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M4 Pharm B3 > 8 - Anti-Parkinsons Drugs > Flashcards

8 - Anti-Parkinsons Drugs Flashcards

1
Q

Neurodegenerative Disorders: Parkinson’s/Huntington’s Disease Defined (2)

A

Loss of neurons from structures of basal ganglia

Results in abnormalities in the control of movement

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2
Q

Neurodegenerative Disorders: Alzheimer’s Disease Defined (2)

A

Loss of hippocampal and cortical neurons

Leads to impairment of memory and cognitive ability

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3
Q

Neurodegenerative Disorders: ALS Defined (2)

A

Degeneration of spinal, bulbar, and cortical motor neurons

Muscular weakness

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4
Q

Parkinson’s Disease Defined (2)

A

Neuronal loss in the substantia nigra

Decrease dopamine the nigrostriatal pathway

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5
Q

Parkinson’s Disease: Less what and more of what?

A

Less dopamine and more acetylcholine

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6
Q

Parkinson’s Disease: Since there’s dopamine, what classes of drugs can be used? (3)

A

Dopamine agonists

Drugs that inhibit breakdown of dopamine

Anti-muscarinics to inhibit ACH

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7
Q

Parkinson’s Disease: Causes - Drugs

A

Typical Antipsychotics (Block D2 Receptors) such as Haloperidol

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8
Q

Parkinson’s Disease: Causes - Genes (2)

A

Alpha-synuclein

Parkin

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9
Q

Parkinson’s Disease: Cause - Chemical (2)

A

MPP

Oxidative stress (free radicals)

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10
Q

Parkinson’s Disease: Symptoms (4)

A
  1. Resting tremor
  2. Muscular rigidity
  3. Bradykinesia
  4. Postural balance impairment
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11
Q

Parkinson’s Disease Drugs: “On Time”

A

When medication is having a benefit and your symptoms are well controlled (e.g. levodopa)

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12
Q

Parkinson’s Disease Drugs: “Off Time”

A

Medication not working and symptoms return

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13
Q

Parkinson’s Disease Drugs: “Wearing-off”

A

Improvement gained from a dose of your medication gradually fades and doesn’t last until next dose (due to short half-life)

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14
Q

Parkinson’s Disease Drugs: “Delayed On”

A

Increased delay after taking your medication before you feel the benefits

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15
Q

Parkinson’s Disease Drugs: “On-Off” Phenomenon

A

Sudden, sometimes unpredictable changes in symptoms varying between mobility and immobility

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16
Q

Parkinson’s Disease Drugs: “Freezing episodes” and Rx

A

Sudden, brief periods of immobility; feet feel like they’re glued to floor

Rx: APOmorphine (very potent opioid dopamine agonist)

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17
Q

Parkinson’s Disease Drugs: Dopamine Precursors (1)

A

Levodopa

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18
Q

Parkinson’s Disease Drugs: Peripheral Decarboxylase Inhibitors (1)

A

Carbidopa

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19
Q

Parkinson’s Disease Drugs: Dopamine Receptor Agonists (CNS) (4)

A

Pramipexole

Ropinirole

Bromocriptine

Apomorphine

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20
Q

Parkinson’s Disease Drugs: Monoamine Oxidase B Inhibitors (2)

A

Selegiline

Rasagiline

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21
Q

Parkinson’s Disease Drugs: COMT Inhibitors (2)

A

Entacapone

Tolcapone

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22
Q

Parkinson’s Disease Drugs: Dopamine Facilitators (Antiviral) (1)

A

Amantadine

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23
Q

Parkinson’s Disease Drugs: CNS Anticholinergic Agents (2)

A

Benztropine

Trihexyphenidyl

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24
Q

Excess ACH causes what?

A

Delirium/psychosis

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25
Q

Decreased ACH causes what?

A

Alzheimer’s

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26
Q

Excess Dopamine in CNS causes what?

A

Psychosis

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27
Q

Decreased Dopamine causes what?

A

Parkinsons

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28
Q

Excess GABA causes what?

A

More sedation, drowsiness, and depression

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29
Q

Decreased GABA causes what?

A

Spasms

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30
Q

Carbidopa inhibits what but can’t?

A

Inhibits AAAD/Dopa decarboxylase

Can’t cross BBB

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31
Q

Pyridoxine (B6) is a co-factor of what, which is why you can’t use it with what drug?

A

Co-factor of AAAD/Dopa decarboxylase

Can’t use it with Levodopa (B6 increases metabolism of Levodopa

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32
Q

Levodopa Outside Brain: What drugs inhibit the enzymes that convert levodopa to other things? (2)

A

Carbidopa (inhibits AAAD)

Entacapone - doesn’t cross BBB (Inhibits conversion to 3-O-Methyldopa)

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33
Q

Levodopa Inside Brain: Levodopa doesn’t get converted to 3-O-Methyldopa by what drug? And what are its side effects

A

Tolcapone (similar to entacapone and crosses BBB)

Causes liver toxicity

34
Q

Levodopa Inside Brain:: Dopamine doesn’t get broken down by what drug?

