pharmocokinetics II

Question 1

biotransformation

Answer 1

• chemically altering the original compound so that it is no longer active
• fast process within min or hours

Question 2

excretion

Answer 2

• active form is excreted (via kidney)
• slow process, not very effective

Question 3

What components are essential in eliminating drugs?

Answer 3

• biotransformation
• excretion

Question 4

What is the responsible organ for biotransformation?

Answer 4

liver (the primary) and others

Question 5

Oxidation

Answer 5

• oxygen is added or hydrogen is removed from original compound
• oxidation comprise predominant method of drug biotransformation in body and primarly enzymes that catalyze these reactions: cytochrome P450 monooxygenase cells aka DMMS (drug microsomal metabolizing system)
• smooth ER

Question 6

Reduction

Answer 6

• remove oxygen or add hydrogen to original compound
• enzymes located in cell cytoplasm are responsible

Question 7

Hydrolysis

Answer 7

• original compound broken in separate parts
• enzymes located several sites in cell

Question 8

conjugation

Answer 8

• intact drug or the metabolite of one of the reactions is coupled to an endogenous substance (aceytl coenzyme A), glucuronic acid, amino acid
• enzymes catalyzing drug conjugations are found in cytoplasm and ER

Question 9

What happens after reactions occur?

Answer 9

• biotransformation create polar compound
• after reaction remaining drug metabolite tends to be ionized in body fluids
• ionized metabolite is more water soluble and transprorted more easily to blood stream and kidneys
• at kidneys the polar metabolite excreted through urine

Question 10

enzyme induction

Answer 10

• prolonged use of certain drugs induces body to adjust and enzymatically destroy the drug more rapidly than expected
• usually because either more metabolizing enzymes are being manufactured or fewer of them are being degraded

Question 11

tolerance

Answer 11

• induction decrease drug effects and leads to tolerance
• the need for increased drug dosages to produce same effect

Question 12

Drug excretion

Answer 12

• kidneys primarily
• nephron is functional unit
• traps water soluble (ionzied) compounds for elimination via urine
• other routes: lungs, GI, liver to bile, breast milk, sweat, saliva

Question 13

pathway of drug excretion

Answer 13

1. metabolized or conjugated version of drug reaches nephron
2. filtered at glomerulus
3. filtration
4. compound tranverses the proximal convoluted tubule
5. loop of henle
6. distal convoluted tubule
7. collecting ducts in renal meduall
   * if compound not reabsorbed while in nephron then excreted in urine

Question 14

What compounds get trapped in nephron and not absorbed back into body?

Answer 14

• metabolite
• polar drugs
• ionized

Question 15

What gets reabsorbed?

Answer 15

• nonpolar compounds filtered by kidney are lipophilic reabsorbed by diffusing passively through wall of nephron

Question 16

What role does lungs play?

Answer 16

• serve as route of both drug administration and excretion
• excreting volatile drugs

Question 17

drug elimination rates

Answer 17

• helps to determine amt and frequency of its dosage
• drug administrated faster than elimniated (excessive accumulation and maybe reach toxic levels)
• elimination faster than administraton (doesnt reach therapeutic levels)
• two primary measures to indicate rate at which drug is eliminated
  1. clearance
  2. half life

Question 18

clearance

Answer 18

• single organ or tissue ability
• CL depends on organ or tissues ability to extract the drug from the plasma and the perfusion of the organ
• systemic clearance: the sum of all organs and tissues abilities to eliminate the drug

Question 19

What determines how much drug will be delivered to the organ for eliminiation?

Answer 19

blood flow

Question 20

half life

Answer 20

• amt of time required for 50% of the drug remaining in the body to be eliminated
• a function of both clearance and volume of distribution Vd
• disease states that affect either clearance or Vd will affect the drugs half life

Question 21

dosing schedules and plasma concentration

Answer 21

desireable to bring plasma concentrations of the drug up to certain level and maintain there

Question 22

if dosing interval is relatively long what does that mean for the dose?

Answer 22

the dose must be considerably large to provide the same relative plasma concentration that would exisit in shorter dosing interval.

Question 23

larger doses given farther apart results in?

Answer 23

greater plasma fluctuations that is greater maximum and minimum plasma levels over the dosing period

Question 24

giving smaller doses more frequently

Answer 24

provides and equivalent average concentration w/o extreme peaks or valleys associated with longer intervals

Question 25

Variations in drug response and metabolism

Answer 25

• genetics: difference might influence drug response
• disease: damage to tissue or organ responsible for drug metabolism and excretion
• drug interactions: cumulative, adverse, or additive effects
• age
• diet
• gender
• smoking, alcohol, obesity, chronic and acute exercise, extensive burn injuries