MINI-EXAM

#6 REVIEW

Review

ANS & Emotions

Cortex via Limbic

System to
Hypothalamus
to ANS

The cingulate, septal,

orbitofrontal, sensory and
medial prefrontal cortical
regions have major inputs
to the hypothalamus.
The insula connects with
the hypothalamus and
brainstem ANS centers.

(NT
S)

You have no conscious

control over ANS response
to emotions.
Centers in the
brainstem reticular
formation and the
NTS help coordinate
the activities of the
ANS. These brainstem
areas receive afferents
from the hypothalamus

The Dorsal Longitudinal Fasciculus (DLF) is the major pathway

connecting the hypothalamus with the ANS. The hypothalamus
controls the ANS; it is the head ganglion.

Brainstem lesions can disrupt spinal ANS.

THE ADRENALIN
RUSH.
The adrenal medulla,
acting via the release
of adrenaline into the
blood stream, spread
the effects of
generalized
sympathetic activity to
all cells of the body.
Blood shunted from GI
system and skin to CNS
and skeletal mm.
Release of glucose;
increased heart rate &
contractility; increased

REGULATION OF
BLOOD PRESSURE
Blood pressure is
constantly monitored
through input from the
baroreceptors in the
carotid sinus and aortic
arch
Orthostatic hypotension,
an acute decrease in
blood pressure when
suddenly assuming an
upright position
indicates an interruption
of the baroreceptor

CONTROL OF BLADDER FUNCTION

MICTURITION
Descending control fibers= CENTERS
Onufs nucleus
Cortex: Sup. frontal
gyrus
Brainstem: Pons
= Somatic
(Barringtons nucl.)

S2-4

Somatic

_
PSNS

SNS via pelvic plexus.

(Presyn. neurons in L1,2)

SNS is tonically
inhibiting the
PSNS from
initiating
detrusor
contraction &
tonically
constricts the
internal
urethral
sphincter.

How can SNS cause both smooth m. contraction and relaxation?

BLADDER FUNCTION: LESIONS

The level of CNS injury
determines bladder function.

Note: an uninhibited
bladder is a result of injury
to the CNS above the pons
that disrupts higher CNS
pathways to the pons. An
infantile bladder.

No afferent or efferent
information to or from
bladder.

Pathway from pontine

storage area disrupted.
Bladder walls contract
upon minimal stretch.
No control over external.
urethral sphincter.

SPINAL CORD INURY ALTERS BLADDER FUNCTION

Damage to the PSNS will result in problems with voiding the bladder. If
the damage is above spinal segments S2-4 a REFLEX (old term =
spastic) neurogenic bladder will result. There are two types of reflexive
bladder: uninhibited and automatic.
With the uninhibited reflex bladder, the lesion lies above the
level of the pons. Since the pontine storage and micturition centers are
intact (but voluntary control over these centers are lost) the bladder
completely empties whenever it gets full - just like in an infant.
With an automatic reflexive bladder, the damage is below the
pontine storage and micturition centers, but above S2-4. In this
condition, the bladder wall contracts with just minor pressure
(generated by the presence of urine) within the bladder. Since the
voluntary control over the external urethral sphincter is lost, the
bladder has frequent involuntary voiding which never completely
empties the bladder.
If the spinal cord is damaged at S2-4, or if the cauda equina is
lesioned, a NON-REFLEX (old term = flaccid) neurogenic bladder will
result. In this case, there are no visceral sensory fibers from the
bladder stretch reflex entering the S2-4 spinal segments and the

HORNER SYNDROME
Disruption of SNS to the
head can occur in spinal
cord lesions above T1,
ventral root lesions of
spinal nn. T1-3, trauma
anywhere along cervical &
upper thoracic
sympathetic chain, trauma
to internal carotid n. or the
internal carotid a. (after
the n. joins it), as well as
disruption of descending
inputs from the
hypothalamus to the
brainstem or cervical
spinal cord.

Hirschprungs disease
Also called congenital aganglionic megacolon
Extreme dilation and hypertrophy of the colon,
with fecal retention
Absence of ganglion cells in the myenteric
plexus (neural crest cells fail to migrate into the
colon)

Familial dysautonomia (Riley-Day syndrome)

Autosomal recessive disorder characterized by
abnormal sweating, unstable blood pressure,
difficulty in feeding (inadequate muscle tone in
the GIT), and progressive sensory loss
Loss of neurons in autonomic and sensory
ganglia
Predominantly affects Jewish children
To determine whether or not a patient has an
intact sympathetic innervation, a small skin
sample is surgically removed and prepared for
immunostaining with antibodies against
NEUROPEPTIDE Y released by many
sympathetic postganglionic fibers, including
those that innervate blood vessels of the skin
Generally, sympathetic ganglion cells use
norepinephrine, rather than epinephrine, as a

Raynaud syndrome
Painful disorder of the terminal arteries of the
extremities
Characterized by idiopathic bilateral cyanosis of
the digits, due to arterial and arteriolar
constriction caused by emotion or cold
Treatment: Preganglionic sympathectomy

Shy-Drager syndrome
Involves preganglionic sympathetic neuron
Now considered as an entity of MULTIPLE SYSTEM
ATROPHY (MSA)
MSA: group of disorders characterized by the presence
of glial cytoplasmic inclusions (GCIs), typically within
the cytoplasm of oligodendrocytes
Three clinicopathologic entities of MSA include:
Striatonigral degeneration,
Shy-Drager syndrome, and
Olivopontocerebellar atrophy
Two principal symptoms - parkinsonism and autonomic
dysfunction, particularly orthostatic hypotension
When these are present in relative isolation, the
syndromes may be referred to as striatonigral
degeneration and Shy-Drager syndrome,
Characterized by orthostatic hypotension, anhidrosis,
impotence and bladder atonicity

Primary brain tumors.

Meninges: meningioma
Glia Astrocytes - astrocytoma
Oligodendrocytes - oligodendroglioma
Ependyma ependymoma, choroid plexus
papilloma, colloid cyst (Ventricles).

Primitive cells: blastoma e.g.

neuroblastoma.
Neuronal * : ganglioglioma, gangliocytoma
Nerve sheath: schwannoma, neurofibroma
Pituitary: adenoma, craniopharyngioma
Vascular & Bone tumors:

Clinical features:
Raised Intracranial Pressure.
Headache, vomiting, slow pulse,
papilledema.

