Chapter 12 (Intro to Psychopharmacology)

Define the Monoamine Oxidase System

MAO is the enzyme that rapidly inactivates monoamines (e.g., serotonin, dopamine, norepinephrine); MAO is present in two forms: (1) MAO-A, which inactivates norepinephrine and serotonin, and (2) MAO-B, which inactivates dopamine.

Dopamine activation (agonist) effects?

• Schizophrenia-like symptoms (hallucinations, delusions)

• Psychosis

• Enhancement of sexual function

• Addictive behaviors

Dopamine antagonism effects?

• Antipsychotic effect

• Negative schizophrenia symptoms (depression, anhedonia)

• Parkinsonism & EPS

• Sexual dysfunction

Effect of tobacco smoke on psychotropic drugs?

Reduces serum levels of medications (causes more CYP-450 1A2 enzyme to be synthesized) → require more of medication → risk toxic levels if not titrated downward as patient stops smoking (clozapine, duloxetine)

Define bioavailability

the fraction of dose that reaches systemic circulation (absorption principle)

Define first-pass metabolism

Enzymatic breakdown of drugs before they reach systemic circulation; drugs with high first-pass metabolism must be significantly reduced in dose level if given IM or IV

Significance of protein-binding?

Protein-bound drugs do not have a pharmacologic effect, cannot be metabolized, and cannot be excreted; diazepam (98% protein binding) produces its results because of the 2% or so of active drug

Protein-binding and drug combinations?

Drug combinations that compete for protein binding sites have the potential of causing significant increases in levels of the free or active drug

Define linear kinetics

The amount of drug in the body decreases by 50% every 4 hours

Define washout period

To discontinue a drug, four half-lives are required to eliminate 96% of the drug

Define downregulation

Chronic exposure to certain drugs causes receptors to change

Define pharmacodynamic tolerance

Reduction in receptor sensitivity (or desensitization)

Enzyme induction v. inhibition?

Induction → Speeds up drug breakdown, which lowers the concentration of active medication in the blood and can cause treatment failure (days → weeks to develop)

Inhibition → Slows down breakdown, causing drug levels to rise in the blood, which increases the risk of side effects and toxicity (develops almost immediately)

3 dimensions of the BBB

• Anatomic (capillaries supplying blood to brain)

• Physiologic (chemical and transport system that recognizes and allows certain molecules into the brain; highly lipid-soluble pass through with relative ease)

• Metabolic (Prevents molecules from entering the brain by enzymatic action)

Significance of BBB with psychotropic drugs?

Only drugs that can pass through this barrier in significant amounts are effective in treating a
psychiatric or medical disorder of the brain

Significance of P-glycoprotein efflux transporters?

• Drugs that induce the P-glycoprotein system
  cause the drug to be less effective.

  • Can cause a second-generation antihistamine
    to be nonsedating

• Drugs that inhibit P-glycoprotein can cause an
  increased central effect without causing a
  change in serum levels

Neurotransmitters and Related Mental Disorders? (6)

• ↑ Dopamine → Schizophrenia
  • ↓ Norepinephrine & Serotonin → Depression
  • ↓ Acetylcholine → Alzheimer disease
  • ↓ GABA → Anxiety
  • ↑ Glutamate → Excitotoxicity leading to neuronal death
  • ↓ Glutamate → Psychotic thinking

Define a ligand

A transmitter substance or molecule that fits and evokes a response from a receptor (drugs, neurotransmitters, hormones, etc.,)

Define an Autoreceptor

A negative feedback mechanism neurons use to increase or decrease the release of neurotransmitters

Effects of serotonin activation?

• Antidepressant effect

• Anxiety

• GI disturbances

• Sexual dysfunction

Effects of serotonin antagonism?

• Depression

• Suicidality

• Compulsive behavior

• Anxiety

Effects of acetylcholine activation?

• Decreased HR

• Enhancement of cognitive processes

• Sweating & salivation & increased UOP (opposite of dry)

• Increased respiratory secretions

Effects of acetylcholine antagonism?

• Increased HR

• Dry mouth & constipation & decreased UOP (dry)

• Decreased respiratory secretions

• Cognitive slowing

Effects of norepinephrine activation?

• Antidepressant effect

• Increased HR

• Vasoconstriction

• Bronchial dilation

Effects of norepinephrine antagonism?

• Depressive effect

• Vasodilation

• Decreased HR

• Sexual dysfunction