Psych Meds Flashcards
1
Q
Lithium: MOA, uses
A
Classical mood stabilizer
- Effective, cheap
Works on multiple neurotransmitters (5-HT, NE, Glu, GABA, DA)
- Modifies 2nd messenger system
Efficacy:
- Bipolar mania
- Prophylaxis
- Adjunct to antidepressants
- Acute tx of mania/agitation
- Better at preventing mania than depression
2
Q
Lithium: Interactions/AEs
A
Side effects:
- Tremor
- Polyuria +/- polydipsia
- Weight gain
- Cognitive slowing/memory problems
- Hypothyroidism
- Decreased renal function
- Dermatologic side effects (eg acne)
- Nausea/vomiting/diarrhea
Pregnancy: category D
- Avoid in 1st trimester (Ebstein’s abnormality, birth defects= congenital defect in heart, septal leaflet of tricuspid valve towards apex of R ventricle)
- can use after 1st trimester if benefits > risks
- Do NOT use breastfeeding
Med interactions:
- Decreased Li Levels:
- Urinary alkalinizers
- Sodium-Bicarb
- Verapamil - Increased Li Levels:
- Diuretics
- NSAIDs
- Antipsychotics (increased toxicity)
- Verapamil - Other side effects:
- Iodide Salts –> inc hypothyroidsim
- Bupropion–> increased seizure risk
Food interactions: Decreased Li levels from:
- sodium, caffeine, green tea
levels
* Must monitor thyroid function (TSH) b/c can get hypothyroid which is reversible if d/c Li
3
Q
Lithium: clinical points
A
Key clinical points:
- Narrow therapeutic window
- Maintain blood level 0.8 – 1.2 mmol/liter
- Li Toxicity
- Coarse tremor, muscle fasciculations, confusion, stupor
- Slurred speech, ataxia, vomiting, arrhythmia & seizures
- Kidneys – Li is excreted through kidneys
- Monitor kidney fnct
- Pt with kidney disease may have inc Li
4
Q
Anticonvulsants (mood stabilizers): MOA
A
Act on sodium, potassium and calcium ion channels in cell
- This modulation changes both excitatory (GLU) and inhibitory (GABA) neurotransmission
- Augment synthesis/release of GABA
- Inhibit reuptake and breakdown of GABA
- Decrease release of Glu
5
Q
Valproic acid
A
MOA: Increases GABA, decreases NMDA
Uses:
Anticonvulsant
- Acute mania
- Seizure disorder
- Bipolar prophylaxis
Side effects: - Weight gain - Sedation - GI upset (take with food) - Dizziness - Hair Loss - Maybe be associated with polycystic ovaries - Thrombocytopenia* More common in children - Pancreatitis * - Hepatitis *
Pregnancy:
- Category D: neural tube defects
Levels:
- Check levels (50-100 g/mL)
- OD effects seen at ideal 20x blood level
Drugs increasing serum level: CAFE Pi (OTC stuff)
- Cimetidine
- Aspirin
- Fluoxetine
- Erythromycin
- Phenothiazines
- ibuprofen
Drugs reducing serum level: CREP (Antiseizure meds)
- Carbamazepine
- Rifampin
- Ethosuximide
- Phenobarbital
Drugs with metabolism inhibited by VPA: I sAW LAND
- Amitriptyline
- Warfarin –> increase risk of bleeding b/c VPA displaces it
- Lamotrigine
- AZT
- Nortriptyline
- Diazepam
6
Q
Carbamazepine
A
Acts on Na and K channels to enhance GABA availability
NOT FDA APPROVED for bipolar d/o
- Except for carbamazepine XR
- FDA approved for acute mania
- Used off label for mixed & rapid-cycling bipolar d/o
- Not used 1st line b/c interacts with SO MANY MEDS**
- used for pts who have failed other meds
FDA approved for siezure d/o
Side effects:
- Sedation
- Dizziness
- Fatigue
- Nausea/vomiting/constipation/diarrhea
- Ataxia
- Thromboycytopenia* & aplastic anemia*
- Hepatitis*
- Exfoliative dermatitis, toxic necrolysis (aka Stephens-Johnson syndrome)
Pregnancy: Category D
- Associated with Spina Bifida
Clinical points:
