atypical antidepressants Flashcards by M K

analogy of the antipsychotic drug loxapine

retains some DA receptor antagonism –> risk of extrapyramindal motor side effecs

may be used for depression in psychotic patients

mixed inhibitions: NET>SERT~SAT

amoxamine

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selective inhibitor of NE reuptake. increased risk of seizures

maprotiline

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moderate inihition of serotoni reuptake but primarily acts as a 5-HT2a antagonist and 5-Ht1a partial agonist (SARI).

useful in tx of depression characterized by anxiety and sleep disturbances. short t1/2(2-9 hr). inhibits CYP3A4. N

trazodone

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why was a nefazodone, a drug similar to trazodone discontinued?

hepatotoxicity

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a potent 5-HT1a partial agonist and SSRI (approved 1.21.2011)

vilazodone

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analog of mianserin

enchances the release of serotonin and NE by antagonizing presynaptic alpha-2ARs. antagonizes 5-HT2 receptors.

potent antihisatiminic—>sedating. increased weight gain. Less GI and sexual disturbances than SSRIs. (tetracyclinc AD)

mirtazepine

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weak blocker of DAT, SERT, and NET

active metabolit is an NE reuptake blcoker

causes agitation, anxiety, resltessness. _risk of seizure _

admin as dividied doses or slow release formulation (medium t 1/2)

also used as aid in smoking cesssation (ZYBAN)

buproprion

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inhibits serotonin and NE reuptake (SNRI)

devoid of antishitaminergic, anticholinergic, and anti-adrenergic properties –>Does not have TCA like ADE

short t 1/2 (4-10hr)

produces a small: _sustained HTN, sweating, dizziness, nausea, anxiety _

venlafaxine

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SNRI (serotonin and norepi reuptake) most potent one available (~100x more potent than VEnlafaxine) ~50% bioavailability, highly bound to plasma proteins (~95%) metabolized to CYP2D6 and CYP1A2.

t 1/2 ~12hr

duloxetine

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recently approved (9/30/2012) “serotonin modulator and stimulator.”

Potent blocker of SERT and high efficacy partial agonist at 5-HT1a receptors. Partial agonist (5-HT-1b) and antagonist at 5-HT1d, 3a, and 7 receptors.

weak block of NET and B1-AR

vortioxetine

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Flashbacks - fluoxetine

Paralyze - paroxetine

Senior - sertraline

Citizens - citalopram

are all ______?

SSRIs

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what are the 5 SSRIs in our block?

FLashbacks

PAaralyze

SEnior

CItiziens?

Fluoxetine

Paroxetine

Sertaline

CItalopram

Fluvoxamine

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first-line therapy in pts diagnosed with major depression.

also used to TX panic, OCD, social anxiety disordrer, ADHD, and some eating disorders

SSRIs

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what are the three general behavior/clinical effects of SSRIs?

ASA

anxiety

stimulation

agitation (they go away after chronic admin (2-6 weeks)

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what are the three ADE’s of SSRIs?

NLSC

Nausea

Low libido

Sexual dysfuncition

decreased CArdio and anti-cholinergic effect

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which SSRI has increased risk of birth defects?

Paroxetine

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which drugs are C/I when taking SSRIs? why?

MAOIs b/c lead to serotonin syndrome

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describes wha:

onset within 24 hours of OD or concurrent MAOI.

due largerly to overstimuation of 5-HT1A receptors in central grey (midbrain) and medulla

serotonin syndrome

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what is a syndrome characterzied by by:

hypepyrexia+hyperreflexia

tremor +shivering

myoclonus+agitation

seizures+confusion

delirium+cardiovascular collapse+coma

seretonin syndrome

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what are the three monoamine oxidase inhibitors?

TIP?

T - tranylcypromine

isocarbazid

phenelzine

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typically only used in pts who unrespeonsive to tx w/other antidepressants and for whom ECT is not suitable

also used for panic disorder, agoraphobia

Monoamine oxidase inhibitors

T-tranylcypromine
I-isocarboxazid

P-phenelzine

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moa of MAOIs?

block oxidative metabolism of monoamines by i_rreversible . inhibition of MAO-A and MAO-B in nerve terminals. _

MAO-A metabolizes primarily NE, 5-HT and tyramine

MAO-B - mostly DA selective

central effects of MAOIs? ASE

CNS stimulation

Agitation

possibly euphoria

chronic (2-6 wks): imporvemnts of most or all symptoms, CNS activation remains

ADE of MOAIs. SOWS

remember as hypotension from fat, sex, and sleep disturbance.

S- sleep disturbance (increase arousal)

O - orthostatic hypotnesion

W- weight gain

S- sex dysfunction

how are MAOIs inactivated?

acetylation

which drugs have an interaction w/foods that contain high amts of tyramine?

MAOIs (cheese)

what does MAO-A metabolize (3)?

NE, 5-HT, and tyramine

what does MAO-B metabolize?

dopamine selective

what are the general behavior side effects for MAOIs? SAE

s-sedation A - agitation E- possible euphoria

pharmacokinetics of MAOIs where are they generally absored from? is daily dosing required? how are they inactivated?

