Kinetics

Question 1

ALTERATIONS IN ADME
*MAIN CAUSES INCLUDE
(4)

Answer 1

*AGE
*GENETIC FACTORS
*END-ORGAN DAMAGE
*DRUG INTERACTIONS

Question 2

TYPES OF VARIABILITY
(3)

Answer 2

• PHARMACOKINETIC
• PHARMACODYNAMIC
• IDIOSYNCRATIC

Question 3

IDIOSYNCRATIC
(3)

Answer 3

• OCCUR IN A SMALL MINORITY OF PATIENTS
• SOMETIMES WITH LOW OR NORMAL DOSES
• POORLY UNDERSTOOD

Question 4

PHARMACODYNAMIC INTERACTION
*INTERACTION BETWEEN 2 OR
MORE DRUGS THAT LEADS TO
(2)

Answer 4

• ACCENTUATION/SYNERGISM
• ATTENUATION/ANTAGONISM

DON’T DIRECTLY INVOLVE
ABSORPTION, DISTRIBUTION,
METABOLISM, OR EXCRETION

Question 5

PHARMACOKINETIC INTERACTION
* INTERACTION THAT CHANGES THE BASIC

Answer 5

KINETIC PROPERTIES
* ABSORPTION
* DISTRIBUTION
* METABOLISM
* ELIMINATION

• EXAMPLE: WARFARIN + SULFAMETHOXAZOLE

Question 6

SKIPPED
RED FLAG DRUGS

Answer 6

∙Warfarin
∙Digoxin
∙TCAs (amitriptyline, doxepin, nortriptyline, desipramine)
∙Phenytoin
∙Carbamazepine
∙Lithium
∙Methotrexate / cyclosporine / tacrolimus
∙HIV medications – protease inhibitors (indinavir, nelfinavir,
ritonavir, saquinavir)
∙Rifampin

Question 7

SKIPPED
CAUTION
(8)

Answer 7

Aminoglycosides
Fluoroquinolones
Tetracyclines
Macrolides
Magnesium
Beta blockers
Procainamide
Neuromuscular blockers*

Question 8

THE UP SIDE – DENTAL DRUGS
(3)

Answer 8

Primarily single-dose or short term Tx
Large margin of safety
Extensive history of use

Question 9

*PHARMACOKINETICS

Answer 9

*WHAT THE BODY DOES TO THE
DRUG

Question 10

*PHARMACODYNAMICS

Answer 10

*WHAT THE DRUG DOES TO THE
BODY

Question 11

HOW WE USE KINETICS
* IMPORTANT IN

Answer 11

DRUG DEVELOPMENT AND CLINICAL
TESTING, NEEDED TO DETERMINE OPTIMAL DOSE

Question 12

KINETICS
IMPORTANT IN THE CLINICAL SETTING
(5)

Answer 12

• TOXICOLOGY
• THERAPEUTIC MONITORING (CLINICAL EFFECT, LABS)
• DRUG INTERACTIONS
• DOSE ADJUSTMENTS
• EFFECT OF ILLNESS, ORGAN DYSFUNCTION

Question 13

KINETICS
* TIME COURSE OF DRUG CONCENTRATION
DEPENDS ON

Answer 13

ADME

Question 14

KINETICS FOCUSES ON CONCENTRATIONS
OF DRUG IN PLASMA
* CAN USE KINETICS TO CALCULATE

Answer 14

PRECISE
DOSES TO ACHIEVE A PRECISE
CONCENTRATION

Question 15

PLASMA CONCENTRATION = CP
* GOAL IS TO GET CP WITHIN A

Answer 15

THERAPEUTIC
WINDOW IN ORDER TO ELICIT APPROPRIATE
RESPONSE WITHOUT CAUSING TOXICITY

Question 16

MTC VS MEC

Answer 16

• MINIMUM TOXIC CONCENTRATION
• MINIMUM EFFECTIVE CONCENTRATION

Question 17

• CLEARANCE – DETERMINES THE

Answer 17

MAINTENANCE DOSE-RATE

Question 18

• VOLUME OF DISTRIBUTION (VD) – DETERMINES THE

Answer 18

LOADING DOSE

Question 19

• HALF-LIFE – DETERMINES THE TIME TO

Answer 19

STEADY STATE AND DOSING INTERVAL

Question 20

KINETICS
* PARAMETERS FOR A DRUG ARE
DETERMINED BY USING

Answer 20

IV INJECTION OR
INFUSION SINCE IV = 100%
BIOAVAILABILITY
* CL, VD, AND T½ ARE THEN DERIVED FROM
A TIME/CONCENTRATION CURVE

Question 21

CLEARANCE
(2)

Answer 21

CLEARANCE
* VOLUME OF PLASMA CLEARED OF DRUG PER
UNIT TIME
* INDEX OF HOW WELL A DRUG IS REMOVED
IRREVERSIBLY FROM THE CIRCULATION

Question 22

INDEX OF HOW WELL A DRUG IS REMOVED
IRREVERSIBLY FROM THE CIRCULATION
* DETERMINES THE DOSE-RATE (DOSE/UNIT TIME)
REQUIRED TO

