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MODULE 3.1: MYASTHENIA maintenance of the NMJ, including the n-
ACh receptor distribution and clustering.
GRAVIS
The inhibition of the complex leads to a
reduced number of n-ACh receptors.The
DEFINITION
ACh released at the nerve terminal, in
 A chronic autoimmune, neuromuscular
turn, is unable to generate the
disease that causes weakness in the postsynaptic potential required to
skeletal muscles that worsens after
generate an action potential in muscle
periods of activity and improves after
due to a reduced number of nACh
periods of rest. receptors leading to the symptoms of
 These muscles are responsible for muscle weakness. The weakness is
functions involving breathing and moving more pronounced with the repeated use
parts of the body, including the arms and of a muscle group since it causes
legs. depletion of the ACh store in the NMJ.

ETIOLOGY/CAUSE OF DISEASE RISK FACTORS

Factors that can worsen myasthenia gravis are:
ANTIBODIES
 Fatigue
 In myasthenia gravis, your immune  Illness or infection
system produces antibodies that block or
 Surgery
destroy many of your muscles' receptor
 Stress
sites for a neurotransmitter called
 Some medications — such as beta
acetylcholine. With fewer receptor sites
blockers, quinidine gluconate, quinidine
available, your muscles receive fewer
sulfate, quinine (Qualaquin), phenytoin,
nerve signals, resulting in weakness.
certain anesthetics and some antibiotics
THYMUS GLAND
 Pregnancy
 Researchers believe that the thymus
gland triggers or maintains the  Menstrual periods
production of the antibodies that block
acetylcholine. Adults with myasthenia CLASSIFICATIONS
gravis have abnormally large thymus Class I: Involves any ocular muscle weakness,
gland. Some people with myasthenia including weakness of eye closure. All other
gravis also have tumors of the thymus muscle groups are normal.
gland (thymoma) which can be
cancerous. Class II: Involves mild weakness of muscles
other than ocular muscles. Ocular muscle
PATHOPHYSIOLOGY weakness of any severity may be present.
The pathophysiologic mechanisms in
Myasthenia gravis are dependent on the type of Class IIa: Involves predominant weakness of the
antibodies present. limb, axial muscles, or both. It may also involve
the oropharyngeal muscles to a lesser extent.
 In n-AChR Myasthenia gravis, the
antibodies are of the IgG1 and IgG3
Class IIb: Involves mostly oropharyngeal,
subtype. They bind to the n-ACh receptor
respiratory muscles, or both. It can have the
present in the postsynaptic membrane of
involvement of limb, axial muscles, or both to a
the skeletal muscles and activate the
lesser extent.
complement system leading to the
formation of the membrane attack
Class III: Involves muscles other than ocular
complex (MAC). MAC brings about the
muscles moderately. Ocular muscle weakness
final degradation of the receptors. They
of any severity can be present.
may also act by functionally blocking the
binding of ACh to its receptor or by
Class IIIb: Involves oropharyngeal, respiratory
enhancing the endocytosis of the
muscles, or both predominantly. The limb, axial
antibody-bound n-ACh receptor.
muscles, or both can have lesser or equal
 In MusK MG and LPR4 MG, the
involvement.
antibodies are of the IgG4 subtype and
do not have the complement activating
Class IV: Involves severe weakness of affected
property. They bind to the Agrin–LRP4–
muscles. Ocular muscle weakness of any
MuSK protein complex in the NMJ,
severity can be present.
whose primary function is the

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Class IVa: Involves limb, axial muscles, or both thymus gland is bigger than usual or has
predominantly. Oropharyngeal muscles can be grown abnormally (a thymoma)
involved to a lesser degree. EDROPHONIUM TEST
 It involves having an injection of a
Class IVb: Involves oropharyngeal, respiratory medicine called edrophonium chloride. If
muscles, or both predominantly. The limb, axial you have a sudden but temporary
muscles, or both can have lesser or equal improvement in muscle strength after the
involvement. It also includes patients requiring injection, it's likely you have myasthenia
feeding tubes without intubation. gravis.But this test is rarely done these
days because there's a risk it could cause
Class V: Involves intubation with or without potentially serious side effects, such as a
mechanical ventilation, except when employed slow heartbeat and breathing problems.
during routine postoperative management
MANAGEMENT
CLINICAL MANIFESTATIONS Pharmacologic Algorithms
People with myasthenia gravis may experience
the following symptoms:
 weakness of the eye muscles (called
ocular myasthenia)
 drooping of one or both eyelids (ptosis)
 blurred or double vision (diplopia)
 a change in facial expression
 difficulty swallowing
 shortness of breath
 impaired speech (dysarthria)
 weakness in the arms, hands, fingers,
legs, and neck.

DIAGNOSIS
Myasthenia gravis can be difficult to diagnose
and you may need several tests.

BLOOD TEST
 The main test for myasthenia gravis is a
blood test to look for a type of antibody
(produced by the immune system) that
stops signals being sent between the
nerves and muscles. A high level of these
antibodies usually means you have
myasthenia gravis.
NERVE TESTS
 If your blood test result is normal but the
doctor still thinks you could have
myasthenia gravis, they may suggest an
electrical test of your nerves and
muscles.
 These tests, known as
electromyography, involve inserting very
small needles into your muscles to
measure the electrical activity in them.
 The electrical recordings can show
whether the signals sent from the nerves
to the muscles are being disrupted, which
may be a sign of myasthenia gravis.
SCANS
 You may also have a CT scan or MRI
scan of your chest to check if your

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MODULE 3.2: GLAUCOMA
DEFINITION
 a group of eye diseases that can cause
vision loss and blindness by damaging a
nerve in the back of your eye called the
optic nerve. The symptoms can start so
slowly that you may not notice them. The
only way to find out if you have glaucoma
is to get a comprehensive dilated eye
exam
ETIOLOGY
The fluid inside your eye, called aqueous humor,
usually flows out of your eye through a mesh-like
channel. If this channel gets blocked, or the eye
is producing too much fluid, the liquid builds up.
Sometimes, experts don’t know what causes this
blockage. But it can be inherited, meaning it’s
passed from parents to children. Less-common
causes of glaucoma include a blunt or chemical
injury to your eye, severe eye infection, blocked
blood vessels inside your eye, and inflammatory
conditions. It’s rare, but eye surgery to correct
another condition can sometimes bring it on. It
usually affects both eyes, but it may be worse in
one than the other.
PATHOPHYSIOLOGY
The main problem or pathology in
glaucoma is caused by raised intraocular
pressure. It is this raised pressure that
compresses and damages the optic nerve. Once
the optic nerve is damaged, it fails to carry visual
information to the brain and this results in loss of
vision.
The exact pathophysiology contributing
to this is not fully understood. It is believed that
the raised pressure on the retina causes the cells
and nerve ganglions in the sensitive retina to die
off (retinal ganglion apoptosis) and in addition
the small blood vessels of the retina are also
compressed depriving it of nutrients. This results
in a clinically progressive loss of peripheral visual
field and ultimately vision.
RISK FACTORS
You're more likely to get it if you:
 Are of African American, Irish, Russian,
Japanese, Hispanic, Inuit, or
Scandinavian descent
 Are over 40 years old
 Have family history of glaucoma
 Are nearsighted or farsighted
 Have poor vision
 Have diabetes
 Take certain steroid medications (e.g.
prednisone)
 Take certain drugs for bladder control or
seizures, or some over-the-counter cold
remedies
 Have an injury to eye(s)
 Have corneas that are thinner than usual
 Have high blood pressure, heart disease,
diabetes or sickle cell anemia.
 Have high eye pressure
CLASSIFICATIONS
OPEN-ANGLE GLAUCOMA
1. PRIMARY
 Also known as chronic open angle
glaucoma, is the most frequent type of
human glaucoma.
 characterized by elevated intraocular
pressure (IOP), cupping and atrophy of
the optic nerve head, and typical visual
field defects. By definition, in “primary”
glaucomas there are no specific ocular
abnormalities or systemic diseases
causing the glaucoma
2. SECONDARY
 Similar to primary open angle glaucoma,
patients with secondary open angle
glaucoma have an anterior chamber
angle which can easily be visualized
without obvious obstruction of angle
structures. However, in secondary open
angle glaucoma, there is an increased
resistance to outflow and elevated
intraocular pressure associated with an
ocular or systemic cause.
ACUTE ANGLE-CLOSURE GLAUCOMA
Acute angle-closure glaucoma is a
dramatic disorder of sudden onset and
represents a true ophthalmic emergency. If not
properly diagnosed and treated, progressive and
permanent ocular damage occurs in a matter of
hours to days. The history is characterized by the
sudden onset of pain, redness of the eye, and
blurred vision. The pain is usually severe and
generally centered over the brow. Nausea,
vomiting, and profuse sweating are commonly
associated symptoms which may lead to
improper diagnosis and treatment in an
emergency room setting.
CONGENITAL GLAUCOMA
Children born with congenital glaucoma
have a defect in the angle of their eye, which
slows or prevents normal fluid drainage.
Congenital glaucoma usually presents with
symptoms, such as cloudy eyes, excessive
tearing, or sensitivity to light. Congenital
glaucoma can run in families.
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SECONDARY GLAUCOMA photographs of your optic nerve to conduct a
Secondary glaucoma is often a side side-by-side comparison over time.
effect of injury or another eye condition, such as
cataracts or eye tumors. Medicines, such as MANAGEMENT
corticosteroids, may also cause this type of Pharmacologic Algorithm
glaucoma. Rarely, eye surgery can cause
secondary glaucoma

CLINICAL MANIFESTATIONS
Most people with open-angle glaucoma
don’t have symptoms. If symptoms do develop,
it’s usually late in the disease. That’s why
glaucoma is often called the "sneak thief of
vision." The main sign is usually a loss of side, or
peripheral, vision.
Symptoms of angle-closure glaucoma
usually come on faster and are more obvious.
Damage can happen quickly. If you have any of
these symptoms, get medical care right away:
 Seeing halos around lights
 Vision loss
 Redness in your eye
 Eye that looks hazy (particularly in
infants)
 Upset stomach or vomiting
 Eye pain

DIAGNOSIS
To diagnose glaucoma, your
ophthalmologist will want to perform a
comprehensive eye examination. They’ll check
for signs of deterioration, including loss of nerve
tissue.
They may also use one or more of the
following tests and procedures:
DETAILED MEDICAL HISTORY
Your doctor will want to know what
symptoms you’ve been experiencing and if you
have any personal or family history of glaucoma.
They’ll also ask for a general health assessment
to determine if any other health conditions may
be impacting your eye health, such as diabetes
or high blood pressure.
TONOMETRY TEST
Measures your eye’s internal pressure.
PACHYMETRY TEST
People with thin corneas have an
increased risk of developing glaucoma. A
pachymetry test can tell your doctor if your
corneas are thinner than average.
PERIMETRY TEST
This test, also known as a visual field
test, can tell your doctor if glaucoma is affecting
your vision by measuring your peripheral, or
side, vision and your central vision.
MONITORING YOUR OPTIC NERVE
If your doctor wants to monitor for gradual
changes to your optic nerve, they may take

