Parkinson's

Question 1

What is Parkinson’s

Answer 1

slowly progressive degenerative CNS disorder

Question 2

Characteristics of Pakinson’s

Answer 2

Tremor
Rigidity
Bradykinesia
Postural DIsturbances

Question 3

Aetiology of primary Parkinson’s

Answer 3

Loss of Dopamine-producing neurons in substantia nigra= deficiency of DA in Basal Ganglia.

Question 4

What is the neurotransmitter imbalance caused by Parkinson’s

Answer 4

Too little DA (low inhibitory) and too much ACh (high excitatory)

Question 5

Cause of Tremors

Answer 5

due to involuntary skeletal muscle contractions

Question 6

When is a tremor at its maximum

Answer 6

during rest

Question 7

Is a tremor present during sleep

Answer 7

Nope

Question 8

How does a tremor start

Answer 8

may start in Upper extremity, spread to ipsilateral LL and then to contralateral limb

Question 9

Cause of rigidity

Answer 9

Due to continuous mucle contraction

Question 10

What is Bradykinesia

Answer 10

slowness and poverty of movement

Question 11

What is Hypokinesia

Answer 11

Muscular movements performed with decr. range of motion

Question 12

Cause of Postural disturbance

Answer 12

there is loss of postural reflexes = tendency to fall forward (propulsion) or backward (retropulsion) when center of gravity is displaced

Question 13

What other symptoms may be seen in Parkinson’s

Answer 13

Speech may be affected
Depression: common
Dementia: common

Question 14

Which Dopaminergic agents are used?

Answer 14

DA precursors
DA R agonists
COMT inhibitors
MAO Type B inhibitors

Question 15

Which are the DA precursor drugs

Answer 15

Levodopa

Question 16

Which are the DA Receptor agonists

Answer 16

Bromocriptine
Ropinirole
Pergolide
Pramipexole
Apomorphine

Question 17

Which are the COMTi drugs

Answer 17

Tolcapone
Entacapone

Question 18

Which are MAO Type B inhibitors

Answer 18

Selegiline
Rasagiline

Question 19

Which Anticholinergic agents are used

Answer 19

TBB
Trihexyphenidyl
Benzotrpine
Biperidin???

Question 20

MOA of Levodopa

Answer 20

Is a DA precursor= facilitates synthesis of DA in brain
–> restores Dopaminergic neurotransmission in neostriatum by enhancing DA synthesis in surviving neurons of Substantia nigra

Question 21

How is Levodopa therapy initiated (dosage)

Answer 21

With small doses and gradually increased

Question 22

How effective is Levodopa therapy

Answer 22

not effective
Therapy loses its effectiveness after 2 years of use

Question 23

Type of Parkinson Levodopa has no effect on

Answer 23

Drug-induced Parkinson

Question 24

Where is Levodopa absorbed

Answer 24

in SI

Question 25

What inactivates Levodopa

Answer 25

MAO in SI

Question 26

Enzyme that converts Levodopa to DA

Answer 26

Dopa Decarboxylase.

Question 27

Distribution of Levodopa

Answer 27

95% converted to DA in peripheral tissue; <1% enters brain

Question 28

What interferes with Levodopa transport into CNS

Answer 28

ingestion of high protein meals

Question 29

How should Levodopa be taken

Answer 29

On an empty stomach (at least 30mins before meals)

Question 30

AE of Levodopa

Answer 30

Anorexia Nausea Psychiatric disturbances Incr. HR Mydriasis Decr. BP On-Off effect: rapud fluctuations in clinical state- hypokinesia and rigidity may suddenly worsen then improve Development of involuntary choreiform movements- usually affecting face and limbs

Question 31

Drugs that improve Levodopa efficacy

Answer 31

Carbidopa: peripheral Dopa-decarboxylase inhibitor Selegiline: MAO-B inhibitor--> inhibits DA degradation in CNS Rasagiline: irreversibly inhibits MAO-B Domperidone: Peripheral dopamine antagonist

Question 32

SE of Levodopa+Selegiline

Answer 32

HTN crisis Insomnia

Question 33

Potency of Rasagiline

Answer 33

5x more potent than Selegiline

Question 34

SE of Levodopa+Rasagiline

Answer 34

Doesn't cause insomnia

Question 35

MOA of Entacapone

Answer 35

Selective reversible inhibitor of COMT =prevents metabolism of Levodopa to 3-O-methyldopa--> decr. palsma conc. of 3-O-methyldopa Incr. central uptake of Levodopa Incr. conc. of DA in brain

