Pharm - Mood Stabilizers & Anti-psychotics Flashcards
Uses for SSRIs
#1: antidepressant also: OCD, PTSD, anxiety or panic disorders...
Fluoxetine
SSRI (Serotonin Selective Reuptake Inhibitor), antidepressant.
Mech: –l SERT (5-HT transporter) = increase synaptic 5-HT & desensitize autoRs => release more 5-HT & neuroadaptation.
SE: anxiety, insomnia, sexual dysfunction, weight loss.
*** risk of suicide early in Tx, esp. in children so add Bx Therapy!
* taper when discontinue.
Duloxetine
SNRI (Serotoninm & NE Reuptake Inhibitor), antidepressant.
Mech: block NE & 5-HT reuptake = more in synapse;
SE: (few, minor) sedation, increased BP, sexual dysfunction, nausea, dizziness, headache.
Uses: anti-depressant, chronic pain (musculoskel./fibromyalgia)
Nortriptyline
TCA (tricyclic antidepressant)
Mech: block central AND peripheral NE & 5-HT reuptake,
–> desensitize autoRs & neuroadaptation;
SE: (MAJOR!) sedation, tachycardia, weight gain, anti-muscarininc/anti-a1 adrenergic effects!
** lethal if overdose! **
Phenelzine
MAOI (MonoAmine Oxidase Inhibitor), antidepressant.
Mech: block monoamine deamination = prevent NE, DA, 5-HT degradation –> increase NTs @ synapse = adaptive changes.
SE: major food-drug interactions w/ tyramine (in cheese, wine, etc.)
** low therapeutic index ** => last resort therapy.
Trazodone
Atypical antidepressant,
- for depression w/ anxiety or inxomnia.
Mech: blocks 5-HT repuptake, Histamine R antagonist, 5-HT 2A R antagonist, 5-HT 1A R agonist (anxiolytic).
SE: sedation (strong), postural hypOtension, sexual dysfunction.
Buproprion
Atypical antidepressant,
- for depression w/ psychomotor retardation; & nicotine cravings!
Mech: blocks DA & NE reuptake
* can REVERSE sexual dysfunction (often taken w/ SSRI)*
SE: lower seizure threshold, nervousness/insomnia.
Mirtazapine
Atypical antidepressant, – for depression w/ Anxiety.
Mech: blocks a-2 adrenergic Rs & 5-HT (2 & 3) Rs
=> increase NE & 5-HT @ synapse.
SE: sedation, dizziness, weight gain.
Lithium Carbonate (aka: Li+)
Mood stabilizer for acute mania, bipolar disorder (manias)…
Mech: unknown
SE: (MANY!)
- persist w/ tolerance: fine tremor, increased thirst/urination
- disappear w/ tolerance: fatigue, muscle weakness, slurred speech, ataxia.
Buspirone
oral, non-sedating anxiolytic.
Mech: 5-HT partial agonist, delayed onset of action (1 wk)
– low risk of abuse, non-sedating = safe for driving, not metabolized by liver –> can use in elderly w/ liver disease! –
Temazepam
Oral benzodiazepine; = sedative, but NOT anesthetic.
Mech: binds to GABA R, potentiates GABA effect (increase Cl- flux)
fast-acting - best for insomnia
SE: anterograde amnesia, confusion, hangover.
- may induce dependence (flu-like Sx)
Alprazolam
oral benzodiazepine & anxiolytic; NOT anesthetic.
Mech: binds to GABA R, potentiates GABA effect (increase Cl- flux)
* intermediate half-life.*
SE: anterograde amnesia, confusion, hangover.
- may induce dependence (flu-like Sx)
Diazepam
Oral benzodiazepine;
Use: anxiolytic, sedative (NOT anesthetic), anti-convulsant via IM.
Mech: binds to GABA R, potentiates GABA effect (increase Cl- flux)
* long half-life* –> best for daytime anxiety.
SE: anterograde amnesia, confusion, hangover.
- may induce dependence (flu-like Sx)
Zolpidem
1st line oral sedative/hypnotic; (NOT anxiolytic)
Mech: binds to same site as benzodiazepines, potentiates GABA a-1.
SE: LOW risk of tolerance, but NO rebound or dependence.
Secobarbital
oral sedative/hypnotic;
Mech: potentiates GABA signalling, –> reversible depression in all tissues.
SE: high abuse risk, toxicity in overdose (cardiac arrest/respiratory compression) –> withdrawal convulsions could cause death!
* pharmacodynamic AND pharmacokinetic tolerance!
Ramelteon
oral sedative/hypnotic;
Mech: M1R & M2R agonist (M = melatonin)
F(x): decrease sleep latency, no abuse risk & not controlled by FDA.
