Flashcards in anti-depressants and mood stabilizers Deck (83):
what is the biogenic amine hypothesis for depression?
a functional deficit of monoamines (mostly NE & 5-HT) is thought to be involved in the pathophys. of depression
which population of pts needs to be warned about which BBW of antidepressants, especially during the initial weeks of treatment?
children and adolescents with thoughts of suicide
antidepressant drugs that are substrates for ___________ (MDR1; P-gp) which exists at the BBB limits the ability of drugs to accumulate in the brain
name the 4 antidepressants that are substrates for MDR1
"can't volley proper antidepressants"
name the two antidepressants that are not substrates for MDR1
what are some of the indications for TCA therapy?
major depression, pain/anxiety disorders (OCD, phobias, panic), ADHD, nocturnal enuresis (imipramine), depression assoc. w/ schizophrenia
what is the MOA of TCAs?
inhibits the reuptake of 5-HT & NE into presynaptic terminals--> potentiate and prolong the actions of these neurotransmitters--> receptors and transporter regulation w/ repeated treatment
-also block mACh, 5-HT, & histamine receptors
orthostatic hypotension is an AE of TCAs due to antagonism of what receptor?
antagonism of alpha-ARs
blurred vision, worsening of narrow-angle glaucoma, dry mouth, constipation, urinary retention, tachycardia are all AEs of TCAs due to antagonism of what receptor?
antagonism of mAChR
what are some metabolic/endocrine related AEs of TCAs?
what happens in TCA overdose?
has low therapeutic index
CV effects including: arrhythmias, direct myocardial depression, worsening of CHF
-also: acidosis, delirium seizures
"3 C's: convulsions, coma, cardiotoxicity"
describe some of the PKs of TCAs?
high first pass metabolism
high lipid solubility (allows distribution to brain & fat)
highly protein bound (high Vd), which limits excretion (leading to long half-life)
tertiary amines (TCAs) are metabolized to active secondary amines by what?
demethylation (imipramine, amitriptyline--> nortriptyline)
the tricylclic ring is subject to oxidation by what cyp enzyme and also can be conjugated?
subject to CYP2D6 oxidation & conjugation
name the atypical antidepressant drug: moderate inhibition of serotonin reuptake but primarily acts s a 5-HT2a antagonist & 5-HT1a partial agonist (SARI) useful in the treatment of depression characterized by anxiety and sleep disturbances
trazodone inhibits which CYP enzyme?
name the drug: analog of mianserin
name the drug: enhances release of serotonin & NE by antagonizing presynaptic alpha-2ARs. Antagonizes 5-HT2 receptors.
what are the AEs of mirtazepine?
potent antihistaminic--> sedating
increased weight gain
name the drug: weak blocker of DAT, SERT, & NET. active metabolite is a NE reuptake blocker
buproprion (also used in smoking cessation)
what are the AEs of buproprion?
agitation, anxiety, restlessness
risk of seizure, (no sexual AEs)
name the antidepressant drug: inhibits serotonin & NE reuptake (SNRI). Lacks antihistaminergic, anticholinergic, and antiadrenergic properties--> does not have TCA-like side effects
what are the AEs of venlafaxine?
produces a small, sustained HTN, sweating dizzyness, nausea, anxiety
what is the most potent SNRI available?
duloxetine (100x more potent than venlafaxine)
describe the bioavailability and protein binding of duloxetine
highly bound to plasma proteins (95%)
duloxetine is metabolized by what two CYP enzyme?
CYP2D6 & CYP1A2
name the drug: recently approved serotonin modulator and stimulator. potent blocker of SERT & high efficacy partial agonist at 5-HT1a receptors. Partial agonist (5-HT-1b) and antagonist at 5-HT1d 3a, & 7 receptors?
name the 5 SSRIs
Fluoxetine + Fluvoxamine
"Flashbacks paralyze senior citizens"
what is the first line therapy in pts diagnosed with major depression?
SSRIs (also used to treat panic, OCD, social-anxiety disorder, ADHD, and some eating disorders)
describe the general behavior/clinical effects of SSRIs-acute
describe the general behavior/clinical effects of SSRIs-chronic
improvement of most or all clinical symptoms, CNS activation remains
what are the AEs of SSRIs?
low incidence CV & anticholinergic
note: higher therapeutic index
what is the active metabolite of fluoxetine?
norfluoxetine-has half life of 7-9 days
most of the SSRIs are metabolized by what CYP enzymes?
CYP2D6 (strong inhib.)
CYP2C19 (strong inhib.)
what drug class is contraindicated with SSRIs?
MAOIs (taking them together can cause serotonin syndrome)
serotonin syndrome is due largely to overstimulation of what receptors in the central grey (midbrain) and medulla?
what is the clinical presentation of serotonin syndrome?
other than MAOis what other drugs can trigger serotonin syndrome?
can also be triggered by increased 5-HT release (amphetamines, MDMA) or via 5-HT agonists (LSD, buspirone, L-Tryptophan)
name the 4 MAOIs
tranylcypromine (not on drug list)
isocarboxazid (not on drug list)
Selegiline (MAO-B inhibitor)
"MAO Takes Pride in Shanghai"
what are the indications for MAOis?
typically used in pts who are unresponsive to treatment with other antidepressants and for whom ECT is not suitable.
