Parkinson Epilepsy

Question 1

characterized by
progressive and irreversible loss of neurons from
specific regions of the brain

Answer 1

Neurodegenerative disorders

Question 2

Examples of prototypical neurodegenerative

disorders: (4)

Answer 2

Parkinson disease
Huntington’s disease
Alzheimer’s disease (AD)
Amyotrophic lateral sclerosis (ALS)

Question 3

loss of neurons from structures of the basal ganglia

results in abnormalities in the control of movement

Answer 3

Parkinson disease and Huntington’s disease

Question 4

where the loss of
hippocampal and cortical neurons leads to
impairment of memory and cognitive ability

Answer 4

-Alzheimer’s disease (AD)

Question 5

where muscular weakness results from the degeneration of spinal, bulbar, and cortical motor neurons

Answer 5

Amyotrophic lateral sclerosis (ALS)

Question 6

2nd most common neurodegenerative
disease (after Alzheimer’s disease)
– Mean onset = 57 years of age
– Affects 1-2% of population over 60
years of age 
• Disease progression is highly variable
• Can be early onset in some cases

Answer 6

Parkinson Disease

Question 7

Epidemiologic studies suggest increased risk of Parkinsons with
exposure to

Answer 7

pesticides, rural living, and drinking

well water

Question 8

what can reduce risk of PD

Answer 8

reduced risk with cigarette smoking

and caffeine.

Question 9

Four cardinal features of PD (4)

Answer 9

bradykinesia
muscular rigidity
resting tremor
impairment of postural balance

Question 10

slowness and

poverty of movement

Answer 10

bradykinesia

Question 11

stiffness and
resistance to limb movement
caused by increased muscle
tone

Answer 11

muscular rigidity

Question 12

usually abates during voluntary movement

Answer 12

resting tremor

Question 13

leads to disturbances of gait

and falling

Answer 13

impairment of postural balance

Question 14

-characterized by severe loss of
substantia nigra (SN)
dopaminergic neurons
-visible in
brain sections as depigmentation
of the SN in the midbrain.

Answer 14

Parkinson

Question 15

It is estimated that approximately
\_\_\_% to \_\_\_% of the SN dopamine
cells are lost by the time a patient
first presents for clinical
evaluation, diagnosis, and
treatment.

Answer 15

60

70

Question 16

substantia nigra projects to two pathways

Answer 16

direct and indirect

Question 17

the net effect of the ______ pathway is to excite motor cortex, and the net
effect of the _______ pathway is to
inhibit motor cortex.

Answer 17

direct

indirect

Question 18

SN activity excites the direct pathway
(____ receptors) and inhibits the indirect
pathway (___ receptors)

Answer 18

D1

D2

Question 19

reduces the excitation of
motor cortex and its ability to generate
commands for voluntary movement,
resulting in the poverty of movement
of Parkinsonian patients.

Answer 19

Loss of the nigrostriatal dopaminergic pathway

Question 20

The loss of SN neurons puts a brake on the output of motor cortex, inhibiting
_______ motor commands from descending to the brain stem and spinal cord
As a result patients have difficulty initiating voluntary movements although involuntary, reflexive movements can be normal

Answer 20

voluntary

Question 21

Neurons in CNS of PD patients have

abnormal accumulation of the protein called

Answer 21

α-synuclein

Question 22

_______ protein accumulates inside

neurones forming inclusions called _________

Answer 22

α-synuclein

Lewy bodies

Question 23

the unwanted product resulting from the planned synthesis of synthetic heroin.

Answer 23

MPTP (1-methyl-4-phenyl-1,2,3,6-

tetrahydropyridine)

Question 24

Victims became almost completely immobile
(“frozen”), unable to blink and mute only
hours after injecting this drug.

Answer 24

MPTP (1-methyl-4-phenyl-1,2,3,6-

tetrahydropyridine)

Question 25

produce Parkinson-like symptoms in monkeys and has been used to develop animal models for testing new therapies for PD

Answer 25

MPTP

Question 26

Dopamine receptors

Answer 26

G proteincoupled receptors (GPCRs)

Question 27

The D1 and D5 receptors are members of the

Answer 27

D2-like family

Question 28

activates adenylyl cyclase, increasing the intracellular concentration of the second messenger cyclic adenosine monophosphate (cAMP)

Answer 28

Activation of D1-like family receptors coupled to the G protein Gαs

Question 29

directly inhibits | the formation of cAMP by inhibiting the enzyme adenylate cyclase

