Sunday, October 05, 2008

Introduction to pharmacokinetics and pharmacodynamics

The book by Drs Tozer and Rowland is pretty good.
About dose "To paraphrase Paracelsus, who lived some 500 years ago, "all drugs are poisons, it is just a matter of dose." A dose of 25 mg of aspirin does little to alleviate a headache; a dose closer to 300-600 mg is needed, with little ill effect. However, 10 g taken all at once can be fatal, especially in youn children.

About the definition of PK and PD: In simple terms pharmacokinetics may be viewed as what the body does to the drug, and pharmacodynamics as what the drug does to the body.

On genetic variability in drug response: If we were all alike, there would be only one dose strength and regimen of a drug meeded fro the entire patient population. But we are not alike; we often exhibit great interindividual variability in repsonse to drugs. In rare caes, the "one-dose-for-all" idea, suffices.

About Plasma: In practice, plasma is preferred over whole blood primarily because blood causes interference in many assay techniques. Plasma and serum yield essentially equivalent drug concentrations, but plasma is considered easier to prepare because blood must be allowed to clot to obtain serum. During this process, hemolysis can occur, producing a concentration that is neither that of plasma nor blood, or causing an inference in teh assay.

About the differences among Plasma, Serum, and Whold Blood:
Plasma: Whole blood is centrifuged after adding an anticoagulant, such as heparin or citric acid. Cells are precipitated. The supernate, plasma, contains plasma proteins that often bind drugs. The plasma drug concentration includes drug-bound and unbound to plasma proteins.
Serum: Whole blood is centrifuged after the blood has been clotted. Cells and material forming the clot, including fibrinogen and its clotted form, fibrin, are removed. Binding of drugs to fibrinogen and fibrin is insignificant. Although the protein composition of serum is slightly different from that of plasma, the drug concentrations in serum and plasma are virtually identical.
Whole blood: whoe blood contains red blood cells, white blood cells, platelets and various plasma proteins. An anticoagulant is commonly added and drug is extracted into an organic phase often after denaturing the plasma proteins. The blood drug concentration represents an average over the total sample. Concentrations in the various cell fractions and in plasma may be very different.

On site of administration:
Intravascular: refers to the placement of a drug directly into the blood - either intravenously or intra-arterially.
Extravascular: include the intradermal, intramuscular, oral, pulmonary (inhalation), subcutaneous (into fat under skin), rectal, and sublingual (under the tongue) routes.
Parenteral administration: refers to administration aprat from the intestines. Parenteral administration includes intramuscular, intravascular, and subcutaneous routs. Today, the term is generally restricted to those routes of administration in which drug is injected through a needle. Thus, although the use of skin patches or nasal sprays (for systemic delivery) are strictly forms of parenteral administration, this term is not used for them.

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