Myd, Cyclo, Miotics

7/28/2019 Myd, Cyclo, Miotics

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MYDRIATICS, CYCLOPLEGICS

AND MIOTICS

By Misha Devchand (b. Pharm (Hons))

The peripheral nervous system contains:

Autonomic nervous systemSomatic efferent nervesSomatic and visceral afferent nerves

A simple way to understand the difference betweenthe somatic and autonomic systems is that the

neurons of the somatic division innervate skeletal

muscle, whereas the autonomic neurons innervatesmooth and cardiac muscle, glands, and neurons in

the gastrointestinal tract.

Diagram of a Neuron:

Source: Widmaier et al. Vanders Human Physiology themechanism of body function 8 th ed.

Autonomic Nervous system

Conveys all the outputs from the central nervous system tothe rest of the body.

Consists of: Sympathetic Parasympathetic Enteric Nervous system (the nervous system that controls the GI

tract)

The Autonomic nervous system is largely involuntary andthe main functions it regulates are: Contraction and relaxation of vascular and visceral smooth

muscle All exocrine and certain endocrine secretions Heartbeat Energy metabolism

Autonomic pathways are 2 neurons arranged in aseries that connect to the CNS and the effector cells

These neurons are known as preganglionic andpostganglionic neurons

Source: Widmaier et al. Vanders Human Physiology the

mechanism of body function 8 th ed.

The basic difference between the para-

sympathetic and sympathetic nervous system

They leave the CNS at different levels SympatheticFibers leave from the thoracic (chest) and lumbar regions of the

spinal cord

ParasympatheticFibers from the brain and the sacral portion of the spinal cord


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Neurotransmitters

A neurotransmitter is a chemical messenger used byneurons to communicate with each other or with effectorcells

There are two major neurotransmitters that are used in theautonomic nervous system Acetylcholine

Noradrenaline (NA)

Other neurotransmitters that may also be released include ATP

Dopamine

Several neuropeptides

Nitric oxide

Other vasodilators

Neurotransmitters cont.

In the sympathetic and parasympathetic nervoussystem acetylcholine is the major neurotransmitterbetween pre and postganglionic neurons.

In the parasympathetic nervous systemacetylcholine is also the major neurotransmitterbetween the postganglionic neuron and the

effector cell. In the sympathetic nervous system noradrenaline is

usually the major transmitter betweenpostganglionic neuron and the effector cell.

Neurotransmitters cont.

Many drugs that act on the autonomic nervous system act at the receptorsthat acetylcholine and noradrenaline bind to.

I. Receptors for acetylcholine (cholinergic neurons)

Nicotinic receptorsn On postganglionic neurons in the autonomic ganglian At neuromuscular junctions of skeletal muscle (somatic nervous system)n On some central nervous system neurons

Muscarinic receptorsn On smooth musclen On cardiac musclen On gland cellsn On some central nervous system neuronsn On some neurons of autonomic ganglia

II. Receptors for Noradrenaline and adrenaline

On smooth muscle On cardiac muscle On gland cells On some central nervous system neurons

Neurotransmitters cont. Moa of drugs

Drugs that act on the nervous system usually do soby altering synaptic mechanisms. Drugs may act by

interfering with normal synaptic processes:

Neurotransmitter synthesisNeurotransmitter storageNeurotransmitter releaseReceptor activation


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Source: Widmaier et al. Vanders

Human Physiology the mechanism of

body function 8th ed.

Where a drug could act at a synapses:

A) Increase leakage of neurotransmitterfrom vesicle to cytoplasm, exposing it to

enzyme breakdown,

B) increase transmitter release,C) block transmitter release,D) inhibit transmitter synthesis,E) block transmitter reuptake,F) block enzymes that metabolizetransmitter,

G) bind to receptor to block(antagonist)or mimic (agonist) transmitter action,

H) inhibit or facilitate second-messengeractivity

Muscarinic receptors types

Source Rang et Al

Nicotinic Receptor subtypes

Source Rang et Al

CATECHOLAMINES

Catecholamines are compounds containing a catecholmoiety (a benzene ring with two adjacent hydroxylgroups) and an amine side-chain pharmacologically, themost important ones are: Noradrenaline (NA)

n transmitter released by sympathetic nerve terminals

Adrenaline (A)n hormone secreted by the adrenal medulla

Dopaminen precursor of noradrenaline and adrenaline, also a transmitter/

neuromodulator in the central nervous system

Isoproterenol (ISO)n a synthetic derivative of noradrenaline.

