this class is in brief for under graduate examination

1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.
1

2. Reversible
Tertiary amines
Physostigmine
Quaternary Ammonium compounds
Neostigmine
Pyridostigmine
Distigmine
Ambenonium
Demecarium
Tacrine
Miscelloneous Donepezil
Galantamine
Rivastigmine

3. Irreversible Anticholinesterases
(Organophosphorus Compounds)
Ecothiophate
2) War Gases:
Sarin
Tuban,
Soman
3) Insecticides:-
Parathion
Malathion
Diisopropyl Flurophosphate (DFP)
Tetramethyl Pyrophosphate (TMPP)
Octamethyl Pyrophosphotetra amide (OMPA)

4. ACETYLCHOLINESTERASE
1)Present in cholinergic sites,
RBCs, gray matter
2)Very fast hydrolysis of ACh
3)Can hydrolyse methacholine,
4) canot hydrolyse
benzocholine, butyryl choline
5)More sensitive to
physostigmine
6)Termination of Ach action
BUTYRYLCHOLINESTERASE
1)Present in white matter,
plasma, liver, intestine(White PIL)
2)Slow hydrolysis
3)Not hydrolysed
4)benzocholine, butyryl choline
hydrolysed
6)More sensitive to
organophosphates
Hydrolysis of ingested esters

5. Physostigmine
Natural alkaloid
Tertiary amine derivative
Good oral absorption
CNS actions are present
Penetrates cornea
Direct action on cholinoceptors
Absent
Prominent effect on autonomic
effectors
Uses- miotic(glaucoma)
Dose -0.1-1% eye drops
Systemic eff-4-6hrs
Neostigmine
Synthetic derivative
Quaternary ammonium comp
Less oral absorption
Absent
Poor penetration
Action oncholinoceptor is
present
Prominent effect on skeletal
Muscles
Uses –myasthenia gravis
0.5-2.5mg sc
3-4hrs

6. A disease characterized by raised intraocular
pressure(IOP) and progressive optic neuropathy with loss
of retinal neurons and their axons (nerve fiber layer)
resulting in blindness if left untreated.
Aqueous humour pass b/w lens and iris go out
through pupil
Primary –respond to drugs
a)Narrow angle/angle closure/acute congestive-
medical emergency-drug and partial iridectomy
b) simple/open angle/chronic/-loss of trabacular
mesh work patency is lost
Secondary- partly responds
Congenital-less responsive

8. 1) Beta-Blockers [levobunolol, timolol, carteolol,
betaxolol]
Mechanism: Act on ciliary body to  production of
aqueous humor
Administration: Topical drops to avoid systemic effects
Use twice a day (except Timolol)
Side Effects: Cardiovascular (bradycardia, asystole,
syncope), bronchoconstriction (avoid with b1-
selective betaxolol), depression

9. 2) Alpha-2 Adrenergic Agonists [apraclonidine,
brimonidine]
Mechanism:  production of aqueous humor
May become less effective over time
Administration: Topical drops
Side Effects: Lethargy, fatigue, dry mouth
[apraclonidine is a derivative of clonidine
(antihypertensive) which cannot cross BBB to
cause systemic hypotension]
Brimonidine -never used in infants
In younger children can cause slowed breathing
and heartbeat
In older children Stinging / irritation

10. 3)Carbonic Anhydrase Inhibitors [acetazolamide,
dorzolamide]
Mechanism: Blocks Carbonic Anhlydrase-II enzyme
blocks production of bicarbonate ions (transported
to posterior chamber, carrying osmotic water flow)
 production of aqueous humor
Better tolerated in children than adults
Usually used in addition to drops
Administration: Oral
Side Effects: Metabolic disturbances (electrolyte
balance, acid-base balance) malaise, kidney stones,
possible (rare) aplastic anemia

11. 1)Parasympathomimetics [pilocarpine, carbachol,
echothiophate]
Mechanism:  contractile force of ciliary body muscle,
 outflow via TM
Administration: Topical drops or gel, (slow-release
plastic insert)
Side Effects: Headache, induced miopia. Few systemic
SE for direct-acting agonists vs. AchE inhibitors
(diarrhea, cramps, prolonged paralysis in setting of
succinylcholine).

