Antidepressants and Stimulants Flashcards
There are 3 types of depression. What are they?
Major depression
Dysthymia (less sever than major)
Bipolar disorder (cycling moods)
Characterized by enthusiasm, rapid thoughts and speech patterns, extreme self-confidence and impaired judgement. This describes _
Mania
The current hypothesis regarding mood disorders is that they are related to the levels of _. High levels correlate with _ while low levels correlate with _
Biogenic amines (5HT and NE)
Mania
Depression
What is the serotonin metabolite measured to detect its levels? Where is it measured from? What is a postmortem finding in depressed patients indicative of low 5HT?
5-hydroxyindoleacetic acid
CSF
High receptor levels
What is the norepinephrine metabolite measured to detect its levels? What is the effect of norepinephrine depletion on mood
3-methoxy-4-hydroxyphenylglycol
Low NE, likely depression
In general, what is the net effect of drugs used for the treatment of depression?
Increase the monoaminergic neurotransmission (5HT, NE and maybe DA)
What is the major effect of the tri-cyclic antidepressants? What are they used for? What is the prototype?
Block monoamine reuptake
Major depression
Imipramine
The side effects of TCAs arise from their non-specific actions at what 3 receptor signaling systems?
Muscarinic
Adrenergic
Histamine
Four examples of TCAs were provided. They are _
Imipramine
Amoxapine
Amitriptyline
Nortriptyline
Regarding TCAs, where are they primarily absorbed? How long till they start working? Where / What are they metabolized? How are they excreted?
Small intestines
up to 2 weeks
Metabolized by liver microsomal enzymes
Primarily Kidneys
3 major side effects of TCAs include:
Antimuscarinic effects
Cardiovascular effects
Orthostatic hypotension
SSRIs are the most widely prescribed antidepressant in the US. What is a major advantage over TCAs? What is another condition beyond depression that SSRIs are used for?
No cardiotoxic effects
Anxiety disorders
What are 4 examples of SSRIs provided?
Fluoxetine
Citalopram
Escitalopram
Sertraline
What is the mechanism by which SSRIs work?
Selectively block 5HT reuptake
While SSRIs start working immediately, why do their effects take up 2 weeks to show?
Neurogenesis has to occur (e.g. in hippocampus)
Regarding SSRIs, where are they primarily absorbed? How do they interact with P450 enzymes? How are they eliminated?
Small intestines
Block these enzymes
Eliminated via kidneys
Fluoxetine is metabolized to what active metabolite? Where does this occur? How does this metabolism affect its half-life?
Nor-fluoxetine
Liver
It can increase half life up to 30 days
A commonality between TCAs and SSRIs regarding plasma proteins is _
They both bind highly (up to 90%) to plasma proteins
What are 3 early onset (but transient) side effects of SSRIs?
Nausea
Anxiety
Insomnia
What are 3 late onset side effects of SSRIs?
Anorexia
Sexual dysfunction
Mania (in bipolar patients)
What are the 3 CYP enzymes blocked by SSRIs?
2D6
1A2
3A4
What are 4 known drug interactions of SSRIs? i.e. these drugs can increase to toxic levels if used with SSRIs
TCAs
Neuroleptics (haloperidol)
Antiarrhythmics (some)
Beta adrenergics (some)
What are the 2 examples of serotonin-NE reuptake inhibitors (SNRI) provided? What group of patients are they used for?
Venlaflaxine
Duloxetine
Patients refractory to SSRIs
Of the 2 SNRIs, which is more likely to bind plasma proteins? Less likely? Which enzymes metabolize these drugs? Which is contraindicated in patients with liver insufficiency?
More - Duloxetine (97%) Less - Venlaflaxine (27%) 2A6 - Venlaflaxine 1A2 and 2A6 - Duloxetine Duloxetine not for kidney insufficiency patients
What are 4 major side effects of SNRIs?
Nausea Anxiety Insomnia Sexual dysfunction (Same as SSRIs, except anorexia)
What are the 3 examples of atypical antidepressants provided?
Bupropion
Nefazodone
Mirtazapine
What is the mechanism of action of bupropion? What is it used to treat?
Inhibits DA reuptake
Bipolar disorder
What is the mechanism of action of nefazodone? What specific receptor does it block?
Inhibits reuptake of 5HT
Block 5HT2 receptors
What is the net effect of mirtazapine? What receptor is targeted?
Increases NE and 5HT
Blocks alpha-2 receptor
When/how are atypical antidepressants likely to be used?
In combination with TCAs when others don’t work.
What are 5 common side effects for atypical antidepressants?
