AUTONOMIC NERVOUS SYSTEM

Consists of the sympathetic and parasympathetic

nervous system.
Drugs that stimulate the sympathetic nervous system are
called adrenergics.

Adrenergics are also called adrenergic agonists or

sympathomimetics because they mimic the effects of the
Sympathetic nervous system neurotransmitters
norepinephrine ( noradrenaline) and epinephrine
(adrenaline) (catecholamines).
 Sympathetic Nervous System
1. mydriasis- contract pupillary dilator muscle (1 receptor)

2. contract superior tarsal muscle to hold eyelid open (1

receptor)

3. Relax ciliary muscle for distant vision (ß2 receptors)

4. Enhance aqueous humor formation (ß2 receptors)

5. Inhibit aqueous humor formation (2 receptors)

Parasympathetic Nervous System Actions

focus eye for near vision (ciliary muscle contraction)

constrict pupil (miosis)-(pupillary sphincter

contraction)

Enhance drainage of aqueous humor (trabecular

meshwork & canal of Schlemm)

All of these effects mediated by muscarinic receptors

Drugs promoting mydriasis (pupil dilation)
Sympathomimetics (things that stimulate or mimic stimulation of
sympathetic nerves)
Inhibitors of parasympathetic nervous system (Atropine)
Mydriatics
Agents releasing norepinephrine
NICOTINE activates nicotinic receptor (also activates parasympathetics to
produce miosis, which is the more common reaction)
Cocaine blocks axoplasmic pump to increase norepinephrine concentrations
in vicinity of adrenergic receptors
2 - 4% solution used to diagnose simple anisocoria vs Horner’s syndrome
no effect of cocaine indicates sympathetic dysfunction (if nerves were intact,
cocaine would dilate pupil)
Amphetamine reverses axoplasmic pump
hydroxyamphetamine (0.1% solution) used to diagnose post-ganglionic nerve
damage vs. a defect prior to the postganglionic nerve (no reaction means
postganglionic nerve defect)
response to amphetamine indicates normal post- ganglionic nerve
Mydriatics
Alpha1 adrenergic stimulants
PHENYLEPHRINE (mydrifrin) is a drug used in eye drops to dilate pupil
2.5% to 10% solution used to produce mydriasis
also reverses ptosis in Horner’s Syndrome
Epinephrine (Epitrate) 0.5 to 2% solution to treat glaucoma
increases aqueous humor outflow
CYCLOPLEGICS AND MYDRIATICS

Muscles within the eye control the size of the pupil and
the diameter of the ciliary ring.
The latter allows zonular
laxity and a consequent thickening and forward movement
of the lens necessary for the visualization of near objects,
i.e. accommodation. Cholinergic stimulation causes contraction
of both the pupil and the ciliary body, while sympathomimetic
stimulation leads to dilatation of the pupil.
Anticholinergic drugs: These dilate the pupil causing
mydriasis and impair accommodation leading to cycloplegia.
Mydriatics are the drugs that dilate the pupil. Adrenergic agonists are used for routine dilation
of the patient. Phenylephrine (eg Neo-Synephrine) and epinephrine are the only Direct Acting
adrenergic agents available that produce mydriasis without cycloplegia. However ,
epinephrine is not used clinically for its mydriatic effects.

Anticholinergic agents administered topically to the eye for purposes of inhibiting

accommodation are termed Cycloplegics . Their primary use is for cycloplegic refraction and
in the treatment of uveitis. Because these agents also inhibit action of the iris sphincter
muscle , they are effective mydriatics. Of the cholinergic blocking agents , only tropicamide, is
routinely used for mydriasis. For most dilatation procedures , the adrenergic or anticholinergic
agents can be used alone or in combination for maximum mydriasis.
DRUGS PROMOTING MYDRIASIS (PUPIL DILATION)
Sympathomimetics (things that stimulate or mimic stimulation of sympathetic nerves)

Inhibitors of parasympathetic nervous system (Atropine)