12. 2)Nonspecific Adrenergic Agonists [epinephrine,
dipivefrin]
Mechanism:  uveoscleral outflow of aqueous
humor
Administration: Topical drops
Side Effects: Can precipitate acute attack in patients
with narrow iris-corneal angle, headaches,
cardiovascular arrhythmia, tachycardia

13. The defect in neuromuscular transmission in Myasthenia
Gravis is due to:
The muscle end-plate membrane is distorted
Acetylcholine receptors are lost from the tips of the folds,
and antibodies attach to the postsynaptic membrane
Ach is released normally but absence of receptors prevents
the transmitter binding to the muscle membrane

14. Immuno-precipitation assay
Edrophonium (Tensilon test)-2mg IV
Patients with MG have low numbers of AChR at the
NMJ
Ach released from the motor nerve terminal is
metabolized by Acetylcholine esterase
Edrophonium is a short acting Acetylcholine Esterase
Inhibitor that improves muscle weaknessmyasthenia
Condition worsens cholinergic crisispersistant
depolarisation of motar end plate

15. 1.Reversible anti-AchE
Neostigmine-15-30 mg, per day orally
0.5-0.25mg im/sc
Pyridostigmine-60mg-tid orally
Ambenonium-2.5-5mg orally
2.Glucocorticoids –prednisolone-10mg OD
3.Immunosuppressants
Azathioprine 2.5mg/kg per day
Cyclosprine-2-5mg/kg per day
4.Thymectomy –myasthenia with thymoma
5.Plasmapheresis –for non responders to thymectomy and
treatment with steroids

16. Organophosphates = Organic Compounds + Phosphate
Group
No Clinical Uses For These Compounds.
Agricultural Insecticides And Fungicides
Household Garden Sprays
Fly And Insect Sprays
Poisoning -Cutaneous
Ingestion (Accidental Or Suicidal)
Inhalation
Injection

17.  op inactivate acetyl cholinesterase (Ach E).
establishment of a covalent bond with ache.
once Ach E - inactivated, ach accumulates
throughout the nervous system →
overstimulation of muscarinic and nicotinic
receptors.

18. Muscarinic Effects By organ systems include the following:
Cardiovascular - Bradycardia, Hypotension
Respiratory - Rhinorrhea, Bronchorrhea, Bronchospasm, Cough,
Severe Respiratory Distress
Gastrointestinal - Hypersalivation, Nausea And Vomiting,
Abdominal Pain, Diarrhea
Genitourinary - Incontinence
Ocular - Blurred Vision, Miosis
Glands - Increased Lacrimation, Diaphoresis

19. Once an organophosphate binds to AChE, the enzyme
can undergo one of the following:
• Endogenous hydrolysis of the phosphorylated enzyme
by esterases or paraoxonases
• Reactivation by a strong nucleophile such as
pralidoxime (2-PAM)
• Irreversible binding and permanent enzyme
inactivation (aging)
The onset and severity of symptoms depend on the
specific compound, amount, route of exposure, and
rate of metabolic degradation

20. Mild ( ≥ 40% ache)
No specific treatment
Clearing the airway,
Adequate ventilation-consider oxygenation
Remove soiled clothes
Wash contaminated skin to prevent further absorption.

21. 2. Patients With Systemic Features –
Gastric lavage within an hour followed by activated
Charcoal administered via nasogastric tube
Wash the patient – to prevent cutaneous absorption
Wash soiled clothes
IV Atropine 2mgs every 15 minutes till signs of
atropinization are seen
Add an oxime E.G. Pralidoxime
Consider ICU Care If In Coma Or Unconscious
Organophosphorus poisoning-
treatment

23.  PAM-pralidoxime-Current Recommendation Is
Administration Within 48 H Of OP Poisoning.,
Administer Atropine Concomitantly-↓ Respiratory
Secretions.
1-2 G (20-40 Mg/Kg) IV In 100 ml NS/D5W Over 15-30
Min ; Repeat In 1 H If Muscle Weakness Is Not Relieved;
Then Repeat Q3-8h If Signs Of Poisoning Recur.
Alternatively, Continuous Drip; Start With Bolus Of 25-
50 Mg/Kg And Then 10-20Mg/Kg/h
Organophosphorus poisoning-treatment

24.  Potentiate Effects Of GABA And Facilitate Inhibitory
GABA Neurotransmission
 For Treatment Of Seizures. Depresses All Levels Of CNS
(Eg, Limbic And Reticular Formation) By Increasing
Activity Of GABA.
 5-15 Mg IV Q5-10 Min, Repeat As Needed; Consider
Higher Doses If Needed
 Routinely Used In OP Poisoning For Treatment Of
Agitated Delirium And Seizures
 Diazepam Reduces Respiratory Failure (Rats) And
Cognitive Deficit (Primates)