Question 36

What is 3-O-methyldopa

Answer 36

A metabolite of Levodopa that competes with Levodopa for active transport into the CNS

Question 37

SE of Entacapone

Answer 37

GI upsets Postural Hypotension Hallucinations Sleep disorders

Question 38

SE of Tolcapone

Answer 38

Associated with hepatic necrosis

Question 39

MOA of Bromocriptine

Answer 39

Is a Dopamine Receptor Antagonist Is a ergot derivative

Question 40

Cons of Bromocriptine

Answer 40

it has many AEs its very expensive

Question 41

Caution when using Bromocriptine

Answer 41

MI or Peripheral Vascular disease

Question 42

When is Bromocriptine used

Answer 42

Only for cases that cannot be effectively treated with Levodopa

Question 43

AE of Bromocriptine that occur during first few months of use

Answer 43

Nausea Dizziness Drowsiness Postural Hypotension

Question 44

AE of Bromocriptine that occur at high doses over longer periods

Answer 44

Dyskinesia Hallucinations Confusion Behavioural Abberations

Question 45

What does Bromocriptine exacerbate

Answer 45

Peptic ulcers

Question 46

Common AEs of Bromocriptine

Answer 46

Dementia Depression

Question 47

What is Amantadine

Answer 47

An anti-viral agent with moderate anti-Parkinson activity

Question 48

When is Amantidine useful

Answer 48

useful as monotherapy for early, mild Parkinsonism Can be used in combination with Levodopa

Question 49

Effectiveness of Amantidine

Answer 49

It loses its effectiveness after several months

Question 50

MOA of Amantidine

Answer 50

Releases DA from its stores and inhibits the re-uptake of DA from the synaptic cleft

Question 51

AEs of Amantidine

Answer 51

Discolouration of the skin (esp. legs and oedema of ankles) Pulmonary pleursis Stops milk production (decr. prolactin) Acute MI

Question 52

CI of Amantadine

Answer 52

PVO MI Cardiac vascularity

Question 53

AEs of Amantadine that may occur at high doses

Answer 53

Psychotic episodes Convulsions Nausea

Question 54

MOA of Anticholinergics (antimuscarinics)

Answer 54

competitively antagonize ACh at MR. They can cross BBB because they are lipphilic

Question 55

Indications of Biperiden

Answer 55

Parkinsonism

Question 56

When is an injection of Biperiden useful

Answer 56

it can be useful for rapid control of drug-induced acute dystonic reactions

Question 57

AEs of Biperiden

Answer 57

Usual Anti-muscarinic effects Pronounced drowsiness Urinary retention Visual disturbance Aggrevation of glaucoma Postural hypotension Euphoria Aberrations of co-ordination ???

Question 58

What is Orphenadrine

Answer 58

Its an anti-histamine with anticholinergic effects

Question 59

When is Orphenadrine used

Answer 59

for treatment of mild Parkinsonism for elderly patients who cannot tolerate the potent parasympatholytic drugs

Question 60

AEs of Orphenadrine

Answer 60

Drowsiness Para-sympatholytic SEs: dry mouth, visual disturbance, urinary retention, constipation Concurrent intake of alcohol or sedative may cause excessive sedation

Question 61

Uses of Trihexyphenidyl/ Benztropin

Answer 61

its used for both idiopathic and drug-induced Parkinsonism.

Question 62

What do Trihexyphenidyl/ Benztropin relieve

Answer 62

tremors due to Parkinsonism

Question 63

What do large doses of Trihexyphenidyl/ Benztropin do

Answer 63

they induce a feeling of mental well-being and as such is abused for this feeling

Question 64

AES of Trihexyphenidyl/ Benztropin

Answer 64

Parasympatholytic SEs: dry mouth, blurred vision, dizziness and nausea occur at beginning of therapy Elderly: constipation and urinary retention Tachycardia Drowsiness

Question 65

CI of Anticholinergics

Answer 65

Prostatic Hypertrophy: aggravate urinary retention associated with Prostatic Hypertrophy Glaucoma: icr. IOR= exacerbate it GI Obstruction