Central Nervous System is one of the unit in Pharmacotherapeutics Subject which is for Second Year Diploma in Pharmacy. The unit covers diseases like Epilepsy, Parkinson, Alzheimer, Stroke and Migraine. The presentation includes the point as per diploma in pharmacy students may understand very easily. The syllabus is framed by Pharmacy Council of India which is implemented by MSBTE ER 2020-2021

1. Central Nervous System
Epilepsy Parkinson’s disease Alzheimer’s disease Stroke
Migraine

2. Introduction
• Epilepsy is a chronic neurological disorder
characterized by recurrent episodes of
seizures.
• Seizures are sudden and transient episodes
associated with abnormal excessive electrical
discharge from a group of CNS neurons.
• Seizure manifests as brief episodes of loss or
disturbance of consciousness, with or without
characteristic body movements (convulsions),
sensory or psychiatric phenomena.

3. Types of Epilepsy
Based on history, clinical findings, EEG recording and
imaging studies, epilepsies can be classified as:
• 1. Generalized seizures: These seizures affect both
hemispheres of the brain at the same time.
– (i) Grandmal epilepsy or Tonic clonic Seizures: The
usual sequence is aura, epileptic cry, unconsciousness
and sudden fall due to tonic convulsions followed by
clonic jerking and then prolonged sleep and depression.
The attack lasts for 1-2 min. The attack may be
accompanied by tongue biting, frothing and urinary
incontinence

4. – (ii) Petitmal epilepsy or Absence seizures: This is
prevalent in children and episode lasts for few
seconds. No aura, no or only momentary loss of
consciousness, no fall.
– The patient appears to go blank for less than 30
seconds and staring in one direction.
– Absence seizures have two categories:
• Typical and Atypical.
• Atypical absence seizures
are similar to typical
seizures, except that they
tend to begin more slowly,
last longer up to a few
minutes, and can include
falling down. The patient
may feel confused for a
short time after regaining
consciousness

5. • (iii) Tonic seizures: In this seizure, the muscle
tone is greatly increased: the body, arms, or
legs become suddenly stiff or tense. They are
short, usually less than 20 seconds.
• (iv) Atonic seizures: Patient may fall without
accompanying tonic or clonic movements.
There may be brief loss of consciousness with
relaxation of all muscles due to excessive
inhibitory discharges.
• (v) Myoclonic seizures: This is a sudden, brief,
repetitive contraction of muscles of a limb or
the whole body There may be violent fall
without loss of consciousness.

6. • 2. Focal Epilepsy: Focal seizures start in one
side of the brain and seizure activity is
restricted to a discrete area belonging to one
cerebral hemisphere only.
• Focal seizures may or may not become
generalized, and the manifestations depend
on the brain region or regions involved

7. Etiopathogenesis of Epilepsy
• Epilepsy is associated with abnormal excessive
electrical discharges from a group of CNS
neurons. It is due to disruption in the normal
balance between excitatory and inhibitory
currents or neurotransmission in the brain.
• Common causes of epilepsy are:

8. 1. Genetic
• Genetic mutations affecting ion channels or
transmitter receptors
• Chromosomal abnormalities
• Genetic metabolic disorders
• Mitochondrial diseases

9. 2. Structural: It involves chronic cerebral lesion or
abnormality such as
• Perinatal injury, e.g hypoxic-ischemic injury
• Brain tumors and metastases
• Traumatic brain injury
• Hippocampal sclerosis (the commonest cause of drug-
resistant epilepsy in adults)
• Tuberous sclerosis (an uncommon genetic disorder that
causes tumors to develop in many parts of the body)
• Cranial radiation therapy (kills any cancer cells that might have
spread into the brain but are too small to see)

10. 3. Metabolic
• Inborn errors of metabolism (e.g, organic
acidemias, phenylketonuria) OAD’s are considered the
most frequent metabolic disorders among severely ill children. Patients
frequently present with acute symptoms early in life.
• Porphyria (Porphyria is a group of disorders caused by an
over-accumulation of porphyrin which helps haemoglobin,
the protein that carries oxygen in the blood.)

