Parkinson's Disease, Psychosis & Neurocognitive Disorders Pharm

Question 1

Parkinson’s Disease

Answer 1

Degeneration of DA neurons in the extrapyramidal motor pathway; DA & ACh imbalance resulting in GABA stimulation
Symptoms –> rigidity, bradykinesia, tremors, masked facies (don’t show a lot of emotion), pill-rolling
Treatment –> anticholinergic drugs, DA replacement, DA agonists, MAO-B inhibitors, COMT inhibitors (most people are on a cocktail of meds depending on symptoms & severity)

Question 2

Carbidopa-Levidopa

Answer 2

Dopamine replacement
MOA –> carbidopa prevents the breakdown of levodopa in the bloodstream & levodopa converts to DA
Common side effects –> anticholinergic (dry mouth, constipation), N/V (give with food), hypotension, dizziness, weakness, dark urine
Adverse reactions –> rebound parkinsonism, agranulocytosis, cardiac arrhythmias, NMS
MVIs are contraindicated, moderate alcohol can antagonize the drug effects, high protein diet may increase BUN and decrease effectiveness of drug in crossing the blood-brain barrier

Question 3

Carbidopa-Levodopa Administration Considerations

Answer 3

• MVIs are contraindicated (they may contain Vit B6 which decreases effects of levodopa)
• moderate alcohol can antagonize the drug effects
• high protein diet may increase BUN and decrease effectiveness of drug due to issues crossing the blood-brain barrier

Question 4

Psychosis exists in these disorders

Answer 4

• schizophrenia (positive symptoms-ie. hallucinations, delusions)
• mania & depression (mood stabilizer)
• drug/med intoxication
• drug/med withdrawal
• general medical conditions
• delirium
• traumatic brain injury
• dementia

Question 5

Antipsychotic black box warning

Answer 5

• increased mortality in elderly patients with dementia-related psychosis treated with antipsychotic meds r/t cerebrovascular adverse events including stroke, heart failure
• when used as a mood agent, black box warning for increased suicidal thoughts/ideation (usually upon starting & dose changes)

Question 6

Antipsychotic therapy

Answer 6

• Goal: complete remission/significant reduction of psychotic symptoms
• maximum relief: achieved after several weeks or months
• maintenance doses: 6-12 months, gradual taper to lowest dose
• chronic persistent illness = long-term (but always question the need for continuation)

Question 7

Conventional Antipsychotics (FGAs)

Answer 7

• classified by potency in relationship to their ability to antagonize CNS D2 receptors
• aren’t specifically selective to D2 receptor pathways that are associated with psychosis (i.e.. slam DA receptors when they can)

Question 8

Atypical Antipsychotics (SGAs)

Answer 8

• less D2 receptor blockade than traditional

- antagonize other D receptor subtypes & 5HT2 receptor subtype

Question 9

1st generation antipsychotics classification by potency

Answer 9

Chlorpromazine –> low potency phenothiazine
Fluphenazine –> high potency phenothiazine
Haloperidol –> high potency non-phenothiazine; 1st line med for non-psychiatric hospitalized patients experiencing agitation and/or delirium

Question 10

Conventional Antipsychotics MOA

Answer 10

MOA –> block D2 receptor sites in mesolimbic pathway (positive symptoms) & block other D2 receptors (causing EPSE, muscular and other side effects)

• includes partial histamine antagonism, acetylcholine blockage & antagonism of alpha-adrenergic system
• 2 groups: phenothiazines (block NE, causing sedative/hypotensive effects) vs nonphenothiazines (block DA)

Question 11

Antipsychotic adverse effects

Answer 11

Occur with all antipsychotics, but more commonly seen with 1st gen

• Extrapyramidal side effects
• Neuroleptics toxicity
• Neuroleptic malignant syndrome
• Agranulocytosis
• Hypotension (blocks alpha-1; tolerance develops in 2-3 months)
• Sedation (blocks histamine; some block NE)
• Seizures (lower the seizure threshold)
• Arrhythmias associated with sudden death (i.e. QT prolongation)
• Anticholinergic effects: dry mouth, nasal congestion, blurred vision, urinary hesitancy/retention, constipation
• Dermatological: pruritic maculopapular rashes, jaundice
• Metabolic: glucose dysregulation, weight gain & lipid dysregulation