Local damage:
Nerve & tract deficits, Paralysis,
seizures etc.

Meningiomas
Predominantly benign tumors of
adults, usually attached to the dura

Arise from the meningothelial cell of

the arachnoid

Meningioma:

Common sites: parasagittal (falx), sphenoid

ridge, olfactory groove
Females common (2:1)

Well demarcated Compression - No

Invasion

Microscopic: whorls and psammoma bodies

Hyperostosis over the tumor.

Slow growth, well differentiated, no spread

(Benign).

Histologic patterns
Syncytial - whorled clusters of cells
that sit in tight groups without visible
cell membranes;
fibroblastic, with elongated cells and
abundant collagen deposition between
them
whorled pattern of cell growth and
psammoma bodies

At medium power, this meningioma is composed of

whorled nests of cells. A variety of patterns are
possible.

Psammoma bodies

Astrocytoma

Astrocytoma Commonest tumors

of adults. (80%)
Well differentiated, slow growing.
Benign - but malignant behavior.
Infiltrative, poor demarcation
Glioblastoma Multiforme Malignant form of Astrocytoma.

Astrocytoma
s
Adults:
Supratentorial (Cerebrum),
Solid, Malignant, Fibrillary

Children:
Infratentorial (Cerebellum),
Cystic, Benign, Pilocytic

Fibrillary astrocytomas
Grossly solid
Common in cerebral hemispheres
Low grade in young, higher grade
in older
Grading
Diffuse astrocytoma (low grade)
Anaplastic astocytoma
Glioblastoma multiforme (high
grade)

Glioma:

Glioblastoma Multiforme foci of necrosis with

pseudopalisading of malignant nuclei

Fibrillary astrocytoma: microscopic

Low grade- hypercellularity,

pleomorphism
Anaplastic- as above plus mitosis,
vascular endothelial proliferation
Glioblastoma multiforme- as above
plus necrosis and pseudopalisades.
Grossly variegated appearance
(multiforme)

Glioblastoma
Necrosis in serpentine pattern occurs in areas of hypercellularity with
highly malignant tumor cells crowded
along the edges of the necrotic
regions,
Producing a histologic pattern
pseudopalisading

Glioblastoma
Vascular cell proliferation is characterized
by tufts of piled-up vascular cells that
bulge into the vascular lumen;
The minimal criterion is a double layer of
endothelial cells.
When vascular cell proliferation is
extreme, the tuft forms a ball-like
structure, the glomeruloid body

Pilocytic astrocytoma
Common in childhood
Most slow growing of the gliomas
Most childhood brain tumors arise below
the tentorium, which is the reverse of the
adult.
Sites: cerebellum, around III V., optic nerve
Grossly cystic with mural nodule
Microscopic
elongated hair-like (pilo) elongated cells
Rosenthal fibers

Pilocytic astrocytoma - bipolar cells with long, thin

"hairlike" processes that are GFAP-positive; Rosenthal
fibers, eosinophilic granular bodies, and microcysts are
often present

Oligodendroglioma
The lesions are found mostly in the cerebral
hemispheres, with a predilection for white matter.
Frontal lobe mass with areas of calcification.
Personality changes
Does not appear to take an interest in his work,
forgetful.
On physical examination - frontal release signs
and memory loss

Tumors are composed of sheets of regular cells with spherical

nuclei containing finely granular chromatin (similar to normal
oligodendrocytes) surrounded by a clear halo of cytoplasm

Ependymoma
Arise next to the ependyma-lined ventricular
system
occur near the fourth ventricle
Enlargement of the lateral ventricles with a
homogenous, well-circumscribed mass within the
fourth ventricle.
The mass effect can produce an obstructive
hydrocephalus.
The headaches are associated with dull pain and
seem diffuse, in time will become more frequent
and prolonged.

The microscopic appearance of an ependymoma reveals a rosette

pattern with the cells arranged about a central vascular space. It is
histologically benign. (Perivascular pseudorosettes)

Medulloblastoma
Highly malignant cerebellar tumor.
(primitive neuroectodermal tumor)
Can compress 4th ventricle, causing
hydrocephalus
Dissemination through the CSF is a
common complication,
Presenting as nodular masses elsewhere in
the CNS,
metastases to the cauda equina that are
sometimes termed "drop" metastases
because of their direct route of
dissemination through the CSF.

Neurofibroma
Benign soft, fleshy papule, nodule, or tumor
that is a proliferation of neural tissue within
the dermal layer of the skin.

Usually arise during childhood or early

adulthood from proliferation of Schwann cells.
They invaginate into the skin with pressure.
Solitary neurofibromas do not have much
clinical significance.

Multiple neurofibromas
Multiple neurofibromas may be associated
with neurofibromatosis (NF-1), a systemic
disorder affecting many organs and
increasing risk of other benign and malignant
neural tumors.

Microscopically, the neurofibroma is a poorly

circumscribed dermal proliferation of small
delicate, wavy Schwann cells with a few
scattered nerve fibers in the lesion.

Schwannoma
Well-circumscribed
Encapsulated masses
that are attached to the
nerve but can be
separated from it
Firm, gray masses
Discrete firm neoplasm
was removed from the
surface of a peripheral
nerve

The mass lesion here is arising in the acoustic

(eighth cranial) nerve at the cerebellopontine angle.
This is a schwannoma. Patients may present with
hearing loss.

Peripheral nerve tumors

Schwannoma
Schwann cells
Compress the nerve trunk
Encapsulated
Easily resectable without nerve
damage
Microscopic:
Antony A and B fibers
Verocay bodies

Neurofibroma
Schwann cells, neurites,
fibroblasts
Fusiform and involves nerve trunk
Not encapsulated
Not resectable without sacrificing
nerve
Micro- Intermingled cells with
wavy nuclei

Neurofibromatosis - Von Recklinghausen

Dominant inheritance
Multiple neurofibromas
extremities.

involving the skin of trunk and

Central - CNS
peripheral nerves

Increased incidence of:

meningioma
glioma
schwannoma - bilateral VIII N.
pheochromocytomas

Cafe-au-lait (melanosis) in skin

Elephantiasis: increased connective tissue

Neurofibromatosis:

Type I (common):(AD, 17q, 1:3000)

Plexiform & solitary neurofibromas
Optic nerve gliomas, Lisch nodules,
Caf au lait spots.