MYDRIATICS
 Alpha1 adrenergic stimulants

 PHENYLEPHRINE (mydrifrin) is a drug used in eye drops to

dilate pupil
 2.5% to 10% solution used to produce mydriasis
 also reverses ptosis in Horner’s Syndrome

 Epinephrine (Epitrate) 0.5 to 2% solution to treat glaucoma

 increases aqueous humor outflow
MYDRIATICS
Muscarinic receptor antagonists

 ATROPINE (Atriposol)- (0.5 to 3% solution) to produce cycloplegia

MYDRIATICS

Phenylephrine HCL
Phenylephrine is a synthetic alpha- receptor agonist that is structurally similar to
epinephrine . Following topical application on the eye , it contracts the iris dilator
muscle and smooth muscle of thr conjunctiva. Muellers, muscle of the upper eyelid
maybe stimulated , widening the palpebral fissure.

For pupillary dilatation , concentrations of 2.5% and 10% are commercially available.
Maximum dilatation occurs within 45-60 minutes , depending on the concentration
used or number of drops instilled. The pupil size usually returns to predrug levels
within 4-6 hours . Because phenylephrine has little or no effect on the cilliary muscle,
mydriasis occurs without cycloplegia.
Phenylephrine 1% solution can be used in diagnosis of Horner’s Syndrome.
Significant mydriasis can occur in the eye with a postganglionic lesion as
compared with one having normal innervation. The 2.5% concentration is
generally used with caution in patients with cardiac disease , hypertension ,
arteriosclerosis and diabetes. It is contraindicated in patients taking tricyclic
antidepressants ( eg.amitryptaline ), MAO inhibitors ( Reserprine) , Methyldopa.
Hydroxyamphetamine 1% has been combined with tropicamide 0.25 % as a
combination formulation for mydriasis. It produces a Mydriatic effect equivalent to
Phenylephrine 2.5 % followed by tropicamide 0.5% for the first 45 -60 min
minutes. Pupil size is sufficient for binocular indirect ophthalmoscopy . This effect
is independent of age , skin or iris colour
 PHENYLEPHRINE HCI
Actions:
Pharmacology: Phenylephrine ophthalmic solution possesses predominantly α adrenergic
effects. In the eye, phenylephrine acts as a potent vasoconstrictor and mydriatic by constricting
ophthalmic blood vessels and the radial muscle of the iris. The ophthalmic usefulness of
phenylephrine is because of its rapid effect and moderately prolonged action.

Phenylephrine HCl
Mydriasis/ Vasoconstriction
Strength of Maximal Recovery Paralysis of
Solution (%) (min) time (hr) Accomodation
0.12 30 to 90 - -
2.5 15 to 60 3 trace
10 10 to 60 6 slight
Indications:
2.5% and 10%: Decongestant and vasoconstrictor and for pupil dilation in uveitis (posterior
synechiae), open-angle glaucoma, refraction without cycloplegia, prior to surgery,
ophthalmoscopic examination (funduscopy).

Contraindications: Hypersensitivity to any component of the formulation; narrow-angle

glaucoma or individuals with a narrow (occludable) angle who do not have glaucoma; in low
birth weight infants and in some elderly adults with severe arteriosclerotic cardiovascular or
cerebrovascular disease; during intraocular operative procedures when the corneal epithelial
barrier has been disturbed.

Phenylephrine 10%: In infants, small children with low body weights, debilitated or elderly
patients, and patients with aneurysms. The administration of phenylephrine is contraindicated
in patients with long-standing, insulin-dependent diabetes, hypertensive patients receiving
reserpine or guanethidine, advanced arteriosclerotic changes, idiopathic orthostatic
hypotension, and in patients with a known history of organic cardiac disease.
In individuals with an intraocular lens implant, the administration of 10% phenylephrine is
contraindicated because of the possibility of dislodging the lens.
Warnings:
Phenylephrine 10%: There have been rare reports of the development of serious
cardiovascular reactions, including ventricular arrhythmias and myocardial infarctions. These
episodes, some fatal, have usually occurred in elderly patients with pre-existing cardiovascular
diseases.
Elderly- Use with caution. Because of the strong action of phenylephrine 2.5 to 10 % on the
dilator muscle, older individuals also may develop transient Pigment floaters in the aqueous
humor 30 to 45 minutes following administration. The appearance may be similar to anterior
uveitis or microscopic hyphema.
Rebound miosis occurs in some elderly patients. Subsequent instillation of phenylephrine
may produce less mydriasis than the initial instillation. This may be clinical importance when
dilating pupils prior to retinal detachment or cataract surgery. Exercise caution not to overdose
these patients.
Pregnancy: Category C Safety for use has not been established. Use only if needed and
potential benefits to the mother outweigh potential hazards to the fetus.

