Myasthenia gravis is an autoimmune disorder that causes weakness in the voluntary muscles. It results from antibodies blocking or destroying acetylcholine receptors in the neuromuscular junction. Symptoms include drooping eyelids, double vision, difficulty speaking and swallowing. While there is no cure, treatment focuses on improving muscle strength and function through medications like cholinesterase inhibitors, corticosteroids and immunosuppressants. Glaucoma is a group of eye diseases that cause damage to the optic nerve and vision loss. Elevated intraocular pressure is a major risk factor. Topical medications to lower pressure include beta blockers, alpha agonists, prostaglandin analogs, and carbonic an

1. Drugs used in Myasthenia
gravis and Glaucoma

2. Myasthenia Gravis

3. INTRODUCTION
• Myasthenia gravis (MG) is a complex, autoimmune disorder in which
antibodies destroy neuromuscular connections.
• Causes problems with the nerves that communicate with muscles.
• Affects the voluntary muscles of the body, especially the eyes, mouth, throat,
and limbs.

4. • Characterized by weakness and rapid fatigue of any of the muscles under the
voluntary control.
• The cause of myasthenia gravis is a breakdown in the normal
communication between nerves and muscles.
• No cure for myasthenia gravis, but treatment can help relieve signs and
symptoms – such as weakness of arm or leg muscles, double vision,
drooping eyelids, and difficulties with speech, chewing, swallowing and
breathing.

7. TYPES OF MYASTHENIA GRAVIS
Three types of MG in children:
• Congenital MG - Very rare non-immune form of MG that is inherited as an autosomal
recessive disease.
• Symptoms of congenital MG usually begin in the baby's first year and are life-long.
• Transient neonatal MG - Between 10 and 20 percent of babies born to mothers with MG
may have a temporary form of MG.
• Neonatal MG usually lasts only a few weeks, and babies are not at greater risk for
developing MG later in life.
• Juvenile MG - This auto-immune disorder develops typically in female adolescents.
• It is a life-long condition that may go in and out of remission. About 10 percent of MG
cases are juvenile-onset.

8. SYMPTOMS
• Congenital MG symptoms may begin in the first year, with generalized weakness in the
arms and legs, and delays in motor skills such as crawling, sitting, and walking
• Babies with neonatal MG may be weak, with a poor suck, and may have respiratory
difficulty.
• A few babies may need the help of a mechanical breathing machine if their respiratory
muscles are too weak to breathe on their own.
• Juvenile MG symptoms may begin gradually over weeks or months.
• The child may become excessively tired after very little activity, and begin to have problems
chewing and swallowing.
• Drooping eyelids may be so severe that the child cannot see.

9. Eye muscles
In more than half the people who develop MG, their first signs and
symptoms involve eye problems:
• Drooping of one or both eyelids (ptosis)
• Double vision (diplopia), which may be horizontal or vertical
• Blurred vision, which may come and go

10. Face and throat muscles
• In about 15 percent of people with myasthenia gravis, the first symptoms involve face
and throat muscles, which can cause difficulties with:
• Speaking. The speech may be very soft or sound nasal, depending upon which
muscles have been affected.
• Swallowing. May choke very easily, which makes it difficult to eat, drink or take
pills. In some cases, liquids may come out of the nose.
• Chewing. The muscles used for chewing may wear out halfway through a meal,
particularly if eating
• something hard to chew, such as sugarcane.
• Facial expressions. Family members may note "lost smile" if the
muscles that control facial expressions are affected.

11. Arm and leg muscles
▪ Myasthenia gravis can cause weakness in arms and legs, but this usually
happens in conjunction with muscle weakness in other parts of the body –
such as eyes, face or throat.
▪ The disorder usually affects arms more often than legs.
▪ If it affects legs, may waddle when walking.
Normal dumbbell Weakness dumbbell

12. When to see a doctor
• If having trouble with:
• Breathing
• Seeing
• Swallowing
• Chewing
• Walking

13. CAUSES
• Myasthenia gravis may be inherited, genetic disease, acquired by
babies born to mothers with MG
• Nerves communicate with the muscles by releasing chemicals, called
neurotransmitters, which fit precisely into receptor sites on the muscle
cells.
• In myasthenia gravis, immune system produces antibodies that block or
destroy many of the muscles receptor sites for a neurotransmitter called
acetylcholine.
• With fewer receptor sites available, muscles receive fewer nerve
signals, resulting in weakness.