35
Q

Parkinson’s Drugs: What drug binds to D1 and D2 Receptors (1)

A

Bromocriptine

36
Q

Parkinson’s Drugs: Levodopa/L-Dopa Defined (3)

A

Crosses BBB

Prodrug converted to dopamine by AAAD

Stimulates D2 receptors

37
Q

Parkinson’s Drugs: L-Dopa is given in combo with drug?

A

Carbidopa: dopa decarboxylase inhibitor –> peripheral metabolism of levodopa is reduced

38
Q

Parkinson’s Drugs: Levodopa Clinical Use (2)

A

Used in the first few years before tolerance develops

Most effective on BRADYKINESIA and RIGIDITY

39
Q

Parkinson’s Drugs: Levodopa Pharmacologic Effects (3)

A

Tolerance to both beneficial and adverse effects occurs with time

Most effective in the first 2-5 years of treatment

After 5 years –> dose-related dyskinesia, inadequate response or toxicity

40
Q

Parkinson’s Drugs: L-Dopa + Cabidopa name and particularly effective in relieving what?

A

Sinemet

Relieving bradykinesia

41
Q

Parkinson’s Drugs: L-Dopa Adverse Effects - GIT (3)

A

80% of patients: anorexia, NV; with tolerance over time (Rx trimethobenzamide)

Avoid phenothiazine emetics (chlorpromazine, metaclopramide)

Effects become less frequent with L-Dopa + Carbidopa

42
Q

Parkinson’s Drugs: L-Dopa Adverse Effects - Cardiovascular (3)

A

Cardiac Arrhythmias

Tachycardia

Postural hypotension

43
Q

Parkinson’s Drugs: L-Dopa Adverse Effects - Behavioral Effects (8)

A

Depression, Anxiety, Agitation, Insomnia, Confusion, Hallucinations, Nightmares, and Euphoria

44
Q

Parkinson’s Drugs: L-Dopa Adverse Effects - Dyskinesias

A

Choreoathetosis of the face and distal extremities

45
Q

Parkinson’s Drugs: L-Dopa Adverse Effects - Fluctuations in Response (2)

A

Wearing off reactions or end of dose akinesia: rigidity and akinesia return rapidly at the end of the dosing interval

On-off phenomenon: off-periods of marked akinesia alternate with on-periods of improved mobility

46
Q

Parkinson’s Drugs: L-Dopa Adverse Effects - Miscellaneous (2)

A

Mydriasis that may precipitate acute glaucoma, gout, and taste abnormalities

Brownish discoloration of saliva, urine, or vaginal secretions

47
Q

Parkinson’s Drugs: L-Dopa: Never give L-dopa with what drugs (3)

A
  1. Non-Selective MAO inhibitors (e.g. phenelzine) –> may lead to hypertensive crisis and hyperpyrexia
  2. Pyridoxine (B6) –> promotes peripheral conversion of L-dopa to dopamine and reduces L-dopa therapeutic effect
  3. Phenothiazines and Butyrophenones –> antagonize by blocking D2 receptors
48
Q

Parkinson’s Drugs: L-Dopa Contraindications (4)

A
  1. Psychotic patients (worsens)
  2. Angle closure glaucoma (mydriasis)
  3. Peptic ulcer
  4. Melanoma & skin lesions
49
Q

Parkinson’s Drugs: Carbidopa is an inhibitor of and is combined with what drug for what? (2)

A

Inhibitor of dopa decarboxylase

Combined with levodopa to reduce peripheral conversion of levodopa to dopamine

50
Q

Parkinson’s Drugs: Action of MPTP causes? MPTP is converted into MPP+ by what enzyme? What drug inhibits this enzyme?

A

Causes irreversible destruction of nigrostriatal dopaminergic neurons in various species

MPTP converted into MPP+ by MAO-B enzyme

Selegiline inhibits MAO-B

51
Q

Parkinson’s Drugs: MPP+ is taken up by, selective in, and inhibits what, producing? (3)

A

Taken up by the dopaminergic neurons

Selective in destroying nigrostriatal neurons

Inhibits mitochondrial reactions, producing oxidative stress

52
Q

Parkinson’s Drugs: Dopamine Receptor Agonists - Bromocriptine (2)

A

Ergot D2 agonist

Long term use associated with cardiac valve fibrosis

53
Q

Parkinson’s Drugs: Dopamine Receptor Agonists - Pramipexole (3)

A

Preferential affinity for the D3 family of receptors

Used in patients with advanced Parkinson’s disease

Neuroprotective - scavenge hydrogen peroxide

54
Q

Parkinson’s Drugs: Dopamine Receptor Agonists - Ropinirole (1)

A

Relatively pure D2 receptor agonist

55
Q

Parkinson’s Drugs: Apomorphine is used for?