Lactation: lt is not known whether this drug is excreted in breast milk. use caution when
phenylephrine HCI is administered to a nursing woman.
Children: Safety and efficacy for use in children have not been established. Phenyl
ephrine 2.5% has been used for a “1 application method" in combination with
preferred rapid-acting cycloplegic (see Administration and Dosage). Phenylephrine is
contraindicated in infants.
Systemic absorption: Exceeding recommended dosages or applying phenylephrine
2.5% to 100% to an instrumented, traumatized, diseased, or postsurgical eye or
adnexa. Or to patients with supressed lacrimation, as during anaesthesia, may result
in the absorption of sufficient quantities to produce a systemic vasopressor response.
A significant elevation in blood pressure is rare but has been reported following
conjunctival instillation of recommended doses of phenylephrine 10%. Use with
caution in children with low body weight, the elderly. and patients with insulin-
dependent diabetes. hypertension. hyperthyroidism. generalized arteriosclerosis, or
cardiovascular disease. Carefully monitor the posttreatment blood pressure of these
patients and any patients who develop symptoms (see Contraindications).
The hypertensive effects of phenylephrine may be treated with an alpha-adrenergic
blocking agent, such as phentolamine mesylate. 5 to 10 mg IV, repeated as necessary
Narrow angle glaucoma: Ordinarily, mydriatics are contraindicated in glaucoma
patients. However. when temporary pupil dilation may free adhesions, Or when
intrinsic vessel vasoconstriction may lower IOR this may temporarily outweigh danger
from coincident dilation.
Corneal effects: If the corneal epithelium has been denuded or damaged, corneal
clouding may occur if phenylephrine is instilled This may be especially serious following
corneal epithelium removal during retinal detachment or vitrectomy. The corneas of
diabetic patients may manifiest epithelial ulcerations as well as a slow rate of
reepithelization. Use of phenylephrine in such corneas may be especially hazardous.
Rebound congestion: Rebound congestion may occur with extended use of ophthalmic
vasoconstrictors.
Sulfite sensitivity: Some of these products contain sulfites. Sulfites may cause allergic
type reactions (eg. hives, itching. wheezing. anaphylaxis) in certain susceptible people.
Although the overall prevalence of sulfite sensitivity in the general population is low, it is
seen more frequently in asthmatics or in atopic nonasthamatic people. Specific product
containing sulphites are identified in product listings.
Drug Interactions -
1. Anaesthetics: Use anesthetics that sensitize myocardium to sympathomimetics
(e.g. cyclopropane or halothane) cauthously. Local anesthetics can increase ocular
absorption of topical drugs. Exercise caution when applying prior to use of
phenylephrine.
2. Beta-adrenergic blocking agents: Systemic side effects may occur more readily in
patients taking these drugs. A severe hypertensive episode and fatal intracranial
haemorrhage possibly associated with ophthalmic use of phenylephrine was reported
in 1 patient taking propranolol for hypertension.