14. Chemicals messengers, called neurotransmitters, fit precisely into receptor
sites on your muscle cells. In myasthenia gravis, certain receptor sites are
blocked or destroyed, causing muscle weakness.

15. How antibodies against
acetylcholine receptor block
impulse conduction
in synapse

16. • It's believed that the thymus gland, a part of the
immune system located in the upper chest
beneath the breastbone, may trigger or maintain
the production of these antibodies.
• Large in infancy, the thymus is small in healthy
adults. But, in some adults with myasthenia
gravis, the thymus is abnormally large.
• Some people also have tumors of the thymus.
• Usually, thymus gland tumors are
noncancerous.

17. COMPLICATIONS
• Myasthenic crisis: A life-threatening condition, which occurs when the
muscles that control breathing become too weak to do their jobs.
Emergency treatment is needed to provide mechanical assistance with
breathing.
• Thymus tumors: About 15 percent of the people who have myasthenia
gravis have a tumor in their thymus, a gland under the breastbone that is
involved with the immune system. Most of these tumors are
noncancerous.

18. Other disorders
• Underactive or overactive thyroid. The thyroid gland, located in the
neck, secretes hormones that regulate metabolism. If thyroid is
underactive, body uses energy more slowly. An overactive thyroid makes
body use energy too quickly.
• Lupus. Disease of immune system. Common symptoms include painful
or swollen joints, hair loss, extreme fatigue and a red rash on the face.
• Rheumatoid arthritis. Caused by problems with immune system. It is
most conspicuous in the wrists and fingers, and can result in joint
deformities that make it difficult to use hands.

19. Diagnostic tests
• Blood tests
• Genetic tests - diagnostic tests that evaluate for conditions that
have a tendency to run in families.
• Electromyogram (EMG) - a test that measures the electrical activity
of a muscle or a group of muscles.
• An EMG can detect abnormal electrical muscle activity due to
diseases and neuromuscular conditions.
• Muscle biopsy - a small sample of the muscle is removed and
examined to determine and confirm a diagnosis or condition.

20. TREATMENTS & DRUGS
• Specific treatment to age, overall health, and medical history and extent
of the condition
• No cure for MG, but the symptoms can be controlled.
• MG is a life-long medical condition and the key to medically managing
MG is early detection.
• The goal of treatment is to prevent respiratory problems and provide
adequate nutritional care to the child since the swallowing and
breathing muscles are affected by this condition.

21. Medications
• Cholinesterase inhibitors. Drugs like pyridostigmine (Mestinon)
enhance communication between nerves and muscles.
• These drugs don't cure, but improves muscle contraction and strength.
• Corticosteroids. These types of drugs inhibit the immune system,
limiting antibody production.
• Prolonged use of corticosteroids, can lead to serious side effects, like
bone thinning, weight gain, diabetes, increased risk of some infections,
and increase and redistribution of body fat.
• Immunosuppressants.
• Doctor may also prescribe other medications that alter immune system,
like azathioprine (Imuran), cyclosporine (Sandimmune, Neoral) or
mycophenolate (CellCept).

22. Therapy
• Plasmapheresis. This procedure uses a filtering process similar to
dialysis.
• Blood is routed through a machine that removes the antibodies that
are blocking transmission of signals from nerve endings to muscles
receptor sites. However, the beneficial effects usually last only a few
weeks.
• Intravenous immune globulin. This therapy provides body with
normal antibodies, which alters immune system response.
• It has a lower risk of side effects than do plasmapheresis and
immune- suppressing therapy, but it can take a week or two to start
working and the benefits usually last less than a month or two.

23. • Thymectomy - surgical removal of the thymus gland. The role of the thymus
gland in MG is not fully understood, and the thymectomy may or may not improve
a child's symptoms.
• About 15 percent of the people who have MG have a tumor in their thymus
• For people with MG who don't have a tumor in the thymus, it's unclear whether the
potential benefit of removing the thymus outweighs the risks of surgery.
• This is an individualized decision between patient and the doctor, but most doctors
don't recommend surgery if:
• Symptoms are mild
• Symptoms involve only the eyes
• Patients over 60 years old
Surgery

24. • Plasmapheresis - a procedure that removes abnormal antibodies from the
blood and replaces the child's blood with normal antibodies through
donated blood.
• Extent of the problems is dependent on the severity of the condition and the
presence of other problems that could affect the child.
• In severe cases, a breathing machine may be required to help the child
breathe easier.
• It is important to allow the child as machine dependent function and self
care, especially with juvenile MG, as possible and to promote age-
appropriate activities to ensure a sense of normalcy.

