Neuropsychopharmacology Flashcards
Alternative to Lithium
Carbamazepine- blocks sodium channel at therapeutic concentrations; CNS side effects like sedation, confusion, ataxia
Valproic Acid and Divalproex- first line drug in bipolar disorder and is sedating
Warning on suicidal ideation
Haloperidol- for initial control of manic symptoms
Carbamazepine
Blocks Na channels without interacting with GABA
Pharmacokinetics: unpredictable absorption, hepatic enzyme induction
Clinical use: drug of choice for partial seizures
Toxicity: dose related (Diplopia, ataxia, GI upset, drowsiness, rare blood dyscasias)
Valproic Acid
Block Na, Ca and increase GABA concentration
Pharmacokinetics: bound to plasma proteins and distributes in EC fluid
Clinical use: absence seizures, tonic-clinic seizures and partial seizures
Toxicity: GI upset, weight gain, hair loss, idiosyncratic hepato toxicity and teratogenic causing spinal bifida (not dose related)
Treatment of Anxiety and Insomnia
Benzodiazepines SSRI Buspirone Classical antihistamine Alcohol, cannabis, opiates Barbiturates
Diazepam
Agonist of the benzodiazepine receptor
Fast onset of action (orally taken)
High lipid solubility- rapid absorption and entry into the brain
Rapid redistribution after single dose
Active metabolites change this in multiple dose situation
GABAergic agents: action in reducing spasticity in the spinal cord, and used in patients with muscle spasm of any origin, produces sedation in most patients at the dose required to stop spasms
Zolpidem (ambien)
Agonist of benzodiazepines receptor
Flumazenil
Antagonist of benzodiazepines receptor
Use: overcome overdose with sleeping pills, or wake up quickly after surgery
Buspirone
Not as effective as anti anxiety
Partial agonist for 5-HT 1A- inhibit adenylate cyclase and opens K channels
Also binds to dopamine receptor (not important)
Less sedating benzodiazepines and no cross- tolerance
Does not potentiate other sedative-hypnotics and depressants nor suppress symptoms of their withdrawal
Used to treat generalized anxiety syndrome
Therapeutic effects may take 1 to 2 weeks to occur
Benzodiazepines as antianxiety
Alprazolam (Xanax)
Diazepam (Valium)
Lorazepam (Ativan)
Primarily treat anxiety and decrease anxiety before causing sleep
Benzodiazepines for Hypnotics
Flurazepam- rapid onset of action and long duration
Triazolam- rapid onset of action but ultrashort duration
Lorazepam
Zolpidem (newer “Z” drugs)
Affect on sleep: decreased latency to sleep (quicker and more in stage 1 and 2 sleep), decreased in stage 3, 4 and REM, rebound insomnia upon withdrawal
Adverse effects: daytime sedation (flurazepam), ataxia, rebound insomnia, tolerance and dependence, occasional idiosyncratic excitement and stimulation (in children)
Lorazepam
Anti Anxiety
Less lipophilic than diazepam
Absorption and onset of action are slower
Longer duration of action after single dose- better for sleep
No active metabolites
Benzodiazepines
CNS effects: decreased anxiety, sedation, hypnosis, muscle relaxation, anterograde amnesia (IV admin), anticonvulsant, minimal CV and respiratory actions at therapeutic doses
Drug interaction: produce additive CNS depression with most other depressant drugs like ethanol, other sedative hypnotics and sedating antihistamines
Also problems with drugs that affect hepatic metabolism (cimetidine)
Clinical uses: anxiety states, muscle relaxant (diazepam), sleep disorder, seizure treatment, intravenous sedation and anesthesia, alcohol withdrawal
Withdrawal: anxiety, insomnia, irritability, headache, hyperacusis, hallucinations, seizures
Use gradual dose reduction
Anxiety Treatments
Benzodiazepines
SSRI and SNRI for panic attacks and generalized anxiety
Beta-blockers (performance anxiety)
Other sedatives (rarely)