3. MAOIs: When given with, or up to 21 days after MAOIs, exaggerated adrenergic

effects may result. Supervise and adjust dosage carefully. The pressor response of
adrenergic agents may also be potentiated by tricyclic antidepressants, propranolol,
reserpine, guanethidine, methyldopa and anticholinergics (see Adverse Reactions).
Adverse Reactions:
Cardiovascular : Palpitations: tachycardia: Cardiac arrhythmia; hypertension; collapse;
extrasystoles; ventricular arrhythmias (ie, premature ventricular contractions); reflex
bradycardia; coronary occlusion; subarachnoid haemorrhage; myocardial infarction;
stroke; death associate with cardiac reactions. Headache and browache may occur.
Phenylephrine 10%- Significant elevation of blood pressure is rare but can occur after
conjunctival instillation. Exercise caution with elderly patients and children of low body
weight. Carefully monitor the blood pressure of these patients (see Warnings and
Contraindications). There have been rare reports of the development of serious
cardiovascular reactions, including ventricular arrhythmias and myocardial infarctions.
These episodes, some fatal, have usually occurred in elderly patients with pre-existing
cardiovascular diseases.
Ophthalmic: Transitory stinging on initial instillation: blurring cf vision; mydriasis,
increased redness; irritation; discomfort; punctate keratitis: lacrimation; increased IOP
May Cause rebound miosis and decreased mydriatic response to therapy in the elderly
Miscellaneous: Headache; blanching: sweating; dizziness; nausea; nervousness;
drowsiness: weakness; hyperglycemia.
Administration and Dosage:
Vasoconstrictors and pupil dilation: Istill a drop of topical anaesthetic. Follow in a
few minutes with 1 drop of the 2.5% or 10% phenylephrine. The anesthetic
prevents stinging and consequent dilution of solution by lacrimation. It may be
necessary to repeat the instillation after 1 hour, again preceded by a topical
anaesthetic.

Uveitis: The formation of synechiae may be prevented by using the 2.5% or 10%
solution and atropine to produce wide dilation of the pupil. However, the
vasoconstrictor effect of phenylephrine may be antagonistic to the increase of local
blood flow uveal infection.
To free recently formed posterior synechiae, instill 1 drop of the 2.5% or 10%
solution to the upper surface Of the cornea. Continue treatment the following day,
if necessary. In the interim, apply hot compresses for 5 or 10 minutes, 3 times
daily using 1 drop of 1% or 2% solution of atropine sulfate before and after each
series of compresses.
Glaucoma: Instill 1 drop of 10 % solution on the upper surface of the cornea as
often as necessary. The 2.5% and 10% solutions have been used in conjunction
with miotics in patients with open-angle glaucoma. Phenylephrine reduces the
difficulties experienced by the patients because of the small field produced by
miosis. Hence. there may be marked improvement in visual acuity after using
phenylephrine with drugs.
Surgery: When a short acting mydriatic is needed for wide dilation of the pupil
before intraocular surgery, the 2.5% Or 10% solution may be instilled from 30 to
60 minutes before the operation.

Refraction: Prior to determination of refractive errors, the 2.5% solution may be

used effectively with homatropine HBr, atropine sulfate, cyclopentolate,
tropicamide HCl, or a combination of homatropine and cocaine HCI.
 Adults: Instill 1 drop of the preferred cycloplegic in each eye; follow in 5 minutes with 1 drop
phenylephrine 2.5% solution and in 10 minutes with another drop of the cycloplegic in 50 to 60
minutes, the eyes are ready for refraction.
Because adequate cycloplegia is achieved at different time intervals after the necessary
number of drops, different cycloplegics will require different waiting periods.
Children — Instill 1 drop of atropine sulfate 1% in each eye; follow in 10 to 15 minutes with 1
drop of phenylephrine 2.5% solution and in 5 to 10 minutes with a second drop of atropine
sulfate 1%. In 1 to 2 hours, the eyes ready for refraction.
For a “1 application method” combine 2.5 % phenylephrine solution with a cycloplegic, such as
cyclopentolate, to elicit synergistic action. The additive effect varies depending on the patient.
Therefore, when using a “1 application method “It may be desirable to increase the
concentration of the cycloplegic.
Ophthalmoscope examination: Phenylephrine is rarely used alone for mydriasis. Maximum
dilation is achieved 45 to 60 minutes.
Diagnostic procedures: Heavily pigmented irides may require doses in all the following
procedures:
Retinoscopy: When dilution of the pupil without cycloplegic action is desired, the 2.5% solution
may be used alone.
Blanching Test: Instill 1 to 2 drops of the 2.5% solution in the injected eye. After 5 mins,
examine for perilimbal blanching. If blanching occurs, the congestion is superficial and probably
dows not indicate iritis.
Stability: Prolonged Exposure to air or strong light may cause oxidation and discoloration. Do
not use if solution changes color, becomes cloudy, or contains a precipitate
CYCLOPLEGIC MYDRIATIC
Commonly used cycloplegic mydriatics include the following
Atropine
Homatropine
Scopolamine
Cyclopentolate
Tropicamide.
Cycloplegics relax the ciliary spasm seen with anterior uveitis.
Atropine is the most potent and has the longest duration of action, retaining
its activity for 7 days or more. Atropine 1% eye ointment is used for
refraction and fundus examination in children, especially those with darkly
pigmented
irises and those less than 5 years of age.The ointment is instilled twice a
day for three days before examination. Systemic absorption may
occasionally lead to facial flushing hence ointment is preferred over drops in
young children.
Atropine 1% drops or ointment may also be used as
‘penalization’ therapy in the better eye, in patients with amblyopia. Contact
dermatitis occurs relatively frequently when atropine is used for prolonged
periods. Homatropine 2% drops are less potent and used in the treatment of
uveitis and for refraction in children. Its effect lasts for 4–5 days.
Cyclopentolate has a shorter duration of action, lasting up to 24 hours.
Cyclopentolate 1% drops three times
5 minutes apart are used for refraction and fundus examination
in children.