25. Glaucoma

26. What is glaucoma ?
• Glaucoma – ancient meaning (Greek) clouded or
blue- green hue
• Glaucoma – blindness coming from advancing years
(!)
• Second leading cause of blindness
• Glaucoma is a group of disorders characterized
by a progressive optic neuropathy resulting in a
characteristic appearance of optic disc &
specific pattern of irreversible visual field
defects that are associated frequently but not
invariably with ↑IOP (>21 mm Hg)
• All types of glaucoma – progressive optic
neuropathy due to the death of retinal ganglion
cells (RGCs)

27. Aqueous humor dynamics
• Aqueous is continuously produced by the ciliary
body (2-3 µl/minute)
• Aqueous flows from the posterior chamber
through the pupil into the anterior chamber
• Aqueous filters largely through the trabecular
meshwork (90%) and canal of Schlemm→
episcleral venous plexus and into systemic
circulation.
• Aqueous also exits to a smaller extent through the
ocular venous system (10%)
– Uveoscleral outflow (ciliary body, choroid,
scleral vessels)

28. Types of glaucoma
• Congenital glaucoma
• Primary glaucoma
– Open angle
– Closed angle
• Secondary glaucoma – lens
induced, traumatic or steroid
induced
• Absolute glaucoma

29. Therapeutic goal
• Lower IOT by
– Reduction of aqueous humor secretion
– Promoting aqueous drainage
• Lowering of IOT retards the progression of optic nerve
damage even in normal/low i.o.t

30. Open angle/wide angle/chronic simple glaucoma
• Genetically predisposed degenerative disease affecting patency of
trabecular meshwork
• Meshwork becomes less efficient at draining
• IOP builds up progressively
• Damage of the optic nerve
• Has no symptoms in its early stages after middle age
• Ocular hypotensive drugs - reduce formation of AH, increase drainage or
protect optic nerve

31. Open-angle Glaucoma (OAG)

32. Drugs for Glaucoma
• β- adrenergic blockers: Timolol, Betaxolol and
Levobunolol
• α- adrenergic agonists: Dipivefrine, Apraclonidine and
Brimonidine
• PG analogues: Latanoprost, Travoprost and
Bimatoprost
• Carbonic anhydrase inhibitors: Acetazolamide and
dorzolamide
• Miotics: Pilocarpine and Physostigmine

33. Location of targets of drugs

34. β- adrenergic blocker in glaucoma - MOA
• Topical β- adrenergic blockers have been the first line of drugs - PG F2α
are preferred now
• Contrast to miotics – no effects on pupil size, tone of cilliary
muscle and outflow facility
• Lower IOP by reducing aqueous formation
– Down regulation of adenylylcyclase due to β2 receptor blockade in
cilliary epithelium
– Reduction of blood flow
• Advantages over miotics – produce less ocular side effects,
lipophillic and weak anaesthetic (corneal hyposthesia and damage)

35. β- adrenergic blockers – contd.
• Ocular side effects: mild and infrequent
– Stinging, redness, dryness
– Corneal hypoesthesia
– Blurred vision
• Systemic adverse effects: Major limitation of use
– Nasolacrima duct
– Life threatening bronchospasm – COPD and asthma
– Bradycardia, heart block and CHF – ADRs

36. Individual drugs – beta blockers
• Timolol (0.25-0.5% eye drops): Non-Selective- β1 + β2
• sympathomimetic action
• ↓ IOT by 20-35% - 1 hour to 12 hours
• Smooth and well sustained action after chronic dosing→ high level of clinical
safety – advantage
• 30% patients response
• Betaxolol (0.5 %)
• Selective β1 blocker - Less bronchopulmonary, probably less cardiac, central
and metabolic effects
• Exert protective effect on retinal neurones
• Less efficacious in ↓ IOT than timolol (β2)
• Levobunolol: Once daily dosing alt. to timolol
 Ocular and systemic side effects similar to timolol

37. α – adrenergic agonists
• MOA
– α1 constrict ciliary body - reduced aqueous secretion
– α2 in ciliary epithelium reduce aqueous secretion
– Secondary role in enhancing drainage of aqueous mainly
through uveoscleral outflow and also trabecular outflow
• Dipivefrine (0.1 %)
 Adrenaline – ocular smarting, reactive hyperemia
 Prodrug of adrenaline→ Adr. ↓ IOT by ↑ uveoscleral
outflow,↑ trabecular outflow (β2), ↓ aqueous production (α1
+ α2 )
 Not used now due to systemic effects & ocular intolerance
 Maybe used as an add-on therapy

