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IVMS Pharmacokinetics Drug Elimination 2
IVMS Pharmacokinetics Drug Elimination 2
Companion Notes IVMS BASIC PHARMGeneral Principles, Pharmacokinetics and Pharmacodynamics Notes
Chemotherapy drugs in vials and an IV bottle. (Bill Branson Photographer; image courtesy of National Cancer Institute Visuals Online.)
Drug Elimination II
Topics: Drug Excretion continued Drug Interactions Pharmacogenetics
Enterohepatic Cycle
Liver
2
Portal vein
1
Small intestine
5
Pulmonary Excretion
Factors:
Gaseous Anesthetics
*Rate of pulmonary excretion is
proportional to alveolar tension of the gaseous drug and inversely proportional to its plasma solubility.
N2 O Halothane
Alveolar tension (mm Hg)
Most plasma-soluble
Ether
30
60 Time (min)
120
Age: Renal and Hepatic Metabolism Renal Disease Liver Disease Drug Interactions
10
Birth
Puberty
Adulthood
Old age
Age
11
The Following Conditions Should All Apply for Renal Disease to be of Clinical Importance in the Renal Excretion of Drugs
Renal excretion of active drug is 50%. Renal function drops below 50% of normal adult value.
Drug has low therapeutic index.
13
14
Drug Interactions:
1. Pharmacokinetic Interactions
Interactions that result in an alteration in the concentration of the drug at its site of action.
Pharmacokinetic Interactions:
Gut Absorption
17
18
GI absorption
19
Pharmacokinetic Interactions:
Liver metabolism: Enhance via induction. *Phenobarbital, phenytoin, phenylbutazone.
Inhibit directly.
Renal tubular secretion: Inhibit secretion of weak *Penicillin, salicylates. acids. Inhibit secretion of weak *Cimetidine. bases.
20
Time-toClot
21
22
23
2. Pharmacodynamic Interactions
Interactions that alter the ability of a drug to exert an effect at its site of action.
Pharmacodynamic Interactions
25
Pharmacogenetics or Pharmacogenomics
Definition: the use of genetic information to 1) explain interindividual differences in drug responses or to 2) individualize dosages for patients with known genetic polymorphisms. Idiosyncratic Reaction: genetically determined abnormal drug response.
26
RECESSIVE CODOMINANT
27
Monogenic Inheritance
Trait associated with a pair of genes (e.g., either rapid or slow acetylation).
Slow acetylators
Plasma [Isoniazid]
29
*All major deficiencies in drugmetabolizing activity are inherited monogenically as autosomal recessive traits.
30
31
Polygenic Inheritance
Frequency Distn Shows Normal Variability in Plasma Conc. After a Fixed Dose is Given to a Large Patient Population
Numberof Individuals
Some people display very low or high plasma levels, but most are in the middle.
Plasma level
33