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MODULE
DEFINITION
 a brain disorder characterized by a
persistent propensity to have epileptic
seizures coupled with the neurobiologic,
cognitive, psychological, and social
implications that go along with it
ETIOLOGY/CAUSE OF DISEASE
 Genetic Influence
 Infections
 Head trauma
 Prenatal injury
 Brain abnormalities
 Developmental disorders
PATHOPHYSIOLOGY
 Epilepsy differs from other neurological
conditions because it has no
pathognomonic lesion.
 The hallmark of epilepsy is a rather
rhythmic and repetitive hyper-
synchronous discharge of neurons,
either localized in an area of the cerebral
cortex or generalized throughout the
cortex, which can be observed on an
electroencephalogram (EEG).
 In the case of epilepsy, regular low-
frequency discharges are replaced by
bursts of high frequency discharges
usually followed by periods of inactivity.
Note: It is only when a whole population of
neurons discharge synchronously in an
abnormal way that an epileptic seizure may be
triggered. This abnormal discharge may remain
localized or it may spread to adjacent areas,
recruiting more neurons as it expands. It may
also generalize throughout the brain via cortical
and subcortical routes, including callosal and
thalamocortical pathways.
RISK FACTORS
 Age
 Seizures in childhood
 Family history
 Dementia
 Head injuries
 Brain infections
 Stroke and other vascular diseases
CLASSIFICATIONS
IDIOPATHIC OR GENETIC EPILEPSIES
 are those in which there is a clear genetic
component, and they probably account
for a third of all new cases of epilepsy. In
this class of epilepsy, there is no gross
neuroanatomic or neuropathologic
abnormality
CRYPTOGENIC OR UNKNOWN EPILEPSIES
 an epilepsy of presumed symptomatic
nature in which the cause has not been
identified
SYMPTOMATIC/ STRUCTURAL/METABOLIC
EPILEPSY
 an epilepsy of an acquired or genetic
cause, associated with gross anatomic or
pathologic abnormalities, and/or clinical
features, indicative of underlying disease
or condition. It is where a probable cause
has been identified.
PROVOKED EPILEPSY
 an epilepsy in which a specific systemic
or environmental factor is the
predominant cause of the seizures and in
which there are no gross causative
neuroanatomic or neuropathologic
changes.
CLINICAL MANIFESTATIONS
The clinical manifestation of a seizure will
depend on the location of the focus and the
pathways involved in its spread. ILAE has
recently published a revised classiication that
divides seizure types into three main group
according to its onset (Fisher et al., 2017).
GENERALIZED ONSET
 If it involves initial activation of both
hemispheres of the brain simultaneously
FOCAL ONSET
 If a discharge starts in a localized area of
the brain
UNKNOWN ONSET
 if it is not possible to classify as focal or
generalized.
GENERALIZED SEIZURES
Generalised seizures are subdivided in
motor and non-motor (absence) types.
 The motor includes tonic-clonic, clonic,
tonic, myoclonic, myoclonic-tonic-clonic,
myoclonic-atonic, atonic and epileptic
spasms.
 The non-motor includes typical absence,
atypical absence and absence with
special features (myoclonic, eyelid
myoclonia)
FOCAL SEIZURES
 In focal seizures, discharges are
localised, and manifestations often
reflect activation of the underlying cortical
areas. This seizure may progress into a
bilateral tonic-clonic seizure, which is
termed as focal to bilateral tonic-clonic.
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EPILEPTIC SPASMS If monotherapy is unsuccessful, consider
 They occur in early infancy and are trying an add-on treatment. When starting an
characterised by tonic lexion of the head, add-on treatment, carefully titrate the additional
neck and trunk, with circumlexion of the medicine and review treatment frequently,
upper extremities. including monitoring for adverse effects such as
DIAGNOSIS sedation.
Epilepsy must only be diagnosed when at  If trials of add-on treatment do not result
least one of the three defining ILAE(International in a reduction in seizures, use the
League Against Epilepsy) conditions is present: regimen that provides the best balance
1. At least two unprovoked (or reflex) between effectiveness and tolerability of
seizures occurring more than 24 hours side effects.
apart;  Discuss with the person, and their family
2. One unprovoked seizure (or reflex) and a and carers as appropriate, the benefits of
probability of further seizures similar to taking as few medicines as possible to
the general recurrence risk (at least 60%) maintain seizure freedom or control.
after two unprovoked seizures, occurring PHARMACOLOGICAL MANAGEMENT
over the next 10 years; Antiepileptic drugs for different seizure
3. Signs of recurrent epileptic seizures that types
occur unexpectedly and stop Seizure First-line Adjunctive
spontaneously type treatment Anti-epileptic
ELECTROENCEPHALOGRAM (EEG) drugs
 EEG recording is often the only Focal
examination required in typical Seizure
generalized epilepsies, and it aims to Carbamazepin Brivaracetam
e
record abnormal neuronal discharges
Lamotrigine Clobazam
The chance of recording the discharges of an
Levetiracetam Eslicarbazepin
actual seizure during a routine EEG is slight e
hence, the following are needed: Oxcarbazepin Gabapentin
 Ambulatory EEG allows recording in day- e
to-day circumstances using a small Sodium Lacosamide
recorder valproate
 EEG video-telemetry is useful in the Perampanel
assessment of dificult cases, particularly Phenytoin
if surgery is considered. Pregabalin
MAGNETIC RESONANCE IMAGING (MRI) Topiramate
Zonisamide
Neuroimaging with magnetic resonance
Generalise
imaging (MRI) is the most valuable investigation
d Seizure
when structural abnormalities (e.g. stroke,
Tonic- Carbamazepin Clobazam
tumor, developmental abnormalities, clonic e
hydrocephalus) are suspected. Lamotrigine Levetiracetam
Oxcarbazepin Topiramate
MANAGEMENT e
Use a single antiseizure medication Sodium
(monotherapy) to treat epilepsy whenever valproate
possible. Tonic or Sodium Lamotrigine
If first-line monotherapy is unsuccessful atonic valproate
and epilepsy diagnosis remains confirmed, try Rufinamide
monotherapy with another antiseizure Topiramate
medication, using caution during the changeover Absence Ethosuximide Clobazam
period: Lamotrigine Clonazepam
Sodium Levetiracetam
 Increase the dose of the second
valproate
medicine slowly while maintaining the Topiramate
dose of the first medicine.
 If the second medicine is successful, Summary of newer antiepileptic agents
slowly taper off the dose of the first Antiepileptic Clinical Use Avail
medicine. Drugs Formulation
 If the second medicine is unsuccessful, Brivaracetam Adjunctive Tablets: 10,
slowly taper off the dose of the second for focal 25, 50, 75,
medicine and consider an alternative. seizures 100 mg
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Oral syndrome, infantile spasms syndrome,
Solution: Lennox–Gastaut syndrome and etc.)
10mg/mL RESECTIVE EPILEPSY SURGERY
Injection A surgery that involves removing an area
Solution: of the brain where seizures occur, usually the
10mg/mL site of a tumor, brain injury or malformation. It is
Eslicarbazepin Adjunctive Tablets: done when a child's seizures aren't controlled by
e for focal 800mg
medicine or other treatments. The surgery is
seizures
designed to stop all the seizures or, at least, to
Lacosamide Adjunctive Tablets: 50,
make them happen less often
for focal 100, 150,
VAGUS NERVE STIMULATION
seizures 200 mg
Syrup: Vagus nerve stimulation is a medical
10mg/mL treatment that involves using an implanted pulse
Infusion: generator and lead wire to deliver electrical
200mg/20m impulses to the vagus nerve. It is used as an
L add-on treatment for certain types of intractable
Levetiracetam Monotherap Tablets: epilepsy and treatment-resistant depression
y and 250, 500,  If resective epilepsy surgery is not
Adjunctive 750, 1000 suitable for a person with drug-resistant
for focal and mg seizures, consider vagus nerve
generalised Syrup: stimulation as an add-on treatment to
seizures 100mg/mL antiseizure medication.
Injection:
 Discuss with the person with epilepsy,
500mg/5mL
Granules: and their family or carers if appropriate,
250mg, the benefits and risks of vagus nerve
500mg, 1g stimulation before making a shared
Oxcarbazepine Monotherap Tablets: decision about having this procedure
y and 150, 300,
Adjunctive 600 mg
for focal and Syrup:
generalised 60mg/mL
and tonic-
clonic
seizures
Perampanel Adjunctive Tablets: 2,
for focal 4, 6, 8, 10,
seizures 12 mg
Pregabalin Adjunctive Tablets: 25,
for focal 50, 75, 100,
seizures 150, 200,
225, 300 mg
Syrup:
20mg/mL
Zonisamide Monotherap Capsule: 25,
y and 50, 100mg
Adjunctive
for focal
seizures

NON-PHARMACOLOGICAL MANAGEMENT
KETOGENIC DIET
Ketogenic diet is a special high-fat, low-
carbohydrate diet that helps to control seizures
in some people with epilepsy.
Consider a ketogenic diet under the
guidance of a tertiary epilepsy specialist, in
people with:
 certain childhood-onset epilepsy
syndromes (e.g. GLUT1 deficiency

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ALGORITHM

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MODULE 4.2: STATUS however, the body is unable to compensate,
resulting in hypoglycemia, hyperthermia,
EPILEPTICUS
respiratory failure, hypoxia, respiratory and
metabolic acidosis, hyperkalemia,
DEFINITION
hyponatremia, and uremia. Motor activity may
 continuous seizure activity lasting more
not be clinically evident during prolonged
than 5 minutes or two or more seizures seizures, but electrical activity may still exist (ie,
without complete recovery of
NCSE) requiring prompt recognition and
consciousness. A neurologic emergency
aggressive treatment.
that can lead to permanent brain damage
or death RISK FACTORS
There are many risk factors for status epilepticus
ETIOLOGY/CAUSE OF DISEASE
including: (Hopskin, 2018)
Causes of SE include:
 Poorly controlled epilepsy
 metabolic disturbances (eg,
 Low blood sugar
hyponatremia, hypernatremia,
 Stroke
hyperkalemia, hypocalcemia,
 Kidney failure
hypomagnesemia, hypoglycemia)
 Liver failure
 Central nervous system (CNS) disorders,
 Encephalitis (swelling or inflammation of
 Central nervous system (CNS) infections
the brain)
(meningitis, encephalitis, and intracranial
abscess)  HIV
 Cerebrovascular accidents  Alcohol or drug abuse
 Head trauma (with or without intracranial  Genetic diseases such as Fragile X
bleed) syndrome and Angelman syndrome
 Hypoxia  Head injuries
 drug toxicity (eg, theophylline, isoniazid,
CLASSIFICATIONS
cyclosporine, cocaine).
Nonconvulsive Status Epilepticus (NCSE)
Chronic causes of SE include:
Characterized by persistent impaired
 preexisting epilepsy
consciousness without clinical seizure activity
 chronic alcoholism (withdrawal seizures),
and is diagnosed with electroencephalography
 CNS tumors
(EEG).
 Stroke Generalized Convulsive status epilepticus
(GCSE)
PATHOPHYSIOLOGY GCSE is characterized by full-body motor
Systemic changes appear in two phases during seizures and involves the entire brain.
SE. Phase I occurs during the first 30 minutes,
and phase II occurs after 30 to 60 minutes. CLINICAL MANIFESTATIONS
PHASE I PHASE I
During phase I, autonomic activity increases,  Generalized convulsions
resulting in hypertension, tachycardia,
 Hypertension, tachycardia
hyperglycemia, hyperthermia, sweating, and
 Fever and sweating
salivation. Cerebral blood flow increases to
 Muscle contractions, spasms
preserve oxygen supply to the brain. Increases
in sympathetic and parasympathetic stimulation  Respiratory compromise
with muscle hypoxia can cause ventricular  Incontinence
arrhythmias, severe acidosis, and PHASE II
rhabdomyolysis which can lead to hypotension,  Respiratory failure with pulmonary
shock, hyperkalemia, and acute kidney injury. edema
 Cardiac failure (arrhythmias, shock)
Systemic changes appear in two phases during  Hypotension
SE. Phase I occurs during the first 30 minutes,  Hyperthermia
and phase II occurs after 30 to 60 minutes.  Rhabdomyolysis and multiorgan failure
PHASE II
After 30 to 60 minutes of continuous seizure DIAGNOSIS
activity, loss of cerebral autoregulation,
decreased cerebral blood flow, increased ELECTROENCEPHALOGRAM (EEG)
intracranial pressure, and systemic hypotension EEG is required to identify SE in a
occur. Cerebral metabolic demand remains high; comatose patient. Continuous EEG monitoring
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should be used in patients who remain do not already have one and there is
unconscious after initial antiepileptic treatment, concern that status epilepticus may recur
those receiving long-acting paralytic agents, or NON-PHARMACOLOGIC MANAGEMENT
those requiring prolonged RSE therapy. Oxygen administration or intubation for
Treatment should not be delayed while awaiting mechanical ventilation should be performed in
EEG results. cases of hypoxia, and temperature management
CT SCANS AND MRI should be considered for febrile seizures.
CT and MRI scans are useful to identify Specialists in neurology or epileptology should
traumatic injury, mass lesions, or evidence of be consulted as appropriate. Admission to an
infection as the cause of SE intensive care unit (ICU) allows for aggressive
treatment and monitoring
MANAGEMENT

PHARMACOLOGICAL MANAGEMENT
 Provide resuscitation and immediate
emergency treatment for children, young
people, and adults who have convulsive
status epilepticus (seizures lasting 5
minutes or more).
 If the person with convulsive status
epilepticus has an individualized
emergency management plan that is
immediately available, administer
medication as detailed in the plan.
 If the person with convulsive status
epilepticus does not have an
individualized emergency management
plan immediately available:
 Prescribe buccal midazolam or rectal
diazepam for use in the community.
 Buccal midazolam is the first-line
treatment.
 Rectal diazepam is prescribed if the
previous is not available or if it is
preferred.
 Intravenous lorazepam is prescribed if
intravenous access is established and
resuscitation facilities are available.
 If unavailable, then intravenous
diazepam should be administered or
buccal midazolam if immediate
intravenous access cannot be secured.
 If seizures continue, intravenous
phenytoin or sodium valproate, or
phenobarbital should be administered as
second-line treatment
 If convulsive status epilepticus does not
respond to a second-line treatment,
consider trying an alternative second-line
treatment option under expert guidance.
If convulsive status epilepticus does not
respond to the second-line treatment
options tried, consider the following third-
line options under expert guidance:
 Phenobarbital or general anaesthesia.
 After an episode of convulsive status
epilepticus, agree an emergency
management plan with the person if they

