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Nursing Pharmacology Chapter 2: General Principles: Pharmacokinetics
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Basis for individual to individual variation in drug responses
Response Variation Secondary to Pharmacokinetic Differences in:
Bioavailability
Renal function
Liver function
Cardiac function
Patient Age
Response Variation Secondary to Pharmacodynamic Differences may be due to:
Enzyme activity
Genetic differences
Response Variation may be due to drug-drug interactions.
Genetic Factors: in Biotransformation of Drugs
Genetic influences: Variation in drug metabolism rates or in receptor sensitivity:
Metabolism:
Patients can be categorized as either rapid or slow acetylators.
This classification refers to the patients ability to relatively rapidly or slowly catalyze acetylation reactions.
Biotransformation of some drugs are affected by acetylation rates, examples include hydralazine (Apresoline) and isoniazid (INH).:
Pharmacogenetics: One major concern is that on underlying disease state may not be appreciated until an unexpected reaction to an anesthetic agent in fact occurs. The anesthetic agent essentially exposes on underlying disease state and then appropriate inner operative responses required. Examples:
Atypical cholinesterase enzyme suggested by prolonged succinylcholine (Anectine) or mivacurium (Mivacron)- induced neuromuscular blockade
Succinylcholine (Anectine) or volatile anesthetic induced malignant hyperthermia-Malignant hyperthermia is a very serious reaction requiring a definitive treatment approach including dantrolene (Dantrium).
If the patient exhibits glucose-6-phosphate dehydrogenase deficiency certain drugs may induce hemolysis
Barbiturates may induce intermittent porphyria attacks. It is extremely important to determine therefore preoperatively if the patient has history of intermittent porphyria.
Influence of Age on Drug Responses
Variation in drug responses may be due to several factors such as:
Diminished cardiac output:
A reduction in cardiac output reduces hepatic perfusion which may decrease delivery of drug to the liver for metabolism. This type of an effect would prolonged duration of action of, for example, lidocaine (Xylocaine) or fentanyl (Sublimaze).
Increased body fat:
An increase in body fat tends to increase Vd . An increased Vd would tend to prolong clearance time.
Increased body fat also promotes accumulation of highly lipid-soluble agents such as diazepam (Valium) and thiopental (Pentothal).
Altered protein binding can affect drug responses because only the "free", unbound drug is active and for a highly protein-bound drug small changes in the extent of protein binding can substantially influence the free drug concentration [free drug].
Decreased or compromised renal function can prolong drug action if renal excretion is the primary mechanism for clearance.
Definition: Drug interaction
occurs when one drug
affects the pharmacological response of a second
drug given at the same time.
Drug interactions may be due to:
Pharmacodynamic effects
Pharmacokinetic effects
Consequences of drug interactions:
Increased drug effects or decreased drug effects
Consequences may be
adverse or undesired effects
Examples of positive, beneficial drug interaction effects include:
Propranolol + hydralazine (reflex tachycardia (undesirable) caused by hypotensive hydralazine-mediated response is prevented by propranolol-mediated β-adrenergic receptor blockade
Opioid-induced respiratory depression may be counteracted by administration of the opioid receptor antagonist naloxone
Adverse effects
or toxic reactions
One drug may interact with another to impede absorption
One drug may compete with another for the same plasma protein-binding sites
One drug may affect metabolism of another by either enzyme induction or enzyme inhibition
One drug may change the renal excretion rate of the other.
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