Answer 29

D2-like family receptors coupled to the Gαi

Question 30

Pharmacological Treatment of PD | • Goal =

Answer 30

Restore dopamine receptor function

Question 31

``` Prodrug – immediate metabolic precursor of dopamine (DA) can cross the BBB while DA can not; 1-3% enters the brain ```

Answer 31

Levodopa

Question 32

increase amount of | L-DOPA that reaches CNS

Answer 32

COMT inhibitors

Question 33

may be given to patients who are taking levodopa and are becoming resistant or having fluctuations in levodopa effect

Answer 33

Dopamine receptor agonists

Question 34

each dose of ________ effectively improves mobility for a period of time, but rigidity and akinesia return rapidly at the end of the dosing interval.

Answer 34

levodopa

Question 35

Increasing the dose of levodopa and frequency of administration can improve adverse effects, but this often is limited by the development of

Answer 35

dyskinesias, excessive | and abnormal involuntary movements.

Question 36

•“On-off” Effect – fluctuations in clinical response to levodopa:

Answer 36

- “Off” = marked akinesia | - “On” = improved mobility but marked dyskinesia.

Question 37

Conditions with PD-like symptoms that result from other causes are referred to as

Answer 37

parkinsonism

Question 38

a natural alkaloid that blocks vesicular transport of monoamines, depletes stored monoamines, including DA

Answer 38

Reserpine

Question 39

drugs used in the treatment of schizophrenia | block the action of DA on its receptors

Answer 39

Antipsychotic drugs (neuroleptics)

Question 40

•Patients who have received neuroleptics for long periods of time may develop

Answer 40

hyperkinetic disorder, | known as tardive dyskinesia

Question 41

``` characterized by involuntary, purposeless movements affecting many parts of the body (abnormal movements of the tongue, mouth and masticatory muscles, choreoathetoid movements of the extremities) ```

Answer 41

Tardive dyskinesia

Question 42

``` Drugs used in the treatment of nausea or vomiting (e.g., Compazine) or gastroesophageal disorders (e.g., metoclopramide) are also _________ agents ```

Answer 42

neuroleptic

Question 43

the clinical manifestation of an abnormal and | excessive synchronization of a population of cortical neurons

Answer 43

Seizure

Question 44

a tendency toward recurrent seizures unprovoked by any systemic or acute neurologic insult

Answer 44

Epilepsy

Question 45

two or more unprovoked | seizures

Answer 45

Epilepsy

Question 46

Epilepsy etiologies of seizures can be grouped into three categories

Answer 46

genetics structural/metabolic unknown course

Question 47

Genetic etiology of epilepsy

Answer 47

Mutations in gene encoding a neuronal ion channel

Question 48

Structural/Metabolic effects that may cause epilepsy

Answer 48

- trauma, tumors and other - space-occupying lesions - Certain drugs, withdrawal from alcohol or drugs, ---metabolic disorders - Vascular diseases

Question 49

originate within networks limited to one cerebral hemisphere | and are usually associated with structural abnormalities of the brain.

Answer 49

•Focal seizures

Question 50

arise within and rapidly engage networks distributed across both cerebral hemispheres and may result from cellular, biochemical, or structural abnormalities that have a more widespread distribution

Answer 50

•Generalized seizures

Question 51

disorders of neuronal excitability

Answer 51

epilepsies

Question 52

occur when a large collection of neurons abnormally undergo synchronous APs that produce stereotypical, involuntary spasms and alterations in behavior

Answer 52

Seizures

Question 53

Which factors can contribute to hyperexcitability of neurons?

Answer 53

* Increase excitatory post synaptic potentials (EPSPs) * Decrease Inhibitory post synaptic potentials (IPSPs) * Changes in voltage gated ion channels * Alteration of local ion concentrations that favor depolarization

Question 54

the principal fast ("classical") excitatory transmitters throughout the CNS

Answer 54

Glutamate and possibly aspartate

Question 55

the major inhibitory mediator in the brain, including being responsible for presynaptic inhibition.

Answer 55

GABA

Question 56

The mechanisms of action of anti-seizure drugs fall into three major categories:

Answer 56

1. promoting the inactivated state of voltage-gated Na+ channels 2. enhanced GABA– mediated synaptic inhibition 3.inhibition of voltage-activated Ca2+ channels

Question 57

Anti-seizure drugs

Answer 57

enhance Na+ channel inactivation thereby reducing the ability of neurons to fire AP at high frequencies

Question 58

Several drugs inhibit seizures by enchansing ____-mediated synaptic inhibition through an action at distinct sites of the synapse

Answer 58

GABA

Question 59

Some _________ drugs act by reducing the metabolism of GABA, resulting in increased GABA concentration available for release

Answer 59

anti-seizure

Question 60

inhibits the GABA reuptake transporter, GAT-1, and reduces neuronal and glial uptake of GABA

Answer 60

Tiagabine

Question 61

activated at a much more negative membrane potential (hence "low threshold") than most other voltage-gated Ca2+ channels expressed in the brain

Answer 61

T-type Ca2+ channels

Question 62

The principal mechanism by which anti– | absence-seizure drugs act is by

Answer 62

inhibition of the | T-type Ca2+ channels

Question 63

a common mechanism of action among anti-seizure drugs, with anti-partial-seizure drugs inhibiting voltage-gated Na+ channels and anti-absence-seizure drugs inhibiting voltage-gated Ca2+ channels

Answer 63

Inhibiting voltage-gated ion channels

Question 64

Seizures can occur as an adverse effect of a large number of drugs from different pharmacological categories: (6)

Answer 64

``` antibiotics e.g. penicillins Immunosuppressant cyclosporine Overdose with tricyclic antidepressants Anesthetics e.g. propofol antineoplastic agents Abrupt withdrawal of therapy ```

Question 65

recommended in protocols for bone | marrow transplantation

Answer 65

antineoplastic agents