Pharmocology
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| Pharmocology | The science that is concerned with drugs, their sources, appearance, chemistry, actions and uses
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| Pharmacokinetics | the movement of drugs within biological systems, as affected by uptake, distribution, binding, elimnation and bio-transformation; the rates thereof
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| 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
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| Why is there such a wide variability in drug effects? (cont.) | 11. Tolerance 12. Genetic fxs
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| 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
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| Plasma protein binding is decreased due to... | diluation from increased plasma volume
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| 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
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| 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
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| Dose | the quantity of a drug that is taken (Prescribed dose versus administered dose)
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| Therapeutic dose | The concentration range that produces the desired effect
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| Subtherapeutic dose | produces no discernible effect, or less effect than desired
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| 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)
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| 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
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| Route of administration largely determines... | 1. Absorption 2. Bioavailability 3. Amount of medication available to the fetus
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| 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
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| 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
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| Placental development: 13 days post-conception | primary chorionic villi develop
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| Placental development: 3 weeks post-conception | feto-placental circulation is established
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| Placental development: 4 weeks post-conception | Physiologic exchange is established
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| 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
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| 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
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| 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...
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| 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
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| Sites of drug elimination | Kidneys, fecal excretion, biliary excretion, pulmonary excretion, breast milk, sweat, saliva, semen, tears, hair, nails
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| 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%
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| After 5 half-lifes... | approximately 97% of a drug has been eliminated
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| Drugs are classified based on ... | the pharmacologic effect they produce
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| Classification may allow assessment of the fetal risk a specific drug presents... | even in the absence of human data
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| Drugs in the same class typically produce similar fetal anomalies or toitiy as the... | index drug
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| 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
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