Pharmacology is defined as the study of the interaction of chemical substances with living systems.
A chemical substance that acts on living systems through chemical processes, which is utilized for diagnosis, prevention and cure of an unwanted health condition ( by FDA)
3. Name and Define two main subdivisions of pharmacology
Pharmacokinetic: Absorption, Distribution, Metabolism, Excretion Pharmacodynamics: Pharmacological effects of drug; Mechanism of action
Pharmacokinetics is the study of the kinetics of drug. (absorption, distribution, metabolism and excretion)
2. Ion trapping
Cell membranes are less permeable to ionized compounds (water solubility)
3. First-pass effect
Before the orally administrated drug reaches the systemic circulation, the drug can be metabolized in the liver or intestines, resulting in a significant reduction of amount of unmetabolized drug reaching the systemic circulation. It reduce: amount of unmetabolized drug, bioavailability and drug effects.
Bioavailability is a measure of the fraction (F) of administered dose of a drug that reaches the systemic circulation in the unchanged form. BA=A/D x 100% (A: Total amount of drug in SC; D: Administrated dose)) * Bioavailability indicates the rate and extent of absorption into the circulation following extravascular administration of drugs.
Time it takes for a drug concentrations to decrease by one half. The half-life of a drug that follows first-order kinetics (linear pharmacokinetics) is independent of the amount or concentration and inversely proportional to the overall elimination rate constant.
The theoretical volume of plasma from which the drug is completely removed in unit time (ml/min). CLtotal = k x Vd. (k: elimination rate constant; Vd: apparent volume of distribution). Elimination clearance means to leave the body or to convert to an inactive form.
7. Apparent volume of distribution
Volume of distribution is a theoretical volume or called as apparent volume distribution. It has no direct physiological significance because it does not represent a real physiological volume. It reflects the extent of the drug distribution in the body.
8. Therapeutic window
It’s the range of dose of a drug which is effective without being harmful. The well-defined range of a drug’s serum concentration at which a desired effect occurs, below which there is little effect, above which toxicity occurs.
1.) What are mechanisms of drug transport?
Ⅰ. Passive diffusion (Lipid diffusion): Passive process, requires no energy Drug permeation dependent on: lipid solubility, concentration difference, surface area and vascularity Ⅱ. Filtration (Aqueous diffusion): Small molecules diffusion through aqueous channels. (Water solubility, small molecule oral; liquor>tablet 2.) Drug Interactions
(1) Pharmacokinetic interactions
(2) Pharmacodynamic interactions: receptor (potentiation/antagonism
b) Biological Factors
Age (liver metabolism; renal elimination; body composition) Gender (Women have more CYP3A in the liver, Estrogen and progestin inhibit CYP450 leading to a lower CL of drugs in women, Women tend to take more medications, including dietary supplements, than men) Body Size / Obesity
Disease (Liver disease-Reduction drug-metabolizing enzyme activity, Kidney disease-excretion decreased ) Placebo effects (Often caused by psychological factors, patient-physician interaction) Variation in response (Tolerance; Resistance)
Genetic factor (Genetic variation is an important source of pharmacokinetic and pharmacodynamic variability. Racial difference in drug response the genetic expression of drug metabolizing enzymes complicate the individualization of drug therapy)
a person’s diminished response to a drug, occurs when drug is used repeatedly&body adapts to the continued presence of the drug;means requirement of higher dose to produce a given response
The ability of microorganisms or cancer cells to withstand the effects of a drug usually effective against them
A drug, given as a 100 mg single dose, results in a peak plasma concentration of 20mg/ml, Vd? A. 0.5L
A drug, with a half-life of 12 hours is administered by continuous IV infusion. How long will it take for the drug to reach 95% of its final steady-state level? A. 18 hours
B. 24 hours
C. 36 hours
D. 48 hours
E. 96 hours
Which of the following statements is correct?
A. If 10 mg of Drug A produces the same response as 100 mg of Drug B, Drug A is more efficacious than Drug B. B. The greater the efficacy, the greater the potency of a drug. C. In selecting a drug, potency is usually more important than efficacy. D. A competitive antagonist increases the ED50.
E. Variation in response to a drug among different individuals is most likely to occur with a drug showing a large therapeutic index.
A. drugs A and C have equal efficacy
B. drug A is more potent than drug B
C. drug B is a partial agonist
D. drugs A and B have the same affinity and efficacy
E. drugs A and B are partial agonists
PK and PD are the Main points.
PD: the relationship of drugs and receptors (agonist, antagonist), dose-effect relationship (potency-affinity, efficacy-intrinsic activity, ED50, ED50, LD50,TI et al), dual effects of drugs (especially ADRs and its reasons) PK: understand the process of ADMR. drugs transport, first pass elimination, biotransformation, elimination kinetics.