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Flashcards in Pharmacokinetics Deck (55):
1

Enteral

Administration of drug that passes through GI tract

Oral or rectal

2

Parenteral

Drug administration that bypasses the GI tract

Intravenous, intramuscular, subcutaneous, intrathecal

3

Active vs. passive transport

Active transport requires ATP and transport/carrier proteins; easily saturates, so amount of drug is limited

Passive transport needs concentration gradient; not readily saturable; more common; less selective

4

Lipid-to-Water Partition Coefficient (P)

= (drug concentration in lipid phase) / (drug concentration in water phase)

Predicts drug entry into the body

The greater the P, the more readily the drug will pass through the GI epithelium membrane

5

pKa

The pH at which the concentrations of protonated and unprotonated forms are equal

6

Weak acid drugs

Drugs with COOH

7

Weak base drugs

Drugs with amino group NH2

8

pH partition hypothesis

At equilibrium, the total drug concentration will be higher in the compartment with the greater degree f pH-dependent ionization

9

Physiological factors affect drug absorption

1. Blood flow: the more blood flow, the more absorption
2. Surface area: the more surface area, the great the absorption
3. Contact time and time to reach efficient area
4. Food: slows absorption

10

Oral bioavailability

Percent of orally administered drug that actually makes it to systemic circulation in a chemically unaltered form

11

Factors that decrease oral bioavailability

1. First-pass hepatic transformation inactivates many drugs

2. Hydrophilicity: drugs that are too hydrophilic will not be able to gain access to circulation

3. Metabolic and pH instability: drugs are altered by GI enzymes or GI pH

4. Drug preparation

12

Bioinequivalent

Different drug preparations can cause differences in bioavailability

Most common in hydrophobic drugs

13

Therapeutic inequivalence

When bioinequivalence of two drugs leads to different therapeutic outcomes

14

Therapeutic index

(Toxic dose) / (effective dose)

15

When is the use of generic drugs problematic?

1. The drugs are bioinequivalent

2. The prescribed drug has a low therapeutic index.

16

Benefits of intravenous administration

1. Can use hydrophilic drugs

2. Avoid GI enzymes that may destroy drugs

3. Increases speed of action

4. Can maintain maximum control of plasma concentrations

17

When drug enters the body, it can distribute into what fluid compartments

1. Intracellular fluid

2. Interstitial fluid

3. Plasma

Interstitial fluid + plasma = extracellular fluid

18

Physical properties of drugs that affect distribution

1. High MW-traps drug in plasma

2. Low MW
-hydrophilic drugs can get in interstitial fluid but cannot passively cross cell membranes to enter intracellular fluid
-hydrophobic drugs can enter all three compartments

3. Drugs that bind to plasma proteins-trapped in plasma because drug-protein complex is too large to enter interstitial or intracellular fluid.

19

Most drugs that bind to plasma proteins bind to...

Albumin

20

Effect of drugs binding to plasma protein

When bound to protein, drug is INERT

Drugs most commonly bound to albumin are anionic hydrophobic drugs

21

Factors affecting total body water

1. Sex-males have higher %age of body water

2. Age-higher percentage of body water in infants; lower percentage in elderly

3. Body composition-amount of body fat inversely proportional to amount of body water

22

Volume of distribution

Because drugs do not exclusively distribute into the water components of the body, drugs divide into a volume different in size than the body's water compartments

Volume constant that relates the amount of drug in the body and the plasma concentration

= (total amount of drug in body) / (plasma concentration of the drug)

23

Assumptions made with Vd

1. Body is one compartment in which drug distributes uniformly

2. Drug concentratio is compartment is same as the plasma concentration

24

If Vd is >>> than total body water

Drug must be tissue bound

25

Vd affected by...

1. Body composition: hydrophobic drug will have higher Vd in fatter person

2. Pathological hemodynamics: may need to increase dose at well perfused areas.

3. Polypharmacy: drug-drug competition for albumin binding sites may impact distribution

26

What two things make blood concentration go down?

1. Distribution
2. Elimination

27

What makes blood concentration go up?

Absorption

28

Normal GFR

125 mL/min

29

Steps of renal elimination

1. Glomerular filtration
2. Tubular secretion
3. Tubular reabsoprtion

30

Glomerular filtration

Only free drug can be filtered

Passive diffusion-->not saturable

31

Tubular secretion

Drug moves from blood to lumen of proximal tubule through active transport

Separate carrier-mediated systems for anions (acids) and cations (bases)

Saturable because requires active transport

Drugs that were free or protein bound can be secreted

32

Tubular reabsorption

Free and uncharged drug diffuse back into the artery along the concentration gradient

33

In case of acidic drug overdose

Add bicarb to alkalize the urine and make the drug charged

34

In case of basic drug overdose

Add ammonium chloride to acidify the urine and increase the amount of charged basic drug

35

Clearance

Volume of biological fluid in which drug is eliminated per period of time

It is a constant

36

Total body clearance

Add clearances via kidney and liver

37

kd constant

Fractional rate of loss of drug from body

= (CL) / Vd

38

Clearance at organ

Certain disease states can impair clearance, particularly disease of organs that are involved in drug elimination

=(organ plasma flow)(extraction ratio)

39

Half life useful indicator in knowing

1. The time it takes to get to steady state after a dosage regimen is initiated
2. The time it takes for drug to be removed from the body
3. The appropriate dosing interval for a drug

40

Extraction ratio

Fractional decline in drug concentration from the arterial to the venous side of the organ

Helpful in determining the impact of disease on an organ's ability for clearance

41

Pharmacokinetics

Time-dependent changes in drug amounts in the body once the drug is administered

42

Major patterns by which drugs are administered

1. Continuous-constant rate of administration, such as IV infusion

2. Discontinuous administration-when patient takes chronic repeated dose at specific intervals

43

R0

Rate of entry of drug into the body

In mL/min

Constant for the valve used to inject drug

Zero-order

=(CLbody)(Css)
Or =(kd)(Vd)(Css)

44

Rate of loss

Depends on blood concentration and total body clearance

=(today body clearance)(plasma concentration)

45

Css

Steady state plasma concentration at which drug in=drug out

Highest plasma concentration at that R0

Can only be changed if you change the valve

46

Relationship between rate of infusion of drug and Css

1:1

Direct relationship

47

Css depends solely on

R0
What is valve is set to

48

Time to reach steady state depends on...

Rate of fractional loss of drug (kd) or half life (0.5t)

Takes four half lives to reach steady state

49

Number of half lives to reach steady state

4

50

Maintenance dose

Dose required to replace the amount of drug lost within the dosing interval

=( (dosing rate) / (% bioavailability)) x (dosing interval)

51

Dosing rate

=rate of elimination

=(CLbody)(Target Cpl)

52

Average amount of drug at steady state

=1.44(D0) x ( (0.5t)/(t*))

Used because hard to determine amount of drug at a given point, so just find the average

53

Problem in dosage in patients with renal disease

1. Sensitivity to drug is unchanged

2. Elimination is impaired, so kd is smaller and half life is longer

Impact of renal disease is determined by the severity of disease and the degree to which the drug taken is cleared by kidneys

54

To avoid toxicity in patients with renal impairment

1. Reduce dose

OR

2. Increase dosing interval

55

Thing that affect half life

Vd
Body clearance