Principles of Psychopharmacology

Principles of Psychopharmacology

  • Psychopharmacology: The study of the ways drugs affect the nervous system and behavior.
  • Drugs: Chemical compounds administered to produce a desired change.
  • Psychoactive drugs: Substances that change the function of the nervous system resulting in alterations of perception, mood, cognition, and behavior.
  • Classification: Drugs can be classified based on the primary neurotransmitter systems they influence.

Routes of Drug Administration

  • Intracerebral: Direct injection into the brain allows rapid action in low doses due to fewer barriers.
  • Oral: Safest and most convenient method; weak acids pass from stomach to bloodstream; weak bases pass from intestines to bloodstream.
  • Intramuscular (IM): Slower absorption; more barriers compared to inhalation.
  • Inhalation: Few barriers; rapid effect on the brain.
  • Intravenous (IV): Encounters the fewest barriers but is hydrophilic.
  • Transdermal: Drugs absorbed through the skin via adhesive patches.

Blood-Brain Barrier (BBB)

  • Structure: Endothelial cells in capillaries have tight junctions in the brain; most substances cannot pass.
  • Barrier-free Areas: Areas like the area postrema (detects and induces vomiting), pituitary & pineal glands allow the entry of hormones and chemicals for necessary functions.

Drug Elimination and Metabolism

  • Process: Drugs are catabolized in the kidneys, liver, and intestines, facilitating easier excretion.
  • Cytochrome P450: A key enzyme in the liver responsible for drug catabolism; some substances can become toxic if not eliminated.

Drug-Receptor Interactions

  • Binding Types:
    • Competitive Binding: Drugs compete with neurotransmitters for receptor sites.
    • Direct Agonist: Binds and activates receptors, enhancing neurotransmitter actions.
    • Direct Antagonist: Binds without activating, preventing neurotransmitter actions.
    • Non-competitive Binding: Occurs at alternative sites, can activate (indirect agonist) or inhibit (indirect antagonist) receptor function.

Tolerance and Sensitization

  • Tolerance: Decreased response to a drug with repeated exposure.
    • Metabolic Tolerance: Increased enzyme levels for drug breakdown (e.g., alcohol).
    • Cellular Tolerance: Brain cells adjust to minimize drug effects.
    • Learned Tolerance: Diminished outward signs of intoxication.
  • Sensitization: Increased response to equal drug doses; linked to changes in neuronal structure and function.

Specific Drug Actions

  • Caffeine: Acts as an adenosine antagonist; inhibits the breakdown of cAMP, enhancing energy availability and alertness. Can lead to mild dependence.
  • Nicotine: Stimulant at low doses; tolerance develops rapidly. Affects acetylcholine receptors leading to increased neurotransmitter release.
  • GABAergic Drugs:
    • Benzodiazepines: Reduce anxiety; increased doses can lead to tolerance and adverse effects.
    • Alcohol: Binds to GABAA receptors, promotes Cl- influx, resulting in neuronal inhibition.
  • Glutamate: Main excitatory neurotransmitter; antagonists like PCP and ketamine are associated with hallucinogenic effects.
  • Dopamine: Agonists include cocaine and amphetamines; antagonists used in treating schizophrenia. Amphetamines increase dopamine by blocking reuptake.
  • Serotonergic Drugs: Treat major depression; SSRIs block the reuptake of serotonin.
  • Opioid Drugs: Pain relief and sleep-inducing; tolerance increases with repeated use. Naloxone acts as an opioid antagonist during overdoses.
  • Cannabis: THC interacts with CB1 receptors to alter mood; therapeutic uses include pain management and anxiety reduction.

Individual Responses to Drugs

  • Factors Influencing Responses:
    • Body Size: Larger individuals have lower sensitivity due to greater blood volume.
    • Sex Differences: Women are generally more sensitive to most drugs than men; often develop dependence more rapidly.
    • Age: Older individuals may be more sensitive to drugs due to decreased metabolic effectiveness.

Addiction Theories

  • Hedonia Hypothesis: Substance abuse linked to pleasure from drugs, leading to impulse control issues.
  • Incentive Sensitization Theory: Separate brain systems for craving (wanting) versus pleasure (liking); craving increases with use, while pleasure decreases.

Neurological Disorders

  • Traumatic Brain Injury (TBI): Results from physical damage; can cause cognitive deficits.
  • Stroke: Can lead to ischemia and cell death, with treatments focusing on restoring blood flow.
  • Epilepsy: Characterized by seizures; treatment involves anticonvulsants and sometimes surgery.
  • Neurodegenerative Disorders: Include Alzheimer's and Parkinson's; involve loss of neurotransmitter function with various treatment approaches.