Tropicamide 0.5%, 1% drops three times 5 minutes apart are short-

acting.Though effective for up to 3 hours, the maximum cycloplegic effect
appears 30 minutes after the last drop and lasts for only 10–15 minutes, so
proper timing of refraction is crucial.
Side effects of cycloplegics are blurred vision and photophobia.
Driving immediately after dilatation or cycloplegia is
not recommended. In patients above 60 years of age having hypermetropia and
a shallow anterior chamber, mydriasis may precipitate acute angle-closure
glaucoma.
USE IN ESOTROPIA – Children with strabismus , especially esotropia, should receive a
cycloplegic examination . It is important to uncover the full amount of hyperopia in young
patients with suspected accommodative esotropia.
Patients who are unresponsive or inconsistent in their responses to subjective refraction will
often benefit from cycloplegia.
Cycloplegic refraction is also indicated to confirm the refractive amount in patients who
exhibit symptoms of malingering or conversion reaction.

CONTRAINDICATIONS

Cycloplegics cause papillary dilatation - ,therefore contraindicated in in patients with

extremely narrow anterior chamber angles or history of angle closure glaucoma. Patients
allergic to atropine can usually be given scopolamine , which will enable similar results.

DRUG SELECTION
Cyclopentolate ahs become the drug of choice for for the cycloplegic refraction of strabismu
patients over 4 years of age and non strabismic patients of any age.

USE IN UVEITIS
Uveitis is inflammation of the iris, cilliary body, or choroid of the eye. The inflammation can
be limited to the anterior strudtures or posterior structures. Cycloplegics is useful in the
treatment of anterior uveitis because they often prevent posterior synaechia. Cycloplegics
places the ciliary body and the iris at rest. Reducing many of the associated symptoms.
Cycloplegics also reduce the anterior chamber reaction.
USE IN UVEITIS
Uveitis is inflammation of the iris, cilliary body, or choroid of
the eye. The inflammation can be limited to the anterior
strudtures or posterior structures. Cycloplegics is useful in the
treatment of anterior uveitis because they often prevent
posterior synaechia. Cycloplegics places the ciliary body and
the iris at rest. Reducing many of the associated symptoms.
Cycloplegics also reduce the anterior chamber reaction
ACTIONS
Anticholinergic agents ( cholinergic
antagonists) block the responses of the
sphincter muscle of the iris and the muscle
of the cilliary body to cholinergic stimulation ,
producing pupilary dilatation ( mydriasis) ,
and paralysis of accommodation (
cycloplegia)
Indications
Mydriasis/Cycloplegia – For cycloplegic
refraction and for dilating the pupil in
inflammatory conditions of the iris and uveal
tract.
CONTRAINDICATIONS
Primary glaucoma or a tendency tpward glaucoma( narrow anterior chamber) ,
hypersensitivity to belladonna or any other alkaloid that produces adhesions
between iris and lens.
Warning –
For topical use only , , no injection
Glaucoma- Determine the intraocular tension and the depth of the anfle of the
anterior chamber before and during use , to avoid glaucoma attacks.
Elderly – with caution ,mayhave increased IOP
Pregnancy- Category C ( Atropine, Cyclopentolate, homatropine). Safety for use
during pregnancy is not established.
Lactation- Atropine and homatropine may be detected , in very small amounts in
breast milk. It is controversial, according to American Academy of Pediatrics,
these agents are combatible with breastfeeding.