- Avoid in patients with cardiac, hematological, liver or kidney disease
- Think of it as a drug that interacts with almost everything
- If you ever rx must check it doesn’t interact with other meds pt is taking
- Must have 14 day washout period before initiate MAOI
7
Q
Lamotrigine
A
MOA – dec the excitatory actions of Glu via interference with Na channels
- Effective for bipolar d/o: Mania, hypomania & depression
Side effects:
- Sedation
- Dizziness
- Ataxia
- Decreased coordination
- Headache
- Nausea/vomiting
- Toxic epidermal necrolysis* (aka Stevens-Johnson syndrome)
- 10% will get rash
- Subset will go on to S-J
- Must d/c if ANY rash
Pregnancy:
- Avoid in first trimester
- Use after first trimester if other meds don’t work
- Avoid in breast feeding – risks unknown
8
Q
Use of Antipsychotics
A
- Psychotic illness – unable to distinguish unreality from reality
- Schizophrenia, Bipolar Mania, Depression w/psychosis - Augmentation of antidepressant (eg SSRI)
- Aripiprazole & Quetiapine - Mood Stabilizer – Acute Mania
- Quetiapine, olanzepine, aripiprazole, ziprasidone & risperidone - Mood Stabilizer – Maintenance
Olanzapine & aripiprazole
9
Q
Typical antipsychotics (1st generation)
A
Dopamine antagonists
- Chlorpromazine
- Thiordazine
- Prochlorperazine (compazine)*
- Trifluoperazine
- Haloperidol
MOA:
- Competitively block Da receptors (D2, D3 & D4 subtypes)
- D2 receptors located in limbic, extrapyramidal & endocrine structures
- D3 & D4 subtypes located primarily in limbic structures - Receptors linked to enzyme adenyl cyclase via G protein which inhibits activation of enzyme
- Blocking receptors decreases +sx (mesolimbic pathway)
- Bind to D2 receptors 10-50x more avidly than D3 receptors
Potency:
- Drug’s ability to bind to DA receptor
1. High potency: - Low anticholinergic & low sedating properties
- Fewer CV abnormalities
- Higher rate of EPS (extrapyramidal symptoms): ex. haloperidol & fluphenazine
2. Low potency: opposite profile
10
Q
Atypical antipsychotics (2nd generation antipsychotics)
A
Serotonin/Dopamine antagonist
- Clozapine
- Risperidone
- Olanzapine
- Quetiapine
- Ziprasidone
Partial Dopamine agonist:
- Ariprazole
MOA:
- More selective for mesolimbic Da pathway (origin + symptoms)
- Less active on nigrostriatal pathway (origine EPS)
- Competitively block serotonin receptors (5-HT2 subtype)
- Have >5x binding affinity for 5-HT2 than D2 : 5-HT2 located in cortical structures where neg sx thought to originate
- Higher degree of binding/blockade of D4 & D3 receptors vs D2
- D4 & D3 receptors located in limbic structures where + sx thought to originate - Blockade of 5-HT receptors therefore:
- Improves negative & positive sx
- Dec EPS
11
Q
Dopaminergic Pathways in Brain
A
- Mesolimbic Pathway: Midbrain ventral tegmental area (VTA= vestibule to addiction) –> nucleus accmbens (pleasure pathway)
- Pathway of all things pleasurable
- Pathways for drugs of abuse to create “high” feeling
- Pathway of delusions and hallucinations of pscyhosis - Mesocortical Pathway: Midbrain ventral tegmental area –> limbic cortex
- May have role in mediating +/- psychotic symptoms
- May have role in cognitive side effects of 1st gen antipsychotics - Nigrostriatal Pathway (nigrostride)
- Substantia nigra –> basal ganglia
- Controls movement - Tuberoinfundibular Pathway
- Hypothalamus –> anterior pituitary gland
- Controls prolactin secretion
- Dopamine & prolactin have an inversely proportionate relationship (i.e. inc of one –> dec of the other)
12
Q
