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Medical Pharmacology Exam 2 > Anti-Parkinsons/ Neurodegenerative Diseases > Flashcards

Anti-Parkinsons/ Neurodegenerative Diseases Flashcards

1
Q

As of now, what is the major role of drugs used to treat neurodegenerative diseases?

A

Retard neuronal degeneration

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2
Q

Neurodegenerative diseases mainly affect extrapyramidal systems. What is an example of 2 areas usually affected? What is usually spared?

A

Substancia Nigra, Striatum

Cortex

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3
Q

What is an example of a hypokinetic neurodegenerative disorder? A hyperkinetic one?

A

Hypo - Parkinson

Hyper - Huntingtons

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4
Q

What is a neurodegenerative disease involving muscle

weakness and atrophy due to degeneration of motor neurons in the spinal cord and cerebral cortex?

A

Amyotrophic lateral sclerosis (ALS)

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5
Q

What is a neurodegenerative disease characterized by

dementia due to degeneration of neurons in the hippocampus and cerebral cortex?

A

Alzheimers

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6
Q

What are three elements that may contribute to Parkinson’s disease?

A

Genetic predisposition
Environmental toxins
Viral Infections

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7
Q

What is a progressive neurological disease characterized by impaired voluntary movement and tremors at rest, bradykinesia, muscular rigidity, mask like facce and impaired speech?

A

Parkinson’s disease

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8
Q

What dopaminergic neuronal population is lost in Parkinson’s disease? How much of the population in lost before symptoms are seen? What is another hallmark of these neurons?

A

Nigrostriatal Dopamine Pathway
80% neuronal loss before symptoms
Lewy bodies in the surviving neurons

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9
Q

What is the protein that aggregates to form Lewy bodies?

A

alpha-Synuclein

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10
Q

Parkinson’s disease is considered an idiopathic disease. Why?

A

Because the exact cause of the disease is not known

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11
Q

What is the difference between Parkinsonism and Parkinson’s disease? What are 2 known drug causes of Parkinsonism?

A

Parkinsonism, known cause for the symptoms
Parkinson’s, no known cause for disease
Haloperidol and Chlorpromazine

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12
Q

Regarding the normal physiology of the basal ganglia, what is the major dopamine receptor of the direct pathway? What is the effect of dopamine on the direct pathway? What is the net effect of direct pathway activation and how?

A

D1 receptor
Dopamine activates the direct pathway
Facilitation of movement, inhibit GABA to thalamus

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13
Q

Regarding the normal physiology of the basal ganglia, what is the major dopamine receptor of the indirect pathway? What is the effect of dopamine on the indirect pathway? What is the net effect of indirect pathway activation?

A

D2
Dopamine inhibits the indirect pathway
Inhibition of movement

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14
Q

What is the effect of degeneration of basal ganglia neurons of dopamine levels? What is the effect of loss of DA on the direct pathway? Indirect pathway? On overall movement and why?

A

Reduction of dopamine release
Direct pathway now inhibited
Indirect pathway now activated
Movement in inhibited because of less excitatory input to cortex

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15
Q

There are 4 examples of drugs used to treat Parkinsons that increase dopamine synthesis. They are _

A

L-DOPA
L-DOPA/Carbidopa
Entacapone
Entacapone/L-DOPA/Carbidopa

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16
Q

There are 2 examples of drugs used to treat Parkinsons that decrease the catabolism of dopamine. They are _

A

Selegiline

Rasagiline

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17
Q

There are 4 examples of drugs used to treat Parkinsons that act as DA receptor agonists. They are _

A

Bromocriptine
Ropinirole
Pramipexole
Apomorphine

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18
Q

There are 2 examples of drugs used to treat Parkinsons that act as muscarinic antagonists. They are _

A

Benzotropine

Trihexyphenidyl

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19
Q

What is L-DOPA? What Parkinson symptoms does it treat? What is the L-DOPA wearing off effect?

A

Dopamine precursor that crosses BBB
Decreases rigidity and tremor
After 3-5 years, decreased effects of the medication in patients

20
Q

What is the enzyme that metabolizes L-DOPA in the periphery such that only 1-3% of the drug reaches the brain?

A

aromatic l-amino acid decarboxylase

21
Q

What is the basis of peripheral side effects of L-DOPA? What are some examples (5)?

A

Peripheral conversion of DA to NE

nausea, vomiting, anorexia, cardiac arrhythmias, orthostatic hypotension

22
Q

What are 3 general CNS side effects of L-DOPA?

A

Hallucinations
Dyskinesia (invol. movements)
Mood changes

23
Q

What is the medication of choice for the treatment of Parkinson’s disease? What is the mechanism? How does this drug improve the side effect profile of L-DOPA

A
  • L-DOPA/Carbidopa
  • Carbidopa blocks aromatic l-amino acid decarboxylase in the periphery, more L-DOPA reaches brain.
  • Use less L-DOPA, less side effects
24
Q

What is the mechanism if action of entacapone/Levodopa/Carbidopa ?