Type II (rare):(22q, 1:40,000)

Bilateral acoustic schwannoma/osis
Multiple meningioma/osis,
ependymoma of spinal cord

NF
The NF1 gene, located at 17q11.2,
has been identified and encodes a
protein termed neurofibromin

The NF2 gene is located on

chromosome 22q12, and the gene
product, merlin

Tuberous Sclerosis

1. Dominant inheritance
2. Clinical triad:
seizures
mental retardation
adenoma sebaceum
3. Retinal hamartoma (phakoma)
4. Tubers (hamartomas) in cerebral cortex
5. Subependymal giant cell astrocytoma
6. Hamartomas in other organs: heart, kidney

Skin lesions are common in tuberous sclerosis

"Ash leaves" - white lesions lacking normal skin
color that have the shape or appearance of an ash
leaf and may appear anywhere on the body.
Shagreen patches: These appear on the lower back
as raised patches of skin with an orange-peel
texture.
Adenoma sebaceum (angiofibroma): red, highly
vascular (containing many blood vessels) lumps on
the face that may resemble irritated acne. These
enlarge with age and may run together (become
confluent) to form larger patches

Tuberous Sclerosis
The more commonly mutated
tuberous sclerosis locus (TSC2) is
found on chromosome 16p13.3 and
encodes a protein (tuberin)

Von Hippel-Lindau
Disease
An autosomal-dominant disease in
which affected individuals develop
tumors (capillary hemangioblastomas)
within the cerebellar hemispheres, the
retina, and, less commonly, the
brainstem and spinal cord.

Cysts involving the pancreas, liver, and

kidneys and have a propensity to
develop renal cell carcinoma of the

Gene for von Hippel-Lindau

disease
A tumor-suppressor gene, is located
on chromosome 3p25-26 and
encodes a protein (pVHL)
One of the targets of the complex
containing pVHL is hypoxia-induced
factor 1 (HIF-1), a transcription factor
involved in regulation of expression
of VEGF

Sturge-Weber syndrome
(also called encephalotrigeminal angiomatosis)

A rare congenital disorder associated with venous

angiomatous masses in the cortical leptomeninges and
ipsilateral facial port wine nevi;

Mental retardation, seizures, hemiplegia, and skull radio

opacities also occur.

Thus, a large facial vascular malformation in a child with

mental deficiency may indicate the presence of more
extensive vascular malformations

Glaucoma: sites of action

1

Site of action of miotics in angle

closure glaucoma: contraction of
sphincter pupillae removes pupillary
block and removes the obliteration of
iridocorneal angle
Site of action of miotics in open angle
glaucoma: contraction of ciliary muscle
pulls on scleral spur and improves
trabecular patency
Site of action of (a) blockers (b) 1
agonists (c) 2 agonists (d) carbonic
anhydrase inhibitors: all reduce aqueous
secretion by acting on ciliary body
Site of action of prostaglandins and
possibly adrenaline: increase
uveoscleral outflow by altering
permeability and/or pressure gradients
Site of action of adrenaline: possibly
increases aqueous conductivity of
trabecular filtering cells (2 action)

Trabecular
outflow

Sphincter
pupillae
Uveosclera
l outflow

Glaucoma
GLAUCOMA:
If the normal aqueous humor flow
through the scleral venous sinuses is
blocked, pressure builds up in the
anterior and posterior chambers of the
eye compressing the retina and the
retinal arteries resulting in blindness, a
condition called GLAUCOMA
Open/wide angle glaucoma: Primary
cause is unknown. Seen in elderly.
Secondary causes include uveitis, trauma,
corticosteroids and vasoproliferative
retinopathly that can obstruct or decrease
the flow of aqueous humor. Peripheral
vision lost first. Painless loss of vision.
Optic disc atrophy with cupping on
fundoscopy.

Closed/narrow angle glaucoma:

Primary cause is unknown. Increased IOP
pushes the iris forward narrowing the

Openangle
glauco
ma

Closedangle
glauco
ma

Glaucoma drugs
Drugs for open/wide angle glaucoma:
Prostaglandin analogues:
Drugs: Latanoprost, bimatoprost, travoprost
Most frequently used antiglaucoma medicines
Increasing uveoscleral outflow, possibly by
increasing permeability of tissues in ciliary muscle or
by an action on episcleral vessels
Blurring of vision, increased iris pigmentation
(browning), thickening and darkening of eyelashes
Carbonic anydrase inhibitors:
Drugs: acetazolamide
Limits generation of bicarbonate ion in the ciliary
epithelium
No pupillary or vision changes

Glaucoma drugs
Drugs for open/wide angle glaucoma:
Cholinomimietics:
Drugs: Direct (Pilocarpine, carbachol); Indirect
(Physostigmine, echothiphate)
Increased outflow of aqueous humor via contraction
of ciliary muscle and opening of trabecular
meshwork
Miosis (contraction of sphincter pupillae) and
cyclospasm (contraction of ciliary muscle)
Pilocarpine in emergencies is very effective in
opening the meshwork into the canal of Sclemm
Drugs for closed/narrow angle glaucoma:
Drugs: acetazolamide, miotics, topical blocker and
aproclonidine
Drugs are used only to terminate the attack. But
surgical or laser iridotomy is the definitive treatment

Antiparkinsonian dugs
ANTIPARKINOSNIAN DRUGS CLASSIFICATION:
I. Drugs affecting brain dopaminergic system
(a) Dopamine precursor : Levodopa (1-dopa)
(b) Peripheral decarboxylase inhibitors : Carbidopa,
Benserazide.
(c) Dopaminergic agonists: Bromocriptine,
Ropinirole, Pramipexole
(d) MAO-B inhibitor: Selegiline
(e) COMT inhibitors: Entacapone, Tolcapone
(f) Dopamine facilitator: Amantadine.
II . Drugs affecting brain cholinergic system
(a) Central anticholinergics: Trihexyphenidyl
(Benzhexol), Procyclidine, Biperiden.
(b) Antihistaminics :Orphenadrine, Promethazine.