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MODULE 4.3: PAIN MANAGEMENT
DEFINITION
 An unpleasant sensory and emotional
experience associated with actual or
potential tissue damage.
 Pain may not be directly proportional to
amount of tissue injury.
 Highly subjective, leading to under
treatment
PATHOPHYSIOLOGY
 Pain is not a disorder or disease
 A consequential reaction by the body to
noxious stimuli.
o Injury
o Disease
 Pain incorporates
o Cognition
o Emotion
o Behavior
 Simple Pathway to the Brain:
o Transduction
o transmission
o Perception
o Modulation
NOCICEPTION/TRANSDUCTION
Painful stimuli are detected by
nociceptors, which are free nerve endings
located in tissues and organs. They have high
thresholds and, under normal circumstances,
only respond to noxious stimuli.
TRANSMISSIONS
Nociceptive Transmission takes place in
A and C- afferent nerve fibers. Stimulation of
large-diameter, sparsely myelinated A fibers
evokes sharp, well-localized pain, whereas
stimulation of unmyelinated small- diameter C
fibers produces dull, aching, poorly localized
pain.
PAIN PERCEPTION
At this point in transmission, pain is
thought to become a conscious experience that
takes place in higher cortical structures.
The brain may accommodate only a
limited number of pain signals, and cognitive and
behavioral functions can modify pain.
MODULATION
The body modulators pain through a
number of complex processes. One, known as
the endogenoses opiate system, consists of
neurotransmitters and receptors that are found
throughout the central nervous system.
This system can inhibit synaptic pain
transmission at the dorsal horn and originates in
the brain.
THREE TYPES OF PAIN
NOCICEPTIVE PAIN
The type of pain felt when tissue in the
body is damage. The pain signal starts in the
pain receptors, or nociceptors, which are located
in the skin and the internal organs and which
register pain. Typically classified as either
somatic or visceral.
INFLAMMATORY PAIN
Inflammation leads to the secretion of
substances that lower the pain threshold and
amplify pain. Occurs temporarily when tissue is
damage, and can be chronic in illnesses such as
rheumatism.
NEUROPATHIC PAIN
Cause by injury or disease in the nervous
system. Both direct damage to the nerve and
pressure on the nerve that can lead to pain. Can
develop as a result of slipped disc, diabetes,
stroke etc.
RISK FACTORS
N/A
CLASSIFICATIONS
ACUTE PAIN
 Can be a useful physiologic process
warning individuals of disease states and
potential harmful situations.
 Severe. Unremitting undertreated, acute
pain , when it outlives its biologic
usefulness, can produce many
deleterious effects. (e.g., psychological
problems).
 Usually is nociceptive
 Common causes include surgery, acute
illness, trauma and medical procedures.
 Subsides quickly as the healing process
decreases the pain-producing stimuli.
CHRONIC PAIN
 This type of pain can be nociceptive,
neuropathic/functional or both.
 Chronic pain is pain that lasts more than
several months to years (variously
defined as 3 to 6 months, but longer than
“normal healing”).
CANCER PAIN
 Pain associated with potentially life-
threatening conditions is often called
malignant pain or simply cancer pain.
 This type of pain includes both chronic
and acute components and often has
multiple etiologies.
 It is pain caused by the disease itself
(e.g., tumor invasion, organ obstruction),
treatment(e.g., chemotherapy, radiation,
surgical incisions), or diagnostic
procedures (e.g.,biopsy).
1
 CLINPHAR
MIDTERM
CLINICAL MANIFESTATIONS
Clinical presentation of pain is best addressed by
proper pain assessment.
1. Comprehensive history and physical
examinations are imperative to evaluate
underlying diseases and posible contributing
factors. ( Baseline of characterization can be
obtained by assessing PQRST characteristics.)
o The site of pain.
o Factors that alter the pain threshold.
o Evaluate components of pain experience
2. Proper patient assessment must include an
evaluation of pain management.
o Pain intensity, pain relief, and medication
side effects must be assessed and
reassessed on a regular basis.
o Postoperative pain and acute
exacerbation of cancer of pain may need
to be assessed hourly, whereas chronic
noncancer pain may require only daily or
less frequent assessment.
o Pain is best diagnosed based on patient
description and history
CHRONIC
GENERAL
o Can appear to have no noticeable
suffering
SYMPTOMS
o shooting. radiating, fluctuating in
intensity, and varying in location (these
often occur without a timely relationship
with an obvious noxious stimuli)
o Over time, the pain stimulus may cause
symptoms that completely change (e.g.,
sharp to dull, obvious to vague)
SIGNS
o Hypertension, tachycardia, diaphoresis,
mydriasis, and pallor are seldom present
o In most cases there are NO obvious
signs
o Comorbid conditions often present (eg,
sleep problems, depression, relationship
problems)
o Outcome of treatment often
unpredictable
LABORATORY TESTS
o Pain is always subjective
o Pain is best diagnosed based on patient
description and history
o There are no specific laboratory tests for
pain: however, history and/or diagnostic
proof of past trauma (eg, computed
tomography) or present disease state
(eg, autoantibodies) may be helpful in
diagnosing etiology

