Review of Pharmacology - 9E (2015)

Autonomic Nervous System
• Carbachol has common activity on nicotinic and muscarinic receptors.
• Pilocarpine and Cevimeline are used to treat dry mouth associated with Sjogren
syndrome and that caused by radiation damage of salivary glands.
INDIRECTLY ACTING DRUGS
These drugs act by inhibiting the enzyme acetylcholinesterase, thus increasing the availability
and prolonging the action of ACh. These drugs are also known as anticholinesterases.
Cholinesterase inhibitors may be reversible or irreversible.
Reversible Anticholinesterases
Physostigmine, neostigmine, pyridostigmine, edrophonium, tacrine, donepezil, galantamine and
rivastigmine are the important drugs in this group. These drugs inhibit the enzyme AChE
reversibly and prolong the duration of action of ACh.
• Physostigmine is naturally occurring tertiary amine and is lipid soluble. Tacrine,
donepezil, rivastigmine and galantamine are also lipid soluble drugs. All other
reversible anti-cholinesterases are synthetic quarternary compounds and are lipid
insoluble. Due to high lipid solubility, physostigmine can be administered orally and
it can cross blood brain barrier and corneal membrane. Lipid insoluble compounds
are ineffective orally and do not enter CNS or eye.
• Physostigmine is used in glaucoma as a miotic drug and in belladona (atropine) poisoning
as a specific antidote.
• Neostigmine is preferred for the treatment of myasthenia gravis. It does not produce
adverse effects in the CNS (does not cross BBB) and it also has direct N M
receptor
agonistic action. It can also be used for the treatment of cobra bite (cobra venom contain
the compounds that cause skeletal muscle paralysis), post operative paralytic ileus,
atony of urinary bladder and the reversal of competitive skeletal muscle relaxants.
• Pyridostigmine is longer acting than neostigmine and can be used for all these
indications. Atropine is added to neostigmine therapy when action is required on
N M
receptors [to avoid adverse effects due to muscarinic receptor stimulation] as in
case of myasthenia gravis and cobra bite.
tahir99 - UnitedVRG
• Edrophonium is a short acting synthetic anticholinesterase and is useful in the
diagnosis of myasthenia gravis. 1-2 mg i.v. dose of edrophonium improves skeletal
muscle activity if the weakness is due to myasthenia whereas it will worsen the
condition if it is due to cholinergic crisis. (Tensilon test)
• Tacrine was the drug of choice for Alzheimer’s disease but due to several limitations
(frequent dosing requirement, hepatotoxicity, diarrhea), other drugs like donepezil,
rivastigmine and galantamine are now the preferred agent.
• Rivastigmine has been approved for the treatment of dementia in Alzheimer’s as
well as Parkinson’s disease.
Uses of neostigmine
1. Nicotinic actions
a. Mysthenia gravis
b. Cobra bite
c. Reversal of
muscle relaxants
2. Muscarinic actions
a. Post operative paralytic
ileus
b. Post operative urinary
retention
Autonomic General Pharmacology
Nervous System
Irreversible Anticholinesterases
This group includes organophosphates (malathion, parathion, ecothiophate, chlorpyrifos, nerve
gases like tabun, sarin, soman etc. and diflos) and carbamates (carbaryl and propoxur).
Atropine is an antidote of choice
for both organophosphate and
carbamate poisoning.
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