Drug Therapy
Dopamine and Tyrosine are not used for PD therapy
Dopamine doesn't cross the blood brain barrier.
Huge amount of tyrosine shuts off rate limiting
enzyme tyrosine hydroxylase that normally converts
tyrosine to dopamine

L-dopa therapy for PD

Pharmacokinetics
Levodopa is absorbed from the duodenum by the
same process that absorbs neutral amino acids.
Dietary amino acids compete with levodopa and can
reduce the drug's absorption and transport into the
brain.
Levodopa is metabolized by two pathways. It is
converted to dopamine by L-aromatic amino acid
decarboxylase (LAAD), and it is metabolized to 3-Omethyldopa (3OMD) by catecholO-methyltransferase
(COMT).

Effects of L Dopa on Cardiovascular System

The cardiovascular effects are cardiac stimulation due to
beta adrenergic effect on heart
tolerance to this effect in several weeks
treat with propranolol to block cardiac stimulation
effects
Must be careful in treatment of elderly, as most will have
underlying cardiovascular problems, can cause transient
tachycardia, cardiac arrhythmias and hypertension
In some individuals, l dopa produces orthostatic
hypotension
tolerance will develop within few weeks

Side Effects of L Dopa

Some are irreversible and dose dependent
Early in therapy, 80% of patients have nausea and vomiting
due to chemoreceptor trigger zone stimulation
30% of patients have orthostatic hypotension; so carefully
regulate dose
Cardiac arrhythmia from stimulation of adrenergic receptors in
heart adjust dose for people with cardiac problems
50% of patients have abnormal involuntary movements; ie.
grimacing of face and tongue movements; slow writhing type
of movements (not jerky movements) in arm and face
this is due to high dose of dopa (peak dose dyskinesias)
and occurs early in therapy at 2 to 4 weeks
best way to handle is by reducing dose

Drug Interactions with L Dopa

Antipsychotic drugs - antipsychotic drugs block
dopamine receptor
Reserpine -reserpine depletes dopamine storage
Nonspecific MAO inhibitors - nonspecific MAO inhibitors
interfere with l dopa breakdown and exaggerate the CNS
(central) effects
The nonspecific MAO inhibitors can precipitate
hypertensive crisis
Anticholinergics - anticholinergics are used
synergistically with l dopa as an antiparkinson agent, but
anticholinergics act to decrease l dopa absorption since
they have an effect on gastric emptying time.

Monoamine oxidase inhibitors

Selegiline for Treating Parkinson Disease
Selectively Inhibits Monoamine Oxidase B Which Metabolizes
Dopamine, but Does Not Inhibit MAO-A Which Metabolizes
Norepinephrine and Serotonin

Provides symptomatic benefit and/or slows

progression of the disease.
Of limited value in advanced disease

Rasagiline another MAO-B inhibitor is more potent than selegiline

Catechol-O-methyltransferase (COMT)
inhibitors
Tolcapone and Entacapone are two well-studied COMT
inhibitors.
Increases the duration of effect of levodopa dose
Can increase peak levels of levodopa
Should be taken with carbidopa/levodopa (not effective
used alone)
Can be most beneficial in treating "wearing off"
responses
Can reduce carbidopa/levodopa dose by 20-30%
Associated with severe hepatotoxicity , so hepatic
enzyme estimation has to be performed during therapy.

Treatments of PD
The belladonna alkaloids have been replaced by
anticholinergic agents with more selective central
nervous system effect.
These include trihexyphenidyl, benztropine mesylate,
biperiden, & procyclidine
Used in early stages of the disease as an adjuvant to Ldopa
They are the only drugs that can provide benefit in the
treatment of the drug induced parkinsonism seen with
antipsychotic drugs.

Amantadine
An antiviral drug, moderately effective in treating
symptoms of parkinsonism.
Mechanism unclear, but might be affecting dopamine
release and uptake.
Antagonism at NMDA receptors might be involved.
Used in early stages as a adjuvant.
N/V, dizziness, insomnia, confusion, hallucinations, ankle
edema and livedo reticularis (reddish blue mottling of the
skin and edema) are common adverse reactions.

Alzheimers disease: Memantine

Memantine: the new NMDA receptor antagonist, related

to amantadine.
Found to slow the functional decline in moderate-tosevere Alzheimers disease (AD); may not help in mild
AD
block excitotoxicity of the transmitter glutamate in a
noncompetitive and use-dependent manner.
Adverse effects include constipation, tiredness,
headache and drowsiness

MS:

Treatment

Interferon beta-1b is the first drug to demonstrate an

ability to halt and even reverse the progression of
multiple sclerosis.
Its use has been shown to reduce the frequency of
relapses and the number of new lesions.
Its effects in patients with multiple sclerosis may be due
to its immunomodulating properties.
Interferon beta-1b increases the cytotoxicity of natural
killer cells and increases the phagocytic activity of
macrophages.

Treatment

The treatment for ALS is largely symptomatic. Spasticity

may be partly controlled with baclofen, a GABAB agonist.
The decline in muscle strength may be slowed by
gabapentin.
The first drug that has been specifically approved for use
in the treatment of ALS is riluzole. It prolongs the time
before patients require a tracheostomy and prolongs life
by about 3 months. Riluzole is believed to protect motor
neurons from the neurotoxic effects of excitatory amino
acids such as glutamate and to prevent the anoxiarelated death of cortical neurons.

Depression: Types
Stable

Mild
Dysthymia

Alternating

Cyclothymia

Severe
Unipolar
(major
depression)
Bipolar
(manicdepression)

Dysthmia is chronic depression for at least 2 years but not

severe enough for hospitalization; patient is functional at
suboptimal level
Cyclothymia is alternate episodes of mania and depression of
chronic duration
Unipolar disorder (major depression) is severe form of
depression with impaired functioning of the individual; suicidal
tendencies; symptoms should present at least for 2 weeks

SYMPTOMS
1 of 2

5+

persistently sad, anxious, or empty moods

loss of pleasure in usual activities (anhedonia)
feelings of helplessness, guilt, or worthlessness
crying, hopelessness, or persistent pessimism
fatigue or decreased energy
loss of memory, concentration, or decision-making
capability
restlessness, irritability
sleep disturbances
change in appetite or weight
physical symptoms that defy diagnosis and do not
respond to treatment (especially pain and
gastrointestinal complaints)
thoughts of suicide or death, or suicide attempts
poor self-image or self-esteem (as illustrated, for
SIGE
M CAPS=
Sleep self-reproach)
disturbance; loss of Interest; Guilt;
example,
by verbal
loss of Energy; depressed Mood; loss of Concentration;
Appetite/weight changes; Psychomotor

