Neuropsychopharm Flashcards
neuropsych drugs pt 1
amitriptyline clomipramine fluoxetine sertraline buproprion mirtazapine duloxetine phenelzine chlorpromazine clozapine thioridazine fluphenazine haloperidol olanzapine risperidone quetiapine aripiprazole
Which drugs are used in the treatment of depressive disorders?
SSRIs, SNRIs, Atypical drugs, Tricyclic antidepressants, MAOIs
5-HT uptake inhibitors
SSRIs- fluoxetine, sertraline
SSRI side effects
nausea, insomnia, and sexual dysfunction no food rxns, but dangerous “serotonin reaction” (hyperthermia, muscle rigidity, CV collapse) can occur if given with MAOIs
Do SSRIs have fewer or more adverse effects than TCAs and MAOIs?
less, so overdose risk is reduced
Symptoms of SSRI withdrawal
-dizziness, light-headedness, vertigo or feeling faint, shock-like sensation, paresthesia, anxiety, diarrhea, fatigue, gait instability, headache, insomnia, irritability, nausea or vomiting, tremor, visual disturbances -symptoms begin within 1-7 days after stopping an SSRI
SSRI approved uses
Major Depression OCD Panic disorder Social Anxiety Disorder PTSD Generalized Anxiety disorder PMS (now PDD) Hot flashes associated with menopause
effects on drug metabolism, long half-life active metabolite (7 days or more). now available as a sustained release product. used to treat PMS
fluoxetine
used to treat OCD, PTSD, Panic attacks; less effects on metabolism than fluoxetine, shorter half life.
sertraline
block both 5-HT and NE reuptake, side effect profile is more SSRI-like than TCA-like
SNRI drugs
12-18 hr half-life. also approved for neuropathic pain syndromes, fibromyalgia, back pain, and osteoarthritis pain. What is the drug and which patients to do you have to use caution with?
duloxetine -use caution in patients with liver disease
neuropsych drugs pt 1
amitriptyline clompiramine fluoxetine sertraline buproprion mirtazapine duloxetine phenelzine chlorpromazine clozapine thioridazine fluphenazine haloperidol olanzapine risperidone quetiapine aripiprazole
drugs without typical TCA structure of SSRI or SNRI action. May or may not block catecholamine uptake
Atypical antidepressants
weakly blocks NE and dopamine uptake. No weight gain or sexual dysfunction. what is the drug and what is it also approved for?
bupropion -also approved for nicotine withdrawal and seasonal affective disorder
blocks presynaptic alpha2 receptors in the brain. increases appetite
mirtazapine -good for AIDS patients with AIDS wasting syndrome
blocks NE and 5-HT reuptake; first highly effective drugs for the treatment of depression; now used secondarily to SSRIs and other newer compounds
tricyclic antidepressants
pharmacokinetics of TCAs
rapidly absorbed after parenteral or oral administration; relatively high concentrations are found in the brain and heart.
demethylated to active metabolites which are used as drugs themselves; long plasma half-life (8-100 hrs)
amitriptyline
side effects of TCAs
sedation cardiac abnormalities (due to anticholinergic effects and increased NE concentrations–>palpitations, tachycardia, and arrhythmias) overdoses: acute toxicity (symptoms include hyperpyrexia, hyper- or hypotension, seizures, coma, and cardiac conduction defects)
side effects of TCAs
sedation cardiac abnormalities (due to anticholinergic effects and increased NE concentrations–>palpitations, tachycardia, and arrhythmias) overdoses: acute toxicity (symptoms include hyperpyrexia, hyper- or hypotension, seizures, coma, and cardiac conduction
contraindications for TCAs?
recent MIs
TCAs and drug interactions?
TCAs effect absorption and metabolism of other drugs TCAs block guanethidine uptake sympathomimetic drugs; particularly indirect acting agents
therapeutic uses of TCAs
major depressive disorder (3rd choice) enuresis in childhood- imipramine chronic pain (neuropathic pain that opiates do not handle as well)- amitriptyline OCD- clomipramine and SSRIs
non-selective MAOI
phenelzine
produces mood elevation in depressed patients; may progress to hypomania particularly in bipolar disease; corrects sleep disorders in depressed patients; may produce stimulation in normals; antidepressant action takes about 2 weeks
MAOIs
symptoms of actue toxicity of MAOIs
agitation, hallucinations, hyperpyrexia, convulsions, and changes in bp
what do you have to restrict in patients on MAOIs?