Answer 22

MAINTAIN A CP

Question 23

• CREATININE CLEARANCE =

Answer 23

WAY TO
CORRELATE
140 – AGE / SCR

Question 24

ZERO ORDER KINETICS
* RATE OF ABSORPTION
/ELIMINATION DOESN’T
DEPEND ON THE

Answer 24

DRUG
CONCENTRATION

Question 25

RATE LIMITED PROCESS

Answer 25

* FIXED NUMBER OF ENZYMES, CARRIER, OR ACTIVE TRANSPORT PROTEINS; SATURATION OCCURS

Question 26

HALF LIFE (T ½ ) --- OVER TIME

Answer 26

DECREASES

Question 27

ZERO ORDER KINETICS ex (6)

Answer 27

* PHENYTOIN * WARFARIN * HEPARIN * ETHANOL * ASPIRIN (HIGH DOSE) * THEOPHYLLINE

Question 28

FIRST ORDER KINETICS * THE DECLINE IN CP IS NOT CONSTANT WITH TIME, BUT VARIES WITH --- * THE HALF LIFE (T ½ ) * CONCENTRATION DECREASES BY ---% PER EACH T ½ * MAJORITY OF DRUGS FOLLOW

Answer 28

CONCENTRATION STAYS THE SAME 50 FIRST ORDER ELIMINATION

Question 29

* RATE OF ABSORPTION OR ELIMINATION CAN BE EXPRESSED * T ½ - TIME REQUIRED FOR ---% ABSORPTION OR ELIMINATION * RATE CONSTANT (KE) –

Answer 29

50 FRACTION ELIMINATED PER UNIT TIME

Question 30

CLEARANCE * INDEX OF HOW WELL A DRUG IS REMOVED IRREVERSIBLY FROM THE CIRCULATION * DETERMINES THE

Answer 30

DOSE-RATE REQUIRED TO MAINTAIN A Cp

Question 31

TO MAINTAIN STEADY STATE (CPSS), , ADMINISTRATION RATE MUST EQUAL

Answer 31

RATE OF ELIMINATION CL = KE X VD

Question 32

STEADY STATE / PLATEAU EFFECT

Answer 32

* WHEN REPEATED DOSES OF A DRUG ARE GIVEN IN SHORT ENOUGH INTERVALS AND ELIMINATION IS 1ST ORDER, THE CP WILL EVENTUALLY REACH STEADY STATE

Question 33

DURING IV INFUSION, DRUG LEVEL INCREASES EXPONENTIALLY IN A WAY EQUIVALENT TO THE DRUG’S T1/2E * 1 HALF LIFE = --% OF FINAL CONCENTRATION * 2 HALF LIVES = --% OF FINAL CONCENTRATION * 3 HALF LIVES = --% OF FINAL CONCENTRATION, ETC.

Answer 33

50 75 87.5

Question 34

VOLUME OF DISTRIBUTION (VD)

Answer 34

* VOLUME INTO WHICH A DRUG APPEARS TO BE DISTRIBUTED WITH A CONCENTRATION EQUAL TO THAT OF PLASMA * TELLS YOU WHERE THE DRUG DISTRIBUTES

Question 35

TO REACH A TARGET CP, YOU HAVE TO

Answer 35

“FILL UP THE TANK”, I.E., V

Question 36

IMPORTANT EQUATION: VD

Answer 36

VD = F X DOSE / CP0

Question 37

VD = F X DOSE / CP0 * REMEMBER: BIOAVAILABILITY (F) FOR IV DRUGS EQUALS * NOTE: VD CAN FAR EXCEED THE * DRUGS WITH SMALL VD TEND TO BE

Answer 37

1 (100%) ACTUAL BODY VOLUME, E.G., DIGOXIN VD = 500L POLAR AND WATER SOLUBLE

Question 38

HALF LIFE (T1/2)

Answer 38

* TIME FOR THE DRUG CONCENTRATION TO HALVE

Question 39

HALF LIFE (T1/2) PROVIDES AN INDEX OF (3)

Answer 39

* TIME COURSE OF DRUG ELIMINATION * TIME COURSE OF DRUG ACCUMULATION * CHOICE OF DRUG INTERVAL

Question 40

TAKES APPROXIMATELY --- HALF-LIVES FOR A DRUG TO EITHER REACH STEADY STATE (CPSS) OR BE ELIMINATED FROM THE BODY

Answer 40

5

Question 41

STEADY STATE KINETICS

Answer 41

* POINT AT WHICH THE AMOUNT ABSORBED EQUALS AMOUNT ELIMINATED PER UNIT TIME CSS = KA / (VD X KE) WHERE: CSS = STEADY STATE CONCENTRATION KA = ABSORPTION RATE CONSTANT VD = VOLUME OF DISTRIBUTION KE = ELIMINATION RATE CONSTANT NOTE: KA = VD X KE X CSS

Question 42

FOR CONTINUOUS INFUSION, KA =

Answer 42

DOSE/TIME, E.G., MG/HOUR