DIAGNOSIS
ACUTE PAIN N/A
GENERAL
o Often obvious distress (e.g., trauma) MANAGEMENT
SYMPTOMS
o Can be described as sharp, dull, shock- NONPHARMACOLOGIC THERAPY
like tingling, shooting, radiating, STIMULATION THERAPY
fluctuating in intensity, and varying in Transcutaneous electrical nerve
location (these occur in a timely stimulation ( TENS) has been used in managing
relationship with an obvious noxious both acute and chronic pain ( e.g., surgical,
stimuli) traumatic, low back, arthritis, neuropathy,
SIGNS fibromyalgia and oral- facial pain).
o Hypertension, tachycardia, diaphoresis, However, the studies are contradictory
mydriasis, and pal lor, but these signs are and fail to show any sustained pain relief.
not diagnostic PSYCHOLOGICAL INTERVENTION
o In some cases there are no obvious signs o Exercise
o Comorbid conditions usually not present o Relaxation training
o Outcome of treatment generally o Imagery
predictable o Hypnosis
LABORATORY TESTS o Biofeedback (Chronic pain)
o Pain is always subjective PHARMACOLOGIC THERAPY
o There are no specific laboratory tests for NONOPIOID AGENTS
pain  Acetaminophen
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 CLINPHAR
MIDTERM
 Acetylsalicyclic acid (aspirin)
 NSAIDs
OPIOID AGENTS
 Codeine
 Morphine
 Fentanyl
 Levorphanol
 Oxycodone
MODULE 4.4: PARKINSON’S
DISEASE
DEFINITION
 Parkinson's disease is slowly
progressive, chronic neurological
disease that effects a smal l area of the
nerve cel ls in an area of the brain known
as the substantia nigra.
 A syndrome that consist of slowing down
in the initiation and execution of
movement (brady kinesia), increased
muscle tone (rigidity), tremor and
postural instability.
ETIOLOGY/CAUSE OF DISEASE
The real cause of PD's intermittent
occurrence is unknown. Environmental and
genetic variables are probably involved in the
etiopathogenesis of PD. A distinguishing feature
is the cel lular degeneration of dopaminergic
neurons that project from the substantia nigra
pars compacta to the striatum. According to
pathologic findings, the severity of several PD
motor characteristics is inversely correlated with
the amount of nigrostriatal dopamine depletion
(eg, bradykinesia and rigidity).
PATHOPHYSIOLOGY
 The substantia nigra is part of the basal
gangl ia, produces dopamine.
 In the substantia nigra, a region of the
midbrain within the brainstem, patients
with PD lose dopamine neurons
RISK FACTORS
AGE
Young adults rarely experience Parkinson's
disease. It ordinarily begins in middle or late life.
People usually develop disease around age 60
or older.
HEREDITY
Having a close relative with Parkinson's
disease increases the chances that you'll
develop the disease.
SEX
Men are more likely to develop
Parkinson's disease than are women.
EXPOSURE TO TOXINS
Ongoing exposure to herbicides and
pesticides may put you at a slightly increased
risk of Parkinson's disease.
CLASSIFICATIONS
STAGE 1
The first stage of Parkinson's disease is
the mildest. There may be symptoms, but they
aren't severe enough to affect everyday activities
or lifestyle in general.
STAGE 2
Stage 2 Parkinson's disease is
considered a moderate form, and the symptoms
are much more noticeable than in stage 1.
Stiffness, tremors, and trembling may become
more noticeable, and facial expressions may
change
STAGE 3
The middle stage of Parkinson's disease,
stage 3, represents a significant turning point in
the course of the illness. Several of the
symptoms are similar to those of stage 2.
STAGE 4
Stage 4 al lows you to stand without
assistance. However, mobility may necessitate
the use of a walker or another type of assistive
device.
STAGE 5
The most advanced stage of Parkinson's
disease. People in this stage frequently need
wheelchairs and can't stand up straight without
falling. To avoid falls, constant help is needed.
CLINICAL MANIFESTATIONS
BRADYKINESIA
It is a lack of speed in the execution of
voluntary movements. It is referred to as poverty
and the repression of independent movements.
It is primarily brought on by muscular rigidity and
motor system inertia, which makes it challenging
to both initiate and cease motor activity
RIGIDITY
Rigidity results from increased muscle
tone. The opposing muscles, flexors and
extensors, are equally affected by the rigidity. It
is characterized by increased resistance to
passive limb movement
TREMORS
Defined as oscillatory rhythmic
movements caused by opposing muscles
around a joint. Parkinson's tremors are slow.
Hand tremors affect al l of the fingers and the
thumb, and they tend to fade during voluntary
activity. The "resting tremors" appear at rest and
vanish during voluntary movements
3
 CLINPHAR
MIDTERM
POSTURAL INSTABILITY
 difficulty balancing, is possibly the most
challenging of the major Parkinson’s
disease (PD) movement symptoms.
 Shakiness, stiffness and slow movement
can change how a person walks. The
addition of postural instability increases
the risk of falls
DIAGNOSIS
NEUROLOGICAL HISTORY
 The neurologist will diagnose
Parkinson's disease based on medical
history, a review of signs and symptoms,
and a neurological and physical
examination.
 The doctor examines your face to see if it
is animated.
 Your arms are examined for tremor,
which may be present when they are at
rest or extended.
 Is there stiffness in your limbs or neck?
RESPONSE TO LEVODOPA
 Levodopa's ability to temporarily restore
dopamine function in the brain may help
confirm a person's diagnosis
IMAGING
 MRI or CT scan to look for evidence of a
brain tumor or stroke. Most MRI or CT
scans of persons with Parkinson's
disease will appear normal if there is no
stroke or brain tumor.
 Positron emission tomography(PET)
scan - this imaging test may occasionally
detect low dopamine levels in the brain
PHYSICAL EXAMINATION
 In order for a neurologist to consider
Parkinson's disease as a diagnosis, the
patient must have two of the four primary
symptoms.
 They must be present over a specific
period.
 The four main symptoms are:
o Tremor or shaking
o Bradykinesia - slowness of
movement
o Rigidity (stiffness) of the arms,
legs or trunk
o Postural instability - balance
problems and possible falls
MANAGEMENT
NONPHARMACOLOGIC
Nonpharmacologic therapy for
Parkinson's disease (PD) should begin early and
be sustained throughout the course of treatment.
This includes education and lifestyle changes
like exercise. The ADLs, gait, balance, and
mental health may al l be improved by these
therapies. The most frequent therapies involve
preserving a healthy weight, physical fitness,
and social contacts.
SURGERY
 When patients' motor symptoms do not
improve despite medical treatment,
surgery with deep brain stimulation
(DBS) may be considered. DBS may
significantly reduce motor symptoms and
complications and improve QOL
compared to medication management.
PHARMACOLOGIC
Pharmacologic options for PD include
anticholinergics (Ach), amantadine, MAOB
inhibitors, dopamine agonists, levodopa/
carbidopa, and catechol-O-methyltransferase
(COMT) inhibitors. Understanding how each
medication might impact dopamine levels is
crucial because the majority of pharmacologic
PD treatments try to prevent degradation of the
dopaminergic nigrostriatal pathway
ANTICHOLINERGIC
 block acetylcholine, lowering the ratio of
acetylcholine to dopamine levels. They
reduce drooling and resting tremor but
are less successful than other treatments
for rigidity, bradykinesia, and gait issues..
 Side effects: include dry mouth, blurred
vision, constipation, cognitive
impairment, hallucinations, urinary
retention, orthostatic hypotension,
temperature sensitivity, and sedation.
AMANTADINE
 is an N-methyl-d-aspartate (NMDA)-
receptor antagonist that inhibits
glutamate transmission, stimulates the
release of dopamine, and inhibits the
action of acetylcholine. It lessens the
severity and duration of the dyskinesia
and improves PD symptoms in those who
are only minimally affected.
 Side effects: include nausea, dizziness,
livedo reticularis, peripheral edema,
orthostatic hypotension, hallucinations,
restlessness, anticholinergic effects, and
insomnia.
MAO-B INHIBITORS
 is selectively and permanently inhibited
by both selegiline and rasagiline. They
reduce off time when used in conjunction
with levodopa therapy, and they might
have a minimal therapeutic impact on
4
 CLINPHAR
MIDTERM
people who prefer to put off using
dopaminergic medications. In the early
stages of therapy, levodopa combined
with selegiline or rasagiline may be
utilized to delay motor issues.
 Side effects:
o Selegiline are minimal but include
nausea, confusion,
hallucinations, headache, and
orthostatic hypotension
o Rasagiline are primarily GI
related
DOPAMINE AGONISTS
 bind to postsynaptic dopamine receptors.
They have the advantages of delaying
levodopa medication and lowering the
chance of developing motor fluctuations.
 Side effects: include nausea, vomiting,
sedation, pedal edema, orthostatic
hypotension and psychiatric effects that
are greater than with levodopa
LEVODOPA/ CARBIDOPA
 the most effective medication for treating
the symptoms of Parkinson's disease
(PD) when combined with the
peripherally acting L-amino acid
decarboxylase inhibitor.
 Side effects: such as drowsiness and
nausea
CATECHOL-O-METHYLTRANSFERASE
(COMT) INHIBITORS
 an enzyme that catalyzes levodopa to 3–
omethyldopa, are added to
levodopa/carbidopa to raise levodopa
concentrations, prolong its half-l ife, and
shorten the time it takes to wear off.
 Side effects: include diarrhea (worse
with tolcapone), nausea, vomiting,
anorexia, dyskinesias, urine
discoloration, daytime sleepiness, sleep
attacks, orthostatic hypotension, and hal
lucinations.
MODULE 4.5: HEADACHE
DEFINITION
A headache is a pain in your head or face that is
often described as a pressure that is throbbing,
constant, sharp or dull
ETIOLOGY/CAUSE OF DISEASE
A primary headache is caused by
overactivity of or problems with pain-sensitive
structures in your head. Chemical activity in your
brain, the nerves or blood vessels surrounding
your skull, or the muscles of your head and neck
can play a role in primary headaches.
Possible causes of secondary
headaches include: Acute sinusitis (nasal and
sinus infection) Arterial tears (carotid or vertebral
dissections) Blood clot (venous thrombosis)
within the brain — separate from stroke
PATHOPHYSIOLOGY
MIGRAINE
The dural vascular structures are
innervated by neurons arising from the trigeminal
nucleus and dorsal portions of the upper cervical
roots. These structures project onto second
order neurons in the trigeminal cervical complex
and trigeminal nucleus caudalis (TNC). Pain is
felt in the head and neck due to convergence of
fibers from the trigeminal nerve via the TNC and
upper cervical roots. This process also activates
neurons in the TNC and causes the inflammatory
process in the meningeal vascular structures to
begin causing pain and headache. Allodynia and
exacerbation of pain by physical activity is
thought to be caused by this process
TENSION-TYPE HEADACHE
Although poorly understood, input from
myofascial trigger points in the pericranial areas
appear to be responsible for episodic tension-
type headache. With prolonged nociceptive
activation of the pericranial myofascia, central
pain pathways are activated and may be
responsible for conversion to chronic tension-
type headache.
CLUSTER HEADACHE
The pathophysiology of cluster headache
is poorly understood, but is believed to be
caused by activation of the posterior
hypothalamus with secondary activation of the
trigeminal autonomic reflex through the
trigeminal-hypothalamic pathway. Severe,
unilateral pain is mediated by activation of the
first division of the trigeminal nerve (V1). The
autonomic symptoms associated with cluster
headache (lacrimation, miosis, sweating) are
thought to be due to parasympathetic outflow
from the superior salivatory nucleus via the
pterygopalatine (sphenopalatine) ganglio
RISK FACTORS
 Some people may also carry genes that
make them more likely to develop such
headaches.
 Stress, tiredness, or anger can cause
tension headaches.
 Not getting enough sleep may also lead
to headaches.
 Depression and anxiety are two health
problems that have been linked to
tension headaches.
 Certain foods and drinks
5
 CLINPHAR
MIDTERM
 Sleep problems extremely effectivefor the treatment of mild-to-
 Stress Alcohol Menstruation moderately severe migraines
Some medicines may raise the risk, such as: NONPHARMACOLOGIC
 Birth control pills or hormone  Good Sleep Hygiene is a preventive
replacement therapy measure for migraine.
 Headache medicine used on a daily or  Staying adequately hydrated also plays
near daily basis an important role in migraine
management, especially in warmer
CLASSIFICATIONS climates
TENSION HEADACHE
PRIMARY HEADACHE PHARMACOLOGIC
A primary headache isn't a symptom of an  Pain relievers.
underlying disease. The most common primary o Aspirin, Ibuprofen and Naproxen
headaches are: Sodium are used for reducing
 Cluster headache headaches
 Migraine  Combination medications
 Migraine with aura o Aspirin or Acetaminophen are
 Tension headache often combined with caffeine or a
 Trigeminal autonomic cephalalgia (TAC), sedative drug in a single
such as cluster headache and medication.
paroxysmal hemicrania  Triptans and narcotics
SECONDARY HEADACHE o For people who experience both
A secondary headache is a symptom of a migraines and episodic tension-
disease that can activate the pain-sensitive type headaches, a triptan can
nerves of the head. effectively relieve the pain of both
 Acute headaches headaches.
 Subacute headaches NONPHARMACOLOGIC
 Acupuncture
CLINICAL MANIFESTATIONS o Acupuncture may provide
Headache symptoms that require immediate temporary relief from chronic
medical care. headache pain.
If you or your child has any of these headache o Acupuncture practitioners treat
symptoms, get medical care right away: you using extremely thin,
 A sudden, new and severe headache. disposable needles that
 Headache with a fever, shortness of generally cause little pain or
breath, stiff neck or rash. discomfort.
 Headaches that occur after a head injury  Massage
or accident. o Massage can help reduce stress
and relieve tension.
 Getting a new type of headache after age
55.  Deep breathing, biofeedback and
Also seek medical care right away if your behavior therapies
headache is associated with neurological o A variety of relaxation therapies
symptoms, such as: are useful in coping with tension-
type headaches
 Weakness
CLUSTER HEADACHE
 Dizziness
PHARMACOLOGIC
 Sudden loss of balance or falling
The most effective pharmacological
 Numbness or tingling
treatment options for acute cluster attack include
subcutaneous sumatriptan, 100% oxygen, and
DIAGNOSIS
intranasal zolmitriptan. Subcutaneous or
N/A
intramuscular dihydroergotamine and intranasal
sumatriptan are additional options
MANAGEMENT NONPHARMACOLOGIC
Because cluster headaches can be so
MIGRAINE
painful, you may want to try alternative or
PHARMACOLOGIC
complementary therapies to relieve your pain.
Medications to treat mild-to-moderate Melatonin has shown modest
migraines include nonsteroidal anti-inflammatory
effectiveness in treating nighttime attacks.
drugs (NSAIDs). Naproxen and Ibuprofen are
There's also some evidence that capsaicin, used
6
 CLINPHAR
MIDTERM
inside your nose (intranasally), might reduce the
frequency and severity of cluster headache
attacks

7

ALZHEIMER DISEASE
TOPIC OUTLINE
1. Definition of the Disease
2. Etiology/Summary of
Pathophysiology/Risk Factors
3. Classifications
4. Clinical Manifestations
5. Diagnosis
6. Management: Pharmacologic and/or
Nonpharmacologic; Algorithms
7. Case Study
a. Summary of the Case
b. Medication list
c. Answer to questions
8. References
ALZHEIMER DISEASE
DEFINIT ION
 Alzheimer disease (AD), which
accounts for about 60% of dementias, is
a progressive and eventually fatal
dementia of unknown cause
characterized by loss of cognitive and
physical functioning, commonly with
behavior symptoms
 Dementias - is not a specific
disease but is rather a general
term for the impaired ability to
remember, think, or make
decisions that interferes with
doing everyday activities
ET IOLOGY
 Most cases of Alzheimer disease are
sporadic, with late onset (≥ 65 years)
and unclear etiology. Risk of
developing the disease is best predicted
by age. However, about 5 to 15% of
cases are familial; half of these cases
have an early (presenile) onset (< 65
years) and are typically related to
specific genetic mutations.
MODULE 4.6: ALZHEIMER DISEASE
 Sporadic - refers to a disease
that occurs infrequently and
irregularly
PAT HOPHYSIOLOGY
 Dominantly inherited forms of AD are
fewer than 1% of cases. More than half
of young-onset, dominantly inherited
cases are attributed to alterations on
chromosomes 1, 14, or 21. Genetic
susceptibility to late-onset AD is
primarily linked to the apolipoprotein E
(APOE) genotype, but an interaction of
multiple genes with the environment
may be at play.
 Signature findings include intracellular
neurofibrillary tangles (NFTs),
extracellular amyloid plaques in the
cortex and medial temporal lobe,
degeneration of neurons and synapses,
and cortical atrophy. Density of NFTs
correlates with severity of dementia.
 Proposed mechanisms for these
changes include:
o (1) β-amyloid protein
aggregation, leading to
formation of plaques;
o (2) hyperphosphorylation of tau
protein, leading to NFTs;
o (3) synaptic failure and
depletion of neurotrophin and
neurotransmitters;
o (4) mitochondrial dysfunction;
and
o (5) oxidative stress. The
amyloid cascade hypothesis
states that there is an
imbalance between production
and clearance of β-amyloid,
with aggregation and
accumulation of β-amyloid
leading to AD. Whether this is
the primary pathology in most
forms of AD remains to be
shown.
JANELLE SHANE L. ABORDE 1

 Of neurotransmitter deficits, loss of
cholinergic activity is most prominent,
and it correlates with AD severity.
Cholinergic cell loss seems to be a
consequence of AD pathology, not the
cause of it.
 Other neurotransmitter considerations
include:
o Serotonergic neurons of the
raphe nuclei and noradrenergic
cells of the locus ceruleus are
lost;
o (2) monoamine oxidase type B
activity is increased;
o (3) glutamate pathways of the
cortex and limbic structures are
abnormal; and
o (4) excitatory neurotransmitters,
including glutamate, may be
neurotoxic
RISK FACT ORS
 Risk factors associated with AD include
age, decreased reserve capacity of the
brain, head injury, Down syndrome,
depression, mild cognitive impairment,
and risk factors for vascular disease,
including hypertension, elevated
homocysteine, elevated low-density
lipoprotein cholesterol, low high-density
lipoprotein cholesterol, obesity,
metabolic syndrome, and diabetes.
CLASSIFICAT IONS
 Mild (MMSE score 26–21): Patient has
difficulty remembering recent events.
Ability to manage finances, prepare
food, and carry out other household
activities declines. May get lost while
driving. Begins to withdraw from difficult
tasks and to give up hobbies. May deny
memory problems
 Moderate (MMSE score 20–10):
Patient requires assistance with
activities of daily living. Frequently
disoriented with regard to time (date,
year, and season). Recall for recent
MODULE 4.6: ALZHEIMER DISEASE
events is severely impaired. May forget
some details of past life and names of
family and friends. Functioning may
fluctuate from day to day. Patient
generally denies problems. May become
suspicious or tearful. Loses ability to
drive safely. Agitation, paranoia, and
delusions are common
 Severe (MMSE score 9–0): Patient
loses ability to speak, walk, and feed
self. Incontinent of urine and feces.
Requires care 24 hours a day, 7 days a
week
MMSE - Mini-Mental State Examination
CLINICAL MANIFEST AT IONS
 Cognitive decline is gradual and
includes memory loss, aphasia, apraxia,
agnosia, disorientation, and impaired
executive function.
o Aphasia - is a language
disorder caused by damage in a
specific area of the brain that
controls language expression
and comprehension.
o Apraxia - (called "dyspraxia" if
mild) is a neurological disorder
characterized by loss of the
ability to execute or carry out
skilled movements and
gestures, despite having the
desire and the physical ability to
perform them.
o Agnosia - is a rare disorder
characterized by an inability to
recognize and identify objects or
persons.
 Other symptoms include depression,
psychotic symptoms, aggression, motor
hyperactivity, uncooperativeness,
wandering, and combativeness. Patients
become increasingly unable to care for
themselves.
DIAGNOSIS
JANELLE SHANE L. ABORDE 2

