Pharm/Drugs for movement and neurodegenerative disorders part deux

Question 1

Simulate Dopamine: Dopamine Agonists

benefits to dopamine agonists vs. L-dopa

Answer 1

Dopamine Agonists

1. do not require enzymatic conversion
2. no toxic metabolites
3. don’t compete with other substances to actively cross into the blood and the BBB
4. have fewer adverse drug reactions (lower incidencec of response fluctions and dyskinesias)

Question 2

Pramipexole

1. uses:
2. what receptor:

Answer 2

Pramipexole

1. uses:
   
   1. mild PD can be used as a monotherapy
   2. advanced PD can be used as an adjunctive therapy
   3. *may reduce AFFECTIVE symptoms (facial expressions)
2. what receptor: Specific for the D3 receptor

Question 3

Drugs that Simulate Dopamine

1. Ropinirole
   
   1. receptor:
2. Rotigotine
   
   1. receptors
   2. administration

Answer 3

Drugs that Simulate Dopamine

1. Ropinirole
   
   1. receptor: D2
2. Rotigotine
   
   1. receptors: D2 and D3
   2. administration: transdermal patch, can be used as adjunct therapy with L-Dopa

Question 4

What is Dopaminergic dysregulation sydrome?

Answer 4

Dopaminergic dysregulation syndrom is seen with L-dopa and dopaminergic agonists.

its a compulsive use of dopaminergic drugs in male patients.

leads to cyclical mood disorders (hypomania/manic), tolerance and impulse control disorders (hypersexuality and pathological gambling)

Question 5

Dopamine Receptor Agonists: Adverse Effects

1. GI:
2. Cardiovascular:
3. Cognitive:
4. Dyskinesias (how are they reversed?)

Answer 5

Dopamine Receptor Agonists: Adverse Effects

1. GI: Anorexia/ N/V
2. Cardiovascular: postural hypotension- at initiation
3. Cognitive: mental disturbances (more severe than with L-Dopa)
   
   1. somnolence, narcolepsy, confusion, hallucinations, psychosis/delusions, etc.
      
      1. psychosis can be treated with Primavanserin
4. Dyskinesias (how are they reversed?) reduce the dose

Question 6

Dopamine Agonist Withdrawl Syndrome

How do you take patients off of a dopamine agonist?

Answer 6

Dopamine Agonists Withdrawl Syndrome is seen in patients who abruptly stop with agonist medication.

It is similar to cocaine withdrawl- anxiety, panic attacks, depression, sweating, nausea, pain, fatigue, dizziness, and drug craving

Symptoms only end by resuming the agonists.

taper medicatio when taking a pt off a dopamine agonist

Question 7

PD drugs Apomorphine:

1. administration
2. MOA
3. use:
4. Adverse Effects:

Answer 7

Apomorphine:

1. administration: SC injection (effect is seen in 10 minutes and lasts for 2 hours)
2. MOA: potent dopamine agonist
3. use: temporary relief of off- periods of akinesia in patients on dopamine therapy
4. Adverse Effects: nausea; pretreat with an anti-emetic (trimethobenzamide)

Question 8

Other PD treatments: ACh Blockers

1. Drugs:
2. dosage:
3. Use:

Answer 8

Other PD treatments: ACh Blockers

1. Drugs: trihexyphenidyl, benztrophine mesylate
2. dosage: start low and increase until benefit or adverse effects are seen
3. Use: improve tremor and rigidity
   
   1. ​has little effect on bradykinesia.

Question 9

Huntington Disease

1. location of mutated gene
2. what is repeated
3. Characteristic Symptoms:
4. Pathology:

Answer 9

Huntington Disease

1. location of mutated gene: chromosome 4
2. what is repeated: glutamine repeat (CAG)
3. Characteristic Symptoms:
   
   1. motor abnormalities: progressive chorea, twitching, lack of coordination, involuntary movements
   2. cognitive decline: dementia, depression, mood swings
4. degeneration of GABA neurons in the basal ganglia may be caused by excessive glutamate toxicity

Question 10

HD treatment-chorea

Tetrabenazine

1. MOA:
2. Metabolism:
3. Adverse drug reactions:
   
   1. Black Box:
4. Other treatment options:

Answer 10

HD treatment-chorea

Tetrabenazine

1. MOA: inhibits vesicular monoamine transporter 2
   
   1. depletes central monoamines
2. Metabolism: CYP2D6
3. Adverse drug reactions: sedation, akathisia (a feeling of inner restlessness), parkinsonism, depression
   
   1. Black Box: Suicide and depression
4. Other treatment options:
   
   1. Antipsychotics (dopamine receptor antagonists- haloperidol, chlorpromazine, risperidone, olanzapine)

Question 11

HD Treatment- Psychiatric

1. Antipsychotics
2. Depression

Answer 11

HD Treatment- Psychiatric

1. Antipsychotics: quietiapine, risperidone, olanzapine, haloperidol, buspirone
2. Depression: tricyclic antidepressants, selective serotonin reuptake inhibitors

Question 12

Multiple Sclerosis (MS)

1. pathology
2. Symptoms
3. trajectory of disease

Answer 12

Multiple Sclerosis (MS)

1. pathology: auto-immune inflammatory demyelinating disease
   
   1. disruption of nerve transmission
   2. accompained by inflammatory response and plaque formation leading to degeneration
2. Symptoms: depend on the area of the brain affected
   
   1. pain, weakness, ataxia, fatigue, problems with speech, vision, gait, and bladder dysfunction
3. trajectory of disease: patients can experience disease progression plateaus, relapses, and remissions

Question 13

MS- Disease modifying agents

1. interferon betas
   
   1. MOA:
2. corticosteroids:
   
   1. uses:
   2. medications
3. what drug can be used to treat severe spasticity?
   