Children- Excessive use in childen may caus systemic toxicity.

TROPICAMIDE and CYCLOPENTOLATE – may cause CNS disturbances that may be

dangerous in infants and children .
We need to keep in mind the possibility of psychotic reaction and behavioral
disturbances caused by hypersensitivity to anticholinergicsdrugs. Feeding disturbances
may follow ophthalmic use of this product in neonates. It is recommendedthat feeding
be withheld for 4 hours after examination. Do not use in concentration greater than
0.5%in small infants.
Anticholinergic Drugs
Classification
Natural alkaloids :
Atropine* (prototype), Scopolamine
(Hyoscine)
Semisynthetic derivatives :
Homatropine*, ipratropium bromide,
tiotropium bromide
Synthetic compounds :
i) Mydriatics – Cyclopentolate*, tropicamide
ii) Antiparkinsonian – Benzhexol, Biperiden,
Benztropine
iii) Antisecretory- antispasmodics – Dicyclomine
Pirenzepine Glycopyrrolate

Pharmacological actions of atropine

CNS :

High doses – restlessness, delirium, disorientation

CVS :
Tachycardia
E ye
Mydriasis : “Passive mydriasis” Photophobia,

abolition of light reflex “Paralysis of accomodation or

cycloplegia” Rise in IOP

Decrease in lacrimation – dry eyes

RESPIRATORY SYSTEM:
BRONCHODILATATION DECREASED SECRETION

GIT :
Reduce gastric acid secretion
Reduced tone and motility of gut, constriction of sphincters – constipation
 GENITOURINARY
TRACT:
Relaxation of ureter and urinary bladder – urinary
retention
Glands :
Decreases sweat, salivary, tracheobronchial and lacrimal
secretion
B o d y temperature :
Rise in body temperature “Atropine
fever”
USES OF
ATROPINE
• Preanaesthetic medication: to decrease secretion
•Oraganophosphorous poisoning
 THERAPEUTIC USES

Motion sickness : Scopolamine

Parkinson’s disease :benzhexol,
benztropine etc.
Bronchial asthma : ipratropium and
tiotropium bromide
Preanaesthetic medication :
glycopyrrolate ,
A s mydriatic during fundoscopy and testing of
refractive error – Tropicamide, cyclopentolate
SIDE EFFECTS OF ATROPINE :