A

Entacapone blocks catechol-O-methyltransferase, which further decreases metabolism of L-DOPA. More L-DOPA reaches brain

25
Q

What is the mechanism of action of selegiline? How is it used to treat Parkinson’s disease?

A

Selegiline blocks monoamine oxidase B, reduces DA catabolism.
Also reduces formation of neurotoxic free radical
Used as adjunct in combination with L-DOPA

26
Q

What is the reason behind the selegiline side effect of insomnia?

A

It is metabolized to methamphetamine and amphetamine

27
Q

In addition to selegiline, what is another MAO-B inhibitor used to treat Parkinson’s? How is it advantageous over selegiline?

A

Rasagiline

It is not metabolized to methamphetamine and amphetamine, so no insomnia

28
Q

Bromocriptine, ropinirole and pramipexole are all agonists at dopamine receptors. What subtypes do they bind to?

A

Bromocriptine - D1 and D2

Ropinirole and Pramipexole - D2 and D3

29
Q

Bromocriptine, ropinirole and pramipexole are all agonists at dopamine receptors. What is the timeline for their use in treating Parkinson’s disease?

A

Early in disease, can use alone

Late in disease, use in combination with L-DOPA

30
Q

What types of side effects can be expected when using Bromocriptine, ropinirole and pramipexole? (3)

A

Cardiovascular
GI
Neurological

31
Q

What patient population should not use Bromocriptine, ropinirole and pramipexole? (2)

A

Mental Problem patients

Heart problem patients

32
Q

What is apomorphine? How is it administered? How should it NOT be administered?

A

Dopamine receptor agonist
Should be administered IM
Should not be administered IV, causes thrombus or pulmonary embolism

33
Q

What are 2 muscarinic antagonists used in the treatment of Parkinson’s disease? What symptoms do they alleviate (2)? Why do these drugs function in Parkinson’s disease?

A

Benztropine and Trihexyphenidyl
Tremor and rigidity
Usually, nigrostriatal DA neurons inhibit Ach release, lost in Parkinson’s disease

34
Q

Of the drugs that are used to treat Parkinson’s disease, which are likely to produce blurred vision, dry mouth, urinary retention, constipation, aggravation of glaucoma?

A

Benztropine and Trihexyphenidyl

Are muscarinic antagonists, list is of typical antimuscarinic effects

35
Q

What are the symptoms alleviated by amantadine? What are the mechanisms (3)?

A

Reduces bradykinesia and rigidity

  • increase DA release
  • Blocks cholinergic receptors
  • Blocks NMDARs
36
Q

What drug used to treat Parkinson’s is associated with the following side effects: hallucinations and confusion, nausea, dizziness, rash of the low extremeties? What patients should not use this drug?

A

Amantadine

Patients with congestive heart disease, patients with glaucoma

37
Q

What disease is associated with degeneration of basal forebrain cholinergic neurons, amyloid plaque, neurofibrilary tangles and loss of Neurons in the cortex and hippocampus?

A

Alzheimers

38
Q

What are the 2 major pathways affected in Alzheimer’s disease?

A

Nucleus Basalis cholinergic pathway

Septohippocampal cholinergic pathway

39
Q

What are the 3 risk factors for Alzheimer’s disease?

A

Age
Gender
Genes

40
Q

What are the 4 genes associated with Alzheimers? Which are associated with early onset AD and late onset AD?

A

Amyloid precursor protein - APP - Early
Presenilin 1 - Early
Presenilin 2 - Early
Apolipoprotein E4 - Late

41
Q

What are 4 drugs used to treat Alzheimer’s disease that work by inhibiting acetylcholinesterase?

A

Donepezil
Galantamine
Rivastigmine
Tacrine

42
Q

Arrange donepezil, galantamine, rivastigmine and tacrine in order of decreasing half life

A

Donepezil - 70 hrs
Galantamine - 7hrs
Tacrine - 3 hrs
Rivastigmine - 1.5 hrs

43
Q

What are the CYP enzymes responsible for the metabolism of donepezil, galantamine, rivastigmine and tacrine? Which is metabolized by plasmacholinesterase as well?

A

CYP3A4 and CYP2D6

Rivastigmine

44
Q

While donepezil, galantamine, rivastigmine and tacrine are all relatively safe, which is likely to be associated with hepatotoxicity? What are other side effects associated with these drugs?

A

Tacrine

Tremors, diarrhea, anorexia, bradycardia, nausea and vomiting

45
Q

What is memantine? What other drug for AD is it related to? What is its mechanism (i,e. how is it protective)? Benefits are observed when administered with what other drug?

A

NMDA receptor antagonist
Derivative of amantadine
Blocks NMDA receptors and assoc. calcium influx that can be neurotoxic
Beneficial if admin. with donepezil

46
Q

Dizziness, headache, confusion, agitation, constipation. These are all side effects associated with _

A

Memantine

Medical Pharmacology Exam 2 (16 decks)

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