   1. MOA

Answer 13

MS- Disease modifying agents

1. interferon betas
   
   1. MOA: unknown but likely due to immunomodulatory properties (inhibits proinflammatory cytokines)
2. corticosteroids:
   
   1. uses:can be used to treat acute attacks
   2. medications: Prednisone (oral), methylprednisone (IV)
3. what drug can be used to treat severe spasticity? Baclofen
   
   1. MOA: Binds to GABA_B receptor ion channel

Question 14

Amyotrophic Lateral Sclerosis (ALS)

1. pathology
2. symptoms
3. treatment:

Answer 14

Amyotrophic Lateral Sclerosis (ALS)

progressive disease of motor neurons

1. pathology: unknown cause, possible defect in superoxide dismutase
2. symptoms: Muscle wasting, weakness and respiratory failure (leads to death in 2-5 years)
3. treatment: symptomatic
   
   1. Riluzole is the only drug specifically approved for ALS (protects motor neurons from toxic effects of excitatory amino acids) inhibits glutamate signaling

Question 15

Drug-induced Dyskinesias

1. What causes the dyskinesia?
2. what drugs cause them?
3. how do you prevent acute attacks?

Answer 15

Drug-induced Dyskinesias

1. What causes the dyskinesia: long-term exposure to dopamine receptor blockage
2. what drugs cause them?
   
   1. Typical (1st generation) Antipsychotics- haloperidol or fluphanazing
   2. metoclopramide (anti-emetic)
3. how do you prevent acute attacks? treat with benztropine, diphenhydramine, trixhexyphenidyl, diazepam

Question 16

Restless Leg Syndrome

treatment:

Answer 16

Restless leg syndrom is characterized by unpleasant, creaping discomfort and occurs when relaxed leading to an URGE to move.

Treatment: Dopamine agonists (ropinirole, pramipexole, rotigotine)

Question 17

Tardive dyskinesia

1. treatment:
   
   1. drugs:

Answer 17

Tardive dyskinesia-

involuntary, repetitive body movements. May include grimacing, suckling, sticking out of the tongue, or smacking of lips

1. treatment: stop the offending drug- switch to atypical antipsychotics
   
   1. drugs: treat with drugs that interfere with dopamine signaling
      
      1. reserpine, tetrabenazine,

**reducing the dopamine receptor blocker often worsens the dyskinesia

Question 18

Tremor

1. Physiologic postural tremor
   
   1. treatment
2. Essential tremor
   
   1. treatment:

Answer 18

Tremor- rhythmic oscillatory movements

1. Physiologic postural tremor: normal; enhanced by anxiety, fatigue, certain drugs (ones that increase sympathetic tone)
   
   1. treatment: remove offending drug. anxiety can be alleviated with propranolol
2. Essential tremor
   
   1. treatment:
      
      1. beta adrenergic antagonists: propranolol (most effective)
      2. antiepiletics- symptomatic control primidone
      3. alprazolam
      4. thalamic stimulation in advanced cases with no response to pharmacotherapy

Question 19

Dystonia

1. treatment:
   
   1. cervical or focal dystonia

Answer 19

Dystonia

characterized by sustained muscle contractions and produce twisting and repetitive movements or abnormal positions.

1. Classifications based on age, area of the body affected, and origin (idiopathic, familial, environmental)
2. treatment: different patients respond to different therapies
   
   1. cervical or focal dystonia- Botulinium toxin

Question 20

Tics

1. definition
   
   1. simple
   2. complex
   3. chronic multiple tics

Answer 20

Tics

1. intermittent, repeated stereotyped movements or sounds either infrequently or continuously
   
   1. simple- cough, grunt, facial twitch, shoulder shrug
   2. complex- word, phrase, series of events
   3. chronic- Gilles de la Tourette’s syndrome
      
      1. other behavioral issues: compulsions, obsessions
2. Treatment: dopamine receptor antagonists (haloperidol or pimozide

Question 21

Tics

Question 23

Wilson’s Disease

1. Definition
2. treatment:

Answer 23

Wilson’s Disease

1. Definition: disorder of Cu metabolism
   
   1. reduced serum copper and increased copper in the brain and viscera causing tremor, choreiform movements, ridigity, hypokinesia
2. treatment:- remove copper
   
   1. penicillamine- copper chelators
   2. potassium disulfide or zinc sulfate to reduce the intestinal absorption of copper

bind the Cu before it can get to the brain