11. 4. Immune:
Autoimmune encephalitis
(causes subacute deficits of memory
and cognition, often followed by
suppressed level of consciousness or
coma.)
Rasmussen's encephalitis
(chronic neurological disorder,
characterised by unilateral
inflammation of the cerebral
cortex)

12. 5. Infectious:
• Chronic CNS infection (e.g, toxoplasmosis,
malaria, neurocysticercosis)
• Complication of acute CNS infection (e.g, viral
or bacterial meningitis or encephalitis)

13. Diagnosis and Investigation of Epilepsy
• Apart from routine laboratory investigations,
EEG and MRI should be done.
• Electroencephalography should be done to
help in the diagnosis and classification of
seizure and epilepsy.
• Brain imaging (MRI) should be done to
identify cause of epilepsy.

14. Management of Epilepsy
• Normally, seizures are not treated unless two or
more unprovoked seizures are demonstrated
within a 12 months period.
• The cause of epilepsy should be searched in the
patient and if found, treat it.
• Drug therapy should always be started with a
single drug (monotherapy) with the smallest
possible dose.
• Use combinations of antiepileptic drugs with
different mechanism of action only when all
reasonable monotherapy fails.

15. Non-Pharmacological Management of Epilepsy
• Avoid precipitating factors like sleep deprivation,
video games, CNS stimulating drugs, etc.
• Non-pharmacological therapy to treat epilepsy is
indicated for pharmacoresistant epilepsy . The
non pharmacological therapy includes
• Surgical procedures including:
– Resection (surgical removal of pathological lesions)
– Disconnection (surgical section of neuronal circuits)
• Stimulation techniques: vagus nerve stimulation,
deep brain stimulation
• Dietary measures: ketogenic diet

16. Pharmacological Management of
Epilepsy
ANTIEPILEPTIC DRUGS
CLASSIFICATION
• Barbiturate: Phenobarbitone
• Deoxybarbiturate: Primidone
• Hydantoin: Phenytoin
• Iminostilbene: Carbamazepine, Oxcarbazepine
• Succinimide: Ethosuximide

17. • Aliphatic carboxylic acid: Valproic acid (sodium
valproate)
• Benzodiazepines: Clonazepam, Diazepam,
Lorazepam,
Clobazam
• Phenyltriazine: Lamotrigine
• Cyclic GABA analogue: Gabapentin
• Newer drugs: Vigabatrin, Topiramate, Tiagabine,
Zonisamide

18. Antiepileptic (anticonvulsant) drugs are
classified as:
• First-generation (classic) agents: e.g.
Valproate, Carbamazepine, Ethosuximide
Phenytoin, Fosphenytoin, Phenobarbital,
Benzodiazepines
• Second-generation agents: e.g Lamotrigine,
Levetiracetam, Gabapentin, Pregabalin.
Vigabatrin, Topiramate. Tiagabine

19. PARKINSON’S DISEASE

20. Introduction
• Parkinson’s disease is a progressive nervous system
disorder that affects movement.
• Symptoms start gradually, sometimes starting with a
barely noticeable tremor in just one hand.
• Tremors are common, but the disorder also
commonly causes stiffness or slowing of movement.
• In the early stages of Parkinson’s disease, your face
may show little or no expression. Your arms may not
swing when you walk.
• Your speech may become soft or slurred. Parkinson’s
disease symptoms worsen as your condition
progresses over time.

21. Clinical Manifestations
• Tremor - A tremor, or shaking, usually begins in a limb, often
your hand or fingers. You may rub your thumb and forefinger
back and forth, known as a pill-rolling tremor. Your hand may
tremble when it's at rest.
• Slowed movement (Bradykinesia) - Over time, Parkinson’s
disease may slow your movement, making simple tasks
difficult and time-consuming. Your steps may become shorter
when you walk. It may be difficult to get out of a chair. You
may drag your feet as you try to walk.

22. • Rigid muscles
• Impaired posture and balance
• Loss of automatic movements - You may have a
decreased ability to perform unconscious
movements, including blinking, smiling or
swinging your arms when you walk.
• Speech changes
• Writing changes

23. Etiopathogenesis
Parkinson’s Disease is caused by loss or
degeneration of dopaminergic neurons in the
substantia nigra of the midbrain. It is commonly
considered idiopathic i.e. the cause behind
degeneration of dopaminergic neurons is
unknown.

24. Diagnosis
• Your doctor may suggest a specific single-
photon emission computerized tomography
(SPECT) scan called a dopamine transporter
scan (DaTscan).
• Although this can help support the suspicion
that you have Parkinson’s disease, it is your
symptoms and neurologic examination that
ultimately determine the correct diagnosis.
Most people do not require a DaTscan.

