Antidepressants Flashcards by Andrew Braaten

Antidepressant Targets

TCAs inhibit the reuptake of NE and 5-HT
SSRIs selectively inhibit the reuptake of 5-HT
SNRIs inhibit the reuptake of NE and 5-HT
DA reuptake inhibitors - Bupropion
MAOIs inhibit the metabolism of NE, DA, and 5-HT

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Tricyclic Antidepressants (TCA) - MoA

 Inhibit re-uptake of NE and 5-HT
 Also block a-adrenergic, histamine and muscarinic 
    receptors
 No euphoria/low abuse potential
 2-4 weeks to have effect

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Tricyclic Antidepressants (TCA) - Uses

depression

chronic pain (TMJ), fibromyalgia
enuresis

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TCAs

Amitriptyline (Elavil®)
Imipramine (Tofranil®)
Nortriptyline (Pamelor®)
Desipramine (Norpramin®)

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Amitriptyline (Elavil®); Imipramine (Tofranil®)

Tertiary amines
Primary inhibit 5-HT re-uptake
Produce more seizures than secondary amines
More sedating than secondary amines

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Nortriptyline (Pamelor®); Desipramine (Norpramin®)

Secondary amines

* Primarily block NE re-uptake

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TCA Pharmacokinetics

 Well-absorbed orally
 Variable and long half-lives (10-90 hrs)
 They are generally given once a day, at bedtime.
 Metabolized by CYP2D6 - drug interactions VERY
common

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TCA Side Effects

 Weight gain
 Histamine receptor blockade
• Drowsiness, fatigue, sedation
 Cholinergic blockade
• Blurred vision, tachycardia, constipation, urinary
retention, dry mouth, palpitations
• Impairment of memory and cognition
alpha1 receptor blockade
• Cardiac depression and arrhythmias
• Postural hypotension, dizziness, reflex tachycardia
Analgesia results from activation of descending
noradrenergic pathways in the spinal cord (NE acts on
α2receptors to decrease glutamate input into pain
pathway going to brain)
 Syndrome of inappropriate antidiuretic hormone secretion (SIADH) may occur. This may lead to water intoxication and hyponatremia.
 Sexual dysfunction
 Decrease in seizure threshold
 Tolerance generally develops to sedation, postural
hypotension and to the anticholinergic effects
 Can be used in pregnancy

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TCA Toxicity and Overdose

Cardiac Toxicity
 Torsadesde pointes 
 prolongedQT interval
 cardiac arrhythmias
 severe hypotension
 agitation, delirium
 seizures, hyperpyrexia
 coma, shock, metabolic acidosis
 respiratory depression

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Treatment of TCA overdose

 Cardiac monitoring, supportive care
 Gastric lavage and activated charcoal
 Magnesium, isoproterenol and cardiac pacing for
Torsadesde pointes
 Lidocaine, propranolol, phenytoin to manage
arrhythmias and/or prevent seizures
 Sodium bicarbonate and potassium chloride to
restore acid/base balance

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TCA Drug Interactions

 Combined with MAOIs can result in serotonin
syndrome: severe CNS toxicity manifested by
hyperpyrexia, convulsions and coma
 TCAs compete for metabolism of SSRIs, thus
combination can lead to toxic levels of TCAs
 TCAs may cause hypertension when combined with
sympathomimetic drugs such as amphetamine
 TCAs potentiate the sedative actions of alcohol/CNS
depressants
 TCAs potentiate the effects of anticholinergic drugs

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Selective Serotonin Reuptake Inhibitors (SSRIs)

Fluoxetine (Prozac®) 
Sertraline (Zoloft®)    
Paroxetine (Paxil®)     
Citalopram (Celexa®)
Escitalopram (Lexapro®)

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Selective Serotonin Reuptake Inhibitors (SSRIs) - Uses

Depression
Panic disorder
Obsessive-compulsive disorder: Paroxetine (Paxil®)
Social anxiety: Paroxetine (Paxil®)
Bulimia
Alcoholism
Children and Teenagers

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Fluoxetine (Prozac®)

• Half-life of 2-3 days; Norfluoxetine, active metabolite,
7-9 days
• Most likely to inhibit CYP450 enzymes (CYP2D6)
• More drug interactions than other SSRIs
• Impairs blood glucose levels in diabetics

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Sertraline (Zoloft®)

Half life of 26 hours; Extensive first-pass elimination
Least likely SSRI to interact with other drugs
Preferred in elderly

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Citalopram (Celexa®) / Escitalopram (Lexapro®)

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• Currently the DOC for depression
• Low incidence of pharmacokinetic interactions and
side effects

Selective Serotonin Reuptake Inhibitors (SSRIs) - MoA

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Selectively inhibits 5-HT reuptake

* 2-3 weeks to be effective

Selective Serotonin Reuptake Inhibitors (SSRIs) - Pharmacokinetics

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Well absorbed by gut
Half life = 24-72 hours
Metabolized by CYP450s (2D6)
Inhibit CYP450s
Many drug interactions

SSRI Side Effects

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 Mild side effects; Less autonomic side effects and
chance for cardiac arrhythmias than TCAs
 GI: nausea, loss of appetite, constipation
 Weight loss or gain possible
 CNS stimulation (anxiety or insomnia) may occur with
fluoxetine or sertraline
 Sedation more likely with other drugs
 Sexual disinterest/dysfunction, impairment of
ejaculation
 Photosensitivity, limit sun exposure