dietary intake of tyramine
therapeutic uses of MAOIs
major depression (not first drug of choice, however) narcolepsy
other treatments for depression
electroconvulsive shock therapy (ECT) transcranial magnetic stimulation (TMS) cortical and subcortical electrical stimulation (still experimental)
nonspecific blockers of NE and 5-HT reuptake
amitriptyline
selective serotonin reuptake inhibitors (SSRIs)
fluoxetine, sertraline
serotonin-norepinephrine reuptake inhibitors (SNRIs)
duloxetine
monamine oxidase inhibitors (MAOI)
phenelzine
drugs with other monamine mechanisms
bupropion, mirtazapine
SSRI-like; used to treat OCD
clomipramine
actions of antipsychotic drugs
(treatments are not curative) decrease in psychotic behavior (negative symptoms of schizophrenia are not well treated by older typical agents) sedation
actions of antipsychotic drugs
decrease in psychotic behavior (negative symptoms of schizophrenia are not well treated by older typical agents) sedation extrapyramidal effects (biggest concern; dystonias, parkinsonism, akathisia, tar dive dyskinesia)
side effects of antipsychotic drugs. How can the long-term side effects be prevented?
extrapyramidal effects (biggest concern; dystonias, parkinsonism, akathisia, tardive dyskinesia); tardive dyskinesia can be prevented by “drug holidays” anticholinergic (dry mouth, blurred vision, urinary retention) orthostatic hypotension neuroendocrine effects (result of dopamine receptor blockade; prolactin effects and gynocomastia) allergic and idiosyncratic effects (liver, blood, and cutaneous) cardiac effects (thioridazine) decreased seizure threshold (particularly phenothiazines) weight gain (diabetes related events are more common with atypicals, particularly olanzapine, risperidone, clozapine, and quetiapine)
what is the potentially lethal side effect of antipsychotic drugs and what does it involve? How do you treat this?
neuroleptic malignant syndrome; potentially lethal hypodopaminergic side effect) hyperthermia, parkinson-like symptoms (muscular rigidity and tremor), mutism, and possible death treatment: cooling and hydration, bromocriptine and dantrolene (muscle relaxants, most common when used with SSRIs or SRNIs
original antipsychotics, currently less commonly used
phenohiazines
phenothiazine; aliphatic side chain; low to medium potency, sedative, pronounced anticholinergic actions
chlorpromazine
phenothiazine; piperidine side chain; low potency, sedative, less exrapyramidal actions, anticholinergic
thioridazine
phenothiazine; piperazine side chain; high potency, less sedative, more exrapyramidal reactions, less cholinergic
fluphenazine
why are atypical antipsychotics used over older typical antipsychotics?
need for better antipsychotic drugs, more acceptable side-effect profile, more efficacious in treating negative symptoms of schizophrenia in general, atypical antipsychotics have lower incidence of extrapyramidal symptoms (better compliance), possible lower incidence of tardive dyskinesia, improve negative symptoms, improve positive symptoms in many antipsychotic-resistant or refractory patients, less impact on cognitive functioning (??), more cost effective (???)
why are atypical antipsychotics used over older typical antipsychotics?
need for better antipsychotic drugs, more acceptable side-effect profile, more efficacious in treating negative symptoms of schizophrenia
atypical antipsychotic agents (5)
clozapine, olanzapine, risperidone, quetiapine, aripiprazone
blocks D4 and 5-HT2 receptors, little effect of D2, muscarinic antagonist, improves positive symptoms even in patients not helped by other drugs, improves negative symptoms
clozapine
side effects of clozapine
lowers seizure thresholds more than other antipsychotics (5-10% incidence) can cause fatal agranulocytosis, which requires monitoring!!
potent 5-HT2 antagonist, D1 and D2 antagonist, some D4, few extrapyramidal symptoms (5-HT>D)
olanzapine
side effects of olanzapine
weight gain and diabetes related adverse events reports of olanzapine abuse no agranulocytosis less seizure incidence than clozapine
combined D2 and 5-HT2 antagonist, greater reduction in negative symptoms and less extrapyramidal symptoms than traditional antipsychotics; paliperidone is the active metabolite, both are available as intramuscular depot preparations
risperidone
side effects of risperidone worse or better than clozapine?
less seizure activity and less antimuscarinic than clozapine
structurally related to clozapine, similar to risperidone and olanzapine in effects on schizophrenia symptoms and side effects; shorter half-life; approved for augmentation in depression. any abuse?
quetiapine; some reports of abuse