Treatment for insomnia
Short term/situational: Benzodiazepine or Z-drug.
Long term:
1. evaluate sleep hygeine, 2. treat underlying disorders if any
3. Z-drug (Zolpidem) (1st line drug)
Benzodiazepines
(Temazepam, Alprazolam, Diazepam)
= dose-dependent CNS depression (NOT anesthetic)!
* all have same mech of action, but unique pharmacokinetics*
–> binds to GABA R, potentiates GABA effect (increase Cl- flux)
Dangers: tolerance; anterograde amnesia - abuse as date rape.
Warnings/Contraindications for Benzodiazepines
Risk Sxs of : anterograde amnesia, tolerance (esp. @ higher doses).
* avoid self-dose escalation.
Contraindications: sleep apnea, eldery
Pharmacokinetic vs. Pharmacodynamic Tolerance
pharmacoKINETIC: metabolizing enzymes upregulated –> decrease drug availability, lower lethal dose!
pharmacoDYNAMIC: de-sensitization of target (R) –> same amt drug but less effect.
Fluphenazine
oral typical anti-psychotic (phenothiazine type),
Mech: strong D2 (dopamine) antagonist, NOT anticholinergic
SE: motor effects (parkinsonism, tardive dyskinesia), low sedative effects
Haloperidol
oral/IV/IM typical anti-psychotic (butyrophenone type),
Mech: strong D2 (dopamine) antagonist, NOT anticholinergic.
SE: motor effects (parkinsonism & tardive dyskinesia),
Thioridazine
oral anticholinergic typical anti-psychotic,
Mech: strong D2 antagonist
SE: high sedative effects, less motor effects (bc = anticholinergic) than other typicals
–> prevents parkinsonism
Risperidone
oral atypical anti-psychotic,
Mech: strong (BOTH) 5-HT and D2 antagonist (anti-cholinergic)
SE: fewer motor effects (less/no parkinsonism & tardive dyskinesia bc less D2 effect)
* FDA approved for kids*
Paliperidone
oral atypical anti-psychotic,
Mech: = same active metabolite as Risperidone (5-HT2 & D2 antagonist) –> strong for BOTH!
SE: fewer motor effects (less/no parkinsonism & tardive dyskinesia bc less D2 effect)
Iloperidone
oral atypical anti-psychotic,
Mech: 5-HT and D2 antagonist
SE: far less motor effects, but orthostatic hypotension and cardiac (QT prolongation)
Clozapine
oral atypical anti-psychotic, (+ weak anticholinergic);
Mech: strong 5-HT 2 antagonist, weak D2 antagonist;
SE: agranulocytosis (may be fatal!), myocarditis, weight gain/diabetes, Low motor effects
* must do regular blood tests to check for agranulocytosis,
** good for pts w/ tardive dyskinesia **
Olanzapine
oral atypical anti-psychotic,
Mech: strong 5-HT antagonist, weak D2 antagonist; (~same as clozapine)
SE: weight gain/diabetes
* may need higher dose to effectively treat *
Quetiapine
oral atypical anti-psychotic,
Mech: strong 5-HT 2, weak D2 antagonist;
SE: less weight gain, no motor effects
* good for psychosis secondary to Parkinson’s Disease, but otherwise not recommended*
Ziprasidone
oral atypical anti-psychotic,
Mech: strong 5-HT antagonist, weak D2 antagonist;
SE: prolonged QT interval (cardiac risk), no motor effects or weight gain
Aripiprazole
oral atypical anti-psychotic,
Mech: mild presynaptic (nigral) D2 agonist, post-synaptic (striatal) D2 antagonist;
SE: no motor disorders or weight gain, use if other drugs don’t work.
Major and Minor Side Effects caused by both Typical AND Atypical anto-psychotic drugs
Major: Neuroleptic Muscle Rigidity (“NMR”)
Minor (5): orthostatic hypotension, SLUD, sedation, tachycardia/palpitations/dizziness, hyperprolactinemia
major potential drug interactions of anti-psychotics
- Potentiate other CNS depressants (opioids, barbiturates, EtOH)
- Lower Seizure threshold (!)
Neuroleptic Muscle Rigidity
concerning potential symptom of all anti-psychotic drugs,
= high temp, muscle rigidity, autonomic dysregulation, impaired consciousness
Tx: immediately stop anti-psychotic drugs, give muscle relaxer and D2 agonist
Pharmacokinetics/dynamics of anti-psychotic drugs
- High therapeutic index (pretty safe at wide range of doses)
- No tolerance development
- mild dependence
* SHOULD taper use of D2 antagonists (typicals), unless emergency