SSRI Drug Interactions

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 Inhibition of CYP3A4 and CYP2D6
• TCAs: Inhibition of metabolism increases toxicity
• Phenytoin and carbamazepine: increased levels and
toxicity
 MAOIs: Serotonin syndrome
 St. John’s Wort or amphetamines - serotonin
syndrome
 beta-blockers: may result in heart block and
hypotension

 Opioids
• Codeine - Fluoxetine inhibits conversion to the
active compound
• Meperidine - Increases 5-HT; potential for serotonin
syndrome
• Tramadol - Increased risk of seizures

Serotonin-norepinephrine reuptake inhibitors (SNRI)

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 SNRIs inhibit NE & 5-HT re-uptake
 More side effects than SSRIs
 Uses: depression, neuropathic pain, post
menopausal hot flashes

 Venlafaxine (Effexor®)
• May increase blood pressure

 Duloxetine (Cymbalta®)
• May cause hepatotoxicity
• May cause bilateral acute angle-closure glaucoma
(ACG)

Monoamine Oxidase Inhibitors (MAOIs)

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Irreversibly inhibit MAOs which metabolize NE, DA and 5-HT

Phenelzine (Nardil®)
Selegiline (Deprenyl®)

Phenelzine (Nardil®)

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Inhibits both MAO-A and MAO-B

Increases NE and 5-HT (and DA)
Actions persist longer than serum levels
Also a substrate for MAOs
Depression that hasn’t responded to other drugs
Drug of last choice - serious side effects

Selegiline (Deprenyl®)

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Selectively inhibits MAO-B

Increases DA
Fewer side effects
Also used in Parkinson’s

MAOIs - Uses

Used for depression which doesn’t respond to other drugs

MAOIs - Pharmacokinetics

Long half life; Effects persist after discontinuing drug

MAOIs - Side Effects

• Hypertensive crisis (phenelzine) – MAO-A is inhibited in GI tract; tyramine causes release of amines and, with limited metabolism by MAO-A, can lead to severe hypertension. Avoid foods with tyramine-red wine, beer, aged cheese etc... • Tremors, sedation or excitation and insomnia • Orthostatic hypotension • Weight gain - very common • Anticholinergic effects -blurred vision, dry mouth, etc

MAOI Drug Interactions

OTC cold and cough medications containing sympathomimetic amines such as phenylephrine, ephedrine, or amphetamines –can lead to severe hypertension.  Serotonin Syndrome - Meperidine, dextromethorphan, TCAs, SSRIs – can lead to hyperpyrexia.  MAOIs can also inhibit CYP450 enzymes (2D6) – affects metabolism of SSRIs, Ca++channel blockers, etc...  MAOI metabolism is affected by drugs that induce or inhibit CYP450s

Bupropion (Wellbutrin®) - MoA

 Inhibits DA, and to a minimal extent, NE and 5HT re- uptake  May work where others haven’t; Sometimes combined with SSRIs

Bupropion (Wellbutrin®) - Uses

ADHD, alcoholism (decreases craving) Extended release for quitting smoking (Zyban®)

Bupropion (Wellbutrin®) - Pharmacokinetics

extensive first-pass metabolism and high protein binding; active metabolites

Bupropion (Wellbutrin®) - Side Effects

• Seizures - Contraindicated in patients with history of seizures • CNS effects - anxiety, insomnia, restlessness, tremor, psychosis • Cardiac - Tachycardia • Sexual dysfunction side effects are rare

Mirtazapine (Remeron®) - MoA

 Blocks presynaptic alpha2 receptors, which inhibit release of NE and 5-HT.  Increases release of NE and 5-HT  Blocks 5-HT2A and 5-HT3 receptors

Mirtazapine (Remeron®) - Uses

 Eliminates side effects associated with SSRIs (anxiety, | insomnia, nausea, sexual dysfunction).

Mirtazapine (Remeron®) - Pharmacokinetics

Half-life 20-40 hrs; metabolized by multiple CYP450s

Mirtazapine (Remeron®) - Side Effects

 Blocks histamine receptors, causing drowsiness as a predominant side effect - This may be an advantage in depressed patients with insomnia and anxiety

Atomoxetine (Strattera®)

 Selective inhibitor of norepinephrine reuptake.  First non-stimulant for treatment of ADHD  Does not cause euphoria; good choice for addicts  May increase memory and attention  Side effects - most common are GI distress and insomnia  Liver damage is possible but rare

Trazodone (Desyrel®)

 5-HT2A receptor antagonist. Short half life; high first pass metabolism  Sedating, not good antidepressant, more often used as a sleep aid  Also used for pain management  Side effects - include sedation, dizziness, hypotension, nausea and priapism (rare but serious), which limits use in males

St John’s Wort (hypericin®)

 May be effective in mild depression  Mechanism uncertain - May block reuptake or inhibit MAO  Causes photosensitivity  DO NOT combine with other antidepressants - can cause serotonin syndrome  May prolong effects of general anesthetics  Efficacy of oral contraceptives, digoxin, protease inhibitors and warfarin reduced due to increased metabolism

Antidepressants Flashcards

(39 cards)