neuropsychopharm Flashcards
(25 cards)
primary neurotransmitters involved in the actions of psychotherapeutic drugs
almost all antidepressents affect the functioning of brain biogenic amine (NE, DA, 5HT) some show a selectivity toward a particular amine
neurons containing NE are in the locus coeruleus and innervate nearly every part of the CNS
Neurons containing 5HT are located in 2 groups of raphe nuclei and project to the brain
Neurons containing DA are located in substantia nigra that project to striatum and VTA of midbrain–> prefrontal cortex. Dopamine paths in brain include nigrostriatal, tuberoinfundibular, mesolimbic, mesocortical
MOA antidepressents
biogenic amine systems
Tricyclic antidepressents: block transmitter uptake Ne and 5HT, receptors and second messengers
SSRIs, SNRI (serotonin and NE reuptake inhibitor),
atypical antidepressents Mirtazapine and bupropion
MAOI
major depressive disorders- SSRI
selective serotonin reuptake inhibitors
long and short half life compounds, fluoxetine has a long half life
SE: nausea, vomiting, insomnia, nervousness, sexdysfunction
toxicity less than with TCA and MAOi - less risk of overdose
Serotonin reaction can occur in presence of MAO inhbitors. includes hyperthermia, muscle rigidity and CV collapse. dont use with teens,
SSRI discontinuation syndrome
Use for MDD, OCD, panic, anxiety, PTSD, GAD,
FLUOXETINE (long acting), SERTRALINE (Short half life
SNRI
block both 5HTm NE reuptake.
DULOXETINE- 12-18 hour half life, use with caution in pts with liver disease
atypical antidepressants
no tricyclic structure or SSRI action
Bupropion: nicotine withdrawal and SADs, blocks NE and DA uptake
Miratazapine- blocks presynaptic a2 receptors in brain increases appetite
tricyclic antidepressants TCAs
used secondarily to SSRI for depression
Rapidly absorbed after parenteral or oral admin, found in tbrain and heart, long t.5 up to 100 hrs
produces elevation of mood in depressed pt after about 2-3 weeks, decreases REM and increases stage 4 sleep, prominent anticholinergic effects, sedation, cardiac abnormalities
OD: acute toxicity, symptoms include hyperpyrexia, hyper or hypotension, seizures, coma and cardiac conduction defects
Drug interactions: sympathomimetics (particularly indirect acting ones), effects on absorption and metabolism and other drugs
treats MDD, enurises, chronic pain (AMITIPTYLINE)
MAOi
blocks the oxidative deamination of naturally occuring biogenic amines NE DA and 5HT and ingested amines
MAO is found in the mito in neurons, liver, lung, etc
2 forms MAO- A and MAO-B. Antidepressant action probably due to inhibiton of MAO-A
PHENELZINE: irreversible inhibitors of MAO
antidepressant action takes 2 weeks +, may produce mood elevation in depressed patients that can progress to hypomania, bipolar, acute toxicity can produce agitation, hallucinations, and changes in BP
Tyramine in food can cause hypertensive crisis
psychosis
major mental disorders, loss of contact with reality delusions and hallucinations
Schizophrenia: 2+- symptoms during 1 month period with one being a positive symptom
Dopamine hypothesis (mesolimbic, mesocortical, nigrostriatal, tuberoinfundibular )
MOA of antipsychotics
all interact with dopamine systems
DA receptors
D1- (D1 and D5)- activate adenylyl cyclase
D2- (D2, 3 and 4)- inhibit adenylyl cyclase
Autoreceptors
Atypical antipsychotic drugs- DA and 5HT2 receptors
treats of schizophrenia
decrease in psychotic behaviors CLOZAPINE
sedation, Extrapyramidal actions (results of dopamine receptor blockade)
antipsychotics SE
neuroendocrine effects: result of dopamine receptor blockade, gynecomastia, galactorrhea
anticholinergic action: dry mouth blurred vision, urinary retention
orthostatic hypotension- a adrenergic receptor block
decreased seizure threshold
wt gain: diabetes related events
neuroleptic malignant syndrome: fever, mutism, EPS death
phenothiazines
3 subtypes based on side chain
compounds with aliphatic chains- chlorpromazine (low to medium potency, pronounced anticholinergic action)
compounds with pipeazine- fluphenazine (high potency, less sedative, less anticholinergic, more extrapyrimadal reactions)
butyrophenone derivative- haloperidol
atypical antipsychotics
different side effects and therapeutic profiles
clozapine-less extrapyramidal symptoms, may cause fatal agranulocytosis in a small percentage pf pts, wt gain effective against negative symptoms
olanzapine- like clozapine, pore potent 5HT antagonist, few extrapyrimidal symptoms, no agranulocytosis, wt gain and diabetes risk
risperidone- combined dopamine and serotonin receptor antagonist, low incidence of extrapyrimidal SE, IM injectable
quetiapine- structurally related clozapine with effects on D and 5HT2 receptors shorter half life, abuse potential
aripiprazole: D partial agonist, approved as an adjunct in the treatment of depression
Uses: acute psychotic episodes, chronic shizophrenia, manic episodes, schizoaffective disorder palperidone augmentation of antidepressant action
tourettes syndrome and antiemesis
drugs for mania and bipolar disease
lithium- monovalent cation lightest alkali metal
Pharm- blocks manic behavior (takes time for the effects to appear.
