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Pharmacology > Kinetics > Flashcards

Kinetics Flashcards

1
Q

ALTERATIONS IN ADME
*MAIN CAUSES INCLUDE
(4)

A

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

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2
Q

TYPES OF VARIABILITY
(3)

A
  • PHARMACOKINETIC
  • PHARMACODYNAMIC
  • IDIOSYNCRATIC
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3
Q

IDIOSYNCRATIC
(3)

A
  • OCCUR IN A SMALL MINORITY OF PATIENTS
  • SOMETIMES WITH LOW OR NORMAL DOSES
  • POORLY UNDERSTOOD
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4
Q

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

A
  • ACCENTUATION/SYNERGISM
  • ATTENUATION/ANTAGONISM

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

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5
Q

PHARMACOKINETIC INTERACTION
* INTERACTION THAT CHANGES THE BASIC

A

KINETIC PROPERTIES
* ABSORPTION
* DISTRIBUTION
* METABOLISM
* ELIMINATION

  • EXAMPLE: WARFARIN + SULFAMETHOXAZOLE
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6
Q

SKIPPED
RED FLAG DRUGS

A

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

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7
Q

SKIPPED
CAUTION
(8)

A

Aminoglycosides
Fluoroquinolones
Tetracyclines
Macrolides
Magnesium
Beta blockers
Procainamide
Neuromuscular blockers*

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8
Q

THE UP SIDE – DENTAL DRUGS
(3)

A

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

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9
Q

*PHARMACOKINETICS

A

*WHAT THE BODY DOES TO THE
DRUG

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10
Q

*PHARMACODYNAMICS

A

*WHAT THE DRUG DOES TO THE
BODY

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11
Q

HOW WE USE KINETICS
* IMPORTANT IN

A

DRUG DEVELOPMENT AND CLINICAL
TESTING, NEEDED TO DETERMINE OPTIMAL DOSE

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12
Q

KINETICS
IMPORTANT IN THE CLINICAL SETTING
(5)

A
  • TOXICOLOGY
  • THERAPEUTIC MONITORING (CLINICAL EFFECT, LABS)
  • DRUG INTERACTIONS
  • DOSE ADJUSTMENTS
  • EFFECT OF ILLNESS, ORGAN DYSFUNCTION
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13
Q

KINETICS
* TIME COURSE OF DRUG CONCENTRATION
DEPENDS ON

A

ADME

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14
Q

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

A

PRECISE
DOSES TO ACHIEVE A PRECISE
CONCENTRATION

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15
Q

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

A

THERAPEUTIC
WINDOW IN ORDER TO ELICIT APPROPRIATE
RESPONSE WITHOUT CAUSING TOXICITY

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16
Q

MTC VS MEC

A
  • MINIMUM TOXIC CONCENTRATION
  • MINIMUM EFFECTIVE CONCENTRATION
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17
Q
  • CLEARANCE – DETERMINES THE
A

MAINTENANCE DOSE-RATE

18
Q
  • VOLUME OF DISTRIBUTION (VD) – DETERMINES THE
A

LOADING DOSE

19
Q
  • HALF-LIFE – DETERMINES THE TIME TO
A

STEADY STATE AND DOSING INTERVAL

20
Q

KINETICS
* PARAMETERS FOR A DRUG ARE
DETERMINED BY USING

A

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

21
Q

CLEARANCE
(2)

A

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

22
Q

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

A

MAINTAIN A CP

23
Q
  • CREATININE CLEARANCE =
A

WAY TO
CORRELATE
140 – AGE / SCR

24
Q

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

A

DRUG
CONCENTRATION

25
Q

RATE LIMITED PROCESS

A
  • FIXED NUMBER OF
    ENZYMES, CARRIER, OR
    ACTIVE TRANSPORT
    PROTEINS; SATURATION
    OCCURS
26
Q

HALF LIFE (T ½ )
— OVER TIME

A

DECREASES

27
Q

ZERO ORDER KINETICS
ex (6)

A
  • PHENYTOIN
  • WARFARIN
  • HEPARIN
  • ETHANOL
  • ASPIRIN (HIGH DOSE)
  • THEOPHYLLINE
28
Q

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

A

CONCENTRATION
STAYS THE SAME
50
FIRST ORDER
ELIMINATION

29
Q
  • RATE OF ABSORPTION OR ELIMINATION
    CAN BE EXPRESSED
  • T ½ - TIME REQUIRED FOR —% ABSORPTION
    OR ELIMINATION
  • RATE CONSTANT (KE) –
A

50
FRACTION ELIMINATED
PER UNIT TIME

30
Q

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

A

DOSE-RATE REQUIRED
TO MAINTAIN A Cp

31
Q

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

A

RATE
OF ELIMINATION
CL = KE X VD

32
Q

STEADY STATE / PLATEAU
EFFECT

A
  • WHEN REPEATED DOSES OF A DRUG ARE GIVEN IN
    SHORT ENOUGH INTERVALS AND ELIMINATION IS 1ST
    ORDER, THE CP WILL EVENTUALLY REACH STEADY
    STATE
33
Q

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.

A

50
75
87.5

34
Q

VOLUME OF DISTRIBUTION (VD)

A
  • VOLUME INTO WHICH A DRUG APPEARS
    TO BE DISTRIBUTED WITH A
    CONCENTRATION EQUAL TO THAT OF
    PLASMA
  • TELLS YOU WHERE THE DRUG DISTRIBUTES
35
Q

TO REACH A TARGET CP, YOU HAVE TO

A

“FILL UP THE TANK”, I.E., V

36
Q

IMPORTANT EQUATION: VD

A

VD = F X DOSE / CP0

37
Q

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

A

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

38
Q

HALF LIFE (T1/2)

A
  • TIME FOR THE DRUG CONCENTRATION TO
    HALVE
39
Q

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

A
  • TIME COURSE OF DRUG ELIMINATION
  • TIME COURSE OF DRUG ACCUMULATION
  • CHOICE OF DRUG INTERVAL
40
Q

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

A

5

41
Q

STEADY STATE KINETICS

A
  • 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

42
Q

FOR CONTINUOUS INFUSION, KA =

A

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

Pharmacology (13 decks)

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