Antidepressants, Cyclic Antidepressants, Antidotes, and Decontamination

Vocabulary flashcards covering SSRIs, atypical antidepressants, cyclic antidepressants (TCAs), mechanisms of antidotes, toxidromes, and poison removal techniques.

Selective Serotonin Reuptake Inhibitors (SSRIs)

A class of antidepressants that act through highly selective blockade of the serotonin transporter (SERT), increasing synaptic serotonin levels while exerting minimal effect on the norepinephrine transporter (NET).

Serotonin Transporter (SERT)

A monoamine transporter that undergoes conformational changes to reuptake serotonin from the synaptic cleft, serving as the primary molecular target blocked by SSRIs.

Fluoxetine

An SSRI that also exhibits weak blockade of the norepinephrine transporter (NET) and action at $5\text{-HT}_{2C}$ receptors; it is metabolized to the active metabolite norfluoxetine and acts as a potent CYP2D6 inhibitor.

Sertraline

An SSRI characterized by weak dopamine transporter (DAT) inhibition and binding affinity for sigma receptors.

Paroxetine

An SSRI that exhibits weak NET inhibition, muscarinic $M_1$ receptor antagonism, and inhibition of nitric oxide synthase (NOS); its short half-life increases the risk of drug discontinuation syndrome.

Fluvoxamine

An SSRI that binds sigma receptors and acts as a potent inhibitor of cytochrome P450 enzymes CYP1A2 and CYP2C19.

Citalopram

An SSRI that exhibits mild $H_1$ histamine receptor inhibition and carries a risk of QTc interval prolongation at high doses.

Escitalopram

The active $S$-enantiomer of citalopram, characterized as a pure SSRI without significant secondary receptor actions.

Serotonin Partial Agonist Reuptake Inhibitors (SPARIs)

An antidepressant class, exemplified by vilazodone, that combines serotonin reuptake inhibition with partial agonism at $5\text{-HT}_{1A}$ receptors.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

A class of antidepressants, including venlafaxine, desvenlafaxine, duloxetine, milnacipran, and levomilnacipran, that inhibit the presynaptic reuptake of both serotonin and norepinephrine.

Serotonin Antagonist and Reuptake Inhibitors (SARIs)

A drug class, exemplified by trazodone, that antagonizes $5\text{-HT}_{2A}$ and $5\text{-HT}_{2C}$ receptors, acts as a partial agonist at $5\text{-HT}_{1A}$, weakly inhibits SERT, and blocks $\alpha_1$ adrenergic and $H_1$ receptors in a dose-dependent manner.

Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs)

A drug class exemplified by bupropion, a substituted cathinone ($\beta$-keto amphetamine) that inhibits dopamine reuptake with lesser effects on norepinephrine reuptake.

Noradrenergic and Specific Serotonergic Antidepressants (NaSSAs)

A drug class exemplified by mirtazapine, which antagonizes central $\alpha_2$ adrenergic autoreceptors to enhance NE and 5-HT release, blocks $5\text{-HT}_{2A}$, $5\text{-HT}_{2C}$, and $5\text{-HT}_3$ receptors, and antagonizes $H_1$, $H_2$, peripheral $\alpha_1$, and muscarinic receptors.

Serotonin Toxicity (Serotonin Syndrome)

A severe adverse condition resulting from excess serotonergic stimulation, presenting with neuromuscular hyperactivity (clonus, myoclonus, tremor, lower limb hyperreflexia), autonomic instability, agitation, and hyperthermia leading to rhabdomyolysis and metabolic acidosis.

Drug Discontinuation Syndrome

A constellation of symptoms including dizziness, lethargy, paresthesias, nausea, vivid dreams, irritability, and depressed mood that begins approximately $5\,\text{days}$ after abrupt cessation of short half-life antidepressants and can persist for up to $3\,\text{weeks}$.

Tricyclic Antidepressants (TCAs)

A class of cyclic antidepressants featuring a characteristic three-ring structure that inhibit serotonin and norepinephrine reuptake and block muscarinic acetylcholine, $\alpha_1$-adrenergic, $H_1$ histamine, and cardiac fast sodium channels.

Tertiary Amine TCAs

A subclass of TCAs, including imipramine, amitriptyline, clomipramine, doxepin, and trimipramine, that are more potent inhibitors of serotonin reuptake and undergo hepatic demethylation into active secondary amine metabolites.