Dopamine hypothesis of Schizophrenia
A
- Hyperdopaminergic activity in mesolimbic system –> positive sx
- Delusions
- Hallucinations
- Catatonia
- Thought disorder - Hypodopaminergic activity in mesocortical system –> neg sx
- Apathy
- Motor retardation
- Social withdrawal
13
Q
Aripirazole
A
Second Generation Antipsychotic: partial DA agonist
- Establishes balanced dopamine availability
- Acts as antagonist when there is xs Da
- Mesolimbic pathway - Acts as agonist when there is too little Da
- Nigrostriatal pathway & frontal lobes
- Serotonin 2A antagonist
- Partial serotonin 1A agonist - Aripiprazole only drug in this class
14
Q
AEs of Antipsychotics
A
Antipsychotics act on other recptors–> Results in MORE side effects:
- Anticholinergic (M1)
- Dry mouth
- Mydriasis
- Urinary retention
- Constipation - Antihistaminergic (H1)
- Weight gain (can be VERY significant): Olanzapine, Risperidone, Quetiapine
- sedation - Alpha Adrenergic Blockade
- Orthostatic (postural) hypotension
- sedation - Dopaminergic Blockade
- EPS
15
Q
Extrapyramidal symptoms of Antipsychotics
A
Due to Da blockade or depletion in basal ganglia
Parkinsonian Syndrome:
- Due to blocking D2 receptors in striatum
- Muscle rigidity, slowed movements, shuffling gate
- Resting tremor, mask-like facial expression
- Cogwheel rigidity
- Acute Dystonia
- Prolonged muscular spasm tx’d with diphenhydramine or benztropine
Tardive Dyskinesia:
- Abnormal writhing movement of tongue, face, limbs or trunk
- Theory caused by D2 blockade in hypthalamus & striatum causing upregulation of D2 receptors
- More common with FGA’s
- May not EVER go away (50%)
Neuroleptic Malignant Syndrome
- Life threatening must recognize and tx ASAP!
- More common in men
- Hyperthermia, hypertension, tachycardia
- Tremor, seizures, dyskinesia
- Must stop antipsychotic
Akathisia
- Absolutely awful subjective feeling of motor restlessness
- Give pt diphenhydramine, propanolol or benzodiazepine
16
Q
Other clinical side effects of antipsychotics
A
- Endocrine:
- Blockade of D2 in hypothalamus &/or anterior pituitary
- Inc prolactin –> gynecomastia in men and galactorrhea in women
- Dec gonadotropin –> amenorrhea
- Dec growth hormone, Luteinizing hormone & ACTH - Cardiovascular
- Prolongation of QT interval on EKG (Torsades)
- Can result in potentially lethal cardiac arrhythmia - Metabolic Syndrome:
- MONITOR: weight, waist circumference, fasting glucose, fasting lipids, blood pressure
- Risk of heart disease, stroke, diabetes (increased BP, insulin, abdominal fat, cholesterol
* * INCREASED risk for Second generation antipsychotics
17
Q
Antipsychotic prescribing: clinical guidelines
A
Choose based on past response and side effects
- SGA’s generally 1st line, especially if past tardive dyskinesia
- Avoid SGA’s for behavioral disorders in patients with dementia –> inc mortality
- Pregnancy category C
- FGA’s – slight inc in anomalies
- SGA’s – need inc data - Smoking increases metabolism of antipsychotics
- Must adjust dose for patients with liver or kidney disease
18
Q
Clozapine
A
2nd gen antipsychotic (Serotonin/Dopamine Antagonist)
AEs:
- Risk of agranulocytosis & neutropenia must monitor CBC : This is 1+ times/mn depending how long pt has been on
- Risk seizures on doses > 600mg/day
- Myocarditis – rare
- Low association with TD
- Sedation, orthostatic hypotension & hypersalivation
Use:
- For patients who have failed 2+ other antipsychotic agents
- Decreased risk of suicide in patients with schizophrenia
