L93 - Antidepressants, Stimulants and Bipolar Drugs Flashcards
What class of drugs are:
- Amitriptyline (Elavil)
- Amoxapine (Asendin)
- Imipramine (Tofranil)
- Nortriptyline (Pamelor
Tricyclics (TCAs)
TCA:
- Use?
- Similar efficacy? Yes or no
- Used to treat severe major depression
2. Yes: all have similar therapeutic efficacy
TCA Mechanism
Block Serotonin and NE reuptake
Off target effects: Also block muscarinic, adrenergic and histamine receptors, which underlies a number of side effects
TCA pharmacokinetics
- oral? yes or no
- absorption? where?
- Therapeutic effect time?
- Lipid solubility? into CNS?
- Half life?
- Binding to plasma proteins? %?
- Metabolism?
- Elimination?
- Yes Orally active
- Readily absorbed, primarily in the small intestine
- Therapeutic effect requires >2 weeks
- Highly lipid soluble, readily penetrate into the CNS
- Long half-life (10-40 hrs)
- High binding to plasma proteins (90-95%); 7. Metabolized by hepatic microsomal enzymes
- Eliminated primarily via the kidneys
TCA Side effects
Off target effects can determine side effects
Antimuscarinic effects; **Cardiovascular; Orthostatic hypotension; Sedation; Metabolic-endocrine; Neurologic; Psychiatric
What class of drugs are these? Citalopram (Celexa) Escitalopram (Lexapro) Fluoxetine (Proxac) Sertraline (Zoloft)
SSRIs (serotonin-reuptake inhibitors)
SSRI
- use?
- Similar efficacy? Yes or no
- most widely prescribed antidepressant
2. Yes: similar therapeutic efficacy
SSRI mechanism
Block Serotonin reuptake only
SSRI drug interactions
Primarily fluoxetine Block several liver P450 enzymes - CYP2D6, CYP1A2 and CYP3A4; TCAs antidepressants Neuroleptic drugs (haloperidol) Some antiarrhythmic drugs Some b-adrenergic antagonists
SSRI pharmacokinetics
- oral? Yes or no
- absorption? where?
- Therapeutic effect time?
- Half life?
- Binding to plasma proteins? %?
- Metabolism?
- Elimination?
- Yes Orally active
- Readily absorbed, primarily in the small intestine
- Therapeutic effect requires >2 weeks
- Long half-life (1-3 days); Fluoxetine is demethylated to the active metabolite norfluoxetine (half-life time up to 30 days);
- High binding to plasma proteins (70-90%);
- high first-pass hepatic metabolism; Block several liver P450 enzymes (potential for drug interactions)
- Eliminated primarily via the kidneys
SSRI Side effects
- early onset
- late onset
- Early Onset, Transient (Nausea, Anxiety, Sleep disturbance/insomnia)
- Late Onset (Anorexia, Sexual dysfunction, Induction of mania in patients with bipolar disorder - common SE of anti-dep)
What class of drugs are these?
Duloxetine (Cymbalta)
Venlafaxine (Effexor)
SNRIs (serotonin-norepinephrine reuptake inhibitors)
SNRI use?
treat depressed patients refractory to SSRIs
SNRI mechanism?
Selectively inhibit reuptake of 5-HT and NE
Which SNRI is only 27% bound to plasma proteins?
Venlafaxine
Which SNRI is 97% bound to plasma proteins?
Duloxetine
CYP2D6 liver enzyme metabolizes which SNRI?
venlafaxine and duloxetine
CYP1A2 liver enzyme metabolizes which SNRI?
duloxetine
Contraindicated in patients with hepatic insufficiency
duloxetine
Which class of drugs are these?
Bupropion (Wellbutrin)
Mirtazapine (Remeron)
Nefazodone (Serzone)
Atypicals
What class of drugs are these?
