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

8 - Anti-Parkinsons Drugs Flashcards

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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
Decreased ACH causes what?
Alzheimer's
26
Excess Dopamine in CNS causes what?
Psychosis
27
Decreased Dopamine causes what?
Parkinsons
28
Excess GABA causes what?
More sedation, drowsiness, and depression
29
Decreased GABA causes what?
Spasms
30
Carbidopa inhibits what but can't?
Inhibits AAAD/Dopa decarboxylase Can't cross BBB
31
Pyridoxine (B6) is a co-factor of what, which is why you can't use it with what drug?
Co-factor of AAAD/Dopa decarboxylase Can't use it with Levodopa (B6 increases metabolism of Levodopa
32
Levodopa Outside Brain: What drugs inhibit the enzymes that convert levodopa to other things? (2)
Carbidopa (inhibits AAAD) Entacapone - doesn't cross BBB (Inhibits conversion to 3-O-Methyldopa)
33
Levodopa Inside Brain: Levodopa doesn't get converted to 3-O-Methyldopa by what drug? And what are its side effects
Tolcapone (similar to entacapone and crosses BBB) Causes liver toxicity
34
Levodopa Inside Brain:: Dopamine doesn't get broken down by what drug?
Selegline
35
Parkinson's Drugs: What drug binds to D1 and D2 Receptors (1)
Bromocriptine
36
Parkinson's Drugs: Levodopa/L-Dopa Defined (3)
Crosses BBB Prodrug converted to dopamine by AAAD Stimulates D2 receptors
37
Parkinson's Drugs: L-Dopa is given in combo with drug?
Carbidopa: dopa decarboxylase inhibitor --> peripheral metabolism of levodopa is reduced
38
Parkinson's Drugs: Levodopa Clinical Use (2)
Used in the first few years before tolerance develops Most effective on BRADYKINESIA and RIGIDITY
39
Parkinson's Drugs: Levodopa Pharmacologic Effects (3)
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
Parkinson's Drugs: L-Dopa + Cabidopa name and particularly effective in relieving what?
Sinemet Relieving bradykinesia
41
Parkinson's Drugs: L-Dopa Adverse Effects - GIT (3)
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
Parkinson's Drugs: L-Dopa Adverse Effects - Cardiovascular (3)
Cardiac Arrhythmias Tachycardia Postural hypotension
43
Parkinson's Drugs: L-Dopa Adverse Effects - Behavioral Effects (8)
Depression, Anxiety, Agitation, Insomnia, Confusion, Hallucinations, Nightmares, and Euphoria
44
Parkinson's Drugs: L-Dopa Adverse Effects - Dyskinesias
Choreoathetosis of the face and distal extremities
45
Parkinson's Drugs: L-Dopa Adverse Effects - Fluctuations in Response (2)
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
Parkinson's Drugs: L-Dopa Adverse Effects - Miscellaneous (2)
Mydriasis that may precipitate acute glaucoma, gout, and taste abnormalities Brownish discoloration of saliva, urine, or vaginal secretions
47
Parkinson's Drugs: L-Dopa: Never give L-dopa with what drugs (3)
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
Parkinson's Drugs: L-Dopa Contraindications (4)
1. Psychotic patients (worsens) 2. Angle closure glaucoma (mydriasis) 3. Peptic ulcer 4. Melanoma & skin lesions
49
Parkinson's Drugs: Carbidopa is an inhibitor of and is combined with what drug for what? (2)
Inhibitor of dopa decarboxylase Combined with levodopa to reduce peripheral conversion of levodopa to dopamine
50
Parkinson's Drugs: Action of MPTP causes? MPTP is converted into MPP+ by what enzyme? What drug inhibits this enzyme?
Causes irreversible destruction of nigrostriatal dopaminergic neurons in various species MPTP converted into MPP+ by MAO-B enzyme Selegiline inhibits MAO-B
51
Parkinson's Drugs: MPP+ is taken up by, selective in, and inhibits what, producing? (3)
Taken up by the dopaminergic neurons Selective in destroying nigrostriatal neurons Inhibits mitochondrial reactions, producing oxidative stress
52
Parkinson's Drugs: Dopamine Receptor Agonists - Bromocriptine (2)
Ergot D2 agonist Long term use associated with cardiac valve fibrosis