D r y mouth
Blurred vision and photophobia
Urinary retention
Constipation
D r y, hot skin
Precipitation of glaucoma
Decreased sweating
DRUGS AFFECTING THE PUPIL
AND ACCOMMODATION
Cycloplegics and Mydriatics
Commonly used cycloplegics are atropine 1%, homatropine
2%, cyclopentolate 1% and tropicamide 0.5%. They
are used in determining the correct refraction of an eye,
especially in children, as well as in adults who are hypermetropic
or those undergoing laser refractive surgery.
Cycloplegics
relax the ciliary spasm seen with anterior uveitis.
Atropine is the most potent and has the longest duration
of action, retaining its activity for 7 days or more. Atropine
1% eye ointment is used for refraction and fundus examination
in children, especially those with darkly pigmented
irises and those less than 5 years of age. The ointment is
instilled twice a day for three days before examination.
Systemic absorption may occasionally lead to facial flushing
hence ointment is preferred over drops in young children.
Atropine 1% drops or ointment may also be used as
‘penalization’ therapy in the better eye, in patients with
amblyopia. Contact dermatitis occurs relatively frequently
when atropine is used for prolonged periods. Homatropine
2% drops are less potent and used in the treatment of uveitis
and for refraction in children. Its effect lasts for 4–5 days.
Cyclopentolate has a shorter duration of action, lasting
up to 24 hours. Cyclopentolate 1% drops three times
5 minutes apart are used for refraction and fundus examination
in children.
Tropicamide 0.5%, 1% drops three times 5 minutes
apart are short-acting. Though effective for up to 3 hours,
the maximum cycloplegic effect appears 30 minutes after
the last drop and lasts for only 10–15 minutes, so proper
timing of refraction is crucial.
Side effects of cycloplegics are blurred vision and photophobia.
Driving immediately after dilatation or cycloplegia is
not recommended. In patients above 60 years of age having
hypermetropia and a shallow anterior chamber, mydriasis
may precipitate acute angle-closure glaucoma.
PARASYMOATHOMIMETICS
INCLUDES
CHOLINESTERSCHOLINOMIMETIC ALKALOIDS ANTI-
CHOLINESTERASES

CHOLINESTERSCHOLINESTERS
11. Carbachol. Carbachol 11%%22. Bethenecol. Bethenecol
11%%
CHOLINOMIMETIC ALKALOIDSCHOLINOMIMETIC ALKALOIDS
PilocarpinePilocarpine 22%%
ANTICHOLINESTERASES ANTICHOLINESTERASES

INCLUDES
REVERSIBLEPHYSOSTIGMINE 1% IRREVESIBLE AS D.F.P 0.1%
DRUGS PRODUCING MIOSIS

 Nicotine activates parasympathetic nerves

 Muscarinic agonists such as Pilocarpine (Pilocar), acetylcholine (Miochol)
 Pilocarpine used as 2% solution
 1% solution to differentiate IIIrd nerve palsy from “Atropinic” mydriasis
 If pilocarpine is active (produces miosis) then the defect must be in the nerve
Mechanism of Action of Sympathomimetics As previously
mentioned, sympathomimetics act by stimulating α, β and/or
dopamine receptors and/or causing release or inhibiting reuptake
of neurotransmitters. Brief review of the neurotransmission of
adrenergic neurons Norepinephrine is synthesized from tyrosine
and stored in vesicles at the end of the neuron. Calcium influx from
an action potential causes the vesicles to fuse with the synapse
membrane and release noradrenaline in the synaptic space. It then
binds to the adrenoreceptor on the effector cells and produces
effects by various mechanisms. The excess norepinephrine not
bound to the postsynaptic receptor binds to α2 presynaptic
receptors to decrease its own release. It then either diffuses out, is
metabolized by COMT or is taken back up by the presynaptic
neuron.
Direct acting sympathomimetics α–receptor stimulation: α1
agonists act by G-protein activation of the enzyme
phospholipase C, resulting eventually in the release of calcium,
thereby increasing the intracellular calcium concentration.
Alpha2 (α2) agonists act by inhibiting adenylyl cyclase, the
enzyme that catalyzes the conversion of adenosine triphosphate
(ATP) to cyclic adenosine monophosphate (cAMP). This leads to
decreased intracellular cAMP levels. Alpha receptors are further
subdivided into α1A, α1B, α1C and α1D as well as α2A, α2B
and α2C. This differentiation is important as the search for more
selective newer drugs continues, and selectivity at the sub-type
level helps narrow down the effects of a drug. R
Indirect acting sympathomimetics Indirect-acting drugs are
those that act indirectly to increase the concentration of the
endogenous neurotransmitter by causing its release (e.g.,
amphetamine derivatives and ephedrine) or inhibiting its
reuptake (e.g., cocaine and tricyclic antidepressants). Mixed-
acting sympathomimetics Mixed-acting drugs employ both
mechanisms, e.g., ephedrine, which, in addition to acting on the
α and β receptors, causes noradrenaline release. Ephedrine is
used to treat nasal congestion.
0