Pharmacology, Pharmacokinetics Flashcards
Dose
Amount of drug given Usually expressed in mg/kg Measure of efficacy See the minimally effective dose Important in drug safety
Dosage
Administration of drug per unit of time
Pharmacodynamics
The action of drugs and their mechanism of action
Affinity
Ability to bind to the receptor
Efficacy
Degree of biological activity
Agonist
Ligand that binds to receptor to elicit a response
Indirect Agonist
Molecule that does not bind directly to a receptor but increases the amount of exogenous ligand
Partial Agonist
Agonist that has an intermediate activity at the receptor
Antagonist-
Molecule that binds to receptor but has no intrinsic activity
Inverse Agonist
Agonist that binds to the receptor but has the opposite effect
Mixed agonist/antagonist
Acts as an agonist that blocks the effect of another agonist
Potency
Amount of drug required to produce a specific effect of given intensity as compared to a standard reference
Considers both affinity and efficacy
4 Principles of Pharmacokinetics
Absorption- Get drug into blood stream
Distribution- Get drug to target organ
Metabolism- Usually inactivates the drug, sometimes makes it more active
Excretion- Removes drug from Body
Time Effect Curves
Provides documentation of how much drug enters the body per unit time
Profile- Gradual increase in levels until peak concentration and then a decrease over time
Many variable control this time profile
Duration of Action
The amount of time spent in the therapeutic range
Routes of Administration
Oral- easy but slow Inhalation- Fastest Injection Topically- Slow and erratic Buccal- gums and cheeks Rectal- Generally Slow
Determinants of Dissolution
Dissolution Rates Gastric Emptying Rate Intestinal Motility Drug Interactions in Gut Lumen Passage Through Gut Wall
Dissolution Rates
Physiochemical properties
Crystal size and form
Special Formulation- sustained release
Gastric Emptying Rate
Stability of drug at acid pH
Solution or solid
Presence of other food items: food, antacids, other drugs, disease of stomach
Intestinal Motility
Dissolution of slowly soluble drugs
Chemical degradation or metabolism by microflora that live in the GI system
Drug Interactions in Gut Lumen
Complexation
Adsorption
Food interactions
Passage Through the Gut wall
-physiochemical characteristics of drug
Metabolism by enzymes in the intestinal endothelium
Drug -Phillic
Lipophilic- Pass easily through gut wall, more easily absorbed
Hydrophillic- Easily dissolved in blood but harder to pass through gut wall
Sustained Release Formulation
Drug levels more stable over time, fewer side effects, better medication compliance
Most offer once a day dosing, but some injections offer once a month
Blood Level Monitoring
Gold Standard for detecting drugs and whether they are biologically active
5-10 ml sample is collected for analysis
Blood Brain Barrier
Keeps large molecules out of the blood
Composed of specialized cells that alter the function of the capillaries
Block the junction between capillaries and cover the area with a glial sheath
Metabolism
Process of breaking down a drug or food so it can be utilizes/eliminated
Generally, lipid soluble chemicals are broken down into water soluble chemicals
Biotransformation
Preparation for elimination
First Pass Effect
Extent to which the liver removes drug from blood as it is passing through the portal vein before entering systemic circulation
Metabolism
Enzymes in the liver regulate metabolism High amount of interindividual variation Cytochrome P450 type is major enzyme Small molecules --> kidney --> urine Large molecule --> intestine --> feces
Cytochrome P450
Enzyme located in hepatocytes
Diverse gene that metabolizes wide range of drugs and food
Elimination
Primary Route through feces/urine
- Also through saliva, tears, breath and sweat
Urine Screen Drug Test
Principal way to measure if someone has taken drugs
Low cost and relatively sensitive
- See active drugs or metabolites
- Gives no indication to amount or when taken
Faking a Urine Screen
- Used at many work locations
Several products, including artificial urine and dispensing devices to help fake
Non-Urine Drug Tests
Hair- 1 week to 3 mos
Oral- 1-2 days
Urine 3-5 days
Blood minutes to days
Hair Drug Test
- Minute amounts of drug get trapped in hair cortex
- Tracks drug use over months
Simple and non-invasive
Results stand up in court
CON
Expensive
Some tests can take 5 days
Only a dozen drug classes can be used
Placebo Response
Inert substance
response can be measured
Works best on symptoms and signs that oscillate throughout the illness
- More related with an expectancy or desire for the drug to work
-Placebo manipulations reduce neuronal activity in regions that are sensitive to pain
- Reductions in activity associates with perceived reduction in pain
