... P-glycoprotein, the product of the
normal expression of the MDR1 gene. P-glycoprotein is expressed on the apical
aspect of the enterocyte and on the canalicular aspect of the hepatocyte (Fig. 5-3); ... from the site of administration (Fig. 5-
2). The extent of absorption may be reduced because a drug is incompletely
released from its dosage form, undergoes destruction at its s...
... Chapter 005. Principles of Clinical
Pharmacology
(Part 7)
Renal Disease
Renal excretion of parent drug and metabolites is generally accomplished ... of lidocaine is
reduced by about 50% in heart failure, and therapeutic plasma levels are achieved
at infusion rates of 50% or less than those usually required. The volume of
distribution of ... linked to the occurr...
... Chapter 005. Principles of Clinical
Pharmacology
(Part 1)
Harrison's Internal Medicine > Chapter 5. Principles of Clinical
Pharmacology
Principles of Clinical Pharmacology: ... accompaniment of drug
therapy, this is not the case. The goal of this chapter is to describe the principles of
clinical pharmacology that can be used for the sa...
... intravenous infusion, plasma concentrations at steady
Chapter 005. Principles of Clinical
Pharmacology
(Part 3)
Clinical Implications of Altered Bioavailability
Some drugs undergo near-complete ... a typical intravenous dose of verapamil is 1–5 mg, compared
to the usual single oral dose of 40–120 mg. Administration of low-dose aspirin can
result in exposure of...
... orally
Chapter 005. Principles of Clinical
Pharmacology
(Part 4)
Clinical Implications of Drug Distribution
Digoxin accesses its cardiac site of action slowly, over a distribution phase
of ... volume of distribution of lidocaine is reduced. Therefore, lower-than-
normal loading regimens are required to achieve equivalent plasma drug
concentrations and to avoid t...
... effect of the drugs, it may produce
severe agonist–mediated effects (such as hypertension or tachycardia) if the
blocking drug is abruptly withdrawn.
Chapter 005. Principles of Clinical
Pharmacology ... site of action, it alters the function of that
molecular target, with the ultimate result of a drug effect that the patient or
physician can perceive. For drugs used i...
... and Response
Chapter 005. Principles of Clinical
Pharmacology
(Part 6)
Principles of Dose Selection
The desired goal of therapy with any drug is to maximize the likelihood of
a beneficial ... an understanding of the relationships
between plasma concentration and anticipated effects. For example, measurement
of QT interval is used during treatment with sotalol...
... drug effects. However,
loss -of- function alleles in these genes have not yet been described.
Chapter 005. Principles of Clinical
Pharmacology
(Part 8)
Principles of Genetic Variation and Human ... advanced at
the end of the nineteenth century, and the first examples of familial clustering of
unusual drug responses due to this mechanism were noted in the mid-twen...
... channel genes that are not themselves the target of QT-
Chapter 005. Principles of Clinical
Pharmacology
(Part 9)
Transferase Variants
One of the most extensively studied phase II polymorphisms ... triggering attacks (Chap. 3 52). Deficiency of glucose-6-
phosphate dehydrogenase (G6PD), most often in individuals of African or
Mediterranean descent, increases risk...
... Chapter 005. Principles of Clinical
Pharmacology
(Part 10)
Multiple Variants Modulating Drug Effects
As this discussion makes clear, for each drug with a defined mechanism of
action ... Indeed, one major result of understanding of the
role of genetics in drug action has been improved screening of drugs during the
development process to reduce the likelihood of...