Intro to neuropsychopharmacology II Flashcards
What are the subdivisions of bipolar disease?
What is experienced during a manic episode?
Bipolar I > Bipolar II > Cyclothymic disorder.
Increased: Self-esteem, talkativeness, distractability, pleasure. Agitation and racing thoughts.
Lithium
What is its mechanism of action?
What are some important drug interactions?
How long-lived is it?
Lithium
Prevents conversion of IP2 to IP1, blocking the IP3/DAG signaling pathway.
It is sensitive to Na+ excretion, so beware: diuretics, ACE inhibitors, and Losartan.
Despite being unbound, its serum half-life is a day or more.
Lithium
What are its indications?
What are its side effects?
Lithium
It is used to treat mania, and may be helpful in unipolar disease and cluster headaches.
It can cause fatigue, tremor, GI upset and ataxia. It can be toxic in high doses, and is contraindicated in pregnant women. VERY NARROW THERAPEUTIC WINDOW.
Carbamazepine
What is the mechanism of action?
What are its indications?
What are some side effects?
Carbamazepine
Blocks voltage-gated Na+ channels.
Used to treat bipolar disorder and epilepsy (partial seizures).
CNS depression: Diplopia, GI upset, drowsiness. In fetuses, increases risk to develop spina bifida.
Valproic Acid
What is the mechanism of action?
What are its indications?
What are its side effects?
Valproic Acid
It blocks voltage-gated Na+ channels (maybe L-type Ca2+ too). Affects GABA.
It is used to treat bipolar disorder and epilepsy (absence/partial/myoclonic seizures)
GI upset, weight gain, hair loss, hepatotoxicity, spina bifida.
Which has better oral absorption: Carbamazepine or Valproate?
Which induces hepatic enzyme?
Valproic acid.
Carbamazepine.
What is the prototypical anxiety disorder? What are its symptoms?
Generalized Anxiety Disorder. Observe ANS arousal and muscle jitters. Patients report intense worry, agitation, and insomnia.
What neurotransmitters regulate REM and slow-wave sleep?
Slow wave sleep is regulated by serotonin.
REM sleep is regulated by norepinephrine.
Describe the GABAnergic synapse. How is GABA eliminated? What is the receptor?
GABA is secreted into the cleft in a Ca2+-dependent exocytosis. It can act on GABA receptors, which are typically pentameric chloride channels. It is eliminated by presynaptic reuptake, and by action of GABA-transaminase.
How do benzodiazepine and barbiturates interact with GABA channels?
What is the only “antagonist” that antagonizes the benzodiazepine receptor?
They bind to separate extracellular sites on the channel, promoting chloride flux (agonists). Note that while benzodiazepines only potentiate the effects of GABA, barbiturates can cause flux by themselves.
Only fluazenil antagonizes the BDZ site.
Buspirone
What is the mechanism of action?
What are its indications?
Describe its kinetics.
Buspirone
It is an agonist for 5-HT1Areceptors. Also antagonizes dopamine receptors.
It is used to treat anxiety disorders, without interacting with other sedatives.
Effects take 1-2 weeks, and the drug has a 2-11hr half-life.
Alprazolam and Diazepam
What class of drugs are they?
What are their indications?
Which is longer acting?
Alprazolam and Diazepam
They are benzodiazepines.
They are indicated in anxiety disorders. Diazepam is also a muscle relaxant.
Diazepam has long duration; a day or more compared to Alprazolam’s 12hrs.
What benzodiazepines are prescribed for sleep?
What traits are desirable for sleep aids?
Flurazepam, Triazolam, Lorazepam (Ativan), and Zolpidem (Ambien)
A good sleep has a fast onset and moderate duration–not long enough to cause daytime drowsiness, but enough to maintain sleep.
How would the following traits affect the kinetics of a benzodiazepine:
Lipophilicity
Activation to an active metabolite
Lipophilicity appears to provide for fast entry, but fast redistribution.
Conversion to active metabolites extends effective half-life.
Summarize the effects of benzodiazepines.
Contrast these with the withdrawal effects.
Anxiolysis, sedation/hypnosis, muscle relaxation, anticonvulsant.
Withdrawal typically involves the reversal of these effects.
What benzodiazepines are indicated for the following specific uses?
Muscle relaxation
Alcohol withdrawal
Acute mania
Diazepam is a potent muscle relaxant.
Chlordiazepoxide is used for alcohol withdrawal.
Clonazepam may reduce mania.
How do hypnotics affect sleep patterns?
What are their side effects?
Sedatives/hypnotics decrease latency to sleep and increase stages 1/2 at the expense of 3/4 and REM.
Daytime sedation including ataxia. Dependence resulting in rebound insomnia. Idiosyncratic stimulation.
Zolpidem
What class of drug is it? What is its mechanism?
Describe its kinetics and interactions.
Zolpidem
It is a non-benzodiazepine hypnotic, though it binds to the BDZ site on GABA receptors.
It lasts 5-6hrs, perfect for nightly use. It is antagonized by flumazenil.
What adverse effects are seen with barbiturates?
What are their clinical uses?
CNS depression including respiration, development of dependence and occasionally poisoning.
They can be used for sedation and muscle relaxation–usually the latter.
Pentobarbital
What class of drug is it? Where does it target?
What are its indications?
Pentobarbital
It is a barbiturate which acts at an extracellular site on GABA receptors.
It is occasionally used as a sedative, anesthetic, or to induce coma.
Phenobarbital
What class of drug is it? Where does it target?
What are its indications?
Phenobarbital
It is a barbiturate which acts at an extracellular site on GABA receptors.
Phenobarbital is the most widely used anticonvulsant.
Chloral Hydrate
What is its mechanism of action?
What are its indications?
Chloral Hydrate
It is a prodrug which forms trichloroethanol (activates GABA receptors)
It is used as a hypnotic (spares sleep stages).
What two drugs are approved for use as skeletal muscle relaxants?
Distinguish between their mechanisms of action.
Diazepam and Baclofen.
Both agonize GABA receptors. Baclofen works at GABAB receptors and has less sedation.
Tizanidine
What is its mechanism of action?
What are its indications?
What are its side effects?
Tizanidine
Agonism of alpha-2 receptors.
By enhancing synaptic inhibition, it can relieve muscle spasm.
Drowsiness, hypotension, and drymouth. It is metabolized by CYP1A2, so avoid its inhibitors.