53
Parkinson's Drugs: Dopamine Receptor Agonists - Pramipexole (3)
Preferential affinity for the D3 family of receptors Used in patients with advanced Parkinson's disease Neuroprotective - scavenge hydrogen peroxide
54
Parkinson's Drugs: Dopamine Receptor Agonists - Ropinirole (1)
Relatively pure D2 receptor agonist
55
Parkinson's Drugs: Apomorphine is used for?
Freezing episodes (unable to move)
56
Parkinson's Drugs: Apomorphine Defined (2)
Potent dopamine agonist Provide quick relief (rescue) of Off-periods/freezing episodes of akinesia in patients on dopaminergic therapy
57
Parkinson's Drugs: Apomorphine Adverse Effects (2)
Nausea and Vomiting (pre-treat with Trimethobenzamide) Dyskinesias (Rx benzotropine (anti-muscarinic))
58
Parkinson's Drugs - MOA Oxidase B Inhibitors: Selegiline Defined
A selective irreversible inhibitor of MAO- B at normal doses, increase dopamine in basal ganglia
59
Parkinson's Drugs - MOA Oxidase B Inhibitors: Selegiline (4)
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
Parkinson's Drugs - MOA Oxidase B Inhibitors: Rasagiline Defined and Adverse Effects (2 overall)
It is more potent than selegiline in In preventing MPTP induced parkinsonism Adverse effect: May enhance adverse effects of levodopa
61
Parkinson's Drugs: COMT Inhibitors - Tolcapone and Entacopone (3)
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
Parkinson's Drugs: COMT Inhibitors - Main Adverse Effect
Orange discoloration of the urine
63
Parkinson's Drugs: COMT Inhibitors - Tolcapone Adverse Effect
May cause an increase in liver enzyme levels and fulminant hepatic failure
64
Parkinson's Drugs: Amantadine is an?
Antiviral agent that's a prophylaxis of influenza A2
65
Parkinson's Drugs: Amantadine MOA (1) and Use (1)
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
Parkinson's Drugs: Amantadine Adverse Effects (1)
Livedo reticularis
67
Parkinson's Drugs: Muscarinic Receptor Antagonists: Benztropine, Trihexyphenidyl and Diphenhydramine - Treat drug induced dyskinesia but has no effect on what symptom of Parkinson's?
Improve the tremor and rigidity of parkinsonism but have little effect on bradykinesia. Used in combo
68
Parkinson's Drugs: Muscarinic Receptor Antagonists: Benztropine, Trihexyphenidyl and Diphenhydramine - Adverse Effects
Dry mouth, agitation, confusion, constipation, dry mouth, memory loss, urianry retention and tachycardia
69
Parkinson's Drugs: Vaccine
4 injections that will hopefully stimlate an immune system response against alpha-synuclein (abs will attack brain proteins and clear them)
70
Parkinson's Drugs: Other - Surgical Procedures (3)
Thalamotomy Deep brain stimulation Transplantation of dopaminergic tissue
71
Parkinson's Drugs: Other - Gene Therapy (1)
Adeno-associated virus type 2 as vector glutamic acid decarboxylase (GAD) gene
72
Drugs for restless legs syndrome (5)
Pramipexole Ropinrole Diazepam Gabapentin Opiates
73
Wilson's Disease defined
Decreased serum copper and ceruloplasmin
74
Drugs for Wilson's Disease (3) and do what?
Penicillamine, Trietntine Chelates copper, tetraothiomolymbdate, and zinc
75
Drugs for ALS (4)
Baclofen (GABA agonist) Tizanidine (alpha 2 agonist) Gabapentin Riluzole (inhibits sodium channels and decreases glutamate)
76
Drugs for MS (6)
Interferons Natalizumab Mitoxantrone Glatiramer Fingolimod Dalfampridine
77
Alzheimer's Disease Gross
Marked atrophy of the cerebral cortex and loss of cortical and subcortical neurons
78
Alzheimer's Drugs: Acetylcholinesterase Inhibitors (4)
Rivastigmine Donepezil Gallanatamine Tacrine
79
Alzheimer's Drugs: Glutamate receptors antagonist (1)
Mementaine
80
Huntington's Disease: NT Levels
Decrease GABA and ACH Increase dopamine
81
Huntington's Disease: Drugs (3)
Tetrabenzine and Reserpine - inhibits VMAT, and limits dopamine vesicle and packaging and release Haloperidol

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