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SchizophreniaParkinsons Epileptics

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... by resting tremor, rigidity, akinesia (difficulty in initiation of movement) ... Akinesia. Depression. Bradykinesia. Nonmotor symptoms. Motor symptoms. Table 1 ... – PowerPoint PPT presentation

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Title: SchizophreniaParkinsons Epileptics

1
Schizophrenia/ParkinsonsEpileptics

Jim Fawcett
Departments of Pharmacology and Surgery
jim.fawcett_at_dal.ca

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Disease of the synapse

Antipsychotic drugs Chapter 7
Depression and Bipolar Chapter 8
Antiepileptic Drugs Chapter 9
Parkinsons disease - Chapter 10

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Psychosis Schizophrenia Altered perception of
reality and disturbances of thought

Social isolation
Apathy
Blunted emotion
Personal neglect
Lacking motivation

Visual and auditory hallucinations
Delusions
Disorganized thinking
agitation

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Schizophrenia

Dopamine hypothesis
Over activity of dopamine pathways in certain
parts of the brain.
L-dopa aggravate symptoms or produce symptoms de
novo.
Blocking dopamine receptors alleviates symptoms.

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D2 receptor and schizophrenia

There is a direct linear relationship between the
strength with which the compounds bind at the
dopamine D2 receptor, and the clinical potency of
the drug.

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Schizophrenia

Since D2 receptors are affected motor pathways
are also affected. Newer drugs more selective and
less adverse affects on motor systems
Antipsychotic interact with other receptor
subtypes including serotonin receptors.

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Schizophrenia

Extrapyramidal side effects
Akathisia motor restlessness, insomnia
Pseudoparkinsonism resting tremor, rigidity
Dystonia/dyskinesia involuntary, uncoordinated
(lower drug dose or change drug)
Long term Tardive Dyskinesia
(lower dose and time of antipsychotic)

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Concerns for Rehab

Behavioural mood swings.
Extrapyramidal side effects postural changes,
balance and involuntary movements.
Orthostatic hypotension.

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Depression and Bipolar

Depression is most prevalent mental illness in
North America
15 adults will experience major depression in
lifetime
Sadness and despair
Lack of interest
Eating issues, sleep disorders, fatigue
Recurrent thoughts of death and suicide

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Depression and Bipolar

Amine systems involved (serotonin,
norepinephrine, dopamine)
Serotonin is the likely candidate
Disease of the synapse

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Pathology of Depression
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1
2
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Depression and MAO

MAO monoamine oxidase inhibitors
- enzyme in synapse
- removes released drug through enzymatic
degradation
- drugs that inhibit this enzyme allow for
transmitter to remain effective
Problems sympathetic activity, hypertension

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Depression and tricyclics

tricyclics three-ring chemical structure
- block transmitter re-uptake
- amitriptyline and nortriptyline
- newer second-generation drugs more common
Problems sedative, fatigue, insomnia
major anti-cholinergic effects, dry mouth,
constipation, arrhythmias.

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Depression and SSRI

New generation block re-uptake similar to
tricyclics more selective
- SSRI selective serotonin reuptake inhibitors
Advantages of SSRI
Fewer side effects
Higher tolerance of drug over longer term

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Depression and Li

Li monovalent cation
Competes with Na, K and Ca
Decreases sensitivity of postsynaptic receptors
by uncoupling with intracellular signaling
Problems
Li not metabolized, collects in body
Ataxia, respiratory complications, seizures

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Concerns for Rehab

Blurred vision and anticholinergic effects.
Dizziness, electrical shock, lethargy.
Takes time to effect change after drug regime
starts suicide and depression may worsen.
Tricyclics lethargy and sedation and muscle
weakness.

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Parkinsons disease

Parkinsons disease is characterized by resting
tremor, rigidity, akinesia (difficulty in
initiation of movement) and bradykinesia
(slowness in the execution of movement).

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Parkinsons Disease

Parkinsons disease results from the degeneration
of dopaminergic neurons in the substantia nigra
These neurons project to other structures that
together control movement

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Parkinsons disease Treatments

Drugs that increase dopamine levels.
Dopamine receptor agonists.
Acetylcholine receptor antagonists.

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Parkinsons disease

Cholinergic neurons also participate in the
interconnections between nuclei of the basal
ganglia
Loss of dopaminergic neurons in the substantia
nigra leads to excessive cholinergic activity in
these pathways.

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Parkinsons disease Treatments

Levodopa is the biosynthetic precursor of
dopamine. L-dopa can cross the blood-brain
barrier.
Large first pass effect before L-dopa reaches
target in CNS due to metabolism in peripheral
tissues by LAAD and COMT

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L-dopa

L-dopa is taken up by dopaminergic neurons in the
substantia nigra and converted to dopamine by
L-amino acid decarboxylase (LAAD)
As the disease progresses, more dopaminergic
neurons die and the effectiveness of L-dopa drops

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Adverse effects of L-dopa

Nausea, orthostatic hypotension and cardiac
arrhythmias can occur
These effects are due to the formation of
dopamine in peripheral tissues

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Adverse effects of L-dopa

Long-term use of L-dopa can lead to the
development of involuntary movement or dyskinesia
Psychotic effects due to excess dopamine in
mesolimbic and mesocortical pathways.

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Carbidopa

Is a peripheral decarboxylase inhibitor
Inhibits the conversion of L-dopa to dopamine by
LAAD in peripheral tissues.
Carbidopa does not cross the bbb.
Combination therapies of L-dopa and carbidopa
allow for a reduction in the amount of L-dopa
needed.
Carbidopa L-dopa (Sinemet)

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Dopamine receptor agonists

Directly activate dopamine receptors in the
striatum.
Different dopamine receptor subunits i.e.. D2
subunit
Can be more selective and less side effects than
L-dopa.

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Anticholinergic Drugs

Benztropine and trihexphenidyl are
anticholinergics drugs, block AchR.
Used in combination with L-dopa to control
tremors and rigidity.

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Anticholinergic Drugs

Drowsiness, inattention, confusion, delusions,
hallucinations.
Peripheral adverse effects include dry mouth,
blurred vision, constipation, urinary retention,
cardiac arrhythmias.

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Treatments of PD

Drugs that increase dopamine levels
Dopamine receptor agonists
Acetylcholine receptor antagonists.

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Concerns for Rehab

Disease is progressive.
Fluctuations in response to drug treatment.
Behavioural concerns.
Orthostatic hypotension.

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Antiepileptics

Epilepsy is chronic neurological disorder
characterized by recurrent seizure activity.
Seizures are sudden, transient disturbances in
neuronal excitation.
Activity can remain localized or spread into
motor cortex activating descending motor pathways
convulsions
Seizures are often self limiting but over time
recurrent seizures lead to neuronal death

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Antiepileptics