2Nd Semester Pharm Week 1

Front 1

Parenteral-overall positives 3

Back 1

Positives
1 relatively rapid response

2 accurate dose

3 circumvents GI tract

Front 2

Parenteral-overall negatives 4

Back 2

1 potentially more toxicity

2 requires sterile drug/access

3 can be painful

4 often more expensive

Front 3

Intravenous (iv) positives 4

Back 3

immediate

emergency use

continuous=control

accurate dose

Front 4

Intravenous (iv) negatives 3

Back 4

potentially more toxicity

req. IV access

req. water soluble form

Front 5

Intramuscular (im) positives 3

Back 5

aqueous drugs-usually rapid

emergency use

vs, depot suspensions

less dependent on solubility or MW

Front 6

intramuscular (im) negatives

Back 6

local irritation/myonecrosis

variable absorption

Front 7

Subcutaneous (sc/sq) positives

Back 7

slow and constant absorption

o/w similar to IM

Front 8

Subcutaneous (sc/sq) negatives

Back 8

absorption blood flow-limited

o/w similar to IM

Front 9

Intraperitoneal (ip) positives

Back 9

moderately fast

popular for animals

Front 10

Intraperitoneal (ip) negatives

Back 10

metabolized in liver

variable absorption

Front 11

Oral (po) positives

Back 11

convenient

slower and safer

economical

Front 12

Oral (po) negatives

Back 12

GI tract irritation

variable absorption rate

proteins inactivated

intestine/liver sees drug first

Front 13

Sublingual (sl) positives

Back 13

convenient

rapid (e.g. nitroglycerin)

bypass liver

Front 14

Sublingual (sl) negatives

Back 14

irritation or bad taste

potential for toxicity

req. potent, lipid-soluble drug

Front 15

Rectal (pr) positives

Back 15

circumvent oral route

can remove easily

Front 16

Rectal (pr) negatives

Back 16

inconvenient

variable absorption

Front 17

Topical (Skin or eye) positives, 4

Back 17

local activity

bypass liver for systemic drugs

can remove easily

continuous-release forms

Front 18

Topical (Skin or eye) negatives

Back 18

irritation, excess absorption





success has been limited

Front 19

Inhalation positives

Back 19

rapid if lipid soluble

local effect on lung

emergency use

Front 20

Inhalation negatives

Back 20

limited by particle size

limited by volatility

Front 21

Spinal Intrathecal, Epidural positives

Back 21

direct access to CNS

direct access to nerves

Front 22

spinal negatives

Back 22

technically challenging

Front 23

Ficks Law

Back 23

dQ/dt = -D • A dC/dx

D is constant that increases with temperature and decreases with MW of drug

Front 24

Henderson Hasselboach for acid and base

Back 24

pH=pKa+log[A-]/[HA], [A-]/[HA]=10(pH-pKa)

pH=pKb-log [BH+]/[B], [BH+]/[B]=10(pKb-pH)

Front 25

bioequivalence vs pharmaceutical equivalence

Back 25

bioequivalent if the rates and extents of bioavailability same in vivo.

pharmaceutical equivalence if same active ingredients and are identical in strength or concentration, dosage form, and route of administration

Front 26

define: prodrug

Back 26

administered in an inactive form and require metabolism to be activated (bioactivation)

Front 27

the three cytochrome P450's

Back 27

CYP 2E1--ethanol, acetone and isoniazid

CYP 3A4--anticonvulsants, St. John’s Wort, rifampin, steroids

CYP 1A--aromatic hydrocarbons

Front 28

cellular locations of Phase I vs Phase II metabolisation

Back 28

Phase I mostly endoplasmic reticulum

Phase II mostly cytosol
--glucuronidation actually in ER

Front 29

non endoplasmic reticulum oxidation, 3 enzymes

Back 29

alcohol dehydrogenase--cytosol

xanthine oxidase, monoamine oxidase

Front 30

Glucuronidation

Back 30

phase II reaction in ER

highly polar sugar conjugates

rapidly excreted in urine and bile

Front 31

Glutathione

Back 31

tripeptide substrate for glutathione-S-transferases that detoxify electrophilic metabolic intermediates using the sulfhydryl group of cysteine

Front 32

how to cause better excretion of weak acids by altering urine pH

Back 32

excretion can be increased by alkalinizing urine relative to plasma

Front 33

how to cause better excretion of weak bases by altering urine pH

Back 33

excretion can be increased by acidifying urine relative to plasma

Front 34

Solving for kel

Back 34

kel = ln (C0 /Ct)/t

Front 35

relationsip of T1/2 and kel

Back 35

T1/2 = 0.693 / kel

Front 36

Relating T1/2 to Vd and Cls

Back 36

T1/2 = 0.693 • Vd / Cls

Cls = systemic clearance

Front 37

calculation of total Systemic Clearance based on

kel
Vd

Back 37

(Clsystemic) = kel • Vd

Front 38

Steady state concentration calculation

Back 38

Css ≈ 1.5 •( T1/2 /T) • C0; T=dosing interval

Front 39

Determining Drug Dose and Interval, 3 factors

Back 39

· Peak level must not give toxicity

· Trough level must not be sub-therapeutic

· Dosing interval must be conducive to patient compliance.