A

Freezing episodes (unable to move)

56
Q

Parkinson’s Drugs: Apomorphine Defined (2)

A

Potent dopamine agonist

Provide quick relief (rescue) of Off-periods/freezing episodes of akinesia in patients on dopaminergic therapy

57
Q

Parkinson’s Drugs: Apomorphine Adverse Effects (2)

A

Nausea and Vomiting (pre-treat with Trimethobenzamide)

Dyskinesias (Rx benzotropine (anti-muscarinic))

58
Q

Parkinson’s Drugs - MOA Oxidase B Inhibitors: Selegiline Defined

A

A selective irreversible inhibitor of MAO- B at normal doses, increase dopamine in basal ganglia

59
Q

Parkinson’s Drugs - MOA Oxidase B Inhibitors: Selegiline (4)

A

Enhances and prolongs the antiparkinsonism effect of levodopa

Reduce mild on-off or wearing-off phenomena.

Adjunctive therapy for patients with a declining or fluctuating response to levodopa

Neuroprotective effect (decreases free radicals), inhibits progression of disease

60
Q

Parkinson’s Drugs - MOA Oxidase B Inhibitors: Rasagiline Defined and Adverse Effects (2 overall)

A

It is more potent than selegiline in
In preventing MPTP induced parkinsonism

Adverse effect: May enhance adverse effects of levodopa

61
Q

Parkinson’s Drugs: COMT Inhibitors - Tolcapone and Entacopone (3)

A

Also prolong action of levodopa by diminishing its peripheral metabolism

Levodopa clearance is decreased and relative bioavailability of levodopa is increased

Helpful in patients receiving levodopa who have developed response fluctuations

62
Q

Parkinson’s Drugs: COMT Inhibitors - Main Adverse Effect

A

Orange discoloration of the urine

63
Q

Parkinson’s Drugs: COMT Inhibitors - Tolcapone Adverse Effect

A

May cause an increase in liver enzyme levels and fulminant hepatic failure

64
Q

Parkinson’s Drugs: Amantadine is an?

A

Antiviral agent that’s a prophylaxis of influenza A2

65
Q

Parkinson’s Drugs: Amantadine MOA (1) and Use (1)

A

May potentiate dopaminergic function by influencing the synthesis, release, or re-uptake of dopamine

It has been used alone to treat early PD and as an adjunct in later stages

66
Q

Parkinson’s Drugs: Amantadine Adverse Effects (1)

A

Livedo reticularis

67
Q

Parkinson’s Drugs: Muscarinic Receptor Antagonists: Benztropine, Trihexyphenidyl and Diphenhydramine - Treat drug induced dyskinesia but has no effect on what symptom of Parkinson’s?

A

Improve the tremor and rigidity of parkinsonism but have little effect on bradykinesia.

Used in combo

68
Q

Parkinson’s Drugs: Muscarinic Receptor Antagonists: Benztropine, Trihexyphenidyl and Diphenhydramine - Adverse Effects

A

Dry mouth, agitation, confusion, constipation, dry mouth, memory loss, urianry retention and tachycardia

69
Q

Parkinson’s Drugs: Vaccine

A

4 injections that will hopefully stimlate an immune system response against alpha-synuclein (abs will attack brain proteins and clear them)

70
Q

Parkinson’s Drugs: Other - Surgical Procedures (3)

A

Thalamotomy

Deep brain stimulation

Transplantation of dopaminergic tissue

71
Q

Parkinson’s Drugs: Other - Gene Therapy (1)

A

Adeno-associated virus type 2 as vector glutamic acid decarboxylase (GAD) gene

72
Q

Drugs for restless legs syndrome (5)

A

Pramipexole

Ropinrole

Diazepam

Gabapentin

Opiates

73
Q

Wilson’s Disease defined

A

Decreased serum copper and ceruloplasmin

74
Q

Drugs for Wilson’s Disease (3) and do what?

A

Penicillamine, Trietntine

Chelates copper, tetraothiomolymbdate, and zinc

75
Q

Drugs for ALS (4)

A

Baclofen (GABA agonist)

Tizanidine (alpha 2 agonist)

Gabapentin

Riluzole (inhibits sodium channels and decreases glutamate)

76
Q

Drugs for MS (6)

A

Interferons

Natalizumab

Mitoxantrone

Glatiramer

Fingolimod

Dalfampridine

77
Q

Alzheimer’s Disease Gross

A

Marked atrophy of the cerebral cortex and loss of cortical and subcortical neurons

78
Q

Alzheimer’s Drugs: Acetylcholinesterase Inhibitors (4)

A

Rivastigmine

Donepezil

Gallanatamine

Tacrine

79
Q

Alzheimer’s Drugs: Glutamate receptors antagonist (1)

A

Mementaine

80
Q

Huntington’s Disease: NT Levels

A

Decrease GABA and ACH

Increase dopamine

81
Q

Huntington’s Disease: Drugs (3)

A

Tetrabenzine and Reserpine - inhibits VMAT, and limits dopamine vesicle and packaging and release

Haloperidol

M4 Pharm B3 (9 decks)

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