MAOIS ON THE MARKET

MAO

Inhibitors (nonselective)

Phenelzine
Tranylcypromine
Isocarboxazid
MAO-B

Inhibitors (selective for

MAO-B)
Selegiline

MAOIS SIDE EFFECTS

Side

effects have put MAOIs in the

second or third line of defense despite
superior efficacy
MAO-A inhibitors interfere with
breakdown of tyramine
High tyramine levels cause hypertensive
crisis (the cheese effect)
Can be controlled with restricted diet
MAOIs

interact with certain drugs

Serotonin syndrome (muscle rigidity, fever,

seizures)
Pain medications and SSRIs must be avoided

TCAS ON THE MARKET

Amitriptyline
Desipramine
Doxepin
Imipramine
Nortriptyline
Protriptyline
Trimipramine

TCAS MECHANISM OF ACTION

TCAs

inhibit
serotonin,
norepinephrine, and
dopamine
transporters,
slowing reuptake
TCAs also allow for
the downregulation
of post-synaptic
receptors

TCAS SIDE EFFECTS

Muscarinic

M1 receptor antagonism anticholinergic effects including dry mouth,

blurred vision, constipation, urinary retention and
impotence
Histamine H1 receptor antagonism - sedation
and weight gain
Adrenergic receptor antagonism tachycardia,
postural hypotension, Arrhythmigenic at toxic
doses
Direct membrane effects - reduced seizure
threshold, arrhythmia
Serotonin 5-HT2 receptor antagonism - weight
gain (and reduced anxiety)

Most important SSRI

Fluoxetine
Fluvoxamine
Paroxetine
Sertraline
Citalopram
Escitalopram

Selective Serotonin Re-uptake

Inhibitors (SSRI)
More

modern (1st drug fluoxetine

available in 1988) and safe
antidepressants

Principal

mechanism of action:

selective inhibition of 5-HT (serotonin)

reuptake (SERT)

Other

indications of SSRI

anxiety disorders

generalized anxiety, panic disorder, social

anxiety disorder, obsessive-compulsive disorder
bulimia nervosa, gambling, drug withdrawal

Adverse effects

Relative improvement to other antidepressants (mostly

mild)

GIT

nausea, vomiting, abdominal cramps,

diarrhea
relatively frequent, higher doses?

Headache
Sexual dysfunctions (loss of libido, erectile
dysfunction)
Restlessness (akathisia)
Anxiety - an increase in anxiety or agitation during
early treatment
Insomnia and fatigue
Serotonin syndrome upon intoxication or drug
interactions

NOREPINEPHRINE-DOPAMINE
REUPTAKE INHIBITORS (NDRIS)

Current drugs
Bupropion
Mechanims of Action
Similar to SSRIs and SNRIs
More potent in inhibiting dopamine
Also an3-4 nicotinic antagonist
Bupropion 1:1
Adverse effects
Lowers seizure threshold
Suicide
Does not cause weight gain or sexual dysfunction
(even used to treat the two)

use: severe depression + SMOKING

CESSATION TREATMENT

PHARMACOLOGY OF
ANTIDEPRESSANTS
ALL

tricyclics block the reuptake of both NE and

5-HT.

SSRIs

block 5-HT reuptake.

SNRIs

block NE reuptake.

other

cyclics have mixed effects on NE and 5HT reuptake.

MAOIs

prevent metabolism of the

neurotransmitters (elevation of synaptic levels).

SYMPTOMS OF MANIA
distractibility
energy
(buying, phoning, sex) racing thoughts
increased
impulsive actions and
gregariousness
decisions
pressured speech,
elevated mood
talkativeness
euphoria
decreased sleep
grandiosity
drunkenness
combative, dangerous irritability/hostility
behavior
(easily angered)
increased

ATLEAST 3 of the following and should last at least 1 week

DIGFAST= Distractibility; Irresponsible behavior (seeks pleasure
without regard to consequences; Grandiosity(increased selfesteem); Flight of ideas; Agitation (psychomotor) and increased
goal-directed activity; Sleep (decreased); Talkativeness or

CLINICAL PHARMACOLOGY
primary

therapy for mania

narrow therapeutic window (0.8-1.2

meq/L; some guides say 0.6-1.4
meq/L)

absolutely

necessary to monitor
serum level (trough level approx. 5
days after initial dose)

solely

eliminated by kidney, therefore

assess patients kidney function

Lithium toxicity and adverse

reactions
Acute

intoxication, symptoms:

GIT: vomiting, profuse diarrhea

CNS: confusion, tremor, ataxia,
convulsions, coma.
Heart: arrhythmias, hypotension

Toxicity

of long-term therapy

Renal toxicity the kidney's ability to

concentrate the urine is decreased
Adverse reactions: polyuria and polydipsia, weight

gain, GIT disturbances (vomiting, nausea, dyspepsia),

alopecia
Drug interactions: thiazides increased Li
reabsorption intoxication

Lithium side effects:

MNOP= Movement (tremor); Nephrogenic diabetes insipidus; O
HypOthyroidism; Pregnancy problems

Coronal sections
The rostral surface of a
section of brain
through the anterior
nucleus of the
thalamus,
mammillothalamic
tract, and mammillary
bodies

Horizontal section
Ventral surface of an
axial section of brain
through the genu of
the corpus callosum,
head of caudate
nucleus, centromedian
nucleus, and dorsal
portions of the pulvinar

Normal CT

A. Anterior Horn of the Lateral

Ventricle
B. Caudate Nucleus
C. Anterior Limb of the Internal
Capsule
D. Putamen and Globus Pallidus
E. Posterior Limb of the Internal
Capsule
F. Third Ventricle

Normal CT

Normal AP carotid
angiogram

Schizophrenia
Subtypes
Paranoid: Delusions of persecution or grandeur;
Often auditory hallucinations; Disorganized speech
and behavior
Catatonic: Motor immobility as evidenced by
catalepsy or complete stupor; rigidity of posture;
Extreme negativism; Echolalia or echopraxia;
alternatively can be excited and show excessive motor
activity
Disorganized: Disorganized speech and behavior;
flat affect; explosive laughter; poor personal
appearance
Undifferentiated: Psychotic symptoms that doesnt
meet criteria for paranoid, catatonic or disorganized
Residual: Previous episode, but no psychotic
symptoms; but negative symptoms are present

