Pharmacokinetics I, lect 5

Question 1

what biological processes does the body employ to handle drugs after they are administered (ADME)

Answer 1

A: absorption

D: distribution

M: metabolism

E: elimination

Question 2

what is the “steady state” of a drug

Answer 2

• when a patient is taking a medication on a regular basis, there is an ongoing process of drug absorption in the form of each dose and an ongoing process of removal with the drug’s metabolism and clearance
• steady state= when the amount of drug going in is the same amount of drug getting taken out

Question 3

how many half lives does it take for a drug to reach steady state

Answer 3

5

Question 4

what is the first pass effect?

Answer 4

orally administered drugs enter circulation almost exclusively by the way of the hepatic portal system

• exposed to the liver first and may be metabolized in liver
• can significantly decrease bioavailability

Question 5

What are some disadvantages to oral drug administration?

Answer 5

• first pass effect
• irritation of intestinal mucosa -> emesis
• desctruction by GI enzymes or low pH
• binding to food
• irregularities in absorption and gastric emptying time

Question 6

bioavailability of a drug given through IV

Answer 6

• 100%

Question 7

this type of parenteral (non-oral) route generally results in drugs being absorbed more slowly than with IV or IM injection and is often used for implantation of drugs in solid pellets

Answer 7

subcutaneous injection

Question 8

this type of parenteral route is useful for drugs in aqeous solution and drugs are usually absorbed fairly rapidly in this method

Answer 8

intramuscular injection

Question 9

this type of parenteral route is used for gaseous anesthetics

Answer 9

inhalation

Question 10

Why use buccal or sublingual route of administration

Answer 10

used for drugs that extensively degraded by the first pass effect (nitroglycerin)

• rapid absorption but limited amount absorbed due to small surface area

Question 11

What affects absorption on the skin

Answer 11

• absorption is proportional to the surface area exposed and lipid solubility of drug
• inflammation and conditions that increase cutaneous blood flow enhance absorption

Question 12

lipid soluble drugs are absorbed via?

Answer 12

simple (passive) diffusion

• concentration gradient or electrochemical gradient

Question 13

Acids and Bases: which is a proton donator? Which is a proton acceptor?

Answer 13

acids: proton