PATHOPHYSIOLOGY

OF REPRESENTATIVE
NERVOUS AND
SPECIAL SENSES
DISORDERS
GLAUCOMA
 GLAUCOMA
• Group of ocular disorders that lead to an optic neuropathy
characterized by changes in the optic nerve head (optic disk)
that is assoc. with loss of visual sensitivity and field
 AQUEOUS HUMOR PRODUCTION and
OUTFLOW

• Aqueous humor is formed in the ciliary body and its

epithelium through filtration and secretion
• secreted in to the posterior chamber at a rate of
approximately 2-3 L/min
• Pressure in the posterior chamber produced by the inflow
pushes the aq humor between the iris and lens
• Aqueous humor in the anterior chamber leaves the eye by
two routes
a. .

b. .
 GLAUCOMA

• If drainage of aq humor is blocked, fluid backs up

• Pressure within the eye may increase to dangerous
levels and compress the delicate retina and optic
nerve. The resulting condition, glaucoma
• Can lead to blindness
• Many forms of glaucoma progress slowly and are
asymptomatic at first
 PATHOPHYSIOLOGY of
GLAUCOMA
There are t w o m a j o r t y p e s :
1. .
2. .

• Either can be a primary inherited disorder, congenital or

secondary to disease, trauma or drugs
• Although IOP is a poor predictor of which patients will have
visual field loss, the risk of visual field loss increases with
increasing IOP.
• IOP is not constant. It changes with pulse, blood pressure,
forced expiration or coughing, neck compression and posture.
• IOP demonstrates ____________________
− Minimum pressure around 6pm
− Maximum pressure upon awakening
 CLINICAL PRESENTATION
SIGNS and SYMTOMS

__________________
− used to measure the IOP
which should be tested
yearly in people over 40
 DIAGNOSIS
OPEN-ANGLE GLAUCOMA
− Confirmed by presence of characteristic optic disc changes
and visual field loss, with or without increased IOP
− _______________________: refers to disc changes, visual
field loss, and IOP <21 mmHg
− _______________________: refers to IOP >21 mmHg w/o
disc changes or visual field loss
CLOSED-ANGLE GLAUCOMA
− Visualized by _____________
− IOP is generally elevated when symptoms are present
− (Addt’l signs) hyperemic conjunctiva, cloudy cornea, shallow
anterior chamber, and occasionally edematous and hyperemic
optic disc
TREATMENT
OPEN-ANGLE GLAUCOMA

GOAL OF TREATMENT
-

• Treat ocular htn if px has a significant risk factor such as IOP >
25mmHg.
• Additional risk factors include family hx of glaucoma, black
race & severe myopia
• An initial IOP reduction of 30% is desired in pxs with primary
open-angle glaucoma
• Initiate drug therapy in a stepwise manner
TREATMENT
OPEN-ANGLE GLAUCOMA

• 1.
− eg Timolol
− Tx of choice
• 2.
− eg Latanoprost, Bimatoprost, Travoprost
−Offer OD dosing, better IOP reduction, good tolerance
• 3.
− Also suitable for first-line therapy
• 4.
−Prodrug of Epinephrine
−Used as third-line therapies because of adverse events
TREATMENT
OPEN-ANGLE GLAUCOMA

• 5.
− Used as last-resort options after failure of less toxic
options
• Laser trabeculoplasty or surgical trabeculectomy are
considered after failure of third or fourth-line drug therapy
TREATMENT
CLOSED-ANGLE GLAUCOMA
• Requires rapid reduction in IOP

________________:
definitive tx; a hole in the iris is made to permit aqueous
humor flow to move directly from the posterior to anterior
chamber
ACUTE ATTACKS:
usually treated w/ an osmotic agent and secretory inhibitor
(eg Beta-blocker, 𝑎2 -agonist, Latanoprost, or CAI) w/ or w/o
Pilocarpine
OSMOTIC AGENTS: to rapidly decrease IOP
1. ___________  1-2 g/kg po
2. ___________  1-2 g/kg IV
 EVALUATION OF THERAPEUTIC
OUTCOMES OF GLAUCOMA TREATMENT

• (For open-angle glaucoma)

Assess IOP response every 4 – 6 weeks initially, every 3-4
months after IOPs become acceptable
• Visual field and disc changes are monitored annually
 MAJOR
DEPRESSIVE
DISORDER
MAJORPATHOPHYSIOLOGY
DEPRESSIVE DISORDER

