BPP VI

Question 1

Approximately when is steady state achieved? Relate steady state and dosage. How do steady state concentrations relate to dose/dosage interval? How do ss concentrations relate to clearance?

Answer 1

After four half-times; time to steady state independent of dosage; directly proportional; inversely proportional

Question 2

At SS what is true of absorption and elimination? What does the time to achieve steady state concentration depend on?

Answer 2

Rate of absorption = rate of elimination; only depends on t1/2

Question 3

Can the steady state be achieved with a single dose? Give examples of drugs administered with a single dose?

Answer 3

No, the dose interval is much greater than t1/2; antibiotics and diuretics

Question 4

When can you achieve the steady state? Give examples

Answer 4

Dose interval is approximately equal to t1/2 or less; antihypertensives

Question 5

What is Css numerically? Describe the parameters involved with ultimately hitting a steady state? Where should Css be found on the graph?

Answer 5

An average because of fluctuation between the doses; see page 1-75; the therapeutic range;

Question 6

What is the range of the therapeutic window?

Answer 6

Minimum effective concentration and minimum toxic concentration

Question 7

What determines the Css average? What would NOT determine the Css average? What is a consequence of wide swings in Css?

Answer 7

The dose per unit time (thus 2 mg per minute would lead to about the same Css average as 180 mg/1.5 hours and 360 mg/3 hours); the route of administration; could be too toxic or subtherapeutic Cp

Question 8

How long does it approximately take to reach steady stage? How do elimination rate and time to steady state relate? Does dose affect time to achieve steady state?

Answer 8

About 4 half-lives; the faster the elimination rate or if clearance is high, the faster the time to steady state, and the same goes with slower elimination rate; NOOOOOO

Question 9

How much of a drug would be eliminated from a system at about four half lives?

Answer 9

93% (92.75)

Question 10

What are two purposes of loading doses? With repeated administration what type of doses are you giving? Does a loading dose shorten time to get to steady state?

Answer 10

1. Rapidly attain therapeutic plasma level (NOT STEADY STATE)
2. Use to change the SS concentration;
   Loading dose followed by maintenance dose;
   NOOOOOOO

Question 11

Define what a loading dose is?

Answer 11

Loading dose = Cp x Vd

Question 12

Who are we trying to account for with drug toxicity?

Answer 12

Sensitive (at lower doses, toxic response), normal, resistant (consider poor, intermediate, effective, ultrarapid)

Question 13

List adverse drug reactions

Answer 13

1. Iatrogenic (could be predictable and dose dependent)
2. Spontaneous (not predictable, not dose dependent): includes allergy (reproducible in the patient) and idiosyncratic (not immunologic, not necessarily reproducible)
3. Tolerance (decreased response to continuous admin): receptors and metabolism
4. Resistance: refractoriness to drug effect
5. Side effects: secondary effects with secondary receptors
6. Cumulation: drug administered faster than eliminated
7. Drug dependence/addiction: tolerance, homeostasis, PHYSICAL WITHDRAWAL SYNDROMES like with alcohol, nicotine, narcotics

Question 14

What is the therapeutic index (TITE)? What are ED50, TD50, LD50? Define margin of safety

Answer 14

TI = Toxic Dose/Therapeutic dose = TD50/ED50;
effective dose in 50% of the pop, toxic dose in 50% of the pop, lethal dose in 50% of the pop;
TD50-ED50

Question 15

Illustrate TD50 vs. ED50 as well as the therapeutic index

Answer 15

See 1-81

Question 16

Give examples of drug interactions (7)

Answer 16

1. Direct molecular (antibiotics and calcium interact)
2. Change absorption (charcoal binds drug molecules, decreases absorption)
3. Protein binding and displacement (potential toxicity)
4. Receptor effects (comp vs. noncomp inhibition)
5. Change metabolism (induction vs. inhibition)
6. Change excretion (active transport inhibitors or simple competitiion for a transporter)
7. Change pH or other electrolytes (alter excretion or protein binding)

Question 17

Give an overview of the unique features of newborn physio?

Answer 17

1. Increased ECF
2. Immature enzyme systems
3. Decreased renal function
4. Constant alteration of fluid composition with age
5. Redistribution of circulation with shunting

Question 18

How can oral drug absorption be affected in the newborn?

Answer 18

1. Gestational age
2. Solubility of the drug
3. Gastric emptying time: shortening increases absorption
4. Gastric acidity
5. Intestinal motility
6. Presence of food in the stomach
7. Splanchnic circulation

Question 19

What are causes of low drug binding in the newborn?

Answer 19

1. Low albumin
2. Competitive binding: e.g. bilirubin and sulfonamides
   Result: increased apparent VD

Question 20

How is rate of biotransformation in newborns? How so?

Answer 20

Slower; oxidation reactions slow, glucuronidation deficient at birth, acetylation somewhat deficient, hydroxylation depressed, sulfation active;

1. rate varies with gestational maturity
2. marked interpatient variability
3. postnatal maturation for individual drugs variable
4. vulnerability to pathologic states
5. alternative pathway activation

Question 21

What factors influence renal excretion of drugs in newborn?

Answer 21

1. Low renal blood flow
2. Low glomerular filtration rate
3. Low tubular function
4. Glomerular predominance
5. Nephron heterogeneity

Question 22

Plasma half-life in the newborn? Example?

Answer 22

1. Much longer than in adults
2. Very large individual variability
   E.g. phenobarbital

Question 23

What must you consider therapeutically with newborns?

Answer 23

1. Elimination phase prolonged relative to distribution (B vs A)
2. Apparent volume of distribution increased
3. Loading dose higher (higher apparent volume of distribution
4. Maintenance dose lower (prolonged t1/2)