MOA- inhibits recycling inosital substrates, depletes 2nd messenger PIP2 so theres a reduction in release of IP3 and DAG
Absorbed after oral admin, eliminated in urine 95%, tubular REAB
Na levels affect lithium excretion and retention (Thiazide diuretics), narrow therapeutic window, plasma levels can be increased by ACE inhibitors and Ang 2 receptor blockers
toxic reactions and side effects: fatigue and muscular weakness, tremor, GI symptoms, goiter, slurred speech ataxia, serious plasma levels about 2-3 times therapeutic levels (impaired consciousness, rigidity hyper active, coma), important to monitor plasma levels , use in caution in pregnancy
antiseizure agents that are not lithium
lamotrigine and divalproex (valproic acid)
MOA: alters ion conductances, use dependent effect on Na channels, inhibits the generation of repetitive action potentials
valproic acid, divalproex
MOA: blocks repetitive neuronal firing, may reduce T-type Ca++ currents, increases GABA concentration
teratogenicity- spina bifida
lamotrigine
MOA: blocks Na channels at therapeutic concentration, does not appear to interact with GABA systems
less effects on drug metabolism and protein binding than other antiseizure agents used
what is anxiety
symptoms of fight or flight, muscle tension and vigilance, disorders in this classification: separation anxiety disorder, selective mutism, specific phobias, sochial anxiety, panic , agoraphobia, generalized anxiety disorder
Sleep stages
drowsy: alpha waves Stage 1-3 sleep: theta waves Stage 2-12: sleep spindles and K complexes Stage 4: delta wavs REM sleep: sawtooth waves
Slow wave sleep: serotonin
REM sleep: NE and Ach
Sleep disorders: insomnia- disorders of initiating and maintaining sleep
hypersomnia- excessive sleep
Benzodiazepines MOA
act at sites on the GABA receptor chloride ion channel complex
GABA: high on substantia nigra, globus pallidus, hippocampus, limbic structure (amygdala, hypothalamus, spinal cord)
GABAa receptor- associated with chloride ion channel. High concentration in striatum, hippocampus, and sp cd. GABA binding increases chloride conductance, complex made up of several subunits
Benzodiazepine receptor: found on GABA receptor- chloride channel complex, enhances action of GABA, GABA induced chloride channel openings, separate from barbituate site, there are also pure antagonist (FLUMAZENIL) and inverse agonist compounds active at the benzodiazepine receptors
buspirone
partial agonist at 5HT1A receptors, also binds to dopamine- D2 receptors, long half life, less sedating than benzos, used in the treatment of GAD
flurazepam and lorazepam
hypnotics
pharmacokinetics are related to relative lipophilicity, the rate of oral absorption is variable between compounds. Diazepam is rapidly absorbed. Lipophilicity determines rate of entry into CNS, the duration of action after a single dose is related to rate of redistribution from CNS
metabolites of benzodiazepines is complex and active metabolites are formed by most. The active metabolites can have very long half lives. Lorazepam dont form active metabolites, glucuronidation occurs
pharmacological effects and drug interaction of benzodiazepam
affect CNS to produce the following: decrease of anxiety, sedation, hypnosis, muscle relaxation, anterograde amnesia, anticonvulsant
drug interaction: produce additive CNS depression with most other depressant drugs like ethanol, drugs that affect hepatic metabolism
clinical uses of the benzodiazepam: Generalized anxiety disorder, panic disorder (alprazolam), sleep disorders, muscle relaxant, seizure treatment, IV sedation and anesthesia, alcohol withdrawal
abuse liability, dependence and withdral,
treatment of sleep disorders
effects of benzodiazepines: decreased latency to sleep, increases in stage 1 and 2 sleep, less in 3 and 4 and REM sleep, rebound insominia upon withdrawal
Adverse effects: daytime sedation, ataxia, rebound insomnia, tolerance and dependence, occasional excitement and stimulation idiosyncratic
Zolpidem
Ambien,
binds to benzodiazepine receptor, less disruption of sleeo architecture
binds to omega-1 BDZ receptor
antagonized by flumazenil, relative lack of muscle relaxant or anxiolytic effect, a longer acting controlled release form is now available, dose reduction to prevent daytime drowsiness