Catecholamines act at adrenoceptors

Adrenoceptors

There are two different classes of these receptors:-adrenoceptorsnAntagonists

n Usedmainlyforcardiovascularindica8ons

-adrenoceptorsnAgonists

n Usedmainlyasbronchodilators

nAntagonistsn Usedmainlyforcardiovascularindica8ons

Adrenoceptor

Subtypes

1 2 1 2 3

Main effects of

receptor

activation:

Vasoconstriction Relaxation ofgastrointestinal

smooth muscle

Salivarysecretion andhepatic

glycogenolysis

Inhibition oftransmitterrelease, platelet

aggregation contraction ofvascular smooth

muscle inhibition ofinsulin release

increasedcardiac rateand force

broncho-dilatation vasodilatation, relaxation of

visceral smoothmuscle, hepatic

glycogenolysis muscle tremor

lipolysis

Agonist potency

orderNA A >>ISO A >NA >>ISO ISO >NA >A ISO > A > NA ISO >NA = A

Selective agonists Phenylephrine,methoxamine

Clonidine,clenbuterol

Dobutamine,xamoterol

Salbutamol,terbutalinesalmeterol,formoterol

BRL 37344

Selective

antagonists

Prazosin,

doxazocin

Yohimbine,

idazoxan

Atenolol,

metoprolol

Butoxamine -

Adrenoceptor subtypes table adapted from Rang et al


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Some examples of receptors in the eyeare:

The Sphincter muscle of the iris contains muscarinic receptors Contraction (through an agonist) = miosis

Blockade (through an antagonist) = mydriasis

The radial muscle of the iris contains 1 receptors Contraction (through an agonist) = mydriasis

Blockade (through an antagonist) = miosis

The ciliary muscle (which controls the angle of refraction ofthe lens) contains cholinergic neurons Contraction = the lens rounds up to accommodate for near vision

Blockade = paralysis of accommodation = permanently focusedon far vision (cycloplegia) may increase IOP

Other examples of receptors in the eyeare:

Iris Cilary bodyMuscarinic and nicotinic receptors

Ciliary bodyCholinergic neuronnOf the adrenergic receptors 90% are 2 types

Ciliary epitheliumAdrenoreceptors (and)nPlay a role in aqueous humor formation and therefore the

control of IOPn 2 -Adrenoreceptors play a role in aqueous humor formation

The Eye

Source: http://www.dartmouth.edu/~rpsmith/Cholinergic_Transmission.html

Mydriatics and Cycloplegics

Indications:1. Dilating the pupil for an ophthalmoscopy2. Paralysing muscles of accommodation (to aid in refraction

especially in younger patients)

3. Dilating the pupils and paralysing accommodation muscles inuveitis (relieves pain and photophobia)

Caution: In patients with narrow anterior chamber angles since either a

mydriatic or a cycloplegic could cause angle closure glaucoma

Do not use after a head injury It is not recommended to reverse mydriasis with a cholinergic

agent (ie pilocarpine)

Dilate the pupil

Mydriatics agents

Mydriatics

Phenylepherine

Mode of action (MOA)n Selective alpha1agonist

Additional indicationsn Prevention of posterior adhesions in uveitisn Relief of mild ocular congestionn Diagnostic vasoconstriction in episcleritisn Dilation of pupil prior to cataract surgery

Dose Onset of action

n Maximal effect occurs after 6090 minutes Duration of action

n 57hours Additional precautions:

n Cardiac patients ie - Recent MI, unstable angina - BP elevation with the 10% drops may be significant if repeated doses given. n Insulin-dependent diabetesn Treatment with MAOImay cause a hypertensive reaction; the 10% drops carry more risk than weaker strengths.n Treatment with systemic atropineincreases risk of severe hypertension with 10% drops.n Elderly (Increased risk of systemic adverse effects.)n Children (Increased risk of systemic adverse effects, especially hypertension and intraventricular bleeding in the first 24 weeks of life in preterm infants).

Do not use 10% drops in children.

n Pregnancy Avoid use; theoretical risk of placental vasoconstriction and fetal hypoxia. ADEs

n rebound miosis, hyperaemia (excessive accumulation of blood in an area of the body), stinging on instillation

Phenylepherine (a Mydriatic)

MOA Selective alpha1agonist (stimulates pupil dilator muscle)

Additional

indications

Prevention of posterior adhesions in uveitisRelief of mild ocular congestionDiagnostic vasoconstriction in episcleritisDilation of pupil prior to cataract

Dose Mydriasis

Adult, 2.5%, 1drop once only as adjunct if mydriasis difficult.

Adult, 10%, 1drop once only as adjunct for rapid maximal mydriasis.Uveitis

Adult, 10%, 1drop 3times daily as adjunct to mydriatic.

Onset of

effect

Maximal effect occurs after 6090minutes

Duration of action 5-7 hours

Additional

precautions:

Cardiac patients ie - recent MI, unstable angina - BP elevation with the 10%drops may be significant if repeated doses given.

Insulin-dependent diabetesTreatment with MAOITreatment with systemic atropineElderlyChildren - Do not use 10% drops in children.Pregnancy

ADEs rebound miosis, hyperaemia (excessive accumulation of blood in an area of thebody), stinging on instillation Main source AMH 2012s


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Dilate the pupil and cause paralysis of accommodation

Cycloplegic agents

1. Atropine (a Cycloplegic)

MOA Reversibly blocks acetylcholine receptors on iris sphincter and ciliary muscle.