 The National Institute on Aging and the
Alzheimer’s Association view AD as a
spectrum beginning with an
asymptomatic preclinical phase
progressing to the symptomatic
preclinical phase and then to the
dementia phase. AD is a clinical
diagnosis, based largely on identified
symptoms and difficulty with activities of
daily living revealed by patient and
caregiver interviews.
 In the future, improved brain imaging
and validated biomarkers of disease will
enable a more sophisticated diagnosis
with identified cognitive strengths and
weaknesses and neuroanatomic
localization of deficits.
 Patients with suspected AD should have
a history and physical examination with
appropriate laboratory tests (serum B12
, folate, thyroid panel, blood cell counts,
serum electrolytes, and liver function
tests), and computed tomography or
magnetic resonance imaging may aid
diagnosis. To exclude other diagnoses,
cerebrospinal fluid analysis or an
electroencephalogram can occasionally
be justified.
 Obtain information on medication use;
alcohol or other substance use; family
medical history; and history of trauma,
depression, or head injury. Rule out
medication use (eg, anticholinergics,
sedatives, hypnotics, opioids,
antipsychotics, and anticonvulsants) as
contributors to dementia symptoms.
Rule out medications that could
contribute to delirium (eg, digoxin,
nonsteroidal anti-inflammatory drugs
[NSAIDs], histamine 2 [H2 ] receptor
antagonists, amiodarone,
antihypertensives, and corticosteroids).
 The Folstein Mini-Mental State
Examination (MMSE) can help establish
a history of deficits in two or more areas
of cognition at baseline against which to
evaluate change in severity over time.
The average expected decline in an
MODULE 4.6: ALZHEIMER DISEASE
untreated patient is 2 to 4 points per
year.
MANAGEMENT : PHARMACO LOGIC
AND/OR NONPHARMACOLO GIC;
ALGORIT HMS
 Goals of Treatment: The goal of
treatment in AD is to maintain cognitive
functioning and activities of daily living
as long as possible, with a secondary
goal to treat the psychiatric and
behavioral symptoms.
 For mild to moderate AD, consider use
of a cholinesterase inhibitor, and titrate
to maintenance dose. For moderate to
severe AD, consider adding memantine,
and titrate to maintenance dose.
Alternatively, consider memantine or
cholinesterase inhibitor alone. Treat
behavioral symptoms with support and
behavioral interventions, and use
pharmacological management only if
necessary.
NONPHARMACOLOGIC T HERAPY
 Sleep disturbances, wandering, urinary
incontinence, agitation, and aggression
should be managed with behavioral and
environmental interventions whenever
possible, for example, redirecting the
patient’s attention and removing
stressors and triggers.
 On initial diagnosis, the patient and
caregiver should be educated on the
course of illness, available treatments,
legal decisions, changes in lifestyle that
will become necessary, and other
quality-of-life issues.
PHARMACOT HERAPY OF COGNIT IVE
SYMPT OMS
 Primary prevention of AD may include
smoking cessation, increasing physical
activity, and reducing midlife obesity,
hypertension, and diabetes. Also
adherence to the Mediterranean Diet or
JANELLE SHANE L. ABORDE 3
 MODULE 4.6: ALZHEIMER DISEASE

 Dietary Approaches to Stop  Those who respond to treatment may

Hypertension Diet may reduce the risk lose the benefits when medication is
of cognitive impairment or decline. stopped.
 Reasonable expectations of treatment
may be a slowed decline in abilities and
delayed long-term care placement.

CHOLINESTERASE INHIBITORS
TABLE 52–2: SUMMARIZES DOSING OF THE CHOLINESTERASE
INHIBITORS AND MEMANTINE
DRUG Brand name Initial Dose Usual range Special Population Other
Dose
CHOLINERASE INHIBITORS

DONEPEZIL Aricept, Aricept 5 mg daily in 5–10 mg daily No dosage Available as: tablet,
ODT the evening in mild to adjustments ODT
moderate AD recommended Can be taken with or
10–23 mg without food
daily in
moderate to Weight loss
severe AD associated with 23 mg
daily dose
RIVASTIGMINE Exelon, Exelon 1.5 mg twice 3–6 mg twice Capsule/oral solution: Available as: capsule,
Patch daily (capsule, a day Renal impairment, oral solution,
oral solution) (capsule, oral hepatic impairment, or transdermal patch
4.6 mg/day solution) 9.5– low body weight (≤50 Take with meals
(transdermal 13.3 mg/day kg [<110 lb]: Patients
patch) (transdermal may be able to only Also indicated for
patch) tolerate lower doses Parkinson disease
dementia
Transdermal patch:
Mild to moderate Application of multiple
hepatic impairment or transdermal patches
low body weight: at same time
consider maximum associated with
daily dose of 4.6 mg hospitalization and
every 24 hours death
GALANTAMINE Razadyne, 4 mg twice 8–12 mg twice Moderate renal or Available as: tablet,
Razdyne ER daily (tablet, a day (tablet, hepatic impairment: oral solution,
oral solution) 8 oral solution) maximum daily dose extended-release
mg daily in the 16–24 mg of 16 mg capsule
morning (extended- Severe renal or Take with meals
(extended- release hepatic impairment:
release capsule) not recommended
capsule)
N-METHYL-D-AAPARTATE (NMDA) RECEPTOR ANTAGONIST

MEMANTINE Nemanda, 5 mg daily 10 mg twice Several renal Available as: tablet,

Namenda XR daily impairment: oral solution,
7 mg daily
recommended extended-release
(extended- 28 mg daily
maintenance dose of capsule
(extended-

JANELLE SHANE L. ABORDE 4

 MODULE 4.6: ALZHEIMER DISEASE

release release 5 mg twice daily Can be taken with or

capsule) capsule) (tablet, oral solution) without food Can
or 14 mg daily open extended-
(extended-release release capsule and
capsule) sprinkle contents on
Several hepatic applesauce for ease
impairment: of administration
administer with
caution
CHOLINESTERASE INHIBITOR + NMDA RECEPTOR ANTAGONIST

MEMANTINE + Namzaric 28 mg/10 mg 14–28 mg/10 Severe renal Available as

DONEPEZIL mg daily impairment: 14 mg/10 memantine extended-
mg daily release and donepezil
capsule
Can be taken with or
without food
Can open capsule
and sprinkle contents
on applesauce for
ease of administration
(ODT, orally disintegrating tablet.)

 No comparative trials have assessed months. Because of their short half-

the effectiveness of one agent over
another. Donepezil, rivastigmine, and
galantamine are indicated in mild to
moderate AD; donepezil is also
indicated for severe AD.
 MMSE is practical to use in the clinical
setting to measure changes in cognitive
function. Successful treatment would
show a decline in MMSE score of less
than 2 points per year.
 The three cholinesterase inhibitors have
similar efficacy in mild to moderate AD,
and duration of benefit lasts 3 to 24
lives, if rivastigmine or galantamine
treatment is interrupted for several days
or longer, retitrate starting at the lowest
dose. Gradual dose titration over
several months improves tolerability.
 The most frequent adverse effects
include mild to moderate gastrointestinal
(GI) symptoms (nausea, vomiting, and
diarrhea), urinary incontinence,
dizziness, headache, syncope,
bradycardia, muscle weakness,
salivation, and sweating. Abrupt
discontinuation can cause effects and
monitoring parameter

TABLE 52–3: MONITORING DRUG THERAPY FOR COGNITIVE SYMPTOMS

DRUG Adverse Drug Reaction Monitoring Parameter Comments

GALANTAMINE Serious skin reactions (Stevens-
Johnson syndrome and acute
generalized exanthematous
pustulosis)
RIVASTIGMINE Allergic dermatitis
Appearance of skin rash
Application site reaction spread
beyond patch size, evidence of
Discontinue galantamine
at first sign of skin rash,
unless clearly not drug-
related
Discontinue rivastigmine
if evidence of

JANELLE SHANE L. ABORDE 5

 MODULE 4.6: ALZHEIMER DISEASE

a more intense local reaction disseminated allergic

(increasing erythema, edema, dermatitis appears
papules, vesicles), and if Patients sensitized by
symptoms do not improve exposure to the
within 48 hours of patch transdermal patch may
removal not be able to take
rivastigmine by mouth
either; allergy testing and
close medical
supervision
recommended
CHOLINESTERASE Dizziness, syncope, Report of dizziness or falls, Dizziness is usually mild,
INHIBITORS bradycardia, atrial arrhythmias, pulse, blood pressure, and transient, and not related
myocardial infarction, angina, postural blood pressure to cardiovascular
seizures, sinoatrial and change problems Routine pulse
atrioventricular block checks at baseline,
monthly during titration,
and every 6 months
thereafter
CHOLINESTERASE Nausea, vomiting, diarrhea, Weight and GI complaints Take with food to
INHIBITORS anorexia, and weight loss decrease GI upset
Usually transient, dose-
related GI adverse
effects seen with drug
initiation, dosage
titration, or drug switch
CHOLINESTERASE Peptic ulcer disease, GI Signs or symptoms of active or Of particular concern for
INHIBITORS bleeding occult GI bleeding patients at increased risk
of developing ulcers,
such as those with a
history of ulcer disease
or concurrently taking
NSAIDs
CHOLINESTERASE Insomnia, vivid/abnormal Complaints of sleep Donepezil can be taken
INHIBITORS dreams, nightmares disturbances, daytime in the morning to
drowsiness decrease risk of sleep
disturbances
MEMANTINE Headache, confusion, dizziness, Report of dizziness or falls, Confusion may be
hallucinations hallucinations observed during dose
titration and is usually
transient Memantine may
mitigate GI adverse
effects associated with
cholinesterase inhibitor
therapy
MEMANTINE Constipation GI complaints

ALGORIT HM OF TREAT MENT

JANELLE SHANE L. ABORDE 6


OT HER DRUGS
 Memantine (Namenda) blocks
glutamatergic neurotransmission by
antagonizing Nmethyl-d-aspartate
receptors, which may prevent excitotoxic
reactions. It is used as monotherapy and
in combination with a cholinesterase
inhibitor. It is indicated for treatment of
moderate to severe AD, but not for mild
AD. It is not metabolized by the liver but
is primarily excreted unchanged in the
urine. Dosing must be adjusted in
patients with renal impairment. It is
usually well tolerated; side effects
include constipation, confusion,
dizziness, and headache.
 Trials do not support the use of estrogen
to prevent or treat dementia.
MODULE 4.6: ALZHEIMER DISEASE
 Vitamin E is under investigation for
prevention of AD and is not
recommended for treatment of AD.
 Because of the incidence of side effects
and a lack of supporting evidence,
neither NSAIDs nor prednisone is
recommended for treatment or
prevention of AD.
 Trials of statin drugs have not shown
significant benefit in prevention or
treatment of AD.
 Because of limited efficacy data, the
potential for adverse effects (eg,
nausea, vomiting, diarrhea, headache,
dizziness, restlessness, weakness, and
hemorrhage), and poor standardization
of herbal products, ginkgo biloba is not
recommended for prevention or
treatment of AD.
JANELLE SHANE L. ABORDE 7