25. • Imaging tests - Such as an MRI, ultrasound of
the brain, and PET scans - also may be used to
help rule out other disorders.
• Imaging tests aren't particularly helpful for
diagnosing parkinson’s disease.

26. Non-Pharmacological Management
• Offer psychosocial help to patient and family.
• Counsel patient and families on how to cope
with the illness.
• Counsel on the adaptation that may be
needed to ensure productivity at work.
• Fall Prevention-prevent falls by wearing
leather-soled shoes.

27. Pharmacological Management
• 1. Drugs acting on brain dopaminergic
system:
• Dopamine precursors: Levodopa
• Peripheral dopamine decarboxylate inhibitors:
Carbidopa, Benserazide
• MAO-B Inhibitors: Selegiline, Rasagiline

28. • Dopamine Agonists:
– Ergot Derivatives
– Non-Ergot Derivatives
• COMT (catechol-O-methyl transferase) inhibitors:
Entacapone, Tolcapone
• NMDA-receptor antagonist (Dopamine releaser):
Amantadine
• 2. Drugs affecting brain cholinergic system:
• Central anti cholinergic: Benztropine
• Antihistaminics: Orphenadrine

29. Alzheimer’s Disease

30. Introduction
• Alzheimer’s disease is a condition that affects
the brain. The symptoms are mild at first and
become more severe over time.
• It is named after Dr. Alois Alzheimer, who first
described the condition in 1906.
• Common symptoms of Alzheimer’s disease
include memory loss, language problems, and
impulsive or unpredictable behaviour.

31. • One of the main features of the condition is
the presence of plaques and tangles in the
brain. Another feature is a loss of connection
between the nerve cells, or neurons, in the
brain.

32. • These features mean that information cannot
pass easily between different areas of the
brain or between the brain and the muscles or
organs. As the symptoms worsen, it becomes
harder for people to remember recent events,
to reason, and to recognize people they know.
• Eventually a person with Alzheimer’s disease
may need full-time assistance.

33. Clinical Manifestations
• Alzheimer's disease is a progressive condition,
meaning that the symptoms get worse over time.
• Memory loss is a key feature, and this tends to be
one of the first symptoms to develop. The
symptoms appear gradually; over months or
years.
• If they develop over hours or days, a person may
require medical attention, as this could indicate a
stroke.

34. • Symptoms of Alzheimer’s disease include:
• Memory loss : A person may have difficulty
taking in new information and remembering
information. This can lead to :
– Repeating questions or conversations.
– Losing objects.
– Forgetting about events or appointments.
– Wandering or getting lost.

35. • Cognitive deficits : A person may experience
difficulty with reasoning, complex tasks, and
judgment. This can lead to :
– A reduced understanding of safety and risks.
– Difficulty with money or paying bills.
– Difficulty making decisions.
– Difficulty completing tasks that have several
stages, such as getting dressed.

36. • Problems with recognition : A person may
become less able to recognize faces or objects
or less able to use basic tools. These issues are
not due to problems with eyesight.
• Problems with spatial awareness : A person
may have difficulty with their balance, trip
over, or spill things more often, or they may
have difficulty orienting clothing to their body
when getting dressed.

37. • Like all types of dementia, Alzheimer’s
develops due to the death of brain cells. It is a
neurodegenerative condition, which means
that the brain cell death happens over time.
• In a person with Alzheimer’s disease, the brain
tissue has fewer nerve cells and connections,
and tiny deposits, known as plaques and
tangles that build up on the nerve tissue.

38. • Amyloid Plaques: extracellular deposits of
the amyloid beta (Aβ) protein mainly in
the grey matter of the brain.
• Neurofibrillary tangles (NFTs) are intracellular
aggregates of hyperphosphorylated tau
protein that are most commonly known as a
primary biomarker of Alzheimer's disease.

39. Diagnosis
• Cognitive and memory tests, to assess the
person’s ability to think and remember.
• Neurological function tests, to test their
balance, senses and reflexes.
• Blood or urine tests.
• A CT scan or MRI scan of the brain. m Genetic
testing.

40. Management
• Unavoidable risk factors: Age, Family History
(Genetic Factor) or having specific gene like
apolipoprotein E.
• Avoidable Factors:
– Diabetes
– High BP
– Low Education
– Head Injury
– Sleep Apnea

41. Pharmacological Management
• Cholinesterase Inhibitors: Donepezil,
Rivastigmine, Galantamine, Tacrine
• N-methyl-D-aspartate (NMDA)-receptor
Antagonist: Memantine
• Memantine is noncompetitive N-methyl-D-
aspartate receptor antagonist.