Secondary Amine TCAs

A subclass of TCAs, including desipramine, nortriptyline, protriptyline, amoxapine, and maprotiline, that are more potent inhibitors of norepinephrine reuptake.

Amoxapine

A dibenzoxazepine cyclic antidepressant derived from loxapine that potently inhibits norepinephrine reuptake and blocks dopamine receptors.

Maprotiline

A tetracyclic antidepressant that predominantly inhibits norepinephrine reuptake.

Membrane-Stabilizing Effect (Sodium Channel Blockade)

The inhibition of cardiac fast sodium channels by cyclic antidepressants in overdose, causing slowed ventricular depolarization, QRS complex prolongation ($>100\,\text{ms}$), a rightward shift of the terminal $40\,\text{ms}$ QRS axis in lead aVR, and risk of severe ventricular arrhythmias.

Antidote

Any agent or substance that neutralizes or opposes a poison or counteracts or minimizes its harmful effects without causing damage to the body.

Physical Antidote

An agent that prevents systemic absorption of toxins through local mechanical or adsorptive actions in the gastrointestinal tract without systemic distribution (e.g., activated charcoal, demulcents).

Chemical Antidote

An agent that directly neutralizes or binds a toxin locally or systemically (e.g., sodium bicarbonate forming insoluble ferrous carbonate with iron, chelating agents like DMSA/BAL, protamine sulfate, antivenoms).

Dispositional Antidote

An agent that modifies the toxicokinetics of a poison by altering its metabolism or accelerating its renal/tissue elimination (e.g., fomepizole inhibiting alcohol dehydrogenase in methanol poisoning, ion trapping via urine alkalinization).

Pharmacological Antidote

An agent that directly acts as a competitive antagonist at specific physiological receptors blocked or overstimulated by a poison (e.g., atropine at muscarinic receptors, naloxone at opioid receptors).

Physiological Antidote

An agent that produces physiological effects opposite to those of the toxin through an independent receptor mechanism or alternative signaling pathway (e.g., epinephrine for anaphylaxis, glucagon for beta-blocker overdose).

Activated Charcoal

A fine, highly adsorptive powder administered as a slurry ($1\,\text{g/kg}$ or $25\text{--}100\,\text{g}$ in adults) ideally within $1\text{--}2\,\text{hours}$ of ingestion to bind organic toxins and alkaloids in the GI tract.

N-Acetylcysteine (NAC)

An antidote for acetaminophen poisoning that replenishes hepatic glutathione stores and provides sulfhydryl groups for detoxification, preventing NAPQI-mediated hepatotoxicity.

Pralidoxime (2-PAM)

An acetylcholinesterase reactivator used in organophosphate pesticide and nerve agent poisoning to remove organophosphate groups from the enzyme before irreversible aging occurs.

Gastric Lavage

A mechanical decontamination procedure performed via an orogastric tube to wash out stomach contents using repetitive instillation and withdrawal of normal saline ($2\text{--}4\,\text{L}$ total), most effective within $1\,\text{hour}$ of exposure.

Urine Alkalinization (Ion Trapping)

A dispositional elimination technique using intravenous sodium bicarbonate to elevate urine $\text{pH} > 8.0$, ionizing weak acid toxins (such as salicylates and phenobarbital) to prevent renal tubular reabsorption.

Urine Acidification

A dispositional technique using ascorbic acid or ammonium chloride to lower urine $\text{pH} < 5.0$ to enhance elimination of weak bases like amphetamines, rarely used due to risks of rhabdomyolysis and severe metabolic acidosis.

Opioid Toxidrome

A toxicological constellation characterized by central nervous system depression, respiratory depression (bradypnea with decreased tidal volume), miosis (pinpoint pupils), and decreased bowel motility.

Cholinergic Toxidrome

A toxicological constellation caused by excessive muscarinic and nicotinic receptor stimulation, summarized by SLUDGE-BBB (Salivation, Lacrimation, Urination, Defecation, GI distress, Emesis, Bronchorrhea, Bronchospasm, Bradycardia).

Anticholinergic Toxidrome

A toxicological constellation resulting from muscarinic receptor blockade, presenting with central nervous system delirium, mydriasis, hyperthermia, dry skin and mucous membranes, urinary retention, and tachycardia.

Sympathomimetic Toxidrome

A toxicological constellation resulting from excessive sympathetic stimulation, presenting with agitation, mydriasis, tachycardia, hypertension, diaphoresis, hyperthermia, and tremors.