1.
− Decreased brain levels of the neurotransmitter NE, 5-HT and
DA may cause depression
2.
− Desensitization or downregulation of NE or 5 − HT1a receptors
may relate to onset of antidepressant effects
3.
− 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.
MAJORPATHOPHYSIOLOGY
DEPRESSIVE DISORDER
4.
− This theory suggests that 5-HT and NE activities are linked, and
that both the serotonergic and noradrenergic systems are
involved in the antidepressant response
THE ROLE OF DOPAMINE
− Some studies suggest that increased DA activity in the
mesolimbic pathway contributes to antidepressant activity
DISRUPTION OF BRAIN DERIVED NEUTROPHIC FACTOR
EXPRESSION IN THE HIPPOCAMPUS
− Brain derived neurotrophic factor (BDNF) is a growth factor
protein that regulates the differentiation and survival of
neurons.
MAJOR DEPRESSIVE DISORDER
CLINICAL PRESENTATION
EMOTIONAL
SYMPTOMS
Diminished ability to experience
pleasure, loss of interest in usual
activities, sadness, pessimism,
crying, hopelessness, anxiety, guilt,
psychotic features (auditory
hallucinations and depression
COGNITIVE
SYMPTOMS
Decreased ability to concentrate or
slowed thinking, poor memory for
recent events, confusion and
indecisiveness
PHYSICAL
SYMPTOMS
Fatigue, pain (esp HA), sleep
disturbance, decreased or
increased appetite, loss of sexual
interest, GI and CV complaints (esp
palpitations)
P S YC H O M O TO R
DISTURBANCES
Psychomotor retardation (slowed
physical movements, thought
processes and speech) or
psychomotor agitation
MAJOR DEPRESSIVE
DIAGNOSIS DISORDER
• Major depressive disorder is characterized by one or more
major depressive episodes
• __________________________________ must have been
present nearly every day during the same 2-week period and
cause significant distress or impairment
• The depressive episode must not be attributable to
physiological effects of a substance or medical condition.
• No hx of manic-like or hypomanic-like episodes unless
induced by a substance or medical condition
• Diagnosis requires a medication review, PE, MSE, CBC w/
differential, thyroid function tests, and electrolyte
determinations
MAJOR DEPRESSIVE
TREATMENT DISORDER
GOALS OF TX
− To reduce symptoms of depression, minimize AE, ensure adherence
to the prescribed regimen, facilitate return to premorbid functioning
and prevent further depressive episodes

1. Non-pharmacologic Treatment
• ___________________: first-line for mild to moderately severe
major depressive therapy; The efficacy of psychotherapy and
antidepressants is considered to be additive.
• _____________________________: safe and effective tx for
major depressive disorder; considered when a rapid response is
needed, there is a hx of poor response to drugs; w/ rapid
therapeutic response (10-14 days)
• _____________________________________ has demonstrated
efficacy and does not require anesthesia as does ECT
MAJOR DEPRESSIVE
TREATMENT DISORDER
2. Pharmacologic Treatment
• In general, antidepressants are equal in efficacy in groups of pxs
when administered in comparable doses
• A _________________ of an antidepressant at maximum
dosage is considered an adequate trial of that medication.
• The _____________ of treatment lasts 6 to 12 weeks, and the
goal is remission (ie, absence of symptoms). The
_______________________ (4–9 months after remission) seeks
to eliminate residual symptoms or prevent relapse. The
_______________________ (12–36 months or more) has a goal
to prevent recurrence of a new episode of depression.
MAJOR DEPRESSIVE
TREATMENT DISORDER
1.
− Inhibit reuptake of 5-HT into the presynaptic neuron
− Gen. chosen as first-line tx
2.
− In addition to inhibiting the reuptake of NE and 5-HT, they have an
affinity for adrenergic, cholinergic, and histaminergic receptors
3.
− Phenelzine and Tranylcypromine:
 Both are nonselective inhib of MAO-A and MAO-B
 Can inc the conc of NE, 5-HT and DA through the inhib of MAO
− Selegiline:
 As transdermal patch
 Inhib MAO-A and MAO-B in the brain but has reduced effect on
MAO-A in the gut
MAJOR DEPRESSIVE
TREATMENT DISORDER
4.
− Trazodone and Nefazodone
 Antagonize the 5-HT2 receptor and inhibit the reuptake of 5-HT
 Nefazodone- w/ black box warning for liver failure
5.
− Bupropion
 Blocks the reuptake of DA, and to a lesser extent NE
6.
− Venlafaxine, Desvenlafaxine and Duloxetine
MAJOR DEPRESSIVE
TREATMENT DISORDER

