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Science that deals with the origin, nature, chemistry, effects, and uses of drugs.
- Describes what the body does to the drug.
Describes what the drug does to the body.
Deals with the use of drugs in the prevention and treatment of disease.
- The percentage or fraction of the administered dose absorbed into the systemic circulation.
- Affected by: solubility, route of administration, metabolism within intestinal wall, first pass effect.
Area Under the plasma concentration Curve
- Total aount of unchanged drug that reaches the systemic circulation.
- Most reliable measure of bioavailability.
F = Amount Drug Reaching Systemic Circulation/Total Amount of Drug (or dose)
F does not take into consideration the rate of drug absorption; it only estimates the extent of absorption.
- Absorption pattern: variable, depends on many factors (emesis, pH, GI...)
- Bioavailability potentially erratic and incomplete.
- GI absorption depends on properties of the drug and the vehicle. Solid forms go through a dissolution phase in the stomach or small intestine.
- Stomach pH 1-2, thick mucous lining, small surface area
- Small intesting pH 3-6, majority of drugs absorbed, semipermeable membrane, extremely large surface area
Food slows gastric emptying and rate of absorption. Enhances absorption for poorly soluble drugs. Reduces absorption for drugs degraded in the stomach.
- Adv: Pt is vomiting, unconscious or very young; local effect; less first pass removal (50%)
- DisAdv: absorption irregular and incomplete, convenience, irritation
- Adv: minimal first-pass effect, steady pharmacological response, decreased adverse effects, convenient, rapidly terminated by removal.
- DisAdv: hydrophilic drugs not absorbed, absorption can take long time, skin irritation
- Drug injected directly into the cerebrospinal fluid.
- Used when not possible to reach high enough plasma levels to reach CSF. Must be highest purity.
Trade vs Generic
Contain the same active ingredient and be identical in strength, concentration, dosage form, and route of administration.
Distribution of Drugs
Phase 1 and 2
- Phase 1
- Highly perfused organs: heart, liver, lungs, kidneys, brain
- Phase 2
- Skeletal muscle
- Less perfused tissue: fat, bone, skin
Concentration of drug (Cp) = Amount of drug (X) / volume in which drug is distributed (Vd) = mg/L
Volume of Distribution
Volume of distribution = Amount of drug (x) / measured concentration in plasma (Cp)
Vd = X / Cp
Volume of Distribution
Factors that affect Vd:
- Water soluble drugs can have Vd similar to plasma volume.
- Lipid soluble drugs can have Vd that exceed total fluid volume in the body.
- Protein binding
- Obesity (IBW vs TBW)
- Tissue binding
LD = (Vd)(Cp) / F
- Vd = volume of distribution
- Cp = desired concentration
- F = bioavailability
Proteins: Albumin, a1-acid-glycoprotein, Lipoproteins
If bound to albumin, can't move around well or go through plasma membrane.
Free drug is available to interact with receptor sites and exert effects.
Degree of protein binding depends on drug concentration, affinity of the drug for plasma proteins, number of binding sites