-also used for panic disorder, agoraphobia
MOA of the monoamine oxidase inhibitors?
blocks oxidative metabolism of monoamines by IRREVERSIBLE inhibition of MAO-A & MAO-B in nerve terminals (MAO-A metabolizes primarily NE, 5-HT, tyramine; MAO-B mostly DA selective)
describe the general behavior/clinical effects of MAOIs-acute
describe the general behavior/clinical effects of MAOIs-chronic
2-6 wks: improvement of most or all symptoms, CNS activation remains
what are the AEs of MAOIs?
sleep disturbances (increased arousal)
some sexual dysfunction
hypertensive crisis ( with ingestion of tyramine)
MAOIs are inactivated by what process?
acetylation (phamacogenomic differences)
what are some of the drug interactions for MAOis?
foods containing high amounts of tyramine (cheese)
what can happen when taking MAOIs & sympathomimetic drugs?
acute hypertensive reaction
what can happen taking MAOis with meperidine, or dextromethorpham?
name the 3 drugs used as mood-stabilizers
"moody lions value carbs"
what are the indications for the mood stabilizers?
maintenance of manic depression (bipolar affective disorder)
MOA of lithium?
most favored hypothesis is Li inhibition of inositol phosphate signaling. also inhibits neurotransmitter-stim. adenylyl cyclase activity. Effective in ~60% of pts
what are the adverse effects for lithium?
very narrow therapeutic window
-neurologic/psychiatric: tremor, ataxia, hyperactivity, aphasia, sedation fatigue
-Glandular: edema, mild hypothyroidism
-renal: polydipsia, polyuria (nephrogenic diabetes insipidus)
-cardiac: bradycardia-tachycardia (sick sinus)
other: acne, folliculitis and exacerbates psoriasis
which drug can cause polyuria (nephrogenic diabetes insipidus?
which drug can cause bradycardia-tachycardia (sick-sinus)?
which drug can exacerbate psoriasis?
what are the drug interactions with lithium?
sensitive to diuretics & NSAIDs
name the two anticonvulsants that are now frequently used in the management of bipolar disorder
valproate & carbamazepine
what are the advantages of valproate and carbamazepine over Lithium?
increase dose faster, quicker response, better therapeutic index
what are the disadvantages valproate and carbamazepine compared to lithium?
less experience, efficacy questionable in severe disease
which drug is first line for bipolar disorder?
lithium (however milder forms of bipolar disorder may be treated with anticonvulsants)
what is the drug of choice when absence seizures are also accompanied with tonic-clonic seizures?
what is the MOA of valproic acid?
inhibits voltage-gated Na+ channels by stabilizing the inactivated state of the channel. Block of channel activity is use-dependent.
-Also blocks Ca2+ channels (T-type) to a lesser extent
-can also stim. GABA synthesis & inhibit GABA degradation
-at high doses may increase resting K+ conductances
valproate inhibits its own metabolism and the metabolism of other drugs via which CYP enzyme?
what are the AEs of valproate?
nausea, abd. pain, heartburn, sedation may be a problem, hepatotoxicity can be common (recomend liver function test)
what is the drug of choice for partial seizures, also may be used for generalized tonic-clonic seizures, also effective for trigeminal neuralgia?
MOA for carbamazepine?
inhibition of Na channels (prolongs recovery time from inactivation)
which drug is metabolized primarily by CYP3A4 to an active metabolite 10,11-epoxide?
name the two SNRIs
name the TCAs (8)
(all TCAs end in iptyline or ipramine except doxepin and amoxapine)
what are the drug interactions for carbamazepine?
carbamazepine is a broad spectrum inducer of CYP2C & 3A families & in addition to induction of UGTs
what are the AEs of carbamazepine?
diplopia & ataxia are common
mild GI upset
at high doses drowsiness
rash common idiosyncratic reaction
some occurences of aplastic anemia
name the drug that matches the pt with most benefit: elderly pt; a pt with agitated depression or pt w/ GI distress
name the drug that matches the pt with most benefit: noncompliant or forgetful pt; excessive fatigue
name the drug that matches the pt with most benefit: less likely to produce initial anxiety &/or insomnia
name the drug that matches the pt with most benefit: the medical/surgical pt on one or more drugs. initial activation and increased alertness desired
name the drug that matches the pt with most benefit: pts with menopausal symptoms or failing an SSRI trial. At higher doses pts with chronic pain
name the drug that matches the pt with most benefit: pt with depression and chronic pain (effects on pain are dose-dependent) pt failing an SSRI trial
name the drug that matches the pt with most benefit: the medically ill pt with weight loss, insomnia and nausea
name the drug that matches the pt with most benefit: the now depressed or potentially bipolar pt. The apathetic, low energy pt. Pts motivated to stop smoking. Helpful for ADHD
which antidepressant is "unlikely" to cause sexual dysfunction?
which antidepressant "rarely" causes sexual dysfunction?
name the drug that matches the pt with the least benefit: pts who are agitated, very anxious &/or panicky. Pts at risk for seizures &/or w/ hx of head trauma, substance abuse, eating disorder or electrolyte disturbance