42. STROKE

43. Introduction
• A stroke occurs when a blood vessel in the brain
ruptures and bleeds, or when there’s a blockage
in the blood supply to the brain.
• The rupture or blockage prevents blood and
oxygen from reaching the brain’s tissues.
According to the Centers for Disease Control and
Prevention (CDC), stroke is a leading cause of
death in the United States.
• Every year, more than 795,000 U.S. people have
a stroke. Without oxygen, brain cells and tissue
become damaged and begin to die within
minutes,

44. • There are three primary types of strokes:
• Transient ischemic attack (TIA) involves a blood
clot that typically reverses on its own.
• Ischemic stroke involves a blockage caused by
either a clot or plaque in the artery. The
symptoms and complications of ischemic stroke
can last longer than those of a TIA, or may
become permanent.

45. • Hemorrhagic stroke is caused by either a
burst or leaking blood vessel that seeps into
the brain.

46. Clinical Manifestation
• The loss of blood flow to the brain damages
tissues within the brain.
• Symptoms of a stroke show up in the body
parts controlled by the damaged areas of the
brain.
• The sooner a person having a stroke gets care,
the better their outcome is likely to be. For
this reason, it’s helpful to know the signs of a
stroke so you can act quickly.

47. Stroke symptoms can include :
• Paralysis.
• Numbness or weakness in the arm, face, and leg,
especially on one side of the body.
• Trouble speaking or understanding others.
• Slurred speech.
• Confusion, disorientation or lack of
responsiveness.
• Sudden behavioral changes, especially increased
agitation.

48. • Vision problems, such as trouble seeing in one or
both eyes with vision blackened or blurred, or
double vision.
• Trouble walking.
• Loss of balance or coordination.
• Dizziness.
• Severe, sudden headache with an unknown
causes.
• Seizures
• Nausea or vomiting.

49. Diagnosis and Investigation of Stroke
Physical Examination:
• Complete physical examination including vital
signs, oxygen saturation and body
temperature.
History
• Identify risk factors for arteriosclerosis and
cardiac diseases.

50. Laboratory Test:
• Hb, CBC, ESR, Liver function Test, Renal
function Test, Serum electrolytes, Glucose,
Lipid profile.
• Computed Tomography (CT)and MRI is useful
in identifying early infarct.

51. Management
• Quit smoking.
• Limit alcohol use.
• Keep a moderate weight.
• Get regular check-ups.
• Control Risk factors such as hypertension,
Diabetes Mellitus and Hyperlipidaemia.

52. Pharmacological Management
• Thrombolytics: Streptokinase, Urokinase,
Alteplase, Reteplase, Tenecteplase
• Anti-platelet Agents: Aspirin, Dipyridamole,
Clopidogrel, Ticlopidine.
• Oral Anticoagulants: Warfarin
• HMG CoA Reductase Inhibitors: Atorvastatin,
Rosuvastatin, Simvastatin
• ACE Inhibitors: Perindopril, Enalapril, Captopril

53. MIGRAINE

54. Introduction
• A migraine is much more than a bad
headache. This neurological disease can cause
debilitating throbbing pain that can leave you
in bed for days.
• Movement, light, sound and other triggers
may cause symptoms like pain, tiredness,
nausea, visual disturbances, numbness and
tingling, irritability, difficulty speaking,
temporary loss of vision and many more.

55. • A migraine is a common neurological disease
that causes a variety of symptoms, most
notably a throbbing, pulsing headache on one
side of your head.
• Your migraine will likely get worse with
physical activity, lights, sounds or smells. It
may last at least four hours or even days.
• About 12% of Americans have this genetic
disorder. Research shows that it’s the sixth
most disabling disease in the world.

56. Types of Migraines
• Migraine with aura (Complicated migraine) :
Around 15% to 20% of people with migraine
headaches experience an aura.
• Migraine without aura (Common migraine):
This type of migraine headache strikes
without the warning an aura may give you.
The symptoms are the same, but that phase
doesn’t happen.

57. • Migraine without head pain : “Silent .
migraine” or “acephalgic migraine,” as this
type is also known as, includes the aura
symptom but not the headache that typically
follows.