 Do not use ginkgo biloba in individuals
taking anticoagulants or antiplatelet
drugs, and use cautiously in those
taking NSAIDs.
 Huperzine A has not been adequately
evaluated and is not currently
recommended for treatment of AD.
PHARMACOT HERAPY OF
NONCOGNIT IVE SYMPTOMS
 Pharmacotherapy for noncognitive
symptoms targets psychotic symptoms,
inappropriate or disruptive behavior, and
depression. General guidelines include
the following:
o Use environmental interventions
first and pharmacotherapy only
when necessary;
o (2) identify and correct underlying
causes of disruptive behaviors
when possible;
o (3) start with reduced doses and
titrate slowly;
o (4) monitor closely;
o (5) periodically attempt to taper
and discontinue medication; and
o (6) document carefully.
 Avoid anticholinergic psychotropic
medications as they may worsen
cognition.
CHOLINESTERASE INHIBITORS AND
MEMANTINE
 Cholinesterase inhibitors and
memantine, individually or in
combination, have shown modest
improvement of behavioral symptoms
over time, but may not significantly
reduce acute agitation.
ANTIPSYCHOTICS
 Antipsychotic medications have
traditionally been used for disruptive
behaviors and neuropsychiatric
symptoms, but the risks and benefits
must be carefully weighed.
MODULE 4.6: ALZHEIMER DISEASE
 A meta-analysis found that only 17% to
18% of dementia patients showed a
modest treatment response with atypical
antipsychotics. Adverse events (eg,
somnolence, extrapyramidal symptoms,
abnormal gait, worsening cognition,
cerebrovascular events, and increased
risk of death [see black-box warning])
offset advantages. Another systematic
review and meta-analysis found small
but significant improvement in
behavioral symptom scores in patients
treated with aripiprazole, olanzapine,
and risperidone.
 Typical antipsychotics may also produce
a small increased risk of death, and
more severe extrapyramidal effects and
hypotension than the atypicals.
 Antipsychotic treatment in AD patients
should rarely be continued beyond 12
weeks.
ANTIDEPRESSANTS
 Depression and dementia share many
symptoms, and the diagnosis of
depression can be difficult, especially
later in the course of AD.
 A selective serotonin reuptake
inhibitor (SSRI) is usually given to
depressed patients with AD, and the
best evidence is for sertraline and
citalopram. Tricyclic antidepressants
are usually avoided
MISCELLANEOUS THERAPIES
 Use of benzodiazepines is not advised
except on an “as needed” basis for
infrequent episodes of agitation.
 Carbamazepine, valproic acid, and
gabapentin may be alternatives for
agitation, but evidence is conflicting.
EVALUAT ION OF THERAPEUT IC
OUT COMES
 At baseline interview both patient and
caregiver to identify target symptoms;
define therapeutic goals; and document
JANELLE SHANE L. ABORDE 8

cognitive status, physical status,
functional performance, mood, thought
processes, and behavior.
 Use the MMSE for cognition, Bristol
Activities of Daily Living Scale for
activities of daily living, and
Neuropsychiatric Inventory
Questionnaire for assessment of
behavioral disturbances to quantify
changes in symptoms and functioning.
 Observe the patient carefully for
potential side effects. The specific side
CASE STUDY
SUMMARY OF THE CASE
 YG, a 72-year-old man, has memory
problems that first appeared 6 to 12
months ago but lately got worse after he
was admitted to the hospital for a fall.
YG’s medical history is significant for
osteoarthritis benign prostatic
hyperplasia (BPH) and hypertension.
His family history is negative for stroke
and positive for heart disease and his
father died of a myocardial infarction at
age 84. On the other hand, his mother
had AD and was diagnosed in her early
70s as well. Physical examination
reveals a pleasant, well-groomed man
who is in good health oriented to person
and place but not time. His blood
pressure (BP) is 120/66 mmHg supine
and 132/72 mmHg standing, with pulse
rates of 56 beats/minute and 62
beats/minute, respectively. The Folstein
MMSE score was 22/30, with errors in
orientation, attention, calculation
(inability to spell “world” backward),
recall, and language (difficulty with word
finding). The rest of the physical
examination was within normal limits.
MEDICAT ION LIST
MODULE 4.6: ALZHEIMER DISEASE
effects to be monitored and the method
and frequency of monitoring should be
documented.
 Assess for drug effectiveness, side
effects, adherence to regimen, and need
for dosage adjustment or change in
treatment after 1 month and at least
every 6 months thereafter. Several
months to 1 year of treatment may be
required to determine whether
medications for cognition are beneficial
 According to the case study, YG is
currently taking tamsulosin 0.4 mg in
the evening for BPH and amlodipine 10
mg daily for HTN.
ANSWER TO QUEST IONS
1. What additional evaluation steps should
be considered for YG?
 YG is referred by his physician
for additional testing. All results
were normal with the exception
of a low B12 level (147 ng/L).
Depression testing revealed a
mildly anxious individual who
was not depressed just worried
about his future.
2. What is the most probable diagnosis for
this patient?
 YG’s score of 22/30 on the
Folstein MMSE is consistent
with mild cognitive impairment
or early dementia as evidenced
by errors in orientation,
calculation, recall, and
language. Secondary medical
causes of cognitive impairment
can be eliminated by YG’s
generally normal physical
examination and laboratory test
results. MRI or CT scanning
may be useful in many cases to
help eliminate brain pathology,
such as stroke.
JANELLE SHANE L. ABORDE 9

3. What is an appropriate initial treatment
strategy?
 YG’s family needs to be
educated about what to expect
as his dementia progresses.
Currently, there are two classes
of medications that are used in
the treatment of Alzheimer’s
disease, cholinesterase
inhibitors (ChEIs) and N-methyl-
D-aspartate (NMDA) receptor
antagonist. They are
pharmacologically distinct and
can be prescribed concurrently
in patients in the moderate to
severe stages of the illness.
ChEIs act on inhibiting
acetylcholinesterase, an
enzyme directly involved in the
destruction of acetylcholine
leading to increasing its
concentration in the nucleus
basalis of Meynert in the brain
and hence ameliorating the
cognitive and functional aspects
of AD. Cholinesterase inhibitors
have been shown to improve
cognition and function, and
delay symptom progression in
people with dementia, however
benefits are limited Cholinergic-
related effects, particularly in the
gastrointestinal (GI) tract, are
the most common adverse
effects cause by all of the
agents.
4. Should treatment with a cholinesterase
inhibitor be instituted in YG; and if so
how should therapy be monitored?
 YG is in the mild stage of the
disease, so a ChEI is an
appropriate choice. It is unlikely
that a ChEI will produce a
dramatic or long-lasting
improvement in YG’s cognitive
abilities. Treatment, however,
may slow his cognitive decline,
help maintain his ability to care
for himself for 1 year or more,
MODULE 4.6: ALZHEIMER DISEASE
and reduce the risk for nursing
facility placement for as much
as 2 years. The choice of drug
is based on the agent most
likely to produce a positive
response with the fewest
adverse effects. Ease of
adherence must also be
considered. All agents exhibit
similar adverse effect profiles.
Donepezil may be an
appropriate agent for YG. His
family and physician should look
for improvements in his
memory, orientation, and ability
to concentrate on complex
tasks, such as managing
finances.
5. What will you counsel your patient?
 I will counsel my patient in a
way that I will put myself in his
situation so that I can
understand his feeling. I will
encourage him to continue
pursuing activities that add
meaning and purpose to his life.
Moreover, I will observe and
take time to know my patient
first, the things that he likes to
do and the things that he don’t
like. Patience and flexibility
along with self-care and the
support of friends and family
can help in dealing the
challenges and frustrations
ahead.
JANELLE SHANE L. ABORDE 10
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MODULE 5.1:
DEFINITION
 The term anxiety disorder encompasses
a variety of conditions that can either
exist on their own or in conjunction with
another psychiatric or physical illness.
 Anxiety is a normal, protective,
psychological response to an unpleasant
or threatening situation.
ETIOLOGY/CAUSE OF DISEASE
SPECIFIC PHOBIA
POST TRAUMATIC STRESS DISORDER
SYMPTOMS:
 Sensitivity to noise
 Dry mouth; difficulty in swallowing
 Palpitations; discomfort in the chest;
awareness of missed beats
OBSESSIVE-COMPULSIVE DISORDER
 Restlessness; tremor; aching muscles
 Constriction in the chest; difficulty
inhaling; feeling of breathlessness
 Fearful anticipation; irritability; poor
concentration; worrying thoughts;
headache; dizziness; insomnia; avoiding
the situation/subject
 GI discomfort; excessive wind; frequent
or urgent micturition; Failure of erection;
Menstrual discomfort; amenorrhoea
PATHOPHYSIOLOGY
 Anxiety occurs when there is a
disturbance of the arousal systems in the
brain. Arousal system is maintained by at
least three interconnected systems: a
general arousal system, an ‘emotional’
arousal system and a somatic arousal
system.
 These arousal systems activate physical
responses to arousal, such as increased
muscle tone and increased sympathetic
activity
RISK FACTORS
 Genetic predisposition
 Brain chemistry
 Family background
 Lifestyle factor
 Social influence
CLASSIFICATIONS
GENERALISED ANXIETY DISORDER
 Condition where there is persistent,
excessive and excessive anxiety on most
days for at least 6 months
PANIC DISORDER
 It is recurrent and unexplained surges of
severe anxiety. Most patients develop a
fear of repeat attacks or the implications
of an attack.
SOCIAL ANXIETY DISORDER
 A marked, persistent and unreasonable
fear of being observed, embarrassed or
humiliated in a social or performance
situation
 It is marked and persistent fear that is
excessive or unrealistic, precipitated by
the presence of a specific object or
situation
 It can occur after an exposure to a
traumatic event which involved actual or
threatened death or serious injury or
threats to the physical integrity of self or
others.
 It can occur after an exposure to a
traumatic event which involved actual or
threatened death or serious injury or
threats to the physical integrity of self or
others.
CLINICAL MANIFESTATIONS
 Anxiety may form part of a depressive
disorder or psychosis and may occur in
rare hormone-secreting tumors such as
phaeochromocytoma or carcinoid
syndrome.
 Apart from the psychological symptoms
of apprehension and fear, somatic
symptoms may be prominent in anxiety
and include palpitations, chest pain,
shortness of breath, dizziness,
dysphagia, gastro-intestinal
disturbances, loss of libido, headaches
and tremor.
 Panic attacks are experienced as storms
of increased autonomic activity combined
with a fear of imminent or severe loss of
control. If panic becomes associated with
a particular environment, commonly a
crowded place, the patient may actively
avoid similar situations and eventually
become agoraphobic.
1
 CLINPHAR
MIDTERM
o Monoamine-oxidase inhibitors
o Selective and noradrenaline
reuptake inhibitor
NONPHARMACOLOGIC
DIAGNOSIS  Physiological therapy
 Blood Test  Exposure and response prevention
 Physical Exam  Self help therapy
 Home remedies  Cognitive behavioral therapy
o Keep physically active  Other medications ocassionally used in
o Avoid alcohol and recreational anxiety
drugs o Hydroxyzine
o Avoid smoking and drinking o Pregabalin
caffeinated beverages o Buspirone
o Make sleep a priority o Propranolol
o Eating healthy foods o Oxprenolol
 Therapies for anxiety disorders in
addition to diagnosis
o Physiological therapy
o Exposure and response
prevention (ERP)
o Self help therapy
o Systematic desensitization
o Cognitive behavioral therapy
 Medications
o Anti-depressants
o benzodiazepine

