Principles of Psychopharmacology

Principles of Psychopharmacology

• Pharmacokinetics is the study of how drugs move through the body.
• There are four stages of pharmacokinetics: absorption, distribution, metabolism, and excretion.
• Routes of administration affect the speed of absorption and blood levels of drugs.
• Intravenous injection is the fastest route of administration.
• Most psychoactive drugs exert effects on cells of the central nervous system (CNS).
• To exert effects, drugs must pass through the blood-brain barrier.
• Lipid-soluble, small, and neutral drug molecules more easily pass through the blood-brain barrier.
• Most drugs are metabolized and deactivated by enzymes in the brain and liver.
• All drugs are eventually excreted, primarily by the kidneys.
• Sometimes enzymes transform drug molecules into active versions (e.g., benzodiazepines).
• A given drug can have more than one effect (e.g., morphine).
• Drugs can produce the same effects through different mechanisms (e.g., analgesia).
• Drug effects vary with dose.
• Margin of Safety is the difference between the therapeutic dose and the toxic dose.
• Tolerance refers to a decrease in drug effectiveness, requiring higher doses for the same effect.
• Sensitization refers to a drug becoming more effective over time.
• Withdrawal symptoms occur when an individual stops taking a drug and are usually opposite to the drug's effects.
• Withdrawal symptoms indicate physical dependence.

Sites of Drug Action

• Pharmacodynamics is the study of how drugs work.
• Most psychoactive drugs act by altering the actions of neurotransmitters.
• Agonists facilitate the action of a neurotransmitter.
• Antagonists block or decrease the action of a neurotransmitter.

Production, Storage, and Release of Neurotransmitters

• L-DOPA is a precursor for dopamine (agonist) and influences production.
• Reserpine prevents storage of monoamines (antagonist).
• Botulinum toxin blocks the release of acetylcholine (antagonist).

Action on Receptors

• Direct effects: Drugs bind to the same receptor as the neurotransmitter.
• Direct agonist: Mimics the action of the neurotransmitter when it occupies the receptor (e.g., nicotine).
• Competitive antagonist: Competes with the neurotransmitter for the same binding site but blocks its action (e.g., chlorpromazine).

Classes of Neurotransmitters

• Amino acids (glutamate, GABA), acetylcholine, monoamines, peptides, and lipids are classes of neurotransmitters.

Neurotransmitters

• Many different neurotransmitters exist.
• Most brain regions involve a balance of glutamate (excitatory) and GABA (inhibitory).
• Other neurotransmitters are found in pathways and modulate brain areas.

Amino Acids

• Glutamate is the main excitatory neurotransmitter.
• GABA is the main inhibitory neurotransmitter.
• Glycine is an inhibitory neurotransmitter in the spinal cord and lower brain stem.

Glutamate

• All sensory neurons release glutamate (except pain).
• Glutamate is stored in vesicles and released by presynaptic neurons during an action potential.
• Three ionotropic receptors for glutamate: NMDA, AMPA, and Kainate receptors. These receptors activate positively charged ion channels (Na+ , Ca++) and cause local EPSPs (excitatory post-synaptic potentials).
• One metabotropic receptor for glutamate (auto-receptor).

NMDA Receptor

• Is chemical and voltage-gated.
• Involves a Ca++ channel.
• Has multiple binding sites, including glutamate and glycine.
• Has a Mg++ binding site deep within the ion channel.

Norepinephrine

• Found in the brain and peripheral nervous system.
• Nearly all brain areas receive norepinephrine from pathways originating in the pons.
• The locus coeruleus is the major source of norepinephrine.
• Norepinephrine leads to increased vigilance (attentiveness to environmental stimuli).
• All norepinephrine receptors are metabotropic.
• Two families of norepinephrine receptors: α and β.
• Termination of norepinephrine: catabolic enzymes (MAO or COMT) and re-uptake.

Serotonin

• Synthesized from tryptophan (amino acid).
• Plays a role in mood regulation, control of eating, sleep, and arousal, and pain regulation.
• Also involved in dreaming.
• The major source is the raphe nuclei of the midbrain, pons, and medulla.
• Released from varicosities along the axons.
• At least 7 types of serotonin receptors: 5-HT1, 5HT2, etc.

Lipids

• Appear to be synthesized on demand, produced or released as needed.
• Not stored in synaptic vesicles.
• Endocannabinoids (anandamide) are the best-known lipid neurotransmitters.
• Involved in pain regulation, appetite.
• Act as retrograde signals, released by post-synaptic neurons back onto pre-synaptic neurons.
• Two types of cannabinoid receptors: CB1 and CB2.
• CB1 receptors are located on pre-synaptic nerve terminals and decrease the activity of the pre-synaptic neuron.

Naloxone

• Is a competitive opioid receptor antagonist used to reverse opioid drug overdose.