Thursday, December 30, 2010

Parasympathomimetic drugs (Miotics)

Parasympathomimetics, also called as cholinergic
drugs, either imitate or potentiate the effects of
acetylcholine.
Classification
Depending upon the mode of action, these can be
classified as follows:
1. Direct-acting or agonists e.g., pilocarpine.
2. Indirect-acting parasympathomimetics or
cholinesterase inhibitors: As the name indicates
these drugs act indirectly by destroying the
enzyme cholinesterase; thereby sparing the
naturallyacting acetylcholine for its actions. These
drugs have been divided into two subgroups,
designated as reversible (e.g., physostigmine)
and irreversible (e.g., echothiophate iodide,
demecarium and diisopropyl-fluoro-phosphate,
DFP3) antic-holinesterases.
3. Dual-action parasympathomimetics, i.e., which
act as both a muscarinic agonist as well as a
weak cholinesterase inhibitor e.g., carbachol.
Mechanism of action
1. In primary open-angle glaucoma the miotics
reduce the intraocular pressure (IOP) by
enhancing the aqueous outflow facility. This is
achieved by changes in the trabecular meshwork
produced by a pull exerted on the scleral spur by
contraction of the longitudinal fibres of ciliary
muscle.
2. In primary angle-closure glaucoma these reduce
the IOP due to their miotic effect by opening the
angle. The mechanical contraction of the pupil
moves the iris away from the trabecular meshwork.
Side-effects
1. Systemic side-effects noted are: bradycardia,
increased sweating, diarrhoea, excessive salivation
and anxiety. The only serious complication noted
with irreversible cholinesterase inhibitors is
‘scoline apnoea’, i.e., inability of the patient to
resume normal respiration after termination of
general anaesthesia.
2. Local side-effects are encountered more frequently
with long-acting miotics (i.e. irreversible
cholinesterase inhibitors). These include problems
due to miosis itself (e.g. reduced visual acuity in
the presence of polar cataracts, impairment of
night vision and generalized contraction of visual
fields), spasm of accommodation which may cause
myopia and frontal headache, retinal detachment,
lenticular opacities, iris cyst formation, mild iritis,
lacrimation and follicular conjunctivitis.
Preparations
1. Pilocarpine. It is a direct-acting parasympathomimetic
drug. It is the most commonly used and
the most extensively studied miotic. Indications: (i)
Primary open-angle glaucoma; (ii) Acute angle-closure
glaucoma; (iii) Chronic synechial angle-closure
glaucoma. Contraindications: inflammatory
glaucoma, malignant glaucoma and known allergy.
Available preparations and dosage are: (a) Eyedrops
are available in 1%, 2% and 4% strengths. Except in
very darkly pigmented irides maximum effect is
obtained with a 4 percent solution. In POAG, therapy
is usually initiated with 1 percent concentration. The
onset of action occurs in 20 minutes, peak in 2 hours
and duration of effect is 4-6 hours. Therefore, the
eyedrops are usually prescribed every 6 or 8 hourly.
(b) Ocuserts are available as pilo-20 and pilo-40. These
are changed once in a week. Pilo-20 is generally used
in patients controlled with 2 percent or less
concentration of eyedrops; and pilo-40 in those
requiring higher concentration of eyedrops.
(c) Pilocarpine gel (4%) is a bedtime adjunct to the
daytime medication.
2. Carbachol. It is a dual-action (agonist as well as
weak cholinesterase inhibitor) miotic. Indications. It
is a very good alternative to pilocarpine in resistant
or intolerant cases. Preparations. It is available as
0.75 percent and 3 percent eyedrops. Dosage: The
action ensues in 40 minutes and lasts for about 12
hours. Therefore, the drops are instilled 2 or 3 times a
day.
3. Echothiophate iodide (Phospholine iodide). It is
a long acting cholinesterase inhibitor. Indications: It
is very effective in POAG. Preparations: Available
as 0.03, 0.06 and 0.125 percent eye- drops. Dosage:
The onset of action occurs within 2 hours and lasts
up to 24 hours. Therefore, it is instilled once or twice
daily.
4. Demecarium bromide. It is similar to ecothiopate
iodide and is used as 0.125 percent or 0.25 per- cent
eyedrops.
5. Physostigmine (eserine). It is a reversible (weak)
cholinesterase inhibitor. It is used as 0.5 percent
ointment twice a day.

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