neuropsychopharm

Question 1

primary neurotransmitters involved in the actions of psychotherapeutic drugs

Answer 1

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

Question 2

MOA antidepressents

Answer 2

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

Question 3

major depressive disorders- SSRI

Answer 3

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

Question 4

SNRI

Answer 4

block both 5HTm NE reuptake.

DULOXETINE- 12-18 hour half life, use with caution in pts with liver disease

Question 5

atypical antidepressants

Answer 5

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

Question 6

tricyclic antidepressants TCAs

Answer 6

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)

Question 7

MAOi

Answer 7

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

Question 8

psychosis

Answer 8

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 )

Question 9

MOA of antipsychotics

Answer 9

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)

Question 10

antipsychotics SE

Answer 10

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

Question 11

phenothiazines

Answer 11

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

Question 12

atypical antipsychotics

Answer 12

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

Question 13

drugs for mania and bipolar disease

Answer 13

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

Question 14

antiseizure agents that are not lithium

Answer 14

lamotrigine and divalproex (valproic acid)
MOA: alters ion conductances, use dependent effect on Na channels, inhibits the generation of repetitive action potentials

Question 15

valproic acid, divalproex

Answer 15

MOA: blocks repetitive neuronal firing, may reduce T-type Ca++ currents, increases GABA concentration

teratogenicity- spina bifida

Question 16

lamotrigine

Answer 16

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

Question 17

what is anxiety

Answer 17

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

Question 18

Sleep stages

Answer 18

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

Question 19

Benzodiazepines MOA

Answer 19

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

Question 20

buspirone

Answer 20

partial agonist at 5HT1A receptors, also binds to dopamine- D2 receptors, long half life, less sedating than benzos, used in the treatment of GAD

Question 21

flurazepam and lorazepam

Answer 21

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

Question 22

pharmacological effects and drug interaction of benzodiazepam

Answer 22

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,

Question 23

treatment of sleep disorders

Answer 23

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

Question 24

Zolpidem

Answer 24

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

Question 25

drugs used to reduce muscle tone (related to MS injuries)

Answer 25

diazepam- its action in reducing spasticity is at least partly mediated in the sp cd, muscle spasm treatment, reduces muscle tone

baclofen- GABA-mimetic on GABAb receptors–> hyperpolarization, results in decreased release of excitatory NTs like glutamate (reduces spasticity and produces much less sedation)

Tizzanidine- a2 adrenergic agonist that is related clonidine