Question 12

Extrapyramidal side effects (EPS)

Answer 12

• drug-induced movement disorders caused by DA receptor blocking agents
• Acute dystonia
• Parkinsonism
• Akathisia
• Tardive dyskinesia

Question 13

Acute dystonia

Answer 13

• severe muscle spasm that develops within 1st few days, often within hours or initiation or dose change
• common muscles involved: tongue, neck, face (oculogyric crisis-involuntarily looking upward), back, laryngeal (airway obstruction)

Question 14

Parkinsonism

Answer 14

• develops within the 1st month & tends to resolve spontaneously if treated or med is stopped
• common S/S: akinesia (lack or slowness of movement), muscle rigidity & posture changes, tremor, hyper salivation & drooling, mask-like facies

Question 15

Akathisia

Answer 15

• extremely uncomfortable profound sense of restlessness characterized by inability to sit or stand still
• subjective reports of internal feelings of restlessness, anxiety & uneasiness
• develops within first 2 months of use

Question 16

Tardive dyskinesia

Answer 16

• more serious side effect, but usually mild
• common S/S: involuntary twisting movements, beginning with tongue/face & progressing to limbs/trunk
• sometimes irreversible
• onset: months to years

Question 17

Treatment of EPS other than TD

Answer 17

Propanolol –> for akathisia
Benztropine & Trihexyphenidyl –> blocks central cholinergic receptors (DA deficiency results in excess cholinergic effects)
Diphenhydramine –> histamine blocker; treats EPS by suppressing central cholinergic activity & prolonging action of DA by inhibiting its re-uptake & storage

Question 18

Treatment for TD

Answer 18

-removal of causative drug via slow taper
-vesicular monoamine transporter 2 inhibitors
-switch to another agent with less potential for TD
-Clonazepam
-Vitamin E
(Convention may make it worse)

Question 19

Neuroleptic Toxicity

Answer 19

Overdose: hypotension, CNS depression, EPSEs (death by overdose is rare)
Atropine psychosis: psychotic delirium caused by excessive anticholinergic effects
-S/S: agitation, confusion, tachycardia, dry flushed skin

Question 20

Neuroleptic malignant syndrome

Answer 20

-caused by prolonged use
-fatality rate: 10-20%
Primary symptoms: (caused by D2 blockade)
-tongue: bag full of worms (tightly bound & wiggling around)
-severe rigidity & tremors
-sudden high fever
-severe sweating & drooling
-autonomic instability
-changing LOC with possible progression to seizures or death

Question 21

Agranulocytosis

Answer 21

severely decreased WBC

• suspect if develops sore throat, fever, malaise during first two months of initiating medication
• potentially fatal due to overwhelming infection

Question 22

Adverse effect differences by potency

Answer 22

Low potency –> more anticholinergic effects, sedation & hypotension common
High potency –> anticholinergic side effects less common, more ESPs

Question 23

Antipsychotic adverse effects by sex

Answer 23

Females –> gynecomastia, galactorrhea, menstrual irregularities, decreased libido & impaired ability to achieve orgasm
Males –> gynecomastia, decreased libido, erectile & ejaculatory dysfunction

Question 24

Benefits of Atypical antipsychotics

Answer 24

• effective for both positive & negative symptoms of schizophrenia
• cause fewer EPSEs
• less risk for developing TD

Question 25

Negative Symptoms & Atypical antipsychotics

Answer 25

- negative symptoms are the result of hypodopaminergic process in the frontal lobe - selective subtypes of 5HT inhibit DA & drugs that antagonize these subtypes will increase frontal lobe DA