Phenelzine (Nardil)
Selegiline (Emsam)
Tranylcypromine (Parnate)
MAO inhibitors
What class of drugs are these? Lithium Carbamazepine (Tegretol) Olanzapine (Zyprexa) Risperidone (Risperdal) Valproic acid (Depakene)
Bipolar treatment
What class of drugs are these? Amphetamine (Adderall) Atomoxetine (Strattera) Dextro-amphetamine (Dexedrine) Methylphenidate (Ritalin) Modafinil (Provigil)
stimulants
inhibits dopamine reuptake; is useful for treating rapid-cycling bipolar disorder (>3-4 cycles of mania)
Bupropion (Wellbutrin®)
inhibits the reuptake of serotonin and blocks the 5-HT2 receptors
Antipsychotic drug and antidepressant
Nefazodone (Serzone®)
increases NE and serotonin release by blocking a2 receptors
Mirtazapine (Remeron®)
T/F: atypicals have more side effects than TCAs?
False: fewer anticholinergic effects and no significant cardiotoxic effects
Common side-effects: headache, nausea, tinnitus, insomnia and nervousness
Third-line drugs for depression in patients who do not respond to SSRIs and TCAs (atypical depression) and work by increasing presynaptic concentration of NT
MAOIs
Use of ______ is limited due to severe and often unpredictable side effects.
What are the SE?
MAOIs
CNS effects; Cardiovascular: orthostatic hypotension, tachycardia;
Drug interaction: when combined with SSRIs may lead a potentially fatal condition, serotonin syndrome, which includes cognitive (delirium, coma), autonomic (hypertension, and tachycardia) and somatic (hyperthermia, hyperreflexia, tremor) effects;
- MAO-A deaminates which 3 NT?
2. MAO-B deaminates which NT?
- MAO-A deaminates NE, 5-HT and dopamine (DA)
2. MAO-B deaminates DA
Tyramine (cheese, chicken, liver, beer, red wine) is metabolized by MAO. In the presence of MAO inhibitors, elevated tyramine will cause the release of large amounts of _________________ leading to headache, tachycardia, hypertension, seizures and potentially, stroke - “cheese effect”
Restrictions in diet?
- catecholamines
2. yes: patients taking MAOIs need to be educated to avoid tyramine-containing foods
Pharmacokinetics of MAOIs:
- Orally active?
- Transdermal patch for ____________?
- Therapeutic effect requires __ weeks;
- Eliminated primarily via the ____
- Block MAO (irreversibly/reversibly), which means that the loss of MAO activity persists long after the drugs are metabolized and eliminated
- No new MAO enzymes must be synthesized for MAO activity to return to normal (several weeks)
- Yes
- Selegiline
- 2-4 weeks
- kidneys
- irreversibly
- False
Drug of choice for maintenance treatment of bipolar illness
Lithium
prophylactic drug significantly decreases the frequency of both manic and depressive attacks in about 70% of patients
Lithium
fluoxetine combined with olanzapine
Antidepressants
risperidone, olanzapine and quetiapine
Antipsychotics
valproic acid, carbamazepine and lamotrigine
Anticonvulsants
Lithium: Pharmacokinetics:
- 2 ways lithium is available:
- Administration?
- Rapidly absorbed from the ____
- insoluble or soluble ion?
- Peak plasma level is reached in __hrs;
- Half-life?
- Elimination?
- How does reduced kidney function affect lithium?
- carbonate and citrate salts
- oral
- GI tract
- Soluble (no binding to plasma proteins)
- 2-4 hours
- 20-24 hrs
- kidneys
- is associated with greater lithium toxicity
Inc release of DA and NE into VMAT; inhibits MAO
Drug for ADHD and narcolepsy; potential for addiction; SE (CNS, cardiovascular, GI)
Amphetamines
Drug for ADHD treatment. NE reuptake inhibitor (not a psychostimulant and non-habit forming)
Atomoxetine
Inc release of DA and NE into VMAT; inhibits MAO. psychomotor stimulant (combats fatigue); prevents narcolepsy, children with ADHD; oral administration, is completely absorbed from GI tract, metabolized by the liver and excreted in the urine; smoking or via IV by abusers
Dextro-amphetamine
Inc release of DA and NE into VMAT; inhibits MAO
prevents narcolepsy; children with attention deficit hyperactivity disorder (ADHD); oral administration, good absorption from GI tract, high concentration in the brain; its de-esterified product, ritalinic acid is excreted in the urine
Methylphenidate
Prevent narcolepsy and shift work disorder. MOA unclear, but likely involves NE and DA systems. Fewer psychoactive and euphoric effects as well as effects on mood and thinking.
Modafinil
tx binge eating disorder
lisdexamfetamine