Schizophrenia
Possible mechanisms
Dopamine:
Drugs that increase dopamine will enhance or produce
positive psychotic symptoms
All known antipsychotics drugs capable of treating positive
psychotic symptoms block the dopamine receptors
Findings of increased dopamine receptor sensitivity in
postmortem studies

Serotonin:
Genes involved in serotonergic neurotransmission are
implicated in the pathogenesis of schizophrenia

Glutamate:
Major neurotransmitter in pathways key to schizophrenic
symptoms
Blocking the NMDA channel may produce positive and
negative psychotic symptoms identical to schizophrenia

Typical antipsychotics
Toxicity:
Extrapyramidal symptoms

Within 1 wk dystonia (muscle spasm, stiffness, oculogyric crisis)

Within 2 wk akinesia (inability to initiate movement)
Within 3-6 wk rigidity, tremor and bradykinesia (parkinsonism)
Within 10 wk akathisia (restlessness)
4 months tardive dyskinesia (long term use: tremors and spasm
of neck, body and limbs)

Endocrine side effects: dopamine receptor antagonism

leading to hyperprolactinemia
Muscarinic blocking may cause dry mouth, constipation;
histamine blocking may cause sedation; 1-blockade may
result in hypotension
Weight gain and sedation common due to H1 receptor
blockade
Adverse effects of thioridazine include cardiotoxicity
(torsades de pointes-quinidine like) and retinal deposits

Neuroleptic malignant
syndrome
Toxic effect of typical antipsychotics (Haloperidol, Trifluoperazine,
Fluphenazine)
A rare but life-threatening reaction to a neuroleptic medication
characterized by:
Mental status changes
Severe muscle rigidity (board-like rigidity)
Fever
Autonomic instability
Mental status changes
Muscular rigidity
Autonomic instability
Clinical
features
Initial
Lead pipe rigidity
Tachycardia most
symptom

Agitated delirium
with confusion
Catatonic signs
Mutism (inability to
speak)
Evolution to profound
encephalopathy and
coma is typical

throughout range of
motion
Superimposed tremor
Dysarthria,
dysphagia
Hyperthermia

Treatment:
Dantrolene
Dopamine D2 agonists

common
Labile blood pressure
Tachypnea
Diaphoresis

Atypical antipsychotics
Mechanism of action:
Affect both positive and negative symptoms
5-HT2A antagnoists
Clozapine has very high affinity for 5-HT2A receptors; but low
affinity to D2 receptors and thus dissociate rapidly. So less
extrapyramidal symptoms
Also 5-HT1A agonists (ziprasidone, quetiapine, clozpaine) that
would increase dopamine release (prefrontal cortex) and reduce
glutamate release

Clinical uses
Schizophrenia
Bipolar disorder
Anxiety disorder
Depression and mania

Adverse effects
Clozapine/olanzapine has high affinity for serotonin receptors; may
cause weight gain
Clozapine causes life-threatening agranulocytosis and seizure;
patients on olanzapine may develop diabetes

Neurotransmitter changes
DISORDER

NEUROTRANSMITTER
CHANGES

Parkinson's disease

Decreased dopamine,
Increased Ach and
Serotonin

Huntingtons disease

Decreased Ach and

GABA, Increased
dopamine

Schizophrenia

Increased dopamine

Alzheimers

Decreased Ach

Depression

Decreased serotonin,
norepinephrine and
dopamine

Anxiety

Increased
norepinephrine,
Decreased GABA and
serotonin

Neuromuscular-blocking
drugs
Used for muscle paralysis in surgery or mechanical ventilation.
Selective for motor (vs . autonomic) nicotinic receptor
Types of neuromuscular-blocking drugs
Depolarizing: Depolarizes the motor-end plate. E.g., succinyl choline
Non-depolarizing: competitive antagonists at the ACh receptor. E.g.,
Tubocurarine, atracurium, mivacurium, pancuronium, vecuronium ,
rocuronium

Reversal of blockade
Depolarizing:
During phase I (depolarizing phase), they cause muscularfasciculations(muscle
twitches) while they are depolarizing the muscle fibers. NO ANTIDOTE. Block is
potentiated by cholinesterase inhibitors
During phase II (desensitizing phase) the muscle is no longer responsive to
acetylcholine released by themotoneurons. Ach receptors are desensitized. At
this point, full neuromuscular block has been achieved. ANTIDOTE is to give
cholinesterase inhibitors.

Non-depolarizing:
Neostigmine, edrophonium, and other cholinesterase inhibitors can reverse the
blockade

Addiction pathway
The basic addiction pathway in the brain is a
dopamine pathway
Mood-altering drugs share a remarkable ability to
elevate brain dopamine levels
It is synthesized by neurons in the ventral
tegmental area, and released onto neurons in the
nucleus accumbens and prefrontal cortex
The series of projections from: 1) prefrontal
cortex to 2) nucleus accumbens to 3) ventral
pallidum is a final common pathway for drug
seeking, which is initiated by stress and drugassociated cues, or by the drug itself

Alcohol: Neuropathology chronic use

Wernickes encephalopathy
Degenerative brain disease
Mental confusion
Due to thiamine deficiency - vitamin B1
Atrophy & brownish discoloration of the mammillary
bodies
Korsakoffs dementia
Severe memory loss & confabulatory effects
Lesions in dorsomedial nucleus of thalamus
Alcoholic Cerebellar Degeneration
Probably a nutritional disorder( continued drinking with
poor nutrition for months)
Ataxia of gait
Lesion: irreversible toxic degeneration of Purkinje cells;
atrophy of anterodorsal midline cerebellum

Alcohol
Effects on fetal exposure in utero (Fetal alcohol
syndrome)
Small stature, underweight for length
Small brain, facial dysmorphia, small mid-face, smooth
philtrum (vertical groove in median part of upper lip),
thin vermilion, small palpebral fissures
Mental deficiency, poor coordination, hyperactivity