Generally well absorbed from GI daily dosing required in spite of irreversible enzyme inhibition!! inactivated by acetylation

b/c block of MAO irreversible, how long to drug effects persist?

drug effects persist 1-3 weeks

drug interactions of MAOIs Food + 3 class of drugs

1. foods containing high amts of tyramine (cheese) 2. sympathomimetic drugs( cold remedies, diet aids, and stimulants) --\> acute hypertensive reaction 3. sympathomimetic drugs(cold remedies, diet aids, stimulants) --\>acute hypertensive reaction 4. meperidine, dextromethorpham --\> hyperpyrexia, delirium, convulsions, coma, death 5. SSRIs.

what are three mood stabilizers? VLC

lithium valproate carbamazepine

what are lithium, valproate, and carbamazepine indicated for?

maintenance of manic depression

what is acute mania typically treated with?

antipsychotics and benzodiazepines

what is the MOA of lithium?

Mechanism of action: poorly understood. Most favored hypothesis implicates L**_i inhibition of inositol phosphate signaling_**. Also inhibits ne**urotransmitter-stimulated adenylyl cyclase activity.** Effective in ~60 % of patients

what are the pharmakokinetic of lithium? how quickly is it absorbed?

Pharmacokinetics: Rapid (30 min- 2hr peak) and complete absorbtion (6-8 hrs). Distributes to total body water, some concentration in bone. Cleared in the urine, t 1⁄2 ~20 hrs. No metbolism.

what are the ADE of litihum? Neuro glandular renal cardiac other

* *Adverse effects: \*VERY NARROW therapeutic window. (target ~0.5-1.0 mEq/L) Toxic effects observed at \> 1.5 mEq/L.** a) **Neurologic**/psychiatric: tremor, ataxia, hyperactivity, aphasia, sedation, fatigue b) **Glandular**: edema, mild hypothyroidism c) **Renal:** polydipsia, **polyuria (nephrogenic diabetes insipidus)**, d) **Cardiac**: bradycardia-tachycardia (“sick sinus”) e) other: acne, folliculitis, and exacerbates psoriasis

two drug classes that lithium interacts with

Drug interactions: Sensitive to diuretics and antiinflammatory drugs (NSAIDs)

what are the two anti-convulsants frequently used in the management of bipolar disorder?

The anticonvulsants **valproate and carbamazepine** are now frequently used in the management of bipolar disorder. **They may be used alone or in combination w/Li or w/ other antipsychotics. Appear effective in either phase of manic depression (particularly valproate).**

what are the advantagesand disadvantages of anti-psychotics?

**Advantages compared to Li: ↑dose faster, quicker response, better TI** ## Footnote **Disadvantages compared to Li: less experience, efficacy questionable in severe disease**

what is the first line drug for bipolar disorder?

**\*Lithium is first line for bipolar disorder, however milder forms may be treated with anticonvulsants.**

``` Valproic Acid Valproic acid (or Na Valproate) (DEPAKENE): is fully ionized at normal physiological pH and therefore valproate is assumed to be the active form. ```

know

indication for valproate

Indications: Used as monotherapy or in combination with Li or antipsychotics.

which drug? Note: Effective in the treatment of **absence, myoclonic, partial and tonic- clonic seizures**. A drug of choice when **absence seizures are also accompanied with tonic-clonic seizures.**

valproic acid

what is the MOA of valproate?

Mechanism of action: **Inhibits voltage-gated Na channels by stabilizing the inactivated state of the channe**l. Block of channel activity is use-dependent. **Also blocks Ca channels (T-type) to a lesser extent**. **Valproate also can stimulate GABA synthesis and inhibit GABA degradation.** At high doses may increase resting K conductances.

what are the drug interactions of valproate?

Drug Interactions: **Valproate inhibits its own metabolism** and the **metabolism of other drugs.** **Valproate also displaces phenytoin from plasma proteins**.

toxicity of valproate (4)

Toxicity: Nausea, abdominal pain, heartburn are common. **Sedation may be a problem. Hepatotoxicity can be common.**C**areful monitoring of liver function is recommended.**

indications of carbamazepine

Indications: Used as monotherapy or in combination with Li or anti-psychotics.

describes which drugs Note: Drug of choice for partial seizures, also may be used for generalized tonic- clonic seizures. Also effective for **_trigeminal neuralgia._**

carbamazepine

which drug described? Pharmacokinetics: **Absorption is from GI tract (100%),** rate varies with patient. Time to peak 6-8 hr. **Poor solubility. Bound (~ 70%) to plasma proteins (albumin).** **Distributes slowly.** No displacement of other drugs which **bind plasma proteins.**

carbamazepine

carbamazepine is metabolized by CYP3a4 to an active metabolit to which metabolite?

Metabolized primarily by CYP3A4 to an active metabolite **(10,11-epoxide).** Varies with patients. t1⁄2 36 hr after initial dose then may decrease to 20 hr. Cleared slowly.

drug interactions for carbamazepine what does it induce?

Drug interactions: Carbamazepine is a broad spectrum inducer of **CYP2C and 3A families**, in addition to **induction of UGTs.** Thus **enhancing the metabolism of many drugs** Note: affects the **metabolism of oral contraceptives**.

toxicity of carbamazepine

**Diplopia (double vision) and ataxia are common.** **Mild GI upset, unsteadiness.** At high doses drowsiness. **Rash common idiosyncratic** reaction. Some occurences of **aplastic anemia.**