drug interactions and anesthesia

88 Pages·2012·3.13 MB·English

DRUG INTERACTIONS AND
ANESTHESIA
Rudolf Klima, M.D.
Central Arkansas Veterans Healthcare System
Associate Professor of Anesthesiology
College of Medicine, UAMS
Little Rock, Arkansas
CEEA 2012 Košice

OBJECTIVES

Introduction

Pharmacokinetic interactions

Pharmacodynamic interactions

In Vitro Interactions

Selected groups of drugs and their
interactions
SIMPLYFIED BASIC
TERMINOLOGY
Pharmacology - study of how
chemical agents affect living processes
Pharmacokinetics - what the body does to the
drug (absorption, distribution and elimination)
Pharmacodynamics - what the drug does to the
body (dose – response relationship)
PHARMACOLOGICAL (DRUG –
DRUG) INTERACTION
A drug interaction
occurs when a drug
interferes in a negative
or positive way
with another drug

PHARMACOKINETIC
INTERACTIONS
♦ Pharmacokinetic interactions are mainly due
to alteration of absorption, distribution,
metabolism, or excretion drug which changes the
amount and duration of a drug's availability at
receptor sites
♦ Pharmacokinetic interactions are more
complicated and difficult to predict because the
interacting drugs often have unrelated actions
RATE OF ABSORPTION AND
ELIMINATION
First order kinetics - constant fraction of the drug
present will be absorbed or eliminated in a unit of time
Half-life t1/2 - time required for 50% of drug to be absorbed
or eliminated
Elimination rate constant (k ) - the fraction of drug absorbed
e
or eliminated per unit time
Zero order kinetics
- processes in which a constant
amount of drug is absorbed or eliminated per unit time
PHARMACOKINETIC CURVE
Cmax: Maximum concentration –
may relate to some side effects
10000
AUC: Area under the curve (filled
n
o area) = overall drug exposure
ti 3000
a
r
t
n
e
c
1000
n
o
C Cmin: minimum or

a trough concentrations:
m
may relate with efficacy
s
a
of drug
l
P
100
0 2 4 6 8 10 12
Time Post-dose (hr.)
http://www.thebody.com/content/art875.html
Pharmacokinetic Interactions
DRUG ABSORPTION
Absorption from gastrointestinal tract:
A/ Nonspecific interactions affecting peristalsis and
perfusion (opioids, vagolytics, vasopressors)
B/ Physicochemical interactions
■ Chelation (ciprofloxacin + 2- and 3-valent cations)
■ Adsorption (activated charcoal)
■ Cation-exchange (sodium polystyrene sulfonate)
C/ P-glycoprotein induction or inhibition