MANAGEMENT

PHARMACOLOGIC
 Benzodiazepine drugs that have
sedative/hypnotic, anxiolytic, amnesic,
muscular relaxant and anticonvulsant
actions, with minor differences in the
relative potency and rate of elimination.
These drugs differ considerably in their
pharmacological action but only slightly
in clinical effects
 Profile of Selected Benzodiazepines
o Alprazolam
o Chlordiazepoxide
o Clonazepam
o Diazepam
o Lorazepam
o Oxazepam
o Temazepam
 Antidepressant drugs- are considered
first line treatment option either alone or
in combination with CBT in patients
suffering from OCD with moderate or
severe impairment. Antidepressants can
provide a long-term treatment option for
those with an anxiety disorder. They are
generally recommended for those who
have not responded to psychological
therapies.
o Selective serotonin reuptake
inhibitors
o Tricyclic antidepressants
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MODULE 5.2: BIPOLAR DISORDER
DEFINITION
 once known as manic depression, is a
severe life-threatening psychiatric
condition that is commonly misdiagnosed
and too often insufficiently treated.
 It is also a chronic progressive illness that
occurs in approximately 4% of the
population.
 It is characterized by recurrent mood
episodes of mania and depression. Life
stressors, substance use, treatment non-
adherence, and medications are
common precipitants of these mood
episodes.
ETIOLOGY/CAUSE OF DISEASE
The precise etiology is unknown.
Thought to be genetically based, bipolar disorder
is influenced by a variety of factors that may
enhance gene expression. These include
trauma, environmental factors, anatomical
abnormalities, and exposure to chemicals or
drugs
PATHOPHYSIOLOGY
BD is a complex disease involving
developmental, genetic, neurobiologic, and
psychological factors. Neuroimaging studies
have demonstrated neurochemical, anatomic,
and functional abnormalities in those with a
diagnosis of BD. Recent studies have
demonstrated that altered synaptic and circuit
functioning accounts for mood and cognitive
changes rather than the previous theory of
dysfunction of individual neurotransmitters.
Environmental, or psychosocial, stressors,
immunologic factors, and sleep dysfunction have
been associated with BD and can negatively
influence the course of illness.
RISK FACTORS
o family history of mood disorders,
o perinatal stress,
o head trauma,
o environmental factors (including
circadian rhythm disorders),
o psychosocial and physical stressors.
A recent systematic review of 16 published
reports with varying study designs suggested
that early phases and suspected precursor
states for those who develop BD include:
o early-onset panic attacks and disorder,
o separation anxiety,
o generalized anxiety disorders,
o attention deficient hyperactivity disorder,
o conduct symptoms and disorder.
CLASSIFICATIONS
Bipolar disorder is categorized into four
subtypes: bipolar I; bipolar II, cyclothymic
disorder, and other specified and unspecified
bipolar and related disorders.
The defining feature of bipolar disorder is
one or more manic or hypomanic episodes in
addition to depressive episodes that are not
caused by a medical condition, substance
abuse, or other psychiatric disorder.
BIPOLAR I
periods of major depressive, manic,
and/or mixed episodes. affects men and women
equally
BIPOLAR II
periods of major depression and
hypomania (Hypomania is an abnormally and
persistently elevated, expansive, or irritable
mood but not of sufficient severity to cause
significant impairment and does not require
hospitalization.) Is more common in women.
CYCLOTHYMIC DISORDER
a chronic mood disturbance lasting at
least 2 years and characterized by mood swings
that include periods of *hypomanic symptoms
that do not meet the criteria for a hypomanic
episode and *depressive symptoms that do not
meet the criteria for a major depressive episode.
Hypomanic symptoms include inflated
self-esteem or grandiosity (nondelusional),
decreased need for sleep, pressured speech
(increased talking), flight of ideas/racing
thoughts (FOI), distractibility, and increased
involvement in goal-directed activities.
CLINICAL MANIFESTATIONS
PHYSICAL AND BEHAVIORAL:
 agitation
 impulsivity
 aggression
 rapid, pressured speech
 insomnia (sometimes for days or weeks)
 hypersexuality
 increased physical energy
 inflated self-esteem, boasting, gradiosity
 heightened interest in pleasurable
activities with a high risk of negative
consequences (e.g., spending sprees,
promiscuity)
 fatigue
 hypersomnia
DIAGNOSIS
Mood disorders like BD are diagnosed using the
criteria established in the Diagnostic and
Statistical Manual of Mental Disorders, Fifth
Edition (DSM-5).
5
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MIDTERM
DSM-5 CRITERIA FOR A MANIC EPISODE
1. a distinct period of abnormally and
persistently elevated, expansive, or
irritable mood, and persistently increased
goal-directed activity or energy lasting ≥1
week (or of any duration if hospitalization
is necessary)
2. during the period of mood disturbance
and increased energy or activity, at least
three of the following symptoms have
persisted (four if the mood is only
irritable) and have been present to a
significant degree
 inflated self-esteem or grandiosity
 decreased need for sleep (e.g.,
feels rested after only 3 hours of
sleep)
 more talkative than usual or
pressure to keep talking
 flight of ideas or subjective
experience that thoughts are
racing
 distractibility (i.e., attention too
easily drawn to unimportant or
irrelevant external stimuli)
 increase in goal-directed activity
(either social, at work, at school,
or sexually) or psychomotor
agitation
 excessive involvement in
pleasurable activities that have a
high potential for painful
consequences (e.g., the person
engages in unrestrained buying
sprees, sexual indiscretions, or
foolish business investing)
3. the mood disturbance is sufficiently
severe to cause marked impairment in
occupational functioning or in usual
social activities or relationships with
others, or to necessitate hospitalization
to prevent harm to self or others, or there
are psychotic features
4. the symptoms are not caused by direct
physiologic effects of a substance (e.g.,
a drug of abuse, a medication, or other
treatment) or a general medical condition
(e.g., hyperthyroidism)
A person who has experienced one or more
manic episodes with or without a depressive
episode is diagnosed as having bipolar I
disorder. An individual who has experienced one
or more episodes of both hypomania and
depression (without a history of manic episodes)
is diagnosed as having bipolar II disorder. The
diagnosis of a cyclothymic disorder is for a
person who has experienced at least 2 years of
both hypomanic and dysthymic periods without
ever fulfilling the criteria for an episode of mania,
hypomania, or major depression.
MANAGEMENT
PHARMACOLOGIC THERAPY
• The primary treatment modality for manic
episodes is mood-stabilizing agents or
antipsychotic drugs, often in
combination. o Mood-stabilizing drugs
are first-line treatments and include
lithium, divalproex, valproic acid,
carbamazepine, and lamotrigine.
• The primary treatment for depressive
episodes in bipolar disorder is
moodstabilizing agents or certain
antipsychotics.
o Quetiapine as monotherapy,
lurasidone as monotherapy or
adjunctive to lithium or
divalproex, and olanzapine in
combination with fluoxetine are
approved.
• The primary treatment for relapse
prevention is mood-stabilizing agents,
often combined with antipsychotic drugs.
o Aripiprazole, olanzapine, and
quetiapine are approved for maintenance
therapy.
NON-PHARMACOLOGIC THERAPY
Interpersonal, family, or group
psychotherapy with a qualified therapist or
clinician assists individuals with bipolar disorder
to improve functional outcomes and may help
treat or prevent mood episodes, establish a daily
routine and sleep schedule, and improve
interpersonal relationships. o Cognitive-
behavioral therapy (CBT) is a type of
psychotherapy that stresses the importance of
recognizing patterns of cognition (thought) and
how thoughts influence subsequent feelings and
behaviors. With CBT, patients are taught self-
management skills to change negative thoughts
even if external circumstances do not change. o
Electroconvulsive therapy (ECT) is the
application of electrical impulses to the brain for
the treatment of severe depression, mixed
states, psychotic depression, and treatment
refractory mania.
6
 CLINPHAR
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MODULE 5.3: MAJOR DEPRESSIVE
DISORDER
DEFINITION
 Major depressive disorder or clinical
depression, is a serious mental disorder
that affects how you feel, think and
behave and can lead to a variety of
emotional and physical problems.
 It is diagnosed when an individual has a
persistently low or depressed mood,
anhedonia or decreased interest in
pleasurable activities, feelings of guilt or
worthlessness, lack of energy, poor
concentration, appetite changes,
psychomotor retardation or agitation,
sleep disturbances, or suicidal thoughts.
ETIOLOGY/CAUSE OF DISEASE
 Biological
 Environmental
 Psychosocial
 Genetic
PATHOPHYSIOLOGY
 Biogenic amine hypothesis: Decreased
brain levels of the neurotransmitters
norepinephrine, serotonin (5-HT), and
dopamine may cause depression.
 Postsynaptic changes in receptor
sensitivity: Studies have demonstrated
that desensitization or downregulation of
norepinephrine or 5-HT1A receptors may
relate to onset of antidepressant effects.
 Dysregulation hypothesis: This theory
emphasizes a failure of homeostatic
regulation of neurotransmitter systems,
rather than absolute increases or
decreases in their activities. Effective
antidepressants may restore efficient
regulation.
 5-HT/norepinephrine link hypothesis:
This theory suggests that 5-HT and
norepinephrine activities are linked, and
that both the serotonergic and
noradrenergic systems are involved in
the antidepressant response.
 The role of dopamine: Several studies
suggest that increased dopamine activity
in the mesolimbic pathway contributes to
antidepressant activity.
 A disruption of brain derived neurotrophic
factor expression in the hippocampus
may be associated with depression
RISK FACTORS
N/A
CLASSIFICATIONS
PERSISTENT DEPRESSIVE DISORDER
 formerly known as dysthymia
 a continuous long term (chronic) form of
depression
DISRUPTIVE MOOD DYSREGULATION
DISORDER
 a childhood condition of extreme
irritability, anger, and frequent, intense
temper outbursts.
PREMENSTRUAL DYSPHORIC DISORDER
 a health problem that is similar to
premenstrual syndrome (PMS) but is
more serious.
SUBSTANCE/MEDICATION-INDUCED
DEPRESSIVE DISORDER
 marked mood changes from a person's
baseline mood associated with the
person's exposure to a substance or
medication
DEPRESSIVE DISORDER DUE TO ANOTHER
MEDICAL CONDITION
 markedly diminished interest/pleasure
thought to be related to the direct
physiological effects of another medical
condition
UNSPECIFIED DEPRESSIVE DISORDER
 any depressive disorder that does not
meet the criteria for a specific disorder
CLINICAL MANIFESTATIONS
EMOTIONAL SYMPTOMS
diminished ability to experience pleasure,
loss of interest in usual activities, sadness,
pessimism, crying, hopelessness, anxiety, guilt,
and psychotic features
PHYSICAL SYMPTOMS
fatigue, pain , sleep disturbance,
decreased or increased appetite, loss of sexual
interest, and gastrointestinal (GI) and
cardiovascular complaints.
INTELLECTUAL OR COGNITIVE SYMPTOMS
decreased ability to concentrate or
slowed thinking, poor memory for recent events,
confusion, and indecisiveness
PSYCHOMOTOR DISTURBANCES
psychomotor retardation (slowed
physical movements, thought processes, and
speech) or psychomotor agitation
DIAGNOSIS
 Depressed mood; diminished interest or
pleasure in almost all activities; weight
loss or gain; insomnia or hypersomnia;
psychomotor agitation or retardation'
fatigue or loss of energy; feelings of
worthlessness or excessive guilt;
diminished concentration or
 CLINPHAR
MIDTERM
indecisiveness; recurrent thoughts of patients who have failed at least 4 medication
death, suicidal ideation without specific trials
plan, suicide attempt or a plan for
committing suicide.
 Diagnosis requires a medication review,
physical examination, mental status
examination, a complete blood count wit
differential, thyroid function tests, and
electrolyte dterminations
Depressive symptoms can be secondary to the
following causes:
 Neurological causes such as
cerebrovascular accident, multiple
sclerosis, subdural hematoma, epilepsy,
Parkinson disease, Alzheimer disease
 Endocrinopathies such as diabetes,
thyroid disorders, adrenal disorders
 Metabolic disturbances such as
hypercalcemia, hyponatremia
 Medications/substances of abuse:
steroids, antihypertensives,
anticonvulsants, antibiotics, sedatives,
hypnotics, alcohol, stimulant withdrawal
 Nutritional deficiencies such as vitamin
D, B12, B6 deficiency, iron or folate
deficiency
 Infectious diseases such as HIV and
syphilis
 Malignancies