• Vilazodone (SSRI) inhibits 5-HT reuptake

• Mirtazapine (TCA) antagonizes 5-HT2 and 5-HT3 receptors
and blocks histamine receptors
• St. John’s wort, an herbal medication containing hypericum,
may be effective for mild to moderate depression.
 BIPOLAR DISORDER

• ____________________ at least one manic episode, w/c have

been preceded by and may be followed by hypomanic or major
depressive episodes
• ____________________  at least one hypomanic episode and a
current or past major depressive episode
Case No. 1
BIPOLAR DISORDER
CLINICAL PRESENTATIONS
Many theories have been proposed for the pathophysiology os
disease:

GENETIC FACTORS
First-degree relatives of bipolar patients have a 15-35% lifetime risk
of developing any mood disorder and a 5-10% lifetime risk for
developing bipolar disorder.
ENVIRONMENTAL FACTORS
Desynchronization of circadian or seasonal rhythms cause diurnal
variations in mood and sleep patterns and results in seasonal
recurrences of mood episodes.
PSYCHOSOCIAL OR PHYSICAL STRESSORS
Stressful life events often precede mood disorders and can increase
recurrence rates and prolong time to recovery from mood
disorders.
BIPOLAR DISORDER
CLINICAL PRESENTATIONS
NUTRITIONAL FACTORS
− Deficiency of essential amino acid precursors in the diet can cause
a dysregulation of neurotransmitter activity
− Deficiency in essential fatty acid (eg omega 3) can cause a
dysregulation of neurotransmitter activity
NEUROTRANSMITTER/NEUROENDOCRINE HORMONAL THEORIES
− Dysregulation between excitatory and inhibitory systems
− Excitatory: NE,DA, glutamate, aspartate
− Inhibitory: 5-HT and GABA
MONOAMINE HYPOTHESIS
− An excess of catecholamines (_________________) cause mania
− Agents that dec. catecholamines are used for the tx of mania
− Deficit of neurotransmitters (primarily NE, DA and/or 5-HT) cause
depression
BIPOLAR DISORDER
CLINICAL PRESENTATIONS
• Essential feature is a history of mania or hypomania that is not
caused by any other medical condition, substance, or psychiatric
disorder.
• Bipolar disorder is a cyclic mood disorder in which patients can
move from one episode to another with or without a period of
normal mood (euthymia) between.
• Four subtypes (based on identification of specific mood episodes):
1. .
2. .
3. .
4. .
BIPOLAR DISORDER
CLINICAL PRESENTATIONS
• The mood states are further separated into 4 subcategories
to differentiate the current or most recent mood episode:
1. Major depressive
2. Manic
3. Hypomanic
4. Mixed
BIPOLAR DISORDER
CLINICAL PRESENTATIONS
_______________________________________
• Bipolar disorder is often misdiagnosed as major depressive
disorder
• Compared to manic episodes, MDE are more frequent, longer
lasting and occur more often in Bipolar II than Bipolar I
• Recurrent depressive episodes are more common in women than
men
• Inc suicide risk, mood lability, hypersomnia, low energy,
psychomotor retardation, cognitive impairment,
anhedonia, slowed speech, wt gain
• Delusions, hallucinations and suicide attempts are
more common in bipolar depression than in
unipolar depression
BIPOLAR DISORDER
CLINICAL PRESENTATIONS
_____________________
• Symptoms must last at least 1 week, mood be elevated (expansive
or irritable), there must be an impairment in functioning
• Common symptoms:
.
.
.
.
BIPOLAR DISORDER
CLINICAL PRESENTATIONS
MANIC EPISODE
• Often mistaken with schizophrenia
Bizarre behavior
Hallucinations
Paranoid delusions
• What can trigger a manic episode?
Seasonal changes
Stressors
Sleep deprivation
Antidepressants
CNS stimulants
Bright light
BIPOLAR DISORDER
CLINICAL PRESENTATIONS

_________________________
• No marked impairment in social or occupational functioning,
(-) delusions, (-) hallucinations
• May rapidly switch to a manic episode
BIPOLAR DISORDER
GOALS of TREATMENT
BIPOLAR DISORDER
GOALS of TREATMENT
BIPOLAR DISORDER
GOALS of TREATMENT

• Bipolar patients should remain on a mood stabilizer (eg, lithium,

valproate, carbamazepine) lifelong. During acute episodes,
medications can be added and then tapered after stabilization.

