Psychopharmacology Study Guide

📖 Core Concepts Psychopharmacology – study of how drugs alter mood, cognition, behavior, and memory. Drug action – the precise molecular interaction (e.g., receptor binding). Drug effect – the downstream physiological/psychological changes that follow the action. Neurotransmitter system modulation – drugs can (1) act as precursors, (2) inhibit synthesis, (3) block storage, (4) change release, (5) stimulate or block postsynaptic receptors, (6) affect autoreceptors, (7) inhibit breakdown, (8) block reuptake. Key receptors – D2 (dopamine), 5‑HT₂A (serotonin), GABAA, NMDA (glutamate), CB1/CB2 (cannabinoid). Monoamine theory of depression – depression linked to low serotonin, norepinephrine, dopamine, but low serotonin alone ≠ depression. 📌 Must Remember All antipsychotics → D2 blockade (60‑80 % occupancy). Typical antipsychotics: broad D‑block → ↑ extrapyramidal side effects. Atypical antipsychotics: higher 5‑HT₂A : D2 antagonism → ↓ EPS. SSRIs: block serotonin transporter → ↑ synaptic 5‑HT; safest in overdose. TCAs: block reuptake of NE & 5‑HT; higher toxicity. MAOIs: inhibit monoamine oxidase → ↑ NE, DA, 5‑HT. Benzodiazepines: positive allosteric modulators at GABAA → ↑ Cl⁻ influx → sedation, anxiolysis. Alcohol: ↓ NMDA (excitatory) and ↑ GABAA (inhibitory). Ketamine: NMDA antagonist → ↑ extracellular glutamate → rapid antidepressant effect (via mTOR pathway). Cannabinoid CB1 activation: ↓ cAMP, block Ca²⁺ channels, open K⁺ channels → ↓ neurotransmitter release. Opioids: analgesia via spinal & descending pathways; ↑ dopamine in nucleus accumbens → reward. Cocaine: blocks reuptake of 5‑HT > DA > NE → ↑ synaptic monoamines. Amphetamines: release catecholamines and block reuptake (indirect agonists). 🔄 Key Processes From drug action to effect Drug binds receptor → conformational change → intracellular signaling (second messengers) → acute physiological change → longer‑term adaptive changes (receptor density, second‑messenger function). Antidepressant adaptation Acute ↑ 5‑HT/NE → homeostatic down‑regulation of autoreceptors → later increase in neurotransmission → clinical mood improvement (weeks). Typical antipsychotic EPS D2 blockade in nigrostriatal pathway → ↓ dopamine → Parkinson‑like motor side effects. Atypical antipsychotic reduced EPS Simultaneous 5‑HT₂A antagonism → disinhibits dopamine release in nigrostriatal tract → balances D2 block. Alcohol‑induced amnesia NMDA inhibition at NMDAR → impaired long‑term potentiation → memory loss. 🔍 Key Comparisons Typical vs. Atypical Antipsychotics Typical: Broad D2 block → high EPS. Atypical: Higher 5‑HT₂A/D2 ratio → lower EPS, metabolic side effects. SSRIs vs. TCAs vs. MAOIs SSRIs: Selective 5‑HT reuptake block → safest overdose. TCAs: Block 5‑HT & NE reuptake + anticholinergic → cardiotoxic in overdose. MAOIs: Inhibit MAO → dietary tyramine interactions; severe hypertensive crisis risk. Alcohol vs. Benzodiazepines Alcohol: Directly inhibits NMDA & enhances GABAA; effects dose‑dependent, can cause thiamine deficiency. Benzodiazepines: Specific positive allosteric GABAA modulators; tolerance, dependence, severe withdrawal. Cocaine vs. Amphetamines Cocaine: Blocks reuptake only (strongest at 5‑HT transporter). Amphetamines: Release catecholamines + block reuptake (indirect agonists). ⚠️ Common Misunderstandings “Low serotonin causes depression.” – Depression is multifactorial; serotonin deficiency alone is insufficient. “All antipsychotics cause the same side effects.” – Atypicals have markedly fewer extrapyramidal symptoms but more metabolic risks. “Alcohol is a GABA agonist.” – It enhances GABAA function and blocks NMDA; the combination causes sedation and memory loss. “MAOIs are just another antidepressant.” – They require strict dietary restrictions; not interchangeable with SSRIs/TCAs. 🧠 Mental Models / Intuition “Lock‑and‑key → door open/closed” – Think of receptors as doors; agonists (keys) open them, antagonists block the keyhole. “Traffic jam analogy” – Reuptake blockers = traffic lights stuck green, keeping neurotransmitter cars on the road longer. “D2 occupancy curve” – 0‑60 %: minimal antipsychotic effect; 60‑80 %: therapeutic; >80 %: high EPS risk. 🚩 Exceptions & Edge Cases SSRIs vs. overdose safety – Generally safer, but can still cause serotonin syndrome when combined with MAOIs or other serotonergic agents. Ketamine’s antidepressant effect – Rapid (hours) unlike typical antidepressants (weeks); requires monitoring for dissociation. Cannabinoid CB2 receptors – Primarily immune, not central; peripheral effects differ from CB1‑mediated psychoactivity. 📍 When to Use Which Depression first‑line: SSRIs (safety) → consider SNRIs or TCAs if inadequate response. Manic episodes: Lithium (classic), atypical antipsychotics for acute agitation. Schizophrenia: Atypical antipsychotic (lower EPS) unless patient has contraindications (e.g., metabolic syndrome). Acute anxiety or alcohol withdrawal: Short‑acting benzodiazepine (e.g., lorazepam). Insomnia: Non‑benzodiazepine hypnotic or melatonin agonist; reserve barbiturates for refractory cases. Severe, treatment‑resistant depression: Consider ketamine infusion (rapid response). 👀 Patterns to Recognize “Block → ↓ → up‑regulation” – Chronic receptor blockade often leads to up‑regulation of receptors (e.g., D2 up‑regulation after long‑term antipsychotic use → tardive dyskinesia). “Dual antagonism = fewer motor side effects” – Presence of 5‑HT₂A antagonism in atypicals predicts lower EPS. “Reuptake inhibition = increased synaptic tone” – Any drug listed as “block reuptake” will increase extracellular monoamine levels. “NMDA inhibition = dissociation/rapid antidepressant” – Ketamine (and other NMDA antagonists) follow this pattern. 🗂️ Exam Traps Distractor: “All antidepressants increase serotonin.” – False; TCAs also increase norepinephrine, MAOIs affect all three monoamines. Distractor: “Typical antipsychotics are safer than atypicals.” – Reverse; typicals have higher EPS risk. Distractor: “Alcohol acts only on GABA.” – Misses NMDA inhibition and resulting memory impairment. Distractor: “Cannabinoid effects are mediated solely by CB1.” – CB2 involvement in immune modulation is also true. Distractor: “Ketamine is a classic antidepressant.” – It works via NMDA antagonism, not monoamine reuptake. --- Study this guide, focus on the bolded high‑yield facts, and practice applying the mental models to sample questions.