MANAGEMENT

PSYCHOTHERAPY
first-line therapy for mild to moderately
severe major depressive episode
 Cognitive-behavioral therapy
 Interpersonal therapy
ELECTROCONVULSIVE THERAPY
considered when a rapid response is
needed, risks of other treatments outweigh
potential benefits, there is history of a poor
response to drugs.
 Acute suicidality
 Severe depression during pregnancy
 Refusal to eat/drink
 Catatonia
 Severe psychosis
TRANSCRANIAL MAGNETIC STIMULATION
demonstrated efficacy and does not
require anesthesia as does ECT.
FDA-approved for treatment-
resistant/refractory depression; for patients who
have failed at least one medication trial
VAGUS NERVE STIMULATION
sends regular, mild pulses of electrical
energy to the brain via the vagus nerve, through
a device that is similar to a pacemaker.
FDA-approved as a long-term adjunctive
treatment for treatment-resistant depression; for
CLINPHAR
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CLINPHAR
MIDTERM
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MIDTERM
CLINPHAR
MIDTERM
 SCHIZOPHRENIA
BRIEF DEFINITION
- Schizophrenia is a chronic disorder
with a lifetime prevalence of 1 in 100
people. There are also many
misconceptions about the condition
of schizophrenia that have led to
prejudice against sufferers of illness.
- Schizophrenia is characterized by
delusions, hallucinations,
disorganized thinking and speech,
abnormal motor behavior, and
negative symptoms
- Schizophrenia is a psychiatric illness
that can lead to lifelong effects on a
patient’s functioning.
- It is a persistent heterogeneous
syndrome that includes positive and
negative symptoms.
ETIOLOGY
- Multiple Neurotransmitter and
physiologic mechanisms have been
hypothesized to explain the complex
etiology of schizophrenia
- Many theories on the role aberrant
neurotransmitter systems play in
schizophrenia are derived from the
pharmacologic actions of
medications used to treat the illness
in addition to direct analysis from
biological samples. Findings on
neurologic scans and other
measurements of neuroanatomy are
also not consistent across patients
to allow for these methods to be
reliably employed in making a
diagnosis of schizophrenia.
DEVELOPMENTAL FACTORS
● Supported by neuroimaging studies
that show structural brain
abnormalities in patients with
schizophrenia.
● When migrant cells do not reach
their goal in fetal development and
when supernumerary neural cells
slough off at adolescence.
ENVIRONMENTAL FACTORS
● Social
● Cultural and family environments
● Population density
● Living in an urban environment
● Individual space
● Family dysfunction
● Socio-economic status
● Social isolation
● Racial status
● Substance misuse,
● Childhood trauma
● Prenatal stressors
● Being bullied or abused
GENETIC MODEL
● Higher incidence in the siblings of
people with schizophrenia and those
with a first-degree relative with
schizophrenia
TRANSMITTER ABNORMALITY
MODEL
● D2 receptors, Due to overactivity of
dopamine receptors.
OTHER RISK FACTORS
● Perinatal insult
● Infections
 SCHIZOPHRENIA
● Season of birth ● Age of onset, which typically for
● Viruses schizophrenia is late teenage to 30
● toxins years.
SUMMARY OF PATHOPHYSIOLOGY ● Reports of a childhood which
- Increased ventricular size and indicate the individual did not mix or
decreased gray matter, have been was rather shy and withdrawn
reported personality
- Schizophrenia causation theories ● A poor work record
include genetic predisposition, ● A desire for social isolation
obstetric complications, increased ● Being single and not seeming to
neuronal pruning, immune system have sexual relationships
abnormalities, neurodevelopmental ● A gradual onset of the illness and
disorders, neurodegenerative deterioration from the previous level
theories, dopamine receptor defect, of functioning
and regional brain abnormalities ● Grossly disorganized behavior
including hyper- or hypo activity of OTHER RISK FACTORS
dopaminergic processes in specific ● Perinatal insult
brain regions. ● Infections
- Positive symptoms may be more ● Season of birth
closely associated with dopamine ● Viruses
receptor hyperactivity in the
toxins
mesocaudate, whereas negative and
CLASSIFICATIONS OF SCHIZOPRENIA
cognitive symptoms may be most
Paranoid schizophrenia
closely related to dopamine
Paranoid schizophrenia is dominated by
receptor hypofunction in the
relatively stable, often paranoid delusions,
prefrontal cortex
usually accompanied by hallucinations,
- Glutametergic dysfunction a
particularly of the auditory variety, and
deficiency of glutamatergic activity
perceptual disturbances. Disturbances of
produces symptoms similar to those
affect, volition and speech, and catatonic
of dopaminergic hyperactivity and
symptoms, are either absent or relatively
possibly schizophrenic symptoms
inconspicuous.
- Serotonin abnormalities. Patients
with abnormal brain scans have
Hebephrenic schizophrenia
higher whole blood 5-HT
A form of schizophrenia in which affective
concentrations, which correlate with
changes are prominent, delusions and
increased ventricular size.
hallucinations fleeting and fragmentary,
RISK FACTORS
behaviour irresponsible and
unpredictable, and mannerisms common.
The mood is shallow and inappropriate,
 SCHIZOPHRENIA
thought is disorganized, and speech is
incoherent. There is a tendency to social
isolation. Usually the prognosis is poor
because of the rapid development of
"negative" symptoms, particularly
flattening ofhypoactivityoss of volition.
Hebephrenia should normally be diagnosed
only in adolescents or young adults.
Catatonic schizophrenia
Catatonic schizophrenia is dominated by
prominent psychomotor disturbances that
may alternate between extremes such as
hyperkinesis and stupor, or automatic
obedience and negativism. Constrained
attitudes and postures may be maintained
for long periods. Episodes of violent
excitement may be a striking feature of the
condition. The catatonic phenomena may
be combined with a dream-like (oneiroid)
state with vivid scenic hallucinations.
Post-schizophrenic depression
A depressive episode, which may be
prolonged, arising in the aftermath of a
schizophrenic illness. Some schizophrenic
symptoms, either "positive" or "negative",
must still be present but they no longer
dominate the clinical picture. These
depressive states are associated with an
increased risk of suicide. If the patient no
longer has any schizophrenic symptoms, a
depressive episode should be diagnosed
(F32.-). If schizophrenic symptoms are still
florid and prominent, the diagnosis should
remain that of the appropriate
schizophrenic subtype (F20.0-F20.3).
Residual schizophrenia
A chronic stage in the development of a
schizophrenic illness in which there has
been a clear progression from an early
stage to a later stage characterized by
long- term, though not necessarily
irreversible, "negative" symptoms, e.g.
psychomotor slowing; underactivity;
blunting of affect; passivity and lack of
initiative; poverty of quantity or content of
speech; poor nonverbal communication by
facial expression, eye contact, voice
modulation and posture; poor self-care and
social performance.
Simple schizophrenia
A disorder in which there is an insidious
but progressive development of oddities of
conduct, inability to meet the demands of
society, and decline in total performance.
The characteristic negative features of
residual schizophrenia (e.g. blunting of
affect and loss of volition) develop without
being preceded by any overt psychotic
symptoms.
CLINICAL MANIFESTATION
Symptoms of the acute episode may
include:
● Being out of touch of reality,
halucinations (especially hearing
voices)
● Delusions: fixed false beliefs
● Ideas of influence (actions
controlled by external influences)
● Ambivalence (contradictory
thoughts)
● Flat
● Inappropriate or labile affect
 SCHIZOPHRENIA
● Autism (withdrawn and inwardly
directed thinking)
● Uncooperativeness
● Hostility and verbal or physical
aggression, impaired self-care skills
and disturbed sleep and appetite.
● After the acute psychotic episode PHARMACOLOGICAL MANAGEMENT
has resolved, typically there are
residual features ● Antipsychotics are essential
● Anxiety treatment for most individuals with
● Suspiciousness schizophrenia and are considered
● Lack of motivation first-line pharmacotherapy.
● Poor insight ● Help treat acute symptoms and
● Impaired judgment maintain remission from the illness.
● Social withdrawal ● A patient should be prescribed only
● Difficulty in learning from one antipsychotic at a time.
experience ● Exceptions would include the short
● Poor self-care skills periods of time when changing from
● Positive one antipsychotic to another,
● Negative symptoms because the antipsychotic should
● Cognitive dysfunction not be stopped abruptly, and the
new one is likely to require titration
DIAGNOSIS
to a therapeutic dose. Therefore,
there will be often a period of a few
weeks of crossover.
 SCHIZOPHRENIA
NON-PHARMACOLOGICAL
MANAGEMENT
● Individual or group psychological
therapy
● Family therapy
● Cognitive skills training
● Vocational skills training
● These interventions have increased
patient understanding of their
illness, decreased patient
symptoms and relapse rates and
improved social and occupational
functioning
ALGORITHM
CASE STUDY
SUMMARY OF THE CASE
S:
● Unusual behavior displayed almost
a year ago after returning from
summer break
● Paranoid and agitated
● Constantly looking around the room
and pacing
● Asks to be release “before they find
me”
● No suicidal or homicidal ideation
O:
● 26 year old female college student
● Bruising on the knuckles from
punching the wall
● Complete blood count found to be
normal
● SMA-28 panel normal
● Thyroid function tests normal
● Urine drug screen negative
● No significant contributory findings
● Psychotic episode, most likely due
to schizophrenia.
 SCHIZOPHRENIA
MEDICATION LISTS
Antipsychotics, (SGAs) except clozapine
are first choice agents for schizophrenia.
Most first-generation and
second-generation antipsychotics have
similar efficacy in the treatment of
schizophrenia. The exception is clozapine,
which has greater efficacy than all other
antipsychotics and is therefore indicated
for treatment-resistant schizophrenia. Its
used is hampered by the mandatory
requirement for regular full blood count
checkups.
QUESTIONS
1. What hallmark symptoms of
schizophrenia is Ansel presenting with at
this time? How
might these symptoms be used in
monitoring treatment?
Ansel presents with a number of hallmark
symptoms of schizophrenia. She has:
● Olfactory hallucinations
● Auditory hallucinations
● Delusions
● Magical thinking
● Conceptual disorganization in her
speech
● Agitate
● Uncooperative
These symptoms should begin to decrease
and subside with time as effective
medication treatment is utilized to
determine if she is responding
appropriately.
2. What information from Ansel’s history
also contributes to a diagnosis of
schizophrenia? What is the prognosis for
Ansel?
Although she has no previous psychiatric
treatment, she is in age range for an initial
psychotic epidsode of schizophrines
● Showing increasingly unusual
behavior for 6 months and possibly
according to her roommate
● Prodomal symptoms (difficulty
interacting with peers and isolating
herself)
● Family history of schizophrenia and
alcoholism
Prognosiss is variable because:
● Young age of onset
● Family history of schizophrenia,
● Unstable home environment at a
young age indicate poor prognosis
● Elatively high baseline functioning
and intelligence increase the
chances for a better long-term
outcome.
3. What are your goals of treatment and
management for this patient?
The goal of treatment is to reduce
symptoms of the illness in order to improve
patient functionality and quality of life. Her
safety must be prioritized and would
require hospitalization to both ensure er
safety and effectively treat her symptoms.
4. What nonpharmacologic treatment
would you recommend for Ansel at this
time?
Nonpharmacologic treatment should
center on stress reduction and education
on her illness. When stress is reduced, She
will allow herself to meaningfully engage in
treatment. This will help through both
individual and group therapy sessions. She
will also benefit from medication
 SCHIZOPHRENIA
education, such as from a pharmacist, once
she is more stable in order to understand
her medications and any potential adverse
effects.
5. How should Ansel be best
communicated with by the staff treating
her at this time? What recommendations
would you provide her family and friends
for communicating with her, both
currently and once she is sent home?
● Use methods of communication
such as verbal and nonverbal
communication
● She should be approached with
calmness in attempt to deescalate
the situation
● To talk to Ansel during times when
she is calm and inquire what
methods she would prefer
employed to calm her down when
she becomes agitated
● Her family and friends should have
knowledge about her illness to help
tem understand how to avoid
upsetting her and increase her
symptoms.
● They should interact with her as
normally as they would, but should
be vigilant that her symptoms may
return at any time.
6. Which type of antipsychotic medication
would you recommend for Ansel at this
time? What factors would you use to
select a treatment regimen for her?
Atypical antipsychotics would most likely
be preferable. As she is young and healthy,
selecting atypical antipsycotic with
minimal long-term risks of metabolic
adverse effects, such as weight gain and
glucose irregularities. Pharmaeconomic
considerations should also be taken into
account, as some atypical antipsychotics
are available generically, some are not.
7. What pharmacologic agents should be
considered first to treat Ansel considering
her acute symptoms?
● A combination of both
antipsychotics and adjunctive
agents should be considered at this
time.
● Benzodiazepines may be useful,
especially during periods of
increased agitation.
● Use of adjunctive treatments to
treat any adverse effects such as
EPS may also be needed.
● Depending upon her compliance to
oral medications or during any
periods of increased agitation, IM
injections of medications, including
antipsychotics, benzodiazepines,
and side effects medications may
need to be utilized acutely.
8. What should be considered in choosing
the appropriate antipsychotic agent?
Patient factors such as :
● treatment history
● Medical comorbidities
● target symptoms
● Adherence history
● Personal and family history of
medication response
● concurrent medications
● patient preferences
● potential cost concerns.
 SCHIZOPHRENIA
9. How long should the patient’s treatment Whittlesea, C. & Hodson, K. (2019). Clinical
last? Pharmacy and Therapeutics (6th ed.).
Medications treatment should be Elsevier.
maintained at least 6 months to be
effective in reducing positive symptoms Zeind, C.S. & Carvalho, M.G. (2018).
during the acute phase. Applied Therapeutics: The Clinical Use of
Maintenance antipsychotic treatment Drugs (11th ed.). Wolters Kluwer.
should be continued for at least one year in
all patients recovering from a psychotic
episode.
Lifelong treatment is recommended in
patients who have experienced multiple
episodes of psychosis, at least two
episodes within 5 years, or those who pose
a significant risk to themselves or others
when symptoms are left untreated.

REFERENCES

Dipiro, J.T., Talbert, R.L., Yee, G.C., Matzke,

G.R., Wells, B.G., Posey, L.M.
(2017). Pharmacotherapy: A
Pathophysiologic Approach (10th
ed.).

ICD-10 Version:2016. (n.d.). Retrieved

October 16, 2022, from
https://icd.who.int/browse10/2016/en

Schwinghammer, T.L., Koehler, J.M.,

Borchert, J.S., Slain, D., Park, S.K. (2017).
Pharmacotherapy Casebook: A
Patient-FocusedApproach (10th ed.).
McGraw-Hill.

Wells, B.G., DiPiro, J.T., Schwinghammer,

T.L., DiPiro, C.V. (2015). Pharmacotherapy
Handbook (9th ed.). McGraw-Hill
Education.