Front 40

relationship b/t

[DR], [Rt], [D], Kd

Back 40

[DR] = ([Rt][D])/([D] + Kd)

Front 41

dose ratio

Back 41

the ratio of the agonist concentrations (or doses) required to elicit equal responses in the presence and absence of antagonist

Front 42

potency

Back 42

reflected by its EC50 in eliciting a response.

The potency of a drug is related primarily to its affinity at the receptor (KD)

Front 43

efficacy

Back 43

capacity to elicit effect

characterized by maximal response

Front 44

Affinity

Back 44

avidity for the receptor

Front 45

EC50 and ED50 in a quantal concentration-response curve

Back 45

EC50 refers to the concentration that produces a specified response in 50% of the subjects

ED50 expresses drug dose

Front 46

therapeutic index

Back 46

Toxic dose 1/Therapeutic dose99

Front 47

dosing approach for wide therapeutic window

Back 47

a maximal efficacy (dose) strategy can be used

Front 48

dosing approach when drug effect is easily measured

Back 48

rial and error approach should be used (< 50% change in dose every 3 to 4 half-lives)

Front 49

dosing approach when drug effects are difficult to measure, or toxicity is seerious

Back 49

target-level strategy should be used.

Front 50

Clearance, CL significance for dosing

Back 50

Defines dosing rate, D(ose)/t (time)

Front 51

Half-life significance for dosing

Back 51

Defines dosing interval, t (time)

Front 52

Bioavailability (F) significance for dosing

Back 52

Defines dosage rate adjustment depending on route of administration (fraction)

Front 53

Volume of distribution (V) significance for dosing

Back 53

Defines the size of loading dose

Front 54

Target Cpss, clearance, and rate of dose relationship

Back 54

Target CPss= dosing rate/Clearance = Rate of infusion/Clearance

Front 55

Cpss, bioavailability (F), dosing interval (t), and clearance, and dose

Back 55

Cpss = (F*D/t)/Cl

Front 56

Estimate Volume of Distribution (Jusko Equation)

Back 56

Vd = 226 + [(298 x CrCl) / (29.1 + CrCl)] x (BSA / 1.73)
where CrCl = normalized creatinine clearance(ml/min)
BSA = Body surface area (square meters)

Front 57

Calculate Loading Dose based on

Vd = Volume of distribution (liters)
Cp = target serum level (mcg/l)
F = bioavailability factor

Back 57

LD = Vd x Cp/F

where Vd = Volume of distribution (liters)

Cp = target serum level (mcg/l)
F = bioavailability factor

IV push = 1

Front 58

Calculate Maintenance Dose
based on

Cl = Clearance (liters/hour)
Cp = target serum level (mcg/l)
tau = dosing interval (hours)
F = bioavailability factor

Back 58

MD = (Cl x Cp x tau) / F

where Cl = Clearance (liters/hour)

Cp = target serum level (mcg/l)
tau = dosing interval (hours)
F = bioavailability factor

Front 59

Estimate steady-state trough level based on

MD = Maintenance dose (mcg)

F = bioavailability factor
Cl = Clearance (liters/hour)
tau = dosing interval (hours)

Back 59

Cpss = (MD x F) / (Cl x tau)

where MD = Maintenance dose (mcg)

F = bioavailability factor
Cl = Clearance (liters/hour)
tau = dosing interval (hours)

Front 60

Calculate clearance based on

MD = Maintenance dose
F = Bioavailability factor
Cp = Steady-state serum digoxin concentration (mcg/l)
tau = Dosing interval (hours)

Back 60

Cl = [(MD x F) / Cp] / tau

where MD = Maintenance dose (mcg)

F = Bioavailability factor
Cp = Steady-state serum digoxin concentration (mcg/l)
tau = Dosing interval (hours)

Front 61

Estimate ration between peak and trough levels at steady state based on

half life
dosing interval

Back 61

Cpmax/Cpmin=e^(0.693x/t1/2)

when x=t1/2, Cpmx/Cpmn=2

Front 62

Determining loading dose based on

MD= maintainance dose
t1/2= half life
x= dosing interval

Back 62

Loading dose = (1.44*MD*t1/2)/x

Front 63

Dose adjustment with 1st order kinetics based on

Desired plasma drug level
Current plasma drug level
Old dose

Back 63

D1= (Cd/Cc)*D0

Front 64

cause of non linear pharmacokinetics important for dose adjustment

Back 64

Dose-response curves may show an unusually large increase in pharmacologic effect with increasing dose, starting at the dose level where “saturation” effects become evident.

Front 65

Principle: Steady-state concentration is directly proportional to ____

Back 65

the drug dosing rate

*except with non-linear pharmacokinetics

Front 66

The time required to reach a steady-state is determined solely by ____

Back 66

drug's elimination half-lif

**completely independent of dosing rate

**essentially complete in 3-5 half lives

Front 67

Principle: Drug accumulation is a function of ____

Back 67

the size of the dose and frequency of administration.

**It is not an intrinsic property of the drug.

Front 68

Principle: During intermittent dosing at a rate calculated to provide a desired steady state, the magnitude of the fluctuation between peak and trough levels is determined by ____

Back 68

the ratio between the dosage interval and the drug's elimination half-life

Front 69

Principle: Unpredictable variability in the pharmacokinetic parameter values
__, __, and __ between individuals is usually quite marked.

Back 69

(F, CL, V)