Lecture 1: Pharmacokinetics Flashcards
What is the meaning of therapeutic range?
Dosage in which a drug is effectively treating ailment without causing impairment (toxicity level = overdose zone)
What are the translations of “pharmacon” and “kineticos”? what language is this?
Pharmacon - drug
Kinetikos - putting in motion (the study of time dependency)
What are the four determinants about bioavailability?
Absorption
Distribution
Metabolism
Elimination
What are the enteral forms of drug administration? Parenteral?
E: Oral (mouth), rectal (suppository)
P: inhalation (lungs), mucous membranes (nose/mouth), skin (patch), injection (iv, muscle, skin)
What are the requirements/characteristics, and negatives of:
- Oral administration
- Rectal administration
- R/C: Must be GI (acid) resistant, passive diffusion (high conc 2 low conc), lipid solubility (the more soluble the easier the travel) through membrane). Disadvantages: vomiting/stomach discomfort, variable levels of absorption (pp differ), insult from stomach acids
- R/C: Used in restricted conditions, delivered via suppository. Disadvantages: poor absorption parameters (not designed to take things in), rectal membrane irritation
What are the characteristics of administration via inhalation, mucous membranes, skin (transdermal patch), injection (include disadvanatges for this one)?
Hint: this speed and method of absorption,
Inhalation - rapid exchange between lung and blood, rapid delivery to brain, used for anesthetic gases
Mucous membranes - absorbed through mucosal membranes directly into bloodstream, sublingual (under tongue) admin
Skin - provides continuous, controlled release, absorbed through epidermis directly into bloodstream
Injection - intravenous (vein - v speedy), intramuscular (muscle - slower), subcutaneous (under skin - v speedy)
Disadvantages: unable to respond to unexpected reaction, must use sterile techniques, essentially irreversible
Why are drug side effects produced?
Only a small portion of the drug is actually interacting with target receptors, other interactions cause side effects
How is a drug distributed in the system when it is administered orally? what enzyme is found in the liver that is of particular interest and denotes bio differences between men and women?
Oral drugs travel through GI tract into portal system (main blood supply system), drug then enters central circulation to the heart
Note: drug may be metabolized by GI tract or liver (first-ass metabolism)
Alcohol dehydrogenase (breaks down alc) - men tend to have more of this enzyme than women
What metabolizing enzyme found in the liver has the ability to break down Buspirone (BuSpar)? how effective is it/what can lessen its effectiveness?
CYP3A
Only 5% of drug enters portal system - pretty damn effective
Grapefruit juice, specifically the active component called furanocoumarin
(Graph shows how old people were drinking gjuice were od-ing on bspar - slide 21)
What are the membranes which affect drug distribution in the body? Describe them and the conditions required for entry
Cell membranes
Capillary vessels - tiny blood vessels with single cell walls, cell walls have small pores that allow for passive diffusion. Entry into body tissue depends on: rate of blood flow through capillary vessel and ability of drug to pass through capillary vessel pores
Blood-brain barrier - capillaries are tightly joined together, covered on outside by glial sheath, no pores present. Entry into brain depends on: size of the drug molecule, lipid solubility (lipid solubility matters more
Placental barrier - drugs cross placenta via passive diffusion, barrier is not selective, similar concentration between mother and fetus
Describe a membrane and its components
Draw a phospholipid bilayer at least once
Hydrophobic tail (inner) and hydrophilic head (outer) Phospholipid bilayer - outside (extracellular fluid), inside (intracellular fluid)
Drugs can exit the body via which pathways?
Kidney excretion
Lungs
Bile
Skin
What specifically occurs in the kidneys when drugs exit the body?
Nephron processes the drugs and we secrete the excess (waste/broken down drugs)
Which enzymes are responsible for the termination of drug action?
Cytochrome P450 enzyme family (major system) - includes enzyme families (CYP-1, CYP-2, CYP-3)
Majority of breakdown is mediate by few enzymes
How do genetics influence drug termination action? what is the significance?
Rates of metabolism vary
Genetic testing reveals different speeds of metabolism which can effect the length and effectiveness of a drug used to treat ex: depression
