anti-depressants and mood stabilizers Flashcards by Kenneth Kennedy

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

antidepressant drugs that are substrates for ___________ (MDR1; P-gp) which exists at the BBB limits the ability of drugs to accumulate in the brain

ABCB1

How well did you know this?

Not at all

Perfectly

name the 4 antidepressants that are substrates for MDR1

citalopram
venlafaxine
paroxetine
amitriptyline
"can't volley proper antidepressants"

How well did you know this?

Not at all

Perfectly

name the two antidepressants that are not substrates for MDR1

mirtazapine

fluoxetine

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

orthostatic hypotension is an AE of TCAs due to antagonism of what receptor?

antagonism of alpha-ARs

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

what are some metabolic/endocrine related AEs of TCAs?

weight gain

sexual disturbances

How well did you know this?

Not at all

Perfectly

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”

How well did you know this?

Not at all

Perfectly

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)

How well did you know this?

Not at all

Perfectly

tertiary amines (TCAs) are metabolized to active secondary amines by what?

demethylation (imipramine, amitriptyline–> nortriptyline)

How well did you know this?

Not at all

Perfectly

the tricylclic ring is subject to oxidation by what cyp enzyme and also can be conjugated?

subject to CYP2D6 oxidation & conjugation

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

trazodone inhibits which CYP enzyme?

CYP3A4

How well did you know this?

Not at all

Perfectly

name the drug: analog of mianserin

mirtazepine

How well did you know this?

Not at all

Perfectly

name the drug: enhances release of serotonin & NE by antagonizing presynaptic alpha-2ARs. Antagonizes 5-HT2 receptors.

mirtazepine

How well did you know this?

Not at all

Perfectly

what are the AEs of mirtazepine?

potent antihistaminic–> sedating
increased weight gain
(tetracyclic antidepressant)

How well did you know this?

Not at all

Perfectly

name the drug: weak blocker of DAT, SERT, & NET. active metabolite is a NE reuptake blocker

buproprion (also used in smoking cessation)

How well did you know this?

Not at all

Perfectly

what are the AEs of buproprion?

agitation, anxiety, restlessness

risk of seizure, (no sexual AEs)

How well did you know this?

Not at all

Perfectly

name the antidepressant drug: inhibits serotonin & NE reuptake (SNRI). Lacks antihistaminergic, anticholinergic, and antiadrenergic properties–> does not have TCA-like side effects

venlafaxine

How well did you know this?

Not at all

Perfectly

what are the AEs of venlafaxine?

produces a small, sustained HTN, sweating dizzyness, nausea, anxiety

How well did you know this?

Not at all

Perfectly

what is the most potent SNRI available?

duloxetine (100x more potent than venlafaxine)

How well did you know this?

Not at all

Perfectly

describe the bioavailability and protein binding of duloxetine

50% bioavailability | 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?

vortioxetine

name the 5 SSRIs

Fluoxetine + Fluvoxamine Paroxetine Sertraline Citalopram "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

CNS stim. anxiety agitation

describe the general behavior/clinical effects of SSRIs-chronic

2-6 wks | improvement of most or all clinical symptoms, CNS activation remains

what are the AEs of SSRIs?

``` Nausea decreased libido sexual dysfunction 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.) CYP3A4

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?

5-HT1A

what is the clinical presentation of serotonin syndrome?

``` hyperpyrexia hyperreflexia tremor shivering myoclonus agitation seizures confusion delirium CV collapse coma ```

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) phenelzine 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

CNS stim. agitation possibly euphoria

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) orthostatic hypotension weight gain 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?

``` hyperpyrexia delirium convulsions coma death ```

name the 3 drugs used as mood-stabilizers

lithium valproate carbamazepine "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?

lithium

which drug can cause bradycardia-tachycardia (sick-sinus)?

lithium

which drug can exacerbate psoriasis?

lithium

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?

valproic acid

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?

CYP2C

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?

carbamazepine

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?

carbamazepine

name the two SNRIs

venlafaxine | duloxetine

name the TCAs (8)

``` Amitriptyline nortriptyline imipramine desipramine protriptyline ``` (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

citalopram

name the drug that matches the pt with most benefit: noncompliant or forgetful pt; excessive fatigue

fluoxetine

name the drug that matches the pt with most benefit: less likely to produce initial anxiety &/or insomnia

paroxetine

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

sertraline

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

venlafaxine

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

duloxetine

name the drug that matches the pt with most benefit: the medically ill pt with weight loss, insomnia and nausea

mirtazapine

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

buproprion

which antidepressant is "unlikely" to cause sexual dysfunction?

mirtazapine

which antidepressant "rarely" causes sexual dysfunction?

buproprion

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

buproprion