Headache Nausea* Tinnitus Insomnia* Nervousness* - *same as SSRI/SNRI/TCA
True or False, MAOIs are widely used drugs for the treatment of depression.
False. Third line treatment because of severe and unpredictable side effects
What is the function of MAO-A? MAO-B
MAO-A - Deaminates NE, 5HT and DA
MAO-B - Deaminates DA
What is the net effect of MAOIs on monoamine levels?
It increases presynaptic levels of monoamines
What are three examples of MAOIs provided? Which is specific to MAO-B (except at high levels)
Phenelzine
Tranylcypromine
Selegiline - MAO-B selective
What type of inhibition do MAOIs exert on MAOs? What is the practical repercussion on enzyme activity if a patient stops using the drug?
Irreversible Inhibition
Need several weeks after stopping drug for levels to return to normal
Which of the MAOIs can be administered transdermally? How are they eliminated?
Selegiline Mainly kidneys (like other antidepressants)
hallucinations, agitation, hyperreflexia, convulsions, orthostatic hypotension and constipation. These are all possible side effects of _
MAOIs
What content of certain foods can be potentially problematic for patients on MAOI? Why?
Tyramine
It is metabolized by MAOs, if levels are high, then it can cause great release of catecholamines
What is serotonin syndrome? What drug combination can cause it?
Potentially fatal condition (fever, diarrhea, excitement, hypomania, ataxia, hyperreflexia, hyperthermia and COMA)
MAOIs and SSRIs
What is the drug of choice for prophylactic treatment of bipolar disorder? What makes this drug unsafe? What is the mechanism of its toxic side effects?
Lithium salts
Low therapeutic index
It substitutes for sodium ions
What is lithium’s interaction with plasma proteins? What group of patients are at risk for toxicity when using lithium?
No binding to plasma proteins
Patients with kidney problems (how its cleared)
Tremors, mental confusion, convulsions and arrthymias are all potential side effects of _
Lithium
What are 2 drug classes with known drug interactions with lithium?
Thiazide diuretics
NSAIDs
In addition to lithium, what other 3 drug classes can be used to treat bipolar disorder?
Antidepressants
Antipsychotics
Anticonvulsants
What are the three examples of stimulants provided? Which has no medical use? Which 2 are psychomotor stimulants (fight fatigue)?
Dextroamphethamine (psychomotor stimulant)
Methylphenidate
Methamphetamine (psychomotor stimulant, no medical use)
Which of the stimulants can be used to treat narcolepsy and ADHD? (2) How are these drugs excreted?
Dextroamphethamine
Methylphenidate
Urine
What are three ways that stimulants increase the levels of DA and NE in the brain?
- Increase vesicular monoamine transporter (VMAT) activity, increase release of vesicles
- Block MAO, less metabolism
- Increase non-vesicular release of DA and NE (reuptake channels)
What are the 3 main traits of ADHD?
– Inattention
– Hyperactivity
– Impulsivity
In addition to stimulants, what other drug can be used to treat ADHD? What is its mechanism? What is a potential advantage over other options?
Strattera
NE reuptake inhibitor
Non-habit forming
In addition to dextroamphetamine and methylphenidate, what other 2 drugs can be used to treat narcolepsy? What are advantages of modafinil?
Amphetamine
Modafinil (less psychoactive and euphoric effects)
What are 5 potential CNS side effects of amphetamines?
Euphoria Anxiety Vertigo Insomnia Confusion
What are 2 GI and 2 cardiovascular side effects of amphetamines?
Cardiovascular - Arrythmias, hypertension
GI - Nausea and diarrhea
True or false: Amphetamines have addiction / abuse potential
True
A major problem associated with using TCAs in the elderly is _. A major area of drug-drug interactions with TCAs are _
Orthostatic hypertension
Binding within plasma proteins
Why are SNRIs an improvement over TCAs?
They are less dirty (no muscarinic, adrenergic or histamine receptor actions) so less side effects
Of the MAOs, which can be used for the treatment of Parkinson’s disease? How is its formulation altered for this purpose?
Selegiline
Used as pills, vs. Patch for depression
MAOIs need to be used carefully to avoid the cheese effect (increased tyramine). What MAOI is an exception and why?
Selegiline
Transdermal patch, bypasses GI where a lot of tyramine is released
What is the proposed mechanism by which lithium works? What class of receptors is affected by this?
Blocks formation of phosphoinositol
Blocks activity of the metabotropic receptos (GPCRs)
Why can lithium cause / precipitate diabetes insipidus?
Too much urination because of non-responsiveness to ADH because ADH receptor is a metabotropic receptor and lithium blocks synthesis of its second messenger
