Antidepressants

Mono Amino Oxidase Inhibitors

• MAO is a mitochondrial enzyme involved in the oxidative deamination
of biogenic amines (Adr, NA, DA, 5- HT)

• MAO-A: Preferentially deaminates 5-HT and NA

Inhibited by clorgyline, moclobemide.

• MAO-B: Preferentially deaminates phenylethylamine.

Inhibited by selegiline
MAO inhibitors
 ANTICHOLINESTERASES
Reversible
• Carbnmates - Physostigmine (Eserine), Neostigmine Pyridostigmine,
Edrophonium Rivastigmine, Donepezil, Galantamine
• Acridine - Tacrine
Organophosphates
• Dyflos (DFP) Echothiophate Parathion*, Malathion* Diazinon* (TIK-
20) Tabun, Sarin, Soman
• Carbamates Carbaryl* (sEVrN), Propoxur* (BAYGON)
• * Insecticides
 Pharmacological actions
• The actions of anti-ChEs are qualitatively similar to that of directly
acting cholinoceptor stimuLants.
• Lipid-soluble agents (physostigmine and organophosphates) have marked
muscarinic and CNS effects.
• Stimulate ganglia but action on skeletal muscles is less prominent.

• Lipid-insoluble agents (neostigmine and other quatemary ammonium

compounds)
• produce more marked effect on the skeletal muscles (direct action on muscle
endplate cholinoceptors as well)
• Stimulate ganglia, but muscarinic effects are less prominent.
• They do not penetrate CNS and have no central effects.
• Ganglia

• Local hydrolysis of ACh is less important in ganglia.

• High doses cause persistent depolarization - blockade of transmission.

CVS - complex.
Muscarinic action –

Bradycardia and hypotension,

Ganglionic stimulation - Increase heart rate and BP.

Medullary centres (stimulation followed by depression).

• Skeletal Muscles

• Ach in NMJ doesn’t immediately gets destroyed.

• Rebinds to the same receptor - activates prejunctional fibres -+ repetitive firing

-+ twitching and fasciculations.

• Force of contraction in partially curarized and myasthenic muscles is increased.

• Higher doses - Persistent depolarization of endplates - Blockade of

neuromuscular transmission - weakness and paralysis.

• Direct action of neostigmine - augmentation of these features.

 Stimulation of smooth muscles and glands
• Write the pharmacology of Ach on the following:
• GIT
• Respiratory
• Urinary tracts
• Eye.
 Myasthenia gravis
• Myasthenia gravis is an autoimmune disease
Deficiency of the postsynaptic neuromuscular ACh receptor

Receptors in myasthenic muscle are degraded and cleared much faster

than normally.
Number of available ACh receptors in the involved muscles is reduced
by as much as 70-90%.
Circulating antibodies to ACh receptors have been demonstrated in 70-
90% of patients with myasthenia.
Many patients with this disorder have thymic hyperplasia or a
thymoma.
 Drugs used in myasthenia Gravis
• Neostigmine

• Relatively short duration of action (< 4 hours), development of tolerance and waxing and waning of muscle
strength.

• Drugs with longer duration of action and fewer side effects, e.g. pyridostigmine (4-6 hr) and ambenonium (4-8 hr)
are now preferred.

• These drugs may, however, be combined with neostigmine as the onset of action of neostigmine is quicker.

• The effect of parenteral neostigmine appears within 30 minutes while oral administration produces a response within
1 hour.

• The therapy is initiated with neostigmine 7.5-15 mg or pyridostigmine 30-60 mg or ambenonium 2.5 to 5 mg orally,
at a time, and the dose is gradually increased until the maximal benefit is obtained.

• The reversible antiChE are usually administered 3 to 4 hourly, orally or parenterally to ensure a smooth and sustained
effect.
 Drugs used in myasthenia Gravis

• Because of the autoimmune basis of myasthenia

•Prednisolone, glucocorticoid has been used in the dose of 25-100 mg once a day.

• Immunosuppresants such as azathioprine, cyclosporine.

• Plasmapheresis have been used as adjunctive therapy in resistant cases.

• Thymectomy can help patients with thymoma