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Pharmocology The science that is concerned with drugs, their sources, appearance, chemistry, actions and uses
Pharmacokinetics the movement of drugs within biological systems, as affected by uptake, distribution, binding, elimnation and bio-transformation; the rates thereof
Why is there such a wide variability in drug effects? 1. Rate and extent of absorption 2. Body size, age and gender 3. Distribution 4. Protein binding 5. Rate and extent of metabolism 6. Elimination rate 7. Drug-receptor interaction 8. Functional rate 9. Placebo effects 10. Interaction with other drugs
Why is there such a wide variability in drug effects? (cont.) 11. Tolerance 12. Genetic fxs
Maternal changes in pregnancy ^Plasma volume ^Cardiac output ^Blood flow to kidneys, stomach and small intestine ^ Rate of oral drug absorption ^Total body water ^Body fat ^Pumonary dunction, Change in hepatic metabolism
Plasma protein binding is decreased due to... diluation from increased plasma volume
Fxs influencing drug exposure to the fetus 1. Chemical characteristics of drug 2. Dose 3. Bioavailability 4. Placental transfer of drugs 5. Distribution 6. Binding or localization in tissues, 7. Bio-transformation 8. Excretion
The MW of a drug may determine its bio-availability Non0ionized drugs with high MW and ionized drugs of any MW cross cell membranes poorly, if at all
Dose the quantity of a drug that is taken (Prescribed dose versus administered dose)
Therapeutic dose The concentration range that produces the desired effect
Subtherapeutic dose produces no discernible effect, or less effect than desired
Bioavailablility the physiological availability of a drug at its site of action (The amount of bioavailable medication is essentially the amount accessible to the fetus)
Crossing the cell membrane depends on... 1. MW 2. Solubility at the site of absorption 3. Degree of ionization 4. Relative lipid solubility 5. Degree of protein binding
Route of administration largely determines... 1. Absorption 2. Bioavailability 3. Amount of medication available to the fetus
Topical administration 1. Effect is usually local, but can be systemic 2. Absorption depends on surface area, lipid solubility, any condition that increases cutaneous blood flow
Placental drug transfer 1. The placenta is unique as a biological membrane because it separates the blood of two dinscint individuals--the mother and the fetus
Placental development: 13 days post-conception primary chorionic villi develop
Placental development: 3 weeks post-conception feto-placental circulation is established
Placental development: 4 weeks post-conception Physiologic exchange is established
Placental drug transfer 1. All drugs equilibrate between the maternal and detal compartment 2. For some drugs, the amount transferred to the detus will be low or none, and produce no known effect 3. Passive diffusion, 4. Facilitated transport 5. Active transport
Placental Drug Transfer: Characteristics of the placenta 1. Surface area 2. Thickness of the placenta 3. Maternal and detal osmotic pressures 4. Transfer increases over gestation because of the above factors
Distribution of the embryo 1. Small compounds cross the placenta more easily than large ones (except AFP and antibodies), 2. Unionized compounds cross better than ionized 3. Weak acids tend to accumulate in the embryo 4. Compounds bound tightly to maternal plasma protein...
Biotransformation (Metabolism) 1. Results from the action (CYP), Factors affecting drug metabolism, rate of hepatic biotransformation is low in the fetus and neonate because liver is immature
Sites of drug elimination Kidneys, fecal excretion, biliary excretion, pulmonary excretion, breast milk, sweat, saliva, semen, tears, hair, nails
Half-life Measured by the rate of drug excretion. It is a function of both clearance and volume of distribution... the time necessary for the amount of a drug in the body to be reduced by 50%
After 5 half-lifes... approximately 97% of a drug has been eliminated
Drugs are classified based on ... the pharmacologic effect they produce
Classification may allow assessment of the fetal risk a specific drug presents... even in the absence of human data
Drugs in the same class typically produce similar fetal anomalies or toitiy as the... index drug
While one can feel fairly confident generalizing from a class of medications with known teratogenic risks,... it is less clear that generalization can be made for a class with negative studies
Created by: KChatham