Additional

indications

examination of peripheral lens and retina;prevention or breakdown of posterior synechiae from iritis;prevention of pupil constriction in iritisdiagnostic refraction;chemical occlusion for treatment of suppression amblyopia

Dose Diagnostic use - 1drop repeated after 5minutes if necessary.Therapeutic use

Uveitis, 1drop 3 or 4timesPostoperative, 1drop 3 or 4times daily.

Onset of

effect

30-40minutes. Maximum effect 2hours

Duration of action May last up to 2days

Additional

precautions:

Significant head injury- always make a note that pupils were dilated intentionally.Treated acute closed-angle glaucomashould be dilated under supervisionLenticular subluxationsmall risk of anterior lens displacement.Resistance to cycloplegiacan occur in young children and in patients with darklypigmented irides; use cautiously to prevent overdose.Children: Use with extreme caution, One drop of 0.5% atropine can causesystemic effects in infants.

ADEs intolerance to bright light, stinging on instillation, blurred vision , may transientlyincrease IOP.

Main source AMH 201

Effects of systemic atropine toxicity:

Decreased Salivation Dry mouth

Decreased Lacrimation Dry Eyes

Decreased Urination Urinary retention

Decreased defecation Constipation

Flushing Delirium Fever

2. Homatropine (a Cycloplegic)


Additional

indications


Dose Diagnostic use - 1drop repeated after 5minutes if necessary.Uveitis

Adult, child >1year, 1drop up to every 34hours (phenylephrineis occasionally usedas an adjunct)

Onset of effect About 40minutes Duration of action May last up to 3hours

Additional

precautions:

Significant head injury- always make a note that pupils were dilatedintentionally.Treated acute closed-angle glaucomashould be dilated under supervisionLenticular subluxationsmall risk of anterior lens displacement.Resistance to cycloplegiacan occur in young children and in patients withdarkly pigmented irides; use cautiously to prevent overdose.

Children: Use with extreme caution, One drop of 0.5% atropine can causesystemic effects in infants.

ADEs intolerance to bright light, stinging on instillation, blurred vision , may transientlyincrease IOP. Main source AMH 2012

3. Cyclopentolate(a Cycloplegic)


Additional

indications


Dose Adult - 1drop repeated after 5minutes if necessary.

Uveitis

Adult, 1drop of 0.5% (1% for deeply pigmented eyes) every 68 hours..

Onset of

effect

30-60minutes. Duration of action Less than 24 hours

Additional

precautions:

Significant head injury- always make a note that pupils were dilated intentionally.Treated acute closed-angle glaucomashould be dilated under supervisionLenticular subluxationsmall risk of anterior lens displacement.Resistance to cycloplegiacan occur in young children and in patients with darklypigmented irides; use cautiously to prevent overdose.Children: Use with extreme caution, One drop of 0.5% atropine can causesystemic effects in infants.


May cause neurotoxicity especially in children Main source AMH 2012

4. Tropicamide (a Cycloplegic)


Additional

indications


Dose Adult, 1drop (0.5% for mydriasis, 1% for cycloplegia) repeated after 5 minutesif necessary (can add phenylephrineif dilation is inadequate).

Examine after 20minutes (30minutes for darkly pigmented eyes)

Onset of

effect

20-25minutes. Duration of action 15-20mins postmaximum effect

Additional

precautions:

Significant head injury- always make a note that pupils were dilatedintentionally.

Treated acute closed-angle glaucomashould be dilated under supervisionLenticular subluxationsmall risk of anterior lens displacement.Resistance to cycloplegiacan occur in young children and in patients withdarkly pigmented irides; use cautiously to prevent overdose.

Children: Use with extreme caution, One drop of 0.5% atropine can causesystemic effects in infants.


Main source AMH 2012


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Causes constriction of the pupil

Miotic agents

1. Pilocarpine(a Miotic)

MOACholinergic effect contracts iris sphincter (miotic) and ciliary muscle, whichincreases outflow through the trabecular meshwork.

Indications Chronic open-angle glaucomaAcute closed-angle glaucoma (2% eye drops)

Dose Chronic open-angle glaucoma

Adult

Initial, 1drop of 1% 3 or 4times daily.Usual, 1drop of 2% 4times daily.

Maximum, 1drop of 4% 4times daily.

Additional

precautions:

Uveitiscontraindicated (exacerbates bloodocular barrier breakdown).Secondary glaucomas associated with extensive outflow obstructioncontraindicated (ineffective, may worsen).High myopia, aphakia, peripheral retinal degeneration, previous retinaldetachmentincreased risk of retinal detachment.Surgery May increase risk of bradycardia and hypotension during surgery.Children - Infrequently iris cysts at the pupillary margin develop withprolonged use; these rarely affect vision.

ADEs fluctuating blurred vision, accommodative spasm and frontal headache in people

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