Lecture 1 Flashcards
What is pharmacokinetics?
The study of the concentration of the drug in the blood plasma during the processes of absorption, distribution, metabolism, and elimination. What body does to drug.
What is pharmacodynamics?
The study of the mechanisms by which drugs produce their intended therapeutic effects. What drug does to body.
What is pharmacotoxicology?
The study of the physiological mechanism by which drugs produce adverse side effects.
Trade Name
Patented, expires after 17 years.
OTC drugs can be different formulations / different drugs
Generic Name
Common name, noncommercial
Chemical Equivalence
Two drugs contain the same amount of an identical chemical compound
Bioavailability
Absorption rate and extent
Can 2 drugs be chemically equivalent with different bioavailability?
Yes. They can dissolve at different rates so are absorbed differently, causing changes in time of onset and intensity.
Why enteric coated drugs and the problem with them.
They are designed to dissolve in intestines b/c:
1. protect drug from stomach acid or pepsin.
2. protect stomach lining from drug (gastric discomfort).
Problem is gastric emptying is variable minutes to 12 hours, so alters time of onset. Might NOT dissolve at all
Aspects of good clinical trial
- Controls
- Random Assignment
- Blinding
Stages of Drug Development
Stage 1: Preclinical testing on animals
Stage 2. Clinical testing on humans.
Preclinical Trials
On animals;
Evaluated for:
1. Toxicity
2. Pharmacokinetic properties
3. Potentially useful biological effects.
1-5 years
Then apply for Investigational New Drug status
Clinical Trials
2-10 years
4 Phases
1-3 are before market
4th phase after marketing
Phase I Clinical Trials
Conducted on healthy volunteers. 3 Goals: 1. Evaluate drug metabolism 2. Pharmacokinetics 3. Biological Effects
Phase 2&3 Clinical Trials
Conducted on patients. Given to 500-5000 patients for 3-6 months Evaluated for: 1. Therapeutic Effects 2. Dosage range 3. Safety 4. Effectiveness Then apply for New Drug Application (NDA)
Phase 4 Clinical Trials
Post marketing surveillance
Observe in general population
Limitations of Clinical Trials
- Poor information on women and children
2. Failure to detect adverse effects (50%)
IM & Sq
Only barrier is capillary wall. Lipid soluble can diffuse across and pass through fenestrations. Polar ions only pass through fenestrations.
Adv: suitable for poorly soluble drugs and depot preparations
Disadv: Pain, inconvenience, injury, variable rate of absorption r/t blood flow and water solubility of drug
Oral
2 Barriers:
1. epithelial lining of GI tract: P-glycoprotein can pump drugs out of cells back into lumen of GI
2. Capillary walls
Variable absorption pattern
Variability of Absorption in oral route
- Solubility and stability of drug
- Gastric and intestinal pH and related enzymatic breakdown.
- Gastric Emptying time
- Food in gut
- Coadministration of other drugs
- Special coatings
- Circulation through hepatic portal system
First Pass Effect
GI–> Hepatic portal vein–> Liver–>inferior VC to systemic circulation OR enterohepatic recirculation–>bile duct–>duodenum–>hepatic portal vein…
What is the difference between a drug and a poison?
Dose
Half life
Time it takes for the concentration of a drug to decrease by half.
Area under the curve (AUC)
Total amount of drug from the time it enters the blood until it disappears.
Bioavailability
The percent of total drug dosage that enters blood stream.
Bioavailability formula
AUC (mg)/dosage (mg) x100
In general, how dooes route of administration influence bioavailability?
Parenteral has the highest, with IV = 100%
Bioequivalence
Manufacturing guidelines that require 2 preparations of the same drug (trade vs Generic) to have smae AUC and same Cmax, increasing the likelihood they will have the same biological effects
Variables influencing Absorption:
- Rate of dissolution
- surface area
- blood flow
- lipid solubility
- GI function/contents
- pH partitioning
Influences on BBB
Infants, elderly, inflammation, infection.