NONPHARMACOLOGIC THERAPY
1. Psychotherapy, interpersonal therapy, and/or cognitive
behavioral therapy
2. Stress reduction techniques
3. Sleep (reg bedtime and awake schedule)
4. Nutrition
5. Exercise
BIPOLAR DISORDER
GOALS of TREATMENT

PHARMACOLOGIC THERAPY
BIPOLAR DISORDER
TREATMENT

PHARMACOLOGIC THERAPY
BIPOLAR DISORDER
TREATMENT
.
• First-line agent for acute mania, acute bipolar depression and
maintenance tx of Bipolar I and II disorders
• May require 6-8 weeks to show antidepressant efficacy

ANTICONVULSANTS
1. _____________________________
• Approved for acute manic or mixed episodes
• Reduces the frequency of recurrent manic, depressive, and mixed
episodes
• Lithium, Carbamazepine, antipsychotics, or benzodiazepines can
augment the antimanic effects of valproate
• Frequent dose-related SE of Valproate  GI complaints, fine
tremor and sedation
- reducing the dose or adding a B-blocker may alleviate
tremors
BIPOLAR DISORDER
TREATMENT
ANTICONVULSANTS
2. __________________
• Commonly used for acute and maintenance therapy
• Usually reserved for lithium-refractory patients, rapid cyclers, or
mixed states
• (+) lithium, valproate or antipsychotics  used for manic
episodes in tx-resistant pxs
• (+) Nimodipine  beneficial for refractory pxs
• Can inc hepatic metabolism of oral contraceptives  need higher
doses of oral contraceptives or alt contraceptive methods
3. _________________
• w/ mood-stabilizing effects similar to carbamazepines but w/
milder SE
BIPOLAR DISORDER
TREATMENT
ANTICONVULSANTS
4. _________________
• Effective for maintenance tx of Bipolar I & II in adults
• With both antidepressant & mood-stabilizing effects
• It seems most effective for prevention of bipolar depression
• The incidence of rash is greatest with concomitant
administration of valproate, rapid dose escalation of
lamotrigine, and higher than recommended lamotrigine
initial doses.
BIPOLAR DISORDER
TREATMENT
A N T I P S YC H O T I C S
− (First and second-gen antipsychotics)

 effective as monotherapy or as add-on therapy to lithium or

valproate for acute mania
A LT E R N AT I V E M E D I C AT I O N T X
− High-potency benzodiazepines (________________________)
as alt to antipsychotics
− IM Lorazepam  may be used for acute agitation
PARKINSON’S
DISEASE
 PARKINSON’S
PATHOPHYSIOLOGY
• Two hallmark features in the substantia nigra pars compacta:
1. .
2. .
• The degree of nigrostriatal dopamine loss correlates
positively with severity of motor symptoms.
 PARKINSON’S
CLINICAL PRESENTATION
• Relatively asymptomatic until profound depletion (70-80%)
of substantia nigra parts compacta neurons has occurred
• Initial symptoms may be sensory  more classic features

• RESTING TREMOR
−Often the sole presenting complaint
−Tremor is present most commonly in the hands, often
begins unilaterally, and sometimes has a characteristic
“pill-rolling” quality. Resting tremor is usually abolished
by volitional movement and is absent during sleep.
• MUSCULAR RIGIDITY
−Inc muscular resistance to a passive range of motion
 PARKINSON’S
DIAGNOSIS
• Upon presence of bradykinesia (+ resting tremor and/or
rigidity)
• Other symptoms may include: decreased dexterity, difficulty
arising from a chair, postural instability, festinating gait,
dysarthria, difficulty swallowing, reduced facial expression,
freezing at initiation of movement, hypophonia,
micrographia, bladder disturbances, constipation, blood
pressure changes, dementia, anxiety, depression, sleepiness,
insomnia, obstructive sleep apnea.
 PARKINSON’S
TREATMENT

GOALS OF TREATMENT
−To minimize symptoms, disability and SE while maintaining
quality of life

GENERAL APPROACH
−Monotherapy usually begins with a ___________________
−If motor fluctuations develop, consider adding COMT
inhibitor to extend L-dopa duration of activity
 PARKINSON’S
TREATMENT

1.
−Can improve tremor and sometimes, dystonic features in
some px
−SE: dry mouth, blurred vision, constipation and urinary
retention
2.
−Provides modest benefit for tremor, rigidity, and
bradykinesia; may also decrease dyskinesia
3.
−L-dopa: precursor of dopamine; most effective drug
available