Zolpidem
Non-benzodiazepines
Bind to BDZ receptor on GABA receptor complex
Weak anxiolytics, muscle relaxant and anticonvulsant
Stage 3 and 4 sleep preserved with minor effects on REM
Duration of action 5-6 hours
Antagonized by Flumazenil
Low abuse liability
Barbiturate
Metabolism: rapidly absorbed and distributed and highly lipid soluble compounds such as thiopental distribute rapidly to brain, induce their own metabolism
Action: Act at GABA site but increased enhanced action
Can cause CNS depression to point of death and respiratory depression
Baclofen
GABAergic agents
GABA mimetic agent that works on GABA B receptors
Results in hyperpolarization causing presynaptic inhibition
Decreased release of excitatory transmitter like glutamate
As effective as diazepam in reducing spasticity with much less sedation
Tizanidine
Alpha 2 adrenergic agonist related to clonidine and enhance presynaptic and postsynaptic inhibition
Same efficacy as Baclofen and diazepam for muscle spasms
Side effects: drowsiness, hypotension, dry mouth and asthenia
Lithium
Mono aren’t cation of the lightest alkali metal
First treatment for bipolar disorder
Blocks manic behavior
No behavioral effects in “normals”
Action: Acts by blcoking enzymes involved in neurotransmission
Therapeutic concentrations-> blocks conversion of IP2 to IP1 and blocks IP1 to inositol (blocks recycling so no second messenger system)
Also affects glycogen synthase kinase (GSK)
Pharmacokinetics: absorbed from oral admin and peak in 2 to 4 hours, half life is 18-24 hours, unbound to plasma proteins
Eliminate in urine 95% with extensive tubular reabsorption
Na affects Li levels (increase Na excretion then increase Li levels in blood so with diuretics)
Narrow therapeutic window (monitor levels)
ACE inhibitors and Ang 2 receptor blockers can raise Li levels
Side Effects: fatigue, tremor, GI symptoms, slurred speech with ataxia, serious toxicity with 2-3 times level (impaired consciousness, rigidity and hyperactive deep reflex, coma), caution with pregnant women
Clinical Uses: treat mania and prevent recurrences of bipolar (only approved use), prevent recurrence of unipolar depression, schizoaffective disorder, cluster headache
Tricyclic Antidepressants
Blockade of transmitter uptake (NE and serotonin)
Pharmacokinetics: rapidly absorbed after parenteral or oral administration and relatively high concentrations found in brain and heart
Side effects: elevation of mood in depressed patients, decreased REM and stage 4, prominent anticholinergic effects, sedation, cardiac abnormality
Overdose: acute toxicity (hyperpyrexia, hyper or hypotension, seizures, coma, cardiac conduction defects)
Drug interaction: guanethidine, sympathomimetic drugs, effects on absorption and metabolism of other drugs
Therapeutic use: major depression, chronic pain (amitryptyline), OcD
Selective Serotonin Re-uptake Inhibitors (SSRI)
Most commonly used anti-depressants
Pharmacokinetics: long and short half life
Side effects: nausea vomiting, insomnia, nervousness, sexual dysfunction
Less risk of overdose
If used with MAO inhibits- hyperthermia, muslce rigidity, cardiovascular collapse
SSRI discontinuing syndrome with shorter acting drugs- dizziness, light headedness, vertigo, anxiety, fatigue, headache, tremor, visual disturbance
Clinical use: major depressive disorder, OCD, panic disorder, generalized anxiety
Fluoxetine
SSRI
Active metabolite with long half life
Sustained release product
Sertraline
Similar in action to fluoxetine with less effects on drug metabolism
Shorter half-life
Serotonin and norepinephrine reuptake inhibitor
Duloxetine
Bupropion
Atypical anti-depressant
Affective disorder treatment, nicotine withdrawal and seasonal affective disorder
Blocks NE and dopamine uptake