Question 26

Adverse effects atypical antipsychotics

Answer 26

- can have some side effects as first generation - decreased likelihood to cause EPS than FGAs but still possible - more likely to cause weight gain & metabolic syndrome

Question 27

Atypical antipsychotics & metabolic syndrome

Answer 27

-insulin resistance -HTN -high serum lipids -obesity -coagulation abnormalities Product label warning for hyperglycemia & DM

Question 28

Aripiprazole

Answer 28

Dopamine-antagonist; Serotonin agonist - Dopamine system stabilizer --> regulates areas where you might need more DA & areas where you might need less DA (stimulates receptors at low levels, blocks at high levels) - has both DA and CNS stimulation blocking side effects & adverse reactions

Question 29

Clozapine

Answer 29

- more effective at symptom management, but with increased risk - significant adverse reactions: seizures, agranulocytosis - requires blood draws for neutrophil counts --> weekly during first 6 months, every other week for second 6 months & every 4 weeks after one year & for duration of treatment

Question 30

Pharm management of schizophrenia

Answer 30

Medication selection & dosing --> individualized based on past hx, trials, family hx & genetic testing Initial & maintenance treatment --> symptoms occur in 1-2 days & gradually improve over the first several months Monitoring for EPSEs & other effects -->AIMS (abnormal involuntary movement scale)

Question 31

Preparations of antipsychotic meds

Answer 31

Traditional meds: oral, intravenous, intramuscular (including DEPOT) Atypical meds: oral, quick dissolve, DEPOT forms (NO IV forms)

Question 32

Depot Preparations

Answer 32

long-acting, injectable formulations used for long-term maintenance therapy of schizophrenia and BPAD -generally given monthly

Question 33

Benefits of depot preparations

Answer 33

- increased adherence (need to come to clinic so you know they get the med) - maximize pharmacokinetic coverage & minimize antipsychotic withdrawal (achieve a steady state) - not influenced by first pass metabolism (decreased potential for drug-drug interactions) - no peaks & troughs of med (reduces side effects, which improves adherence)

Question 34

Interactions with antipsychotics

Answer 34

CNS depressants: antipsychotics increase CNS depression effects Anticholinergics: increased anticholinergic responses Antihypertensives: increased hypotension Levodopa: counteracts effects Smoking: increased metabolism of antipsychotics, decreased med-induces Parkinsonism

Question 35

Caution in combining antipsychotics with...

Answer 35

SSRIs: increased antipsychotic levels, EPSEs, possible serotonin syndrome Lithium & 1st generation AP chlorpromazine: decreased antipsychotic effect TCAs: increased serum levels of both drugs

Question 36

Minimizing adverse/enhancing therapeutic effects

Answer 36

- lowest dose to maintain - treatment of side effects: especially anticholinergic & extrapyramidal - patient teaching: educate about side effects so they recognize them & come to you for help - therapeutic relationship - long-acting injectable meds

Question 37

Neurochemistry to Alzheimer's Disease

Answer 37

- decreased ACh due to a decrease in acetyltransferase (interferes with cholinergic innervation in the brain) - increased glutamate results in overstimulation of NMDA --> increased intracellular calcium --> neuron degradation & cell death - others: NE, 5HT, DA

Question 38

Rivastigmine

Answer 38

Acetylcholinesterase inhibitors - slow progression of DAT by preventing the breakdown of ACh - side effects: N/V, diarrhea, anorexia, dizziness, headache, cholinergic, bronchoconstriction - interactions: traditional antipsychotics, TCAs, antihistamines

Question 39

Memantine

Answer 39

NMDA receptor antagonists - used alone or in combo with cholinesterase inhibitors - MOA: inhibits glutamate, affects NMDA receptors which changes Ca2+ regulation - Adverse effects: dizziness, headache, confusion, constipation

Question 40

Potential Alzheimer's pharm treatments

Answer 40

Nicotine patch --> may make things better or worse NSAIDS --> may protect those with certain genes Vitamin E --> may slow progression Ginkgo Biloba??