Treatment
Behavioral change
Alcoholics anonymous
Disulfiram (inhibits aldehyde dehydrogenase): Interaction
with alcohol produces nausea, vomiting, tachycardia,
chest pain and hyperventilation
Delirium tremens is alcohol withdrawal syndrome
characterized by psychotic symptoms with confusion and
autonomic hyperactivity. Treatment is benzodiazepines

Amphetamine and
methamphetamine
Psychostimulants
Mechanism:
releases high levels of
dopamine
binding to the pre-synaptic membrane
of dopaminergic neurones and
inducing the DA release
interacting with dopamine containing
synaptic vesicles
binding to monoamine oxidase in
dopaminergic neurones and preventing
the degradation of dopamine, leaving
free dopamine in the nerve terminal

Chronic abuse may cause

extensive tooth decay (called
meth-mouth) and a Parkinsonlike movement disorder
Indications
ADHD
Narcolepsy
Short term weight loss

Ecstacy
Derivative of amphetamine
chemical name is 3,4methylenedioxymethamphetamine (MDMA)
Mechanism: serotonin pathways are the
vulnerable pathways; blocks serotonin
transporters; After long-term or repeated
use, Ecstasy causes degeneration of
serotonin nerve terminals
Acute effects of ecstacy
Heightened perceptions (neocortex)
Reduced appetite (hypothalamus)
Stimulation (Basal ganglia)
Elevated mood (Amygdala)
Clouded thinking (short-term effect; neocortex
and hippocampus)
Memory impairment (long-term; neocortex and
hippocampus)
Sometimes, muscle spasms and jaw-clenching
are due to ecstasy's action at the motor neurons
in the spinal cord

Serotoni
n
Serotonin
neuron

Headache

MIGRAINE:
Benign and recurrent syndrome of headache,
nausea and vomiting and varying neurological
deficits
Pulsatile, unilateral and throbbing in nature
aggravated by minor movement
A trigger usually precipitates the attack
May present with aura such as motor or sensory
or vision changes, scintillating scotoma(classical
migraine); Some may not have aura or any
neurological deficit
Treatment:
Avoid the trigger; NSAIDS; acetaminophen
Acute abortive therapy is serotonin receptor
agonist, sumatriptan; Alternative is
dihydroergotamine

Headache

CLUSTER HEADACHE:
Unilateral, excruciating, periorbital pain;
peaking in intensity in 5 min
Common in males
Attacks last from 30 min to 3 hours; 1-3/day over
4-8 week period
Associated symptoms: rhinorrhea, reddening
of the eye, lacrimation, nasal stuffiness, may
induce horners syndrome
Treatment:
Most effective treatment in acute episodes is
100% oxygen;
Sumatriptan is also used for acute attacks;
Other drugs used prednisone, lithium,
ergotamine and verapamil; Sumatriptan
causes coronary vasospasm so it is

Headache

TENSION HEADACHE:
Bilateral, steady tight-band like headaches
Sometimes, associated with tightness of the
posterior neck muscles
May persist for several days with or without
fluctuations
Treatment: Relaxation; acetaminophen and
NSAIDs; if refractory, add a muscle relaxant

Structure of the brachial plexus

Be able to draw this pattern.

The origin of the brachial

plexus is from ventral rami.
Unfortunately, the term
roots has been used. The
brachial plexus does NOT arise
from dorsal or ventral roots,
nor from the dorsal rami.

Randy Travis Drinks Cold Beer

Posterior cord
branches:
ULTRA
U-Upper subscapular
nr(C5,6)
L-Lower subscapular
nr(C5,6)
T-Thoracodorsal
nr(C6,7,8)
R-Radial nr(C5,6,7,8,T1)
A-Axillary nr(C5,6)

Branches of the cords

Lateral cord branches:
Lateral root of median
N(C5,6,7)
Lateral pectoral N
(C5,6,7)
Musculocutaneous N
(C5,6,7)

Medial cord branches: (All Ms)

Medial root of median N(C8,T1)
Medial pectoral N (C8,T1)
Medial cutaneous N of arm (T1) and
forearm (C8,T1)

Long thoracic nerve

Scalenus ant.

WINGING OF SCAPULA

Scalenus med.
Subclavian v., a.

Lat. thoracic a.

erratus ant. m.

bs 1-8
otracts, secures and rotates scapula

Subscapulari
s
muscle
Long thoracic n. (C5,6,7)
Descends behind the roots
Runs along the Serratus anterior
superficially,
During a mastectomy-it could be
cut accidentally resulting in
Winged scapula or Angel scapula
Serratus anterior will no longer
hold the scapula in place

Upper
Trunk Lesion of the Brachial Plexus
Site
of Lesion:
Tearing of upper trunk or
its roots.
Usually occurs proximal to
the branch point of the
suprascapular n. but distal
to the branch point of the
long thoracic n. and dorsal
scapular n

Cause of Lesion:
Trauma
incurred
in
infants
during
complicated delivery;
In adults, by violent falls
on side of head and
shoulder.

Erb's Palsy; Erb-Duchenne Paralysis

Upper Trunk Lesion of the Brachial Plexus

Nerves Involved:

Axillary n.
Suprascapular n.
Musculocutaneous n.
Lateral cutaneous n.
of forearm
Loss
of
function:

motor

Muscles of the proximal

upper limb innervated by
the nerves listed above
(deltoid,
teres
minor,
supraspinatus,
infraspinatus,
biceps
brachii,
coracobrachialis,

Upper Trunk Lesion of the Brachial Plexus

Loss of Sensation:
Posterolateral aspect of
the superior part of the
arm, lateral aspect of
the forearm

Position of the Limb:

Arm: Extended,
adducted and rotated
medially.
Forearm: Extended
and pronated.
*This position of the
limb is often described
as "head waiter's tip"
position.

Anterior
view

Lateral
cutaneous n of
arm (from
axillary)
Lateral
cutaneous n of
forearm (from
musculocutane
ous)

Axillary nerve injury

Site of Lesion:
Usually in the portion of nerve
which is adjacent to the surgical
neck of the humerus.
Cause of Lesion:
Fracture at surgical neck of
humerus. Posterior dislocation of
the head of the humerus
Loss of Muscle Function:
Deltoid and teres minor mm.
Loss of Sensation:
Skin on the posterolateral aspect of
the superior portion of the arm.
Position of the Limb:
Arm: Adducted (loss of
abduction at shoulder joint)
Forearm, Wrist, Hand: No effect

Posterior
view
Lateral
cutaneous n of
arm (from
axillary)

Lower
Lesion of the Brachial Plexus
Also
calledTrunk
Klumpke
Paralysis
Site of Lesion:
Tearing of lower trunk or its
roots.