38. α – adrenergic agonists – contd.
• Apraclonidine (0.5- 1%): Clonidine congener
– No CNS penetration - acts on both α1 & α2 receptors of ciliary body→
↓ aqueous production.
– ↓ IOT by ~25%
– ADRs: itching, lid dermatitis, follicular conjunctivitis, mydriasis, eyelid
retraction, dryness of mouth and nose etc.
– Use is restricted to short term control of IOT spikes (trabeculoplasty or
iridotomy).
• Brimonidine (0.2%): Newer clonidine congener, more selective to α2
– More lipophilic than apraclonidine
– ↓ IOT by 20-27% by ↓ aq. production and ↑ uveoscleral flow.
– Uses both in short term (post surgery) and long term therapy in
glaucoma. – add on therapy

39. Prostaglandin analogues
• Low concentration of PGF2α analogues ↓ IOT by:
• Increase uveoscleral outflow (↑ciliary tissue permeability and vascular
permeability)
• Trabecular outflow less marked
• Latanoprost (0.005% eye drop)
• Topically IOT ↓ 25-35%, well sustained
• ↓ IOT in normal pressure glaucoma also
• Ocular irritation and pain
• Good efficacy, once daily application and absence of systemic
complications – first choice in open angle glaucoma
• Other ADRs: Blurring of vision, iris pigmentation, thickening and
darkening of eye lashes etc.
• Travoprost and Bimatoprost: similar efficacy with Latanoprost

40. Carbonic anhydrase inhibitors
• Carbonic anhydrase present within ciliary epithelial cells generates HCŌ3 ion
secreted into aq. humour.
• Inhibition of carbonic anhydrase - Limits generation of bicarbonate ion →
reduction of aqueous humour
• Acetazolamide:
– Orally – 0.25 gm 6-12 hourly
– Used to supplement ocular hypotensive drugs for short term indication like angle
closure, before & after surgery/laser therapy
– Long term use when IOP not controlled by topical drugs
• Side effects: Systemic s/e – paresthesia, anorexia, hypokalemia,
acidosis, malaise, depression (on long term use)
• Dorzolamide: 2% eyedrop topical – 20% efficacy

41. Miotics
• In 1970s – were standard antiglaucoma drugs
• Last option because of several drawbacks – myopia, diminution of
vision, headache
• Pilocarpine:
 Causes miosis by contraction of iris sphincter muscle →
removes pupillary block and reverses obliteration of iridocorneal
angle
 Contraction of ciliary muscle → pulls on scleral spur and
improves trabecular patency.
 Max of 10-20% IOP reduction - 0.5%to 4% solution

42. OAG – current approach
• Monotherapy with Latanoprost or a topical β - blocker
• If not target attained – change to alternative drug or both
together
• Brimonidine/dorzolamide (or dipivefrine) used when above
two contraindicated
• Acetazolamide and Miotics – last option

43. Angle closure (narrow angle, acute congestive) Glaucoma
• Emergency situation occurring in person with narrow iridocorneal
angle and shallow anterior chamber
• IOT raised after it is being precipitated by mydriasis
• IOT rises rapidly to very high levels (40 - 60 mmHg)
• Marked congestion of eyes and severe headache
• Failure to lower IOT → loss of sight
• Definite treatment – surgery (iridotomy/laser therapy)

44. Closed angle glaucoma

45. Therapy of closed angle glaucoma
1. Hypertonic mannitol (20%) 1.5-2 g/kg or Glycerol (10%):
• IV infusion – decongest eye by osmotic action
• Glycerine 50% - retention enema
2. Acetazolamide (0.5g) IV followed by oral BD started concurrently
3. Miotic: If above reduced the IOP -topical Pilocarpine 1-4 % every 10
mins initially & then at longer intervals.
4. Topical β blocker: Timolol 0.5% 12 hourly in addition.
5. Latanaprost (0.005%) / Apraclonidine (1%) may also be
added.
Chronic narrow angle: miotic/other drugs for longer period

46. Must know
• Different categories of drugs used in open angle glaucoma
• Their sites and mechanism of action
• Management of closed angle glaucoma

47. Thank you