Kinetics Flashcards
What are the 3 types of variabilities of drug interaction?
- PHARMACOKINETIC
- PHARMACODYNAMIC
- IDIOSYNCRATIC
•INTERACTION BETWEEN 2 OR MORE DRUGS THAT LEADS TO •ACCENTUATION/SYNERGISM •ATTENUATION/ANTAGONISM •DON’T DIRECTLY INVOLVE ABSORPTION, DISTRIBUTION, METABOLISM, OR EXCRETION
Pharmacodynamic interaction
\_\_\_\_\_\_ interaction •INTERACTION THAT CHANGES THE BASIC KINETIC PROPERTIES •ABSORPTION •DISTRIBUTION •METABOLISM •ELIMINATION •EXAMPLE: WARFARIN + SULFAMETHOXAZOLE
PHARMACOKINETIC INTERACTION
The following drugs need to be checked for _____:
∙Warfarin
∙Digoxin
∙TCAs (amitriptyline, doxepin, nortriptyline,
desipramine)
∙Phenytoin
∙Carbamazepine
∙Lithium
∙Methotrexate / cyclosporine / tacrolimus
∙HIV medications – protease inhibitors (indinavir,
nelfinavir, ritonavir, saquinavir)
∙Rifampin
Negative Drug interactions
If you give Tetracycline and antacids, how do the drugs interact?
antacid impairs absorption of ABX → ↓ ABX efficacy
If erythromycin / clarithromycin /
metronidazole / ciprofloxacin /
trimethaprim-sulfamethoxazole +
warfarin interact, what happens?
ABX inhibit the metabolism of warfarin → ↑ serum concentration of
warfarin → ↑ risk of bleeding
If NSAID + warfarin are combined, what happens?
Additive effect on ↓ platelet aggregation → additive risk for
bleeding (especially GI bleeding)
If ASA + warfarin are combined, what happens?
Additive effect on ↓ platelet aggregation → additive
risk for bleeding (especially GI bleeding)
If Tramadol +
antidepressants (DDI
highest risk for MAO-I) are combined, what happens?
↑ risk of serotonin syndrome (looks like malignant hyperthermia)
If Protease inhibitors (indinavir,
nelfinavir, ritonavir, saquinavir) +
BZD are combined, what happens?
protease inhibitors are CYP450 3A4 inhibitors → ↓ metabolism of benzodiazepine → ↑
benzodiazepine concentrations → ↑ risk of benzodiazepine side effects (↑ sedation depth
and duration)
How does pregnancy affect CO, renal blood flow, and albumin?
Increased CO
Increased renal blood flow
Decreased albumin
What 2 things are caused due to diabetes?
Gastric stasis
Nephrotic syndrome
An effect that is unrelated to clinical drug effect
- Predictable
- Dose related
Side effect
An exaggeration of clinical drug effect;
- predictable
- dose related
Toxic reaction
An immunologic response to a drug
Allergic reaction
•WHAT THE BODY DOES TO THE DRUG
PHARMACOKINETICS
•WHAT THE DRUG DOES TO THE BODY
PHARMACODYNAMICS
HOW WE USE \_\_\_\_\_\_\_: •IMPORTANT IN DRUG DEVELOPMENT AND CLINICAL TESTING, NEEDED TO DETERMINE OPTIMAL DOSE •IMPORTANT IN THE CLINICAL SETTING •TOXICOLOGY •THERAPEUTIC MONITORING (CLINICAL EFFECT, LABS) •DRUG INTERACTIONS •DOSE ADJUSTMENTS •EFFECT OF ILLNESS, ORGAN DYSFUNCTION
PHARMACOKINETICS
(kinetics)
•TIME COURSE OF DRUG CONCENTRATION
DEPENDS ON
ADME
KINETICS FOCUSES ON CONCENTRATIONS
OF DRUG IN ______
PLASMA
What are the 2 most important things that kinetics tell us?
How quick it works and how long it works
_______ = CP
PLASMA CONCENTRATION
MTC
Minimum toxic dose
MEC
Minimum effective dose
– DETERMINES THE
MAINTENANCE DOSE-RATE
CLEARANCE
–
DETERMINES THE LOADING DOSE
VOLUME OF DISTRIBUTION (VD)
– DETERMINES THE TIME TO
STEADY STATE AND DOSING INTERVAL
HALF-LIFE
PARAMETERS FOR A DRUG ARE
DETERMINED BY USING ___ INJECTION OR
INFUSION SINCE it is = 100%
BIOAVAILABILITY
IV injection
•VOLUME OF PLASMA CLEARED OF DRUG PER UNIT
TIME
•INDEX OF HOW WELL A DRUG IS REMOVED
IRREVERSIBLY FROM THE CIRCULATION
•DETERMINES THE DOSE-RATE (DOSE/UNIT TIME) REQUIRED
TO MAINTAIN A CP
Clearance
The following equations are used to calc _____:
140 – AGE / SCR
140 – AGE / SCR) X 0.85
Clearance
•RATE OF ABSORPTION /ELIMINATION DOESN’T DEPEND ON THE DRUG CONCENTRATION •RATE LIMITED PROCESS •FIXED NUMBER OF ENZYMES, CARRIER, OR ACTIVE TRANSPORT PROTEINS; SATURATION OCCURS •HALF LIFE (T ½ ) DECREASES OVER TIME - Linear - Saturable •PHENYTOIN •WARFARIN •HEPARIN •ETHANOL •ASPIRIN (HIGH DOSE) •THEOPHYLLINE
ZERO ORDER KINETICS
•THE DECLINE IN CP IS NOT CONSTANT WITH TIME,
BUT VARIES WITH CONCENTRATION
•THE HALF LIFE (T ½ ) STAYS THE SAME
•CONCENTRATION DECREASES BY 50% PER EACH T ½
•MAJORITY OF DRUGS FOLLOW This
- Logarythmic
First order kinetics
– FRACTION ELIMINATED PER UNIT TIME
•RATE CONSTANT (KE)
•INDEX OF HOW WELL A DRUG IS REMOVED IRREVERSIBLY FROM THE CIRCULATION •DETERMINES THE DOSE-RATE REQUIRED TO MAINTAIN A CP •TO MAINTAIN STEADY STATE (CPSS), , ADMINISTRATION RATE MUST EQUAL RATE OF ELIMINATION CL = KE X VD
Clearance
•WHEN REPEATED DOSES OF A DRUG ARE GIVEN IN SHORT
ENOUGH INTERVALS AND ELIMINATION IS 1ST ORDER, THE CP
WILL EVENTUALLY REACH This
Steady staet
How many half lives does it take to teach steday state?
5 half lives
How many half lives is needed to completely eliminate a drug from body?
5 half lives
•VOLUME INTO WHICH A DRUG APPEARS TO BE DISTRIBUTED WITH A CONCENTRATION EQUAL TO THAT OF PLASMA •TELLS YOU WHERE THE DRUG DISTRIBUTES •TO REACH A TARGET CP, YOU HAVE TO “FILL UP THE TANK”, I.E., VD
Volume of distrbution