Cause of Lesion:
Trauma incurred in infant
during complicated
delivery, often in breech
presentations where arm is
carried over the head.
In adults, falling with the
arm outstretched over
the head (as in falling from
a ladder and attempting to
catch oneself by one hand)
from a tumor at the apex

Lower Trunk Lesion of the Brachial Plexus

Nerves involved:
Ulnar,
medial cutaneous n of arm,
medial cutaneous n of
forearm.

Loss
of
function:

motor

Muscles of the distal upper

limb that are innervated by
ulnar nerve, i.e., flexor carpi
ulnaris, medial 1/2 of flexor
digitorum profundus m.,
medial two lumbrical mm.,
all interosseous mm.,
adductor pollicis m.

Also called Klumpke

Lower Trunk Lesion of the Brachial Plexus
Paralysis
Loss of sensation:
Widespread loss of sensation on
the medial aspect of the arm
(medial cutaneous nerve of
arm),
The medial aspect of forearm
(medial cutaneous nerve of
forearm),
wrist and hand (cutaneous
distribution of the ulnar nerve).

Position of the Limb:

Arm: No change
Forearm: No change
Hand: Somewhat abducted;
unable to adduct and abduct
digits 2 through 5; unable to
adduct thumb;

Medial
cutaneous
n of arm
(from
medial
Medial
cord)
cutaneous
n of
forearm
(from
medial
cord)
Cutaneous
and
supericial br
of ulnar n

Median nerve injury

Site of Lesion:
Usually at the wrist
where the median nerve
passes through the carpal
tunnel (carpal tunnel
syndrome).
Cause of Lesion:
Pressure on the nerve in
the carpal tunnel, most
often related to nonspecific
inflammation of the flexor
tendon sheaths; also may
be caused by fractures at
the wrist, arthritis, etc.

Loss of Muscle Median nerve injury

Function:
Lateral two lumbrical
mm.; All thenar
muscles: flexor pollicis
brevis m., abductor
pollicis brevis m.,
opponens pollicis m.
Loss of Sensation:
Lateral aspect of the
palm and lateral 3 1/2
digits (loss of sensation
in thumb and index
finger)
Effect on Limb:

Ape hand
Median n

Ulnar nerve injury

Site of Lesion:
1) most commonly at the
level of the elbow due to
compression of the nerve
in the groove for the
ulnar nerve, or a
fracture of the medial
epicondyle of the
humerus or a laceration
at this location;
2) occasionally the ulnar
nerve is lesioned at the
wrist due to a
laceration.

Ulnar nerve injury

Loss of muscle function:

(1)Lesion at medial epicondyle (2)Lesion at
wrist
Medial two heads of flexor
Medial two lumbricals,
digitorum profundus, flexor
all interossei,
adductor
carpi ulnaris, medial two
pollicis and mm. of
lumbricals, all interossei
hypothenar eminence.
adductor pollicis, mm of
hypothenar eminence.

Loss of sensory function:

Ulnar nerve injury
(1)Lesion at medial epicondyle
(2)Lesion at
wrist
Loss of sensation for medial
Loss of sensation over
the
aspect of hand including the
hypothenar eminence
and
hypothenar eminence and
palmar surface of the
medial 1 1/2 digits - both
medial 1 1/2 digits
(dorsal
dorsally and ventrally
surfaces of these digits
are
unaffected because the
dorsal branch of the ulnar
nerve is spared)
Ulnar n

Ulnar nerve injury

Position of the Limb:

(1)Lesion at medial epicondyle (2)Lesion at
wrist
Hand slightly abducted.
Inability to abduct
and adduct
Inability to abduct and adduct digits 2 - 5,
digits 2 - 5, inability to adduct
inability to
adduct
the thumb
the thumb

Site of Lesion:

Radial nerve injury

Usually at the mid-shaft of the

humerus. Chronic pressure in the
axilla e.g. Crutch use
Cause of lesion:
Fracture of mid-shaft of the
humerus; pressure on the nerve
caused by crutches.
Loss of muscle function:
Extensors of the wrist and fingers;
supinator (but supination will not
be completely lost because the

Radial nerve injury

Loss of sensation::
Posterior forearm; dorsum of the hand on the radial
side, including the dorsum of the lateral 3 1/2 digits
(except over the distal phalanx). The skin on the
dorsum of the hand, overlying the interval between the
1st and 2nd metacarpals, can be tested in evaluating
the function of the radial nerve.

Posterior
cutaneous
n of
forearm
(from
radial
nerve)
Superificia
l br. of
radial n

Position of the Limb:

Radial nerve injury
Wrist and fingers are flexed and they
cannot be extended. However, this does
not mean that an object can be gripped
firmly in the flexed hand because an
extended wrist is needed to make a "tight
fist".
Note about testing the ulnar nerve in
cases of radial nerve injury: To spread the
fingers (ulnar nerve), the
metacarpophalangeal joints must be
extended. Therefore, to check for
spreading of the fingers (abduction) in a
patient with a radial nerve palsy, the hand
should be placed flat on the table to
passively extend the fingers.
Radial nerve injury results in a condition
commonly called wrist drop; it has also

Injuries involving lowerlimb

Common Fibular (Peroneal)

Nerve Injury :
Injury generally occurs as the
nerve wraps around the lateral
aspect of the fibula.
A compartment syndrome can
also injure the nerve
Loss of innervation to the
anterior compartment of the leg
results in loss of ability to
dorsiflex the foot.
Commonly called foot drop.
There will be loss of sensation
over the lateral aspect of the

Femoral fracture
very close to
peroneal nerve
may also lead to
foot drop

Injuries involving lowerlimb

Superior Gluteal
Nerve Injury :
Injury to this nerve
leads to a gluteus
medius limp due to the
gluteus minimus and
medius being
denervated.
The person leans away
from the unsupported
side (i.e., leans toward
the side of the injury)
when walking; this is a
Positive Trendelenberg

THANK YOU
ALL THE BEST