanechol/Neostigmine)
Post-operative ileus (atony or paralysis of the stomach or bowel following surgical operation) Neostigmine (0.5-1.0 mg).
Congenital megacolon.
3.Urinary: (Bethanechol/Neostigmine)
Postoperative urine retention.
Neurogenic bladder (urine retention due to spinal cord injury/disease).
4.Neuro-muscular junction:
➤ Diagnosis & treatment of myasthenia gravis. [Pyridostigmine is the drug of choice due to its longer duration of action (4-6h), Neostigmine is an alternative (short acting)].
➤ Neostigmine is routinely used during reversal from general anaesthesia to reverse the effects of non-depolarizing muscle relaxants (e.g. Vecuronium, Rocuronium etc.).
5.Cardiovascular use: Paroxysmal supra-ventricular tachycardia (Edrophonium), but now-a-days, Adenosine (drug of choice in SVT), Verapamil & Diltiazem are used.
6.In poisoning:
➤ Atropine poisoning (Physostigmine).
➤ D-tubocurarine poisoning (Neostigmine).
7.CNS: Alzheimer’s disease (Donepezil, Galantamine & Rivastigmine).
Differentiate between physostigmine & neostigmine. (DU-22N)
Physostigmine
Source:Natural alkaloid.
Chemistry:Tertiary amine.
Lipid solubility:More.
Blood brain barrier:Can cross.
Cns effects: More.
Muscarinic& nicotinic effects:Muscarinic effect is more prominent.
Action on eye:Good (So can be used in Glaucoma)
Clinical uses:Glaucoma (along with Pilocarpine).
Atropine poisoning (As an antidote).
Neostigmine:
Source:Synthetic.
Chemistry: quaternary amine.
Lipid solubility: less
Blood brain barrier:Cannot cross.
Cns effects:Less.
Muscarinic& nicotinic effects: Nicotinic effect is more prominent.
(Remember: N-N)
Action on eye:Less or no
Clinical uses:Treatment of Myasthenia gravis.
D-Tubocurarine poisoning.
To prevent post-operative abdominal distension & urinary retentio
the management of OPC poisoning. (DU-22/21M,19/18Nov, 14Ja, 12Ju)
A) General management (non-pharmacological approach):
Immediate ABC (airway, breathing & circulation) resuscitation.
A short & complete history to confirm & make a treatment plan.
Examination of vital signs: BP, pulse, respiratory rate, temperature, urine output, pupil, lung base & heart. Examination & resuscitation should continue simultaneously.
Contaminated clothing’s should be removed & stored for medico-legal purpose.
Contaminated skin should be washed by normal saline (OPC absorbs from skin).
Gastric suction: By 2% KMnO4.
Catheterization (before giving the 1” dose of Atropine).
B) Specific management (pharmacological approach):
Atropine (I/V) as antidote: 0.6 - 1.8 mg i.v., repeated every 10-25 minutes until full atropinization.
Pralidoxime (I/V): 1-2 g IV over 15-30 minutes, repeated 4-6 times daily.
Midazolam / Diazepam: If convulsion present.
MgSO4 (for details please see below).
Sodi-bi-carb (NaHCO3), if metabolic acidosis present.
C) Monitoring of the patient:
Vital signs (Please see above).
Broken neck sign (for intermediate syndrome).
D) Follow up:
After discharging from the hospital, the patient should be advised to take rest for at least 6 weeks for re-synthesis of the cholinesterase enzyme.
Patient should be advised to consult with a psychiatrist after discharge.
Role of pyridostigmine in myasthenia gravis
Mechanism of action of pyridostigmine / neostigmine in myasthenia gravis:
Neostigmine has a prominent nicotinic effect than muscarinic effect.