58. • Hemiplegic migraine: You will have temporary
paralysis (hemiplegia) or neurological or
sensory changes on one side of your body. The
onset of the headache may be associated with
temporary numbness, extreme weakness on
one side of your body, a tingling sensation, a
loss of sensation and - dizziness or vision
changes.

59. • Retinal migraine (ocular migraine) : You may
notice temporary, partial or complete loss of
vision in one of your eyes, along with a dull
ache behind the eye that may spread to the
rest of your head. That vision loss may last a
minute, or as long as months.

60. • Chronic migraine : A chronic migraine is when
a migraine occurs at least 15 days per month.
The symptoms may change frequently, and so
may the severity of the pain.

61. • Migraine with brainstem aura: With this
migraine, you'll have vertigo, slurred speech,
double vision or loss of balance, which occur
before the headache. The headache pain may
affect the back of your head. These symptoms
usually occur suddenly and can be associated
with the inability to speak properly, ringing in
the ears and vomiting.

62. Etiopathogenesis
• Migraine is a primary brain disorder.
• Its pathogenesis is yet to be understood clearly. It
is suggested that 5-HT (Serotonin) is a key
mediator in the pathogenesis of migraine.
• Genetic factors may also play a role in migraine
attack.
• According to some theories, nerves branching off
the brainstem may become overexcited, leading
to dilation of blood vessels, inflammation and
pain.

63. • Potential triggers for Migraine attacks are:
• Certain food and beverages: Alcohol, Nicotine,
Citrus fruits, Dairy products, Food Containing
tyramine (e.g. Chocolate, Red Wine)
• Poor Sleeping Habits
• Emotional stress
• Weather changes
• Hormonal changes in women: Menstruation,
Hormone intake (Oral Contraceptive Pills)

64. • The four stages in chronological order are the
prodrome (pre-monitory), aura, headache and
postdrome. About 30% of people experience
symptoms before their headache starts.
• The phases are :

65. • Prodrome: The first stage lasts a few hours, or
it can last days. You may or may not
experience it as it may not happen every time.
Some know it as the “preheadache” or
“premonitory” phase.
• Aura: The aura phase can last as long as 60
minutes o as little as five. Most people don’t
experience an aura, and some have both the
aura and the headache at the same time.

66. • Headache: About four hours to 72 hours is
how long the headache lasts. The word “ache”
doesn’t do the pain justice because
sometimes it’s mild, but usually; it's described
as drilling, throbbing or you may feel the
sensation of an icepick in your head. Typically
it starts on one side of your head and then
spreads to the other side.

67. • Postdrome: The postdrome stage goes on for
a day or two. It’s often called a migraine
“hangover” and 80% of those who have
migraines experience it.

68. Diagnosis and Investigation
• Migraine is a clinical diagnosis that is based on
patient history and physical examination.
Neurological imaging is not routinely indicated
for uncomplicated migraine.

69. Management of Migraine
• Currently, there is no cure for migraine, but a
number of treatments are available to help
reduce the symptoms of migraine.

70. Non-Pharmacological Management
• Identify the triggers for the migraine attack
(Lack of Sleep, Chocolates, Wine etc.) and
avoid them.
• Adopt suitable lifestyle modification.

71. Pharmacological Management
Abortive Treatment:
• NSAIDs such as Paracetamol, Aspirin and
Caffeine are used for the treatment of mild to
moderate migraine.
• If NSAIDs/Analgesics fail, Tab. Sumatriptan 50
mg or 100 mg PO (per oral) or Zolitriptan 2.5
mg PO (per oral) is given.

72. • In case of nausea or difficulties taking tablets,
Zolmitriptan 5mg Nasal Spray or Sumatriptan
20mg nasal spray is used.
• Parenteral administration of drugs such as
dihydroergotamine and sumatriptan is used
for the rapid relief of a migraine attack.
In case of severe nausea and vomiting,
antiemetics such as intravenous (IV) or
intramuscular (IM) prochlorperazine can be
used.

73. Preventive Treatment:
• Use preventive treatment in patients with an
increasing frequency of migraine attacks or with
poor response to abortive treatment. In general,
a preventive treatment should be considered in
the patients with five or more attacks a month.
The drugs used for the preventive treatment of
migraine include:
• Tab. Propranolol: 40-120 mg BD or Tab. Sodium
Valproate 400-600mg BD
• Tab. Topiramates: 25-200mg OD
• Tab. Flunarizine: 10mg at bed time

74. References