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Understand how drugs affect the brain, behavior, and mental processes.
The four stages of pharmacokinetics.
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Psychopharmacology is the study of how drugs affect mood, sensation, thinking, and behavior. This field examines the mechanisms by which psychoactive substances influence neural function, their therapeutic applications in treating mental disorders, and their potential for abuse. Understanding psychopharmacology is essential for clinical practice, research, and public health.
Routes of Administration: - Oral: Convenient but slow absorption, first-pass metabolism - Intravenous: Rapid onset, precise dosing - Intramuscular/Subcutaneous: Intermediate absorption - Inhalation: Very rapid onset (lungs to brain) - Transdermal: Slow, sustained release
ADME Processes: - Absorption: Drug enters bloodstream - Distribution: Drug distributed to tissues; blood-brain barrier limits CNS access - Metabolism: Liver enzymes (especially CYP450) break down drugs - Excretion: Removal via kidneys, liver, lungs
Key Concepts: - Half-life: Time for plasma concentration to decrease by half - Bioavailability: Proportion reaching systemic circulation - Tolerance: Decreased response with repeated use - Dependence: Physical/psychological need for drug
Drug-Receptor Interactions: - Agonists: Bind to and activate receptors (mimic neurotransmitter) - Antagonists: Bind to but do not activate receptors (block neurotransmitter) - Partial Agonists: Activate receptors with submaximal response - Inverse Agonists: Produce opposite effect of agonists
Mechanisms of Action: - Affect neurotransmitter synthesis - Affect neurotransmitter storage/release - Block or activate receptors - Inhibit reuptake transporters - Inhibit degradation enzymes
Dose-Response Relationships: - Potency: Amount needed for effect - Efficacy: Maximum effect achievable - Therapeutic index: Ratio of toxic to therapeutic dose
Selective Serotonin Reuptake Inhibitors (SSRIs): - Examples: Fluoxetine, sertraline, escitalopram - Mechanism: Block serotonin reuptake - First-line for depression and anxiety - Delayed therapeutic effect (2-4 weeks)
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): - Examples: Venlafaxine, duloxetine - Block both serotonin and norepinephrine reuptake
Tricyclic Antidepressants (TCAs): - Examples: Amitriptyline, imipramine - Block multiple neurotransmitter systems - More side effects than SSRIs
Monoamine Oxidase Inhibitors (MAOIs): - Examples: Phenelzine, tranylcypromine - Inhibit enzyme that breaks down monoamines - Dietary restrictions required
Atypical Antidepressants: - Bupropion: Dopamine/norepinephrine; also for smoking cessation - Mirtazapine: Alpha-2 antagonist, enhances release
Benzodiazepines: - Examples: Diazepam, lorazepam, alprazolam - Mechanism: Enhance GABA-A receptor function - Effects: Anxiolytic, sedative, muscle relaxant, anticonvulsant - Risks: Tolerance, dependence, withdrawal, cognitive impairment
Z-Drugs (Non-benzodiazepine hypnotics): - Examples: Zolpidem, zaleplon - Similar mechanism but more selective for sleep
Buspirone: - 5-HT1A partial agonist - Anxiolytic without sedation or dependence - Delayed onset (2-4 weeks)
Other Anxiolytics: - Beta-blockers: Reduce physical symptoms of anxiety - Antihistamines: Hydroxyzine - Gabapentinoids: Pregabalin, gabapentin
First-Generation (Typical) Antipsychotics: - Examples: Haloperidol, chlorpromazine - Mechanism: D2 receptor antagonism - Effective for positive symptoms - High risk of extrapyramidal symptoms (EPS)
Second-Generation (Atypical) Antipsychotics: - Examples: Risperidone, olanzapine, quetiapine, clozapine, aripiprazole - Block D2 and 5-HT2A receptors - Lower EPS risk - Metabolic side effects (weight gain, diabetes)
Movement Disorders: - Acute dystonia: Muscle spasms - Akathisia: Restlessness - Parkinsonism: Tremor, rigidity - Tardive dyskinesia: Involuntary movements (late-onset, potentially irreversible)
Lithium: - First-line for bipolar disorder - Mechanism not fully understood (multiple effects) - Narrow therapeutic index; requires monitoring - Effective for acute mania and prophylaxis
Anticonvulsants as Mood Stabilizers: - Valproate: Acute mania, rapid cycling - Carbamazepine: Alternative for mania - Lamotrigine: Bipolar depression, maintenance
Atypical Antipsychotics: Increasingly used as mood stabilizers (quetiapine, olanzapine, aripiprazole).
ADHD Medications: - Methylphenidate: Blocks dopamine/norepinephrine reuptake - Amphetamines: Release and block reuptake of dopamine/norepinephrine - Both enhance prefrontal cortex function - Schedule II controlled substances
Non-Stimulant ADHD Medications: - Atomoxetine: Norepinephrine reuptake inhibitor - Guanfacine, clonidine: Alpha-2 agonists
Cognitive Enhancement in Dementia: - Cholinesterase Inhibitors: Donepezil, rivastigmine, galantamine - NMDA Receptor Antagonist: Memantine - Modest symptom improvement; do not halt progression
Reward Pathway: Mesolimbic dopamine system (VTA → nucleus accumbens)
Major Drug Classes:
Depressants: - Alcohol: GABA enhancement, glutamate reduction - Opioids: Mu receptor agonism (heroin, morphine, fentanyl)
Stimulants: - Cocaine: Blocks dopamine reuptake - Methamphetamine: Releases and blocks reuptake of monoamines
Hallucinogens: - LSD, psilocybin: 5-HT2A agonism - MDMA: Serotonin release
Cannabis: - THC: CB1 receptor agonism - Endocannabinoid system modulation
Addiction Mechanisms: - Neuroadaptation and tolerance - Sensitization of incentive salience - Prefrontal cortex impairment - Stress system dysregulation
Comparison of first and second-generation antipsychotic medications.
| First-Generation (Typical) | Second-Generation (Atypical) | |
|---|---|---|
| Primary Mechanism | D2 Antagonism | D2 + 5-HT2A Antagonism |
| EPS Risk | High | Lower |
| Metabolic Risk | Lower | Higher (weight gain, diabetes) |
| Effect on Negative Symptoms | Minimal | Potentially better |
4 questions to test your understanding of this topic
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