It inhibits cholinesterase enzyme → no hydrolysis of ACh → ↑ concentration of ACh in the NMJ
→ opposite effect of Myasthenia gravis
Explain role of Atropine in OPC poisoning. [DU-18M,17M/J; CMU-23M;
In OPC poisoning:
OPC irreversibly binds with cholinesterase enzyme by a covalent bond and prevents hydrolysis of Acetylcholine (ACh)
As a result, there is increased concentration of Acetylcholine at cholinoceptors and causes toxic effects of excess acetylcholine (ACh)
Role of Atropine in OPC poisoning:
Atropine binds with cholinergic receptors & antagonizes the action of Acetylcholine
So, Atropine reverses the toxic effects of Acetylcholine excess in OPC poisoning (Competitive reversible antagonism)
That’s why Atropine is used in OPC poisoning as antidote (competitive reversible antagonism).
Explain the role of oxime compound / Pralidoxime [DU-23M, 18M, 17J; CMU-23M, BUP-22N, 20N/M] in OPC poisoning?
Pralidoxime increases acetyl-cholinesterase enzyme before the aging process. So it is very helpful in OPC poisoning management.
Mechanism / role of oxime compound on OPC poisoning:
The oxime group has high affinity for the phosphorus atom.
Thus they are able to hydrolyze the phosphorylated enzyme (before the aging process)
Regeneration of acetyl cholinesterase enzyme → increased hydrolysis of acetylcholine.
Pralidoxime’s primary action is restoring acetylcholinesterase enzymes at nicotinic sites in the body, relieving symptoms like muscle weakness, fasciculation & paralysis. Its muscarinic action is insignificant.
Aging process:
This process involves breaking of one of the ‘oxygen-phosphorus’ bond of the inhibitors & further strengthening the ‘phosphorus-choline-acetyltransferase enzyme’.
Enumerate the anti-muscarinic drugs according to their indication. What are their adverse effects? (DU-17Nov)
1.Atropine substitutes/atropine-like drugs:
.Mydriatics - homatropine, cyclopentolate, tropicamide
.Bronchial asthma - ipratropium, tiotropium
.Antiparkinsonian drugs - benztropine, benzhexol, orphenadrine
.Antispasmodics - hyoscine N-butyl bromide, dicyclomine
.Peptic ulcer disease - pirenzepine, telenzepine M₁ blocker
.Urinary incontinence - oxybutynin, tolterodine, propiverine
.Motion sickness - scopolamine
.For reversal of action of neostigmine - glycopyrronium
2.Atropine:
.Pre-anesthetic medication
.Antidote for OPC poisoning
.Post-MI bradycardia
.To prevent synechia formation in iridocyclitis
Classify antimuscarinic drugs
Enlist the currently used mydriatic agents
Homatropine
Cyclopentolate
Tropicamide
Name anti-mascarinic mydriatic drugs. Discuss their ophthalmological indications. Write down their contraindications. (DU-17M)
Ophthalmic indications
For fundoscopic examination of retina, to measure refractive error - homatropine, cyclopentolate, tropicamide
To prevent synechia formation (adhesion) in iritis and uveitis - atropine
Contraindications
Glaucoma
Gastric ulcer
Pts with benign prostatic hyperplasia
Effects of atropine on cvs
CVS effects: ↑ HR, ↑ PR → ↑ BP
Moderate-high dose of Atropine: Block M₂-receptor on SA nodal pacemaker cells → blockade of vagus nerve → antagonizez parasympathetic tone of heart → no inhibitory effect of vagus (i.e. no bradycardia) → tachycardia.
Low dose atropine: Block pre-junctional M₁ auto receptors on vagal post-ganglionic fibers → facetylcholine release in SA node & other tissue → bradycardia.
On endothelium: Atropine has little effect on blood vessels because most vessels lack significant cholinergic innervation.
Explain pharmacological effects of atropine
1.CVS effects: ↑ HR, ↑ PR → ↑ BP
➤ Moderate-high dose of Atropine: Block M₂-receptor on SA nodal pacemaker cells → blockade of vagus nerve → antagonizez parasympathetic tone of heart → no inhibitory effect of vagus (i.e. no bradycardia) → tachycardia.
➤ Low dose atropine: Block pre-junctional M₁ auto receptors on vagal post-ganglionic fibers → Tacetylcholine release in SA node & other tissue → bradycardia.
➤ On endothelium; Atropine has little effect on blood vessels because most vessels lack significant cholinergic innervation.
Blocks M3 receptor which inhibits the release of EDRF ( End DER relaxing factor) tht blocks vasodilation and inc pvr
2.Effects on ocular smooth muscles:
➤ Effects on constrictor (sphincter) pupillae muscle: Relaxation of constrictor (sphincter) pupillae muscle → dilation of pupil (Mydriasis).
➤ Effects on cilliary muscle: Relaxation of cilliary muscle → cycloplegia → obstruction of the “canal of Schlemm” & loss of light & accommodation reflex & photophobia → ↓ drainage of aqueous humor → ↑ intra-ocular pressure.
➤ Effects on lacrimal glands: ↓ Lacrimal gland secretion → ↓ lacrimation → dry eyes.
- Git:
Decreased intestinal tone and motility by blocking M3 receptor and decreased peristalsis
Decreased salivary and gastric secretion by blocking M1 Receptor.
4.Effects on bronchial tree: Bronchodilation & ↓ bronchial gland secretion → relief of bronchial asthma
5.Effects on genitor-urinary system:
➤ Relaxation of Detrusor muscle of urinary bladder, contraction of trigone & contraction of sphincter → retention of urine.
➤ Long term use → smooth muscle relaxation in genital erectile tissue → impotence.
➤ No significant effect on the uterus.
Adverse effects of antimuscarinic drugs
1.Dry mouth
2.Dry eye, blurred vision
3.Hyperthermia
4.Tachycardia
5.Restlessness, delirium, hallucinations , depression and coma
6.Urinary retention
7.Constipation
Why atropine is contraindicated in pts with glaucoma
Atropine causes relaxation of cilliary muscle → cycloplegia → obstruction of the ‘canal of Schlemm’ & loss of light & accommodation reflex & photophobia → ↓ drainage of aqueous humor → ↑ intra-ocular pressure.
Atropine poisoning short note
Clinical features
Eye : Raised IOP, mydriasis, loss of accommodation reflex, dry eye, blurred visio
CVS : Tachycardia, hypertension.
GIT : Constipation
Urinary : Urine retention
Exocrine : ↓salivation (dry mouth), ↓sweating (dry skin), hyperthermia etc.
CNS : Restlessness, agitation, excitement, hallucination, drowsiness etc.
Management of atropine poisoning:
General :
A short & complete history.
Initial ABCD management.
Vital sign monitoring: Pulse, BP, temperature & pupil etc.
Catheterization: To prevent excessive urine retention.
Gastric suction: By 2% KmnO4
Treatment:
Physostigmine: Adult dose is 0.5-1mg I/V slowly (as antidote).
Diazepam: In case of agitation or convulsion.
Anti-pyretic: Paracetamol (to control hyperthermia).
Name the competitive neuromuscular blocking drugs. [DU-17N]
Peripheral Muscle Relaxants:
Depolarizing/Non-competitive - Succinylcholine
Non-depolarizing/Competitive -
a. Isoquinoline derivatives
Atracurium
Cisatracurium
Doxacurium
Metocurine
Mivacurium ☆
Tubocurarine
b. Steroid derivatives
Pancuronium
Pipecuronium
Rocuronium
Vecuronium
c. Others
Gallamine
Classify muscle relaxants
Classification of Muscle Relaxants:
Central muscle relaxant (Spasmolytics) - Used to reduce spasticity in different neurological conditions like chronic back pain and fibromyalgic conditions. E.g.
Diazepam, Baclofen, Tizanidine
Peripheral muscle relaxants (Neuromuscular blockers) - Used during surgical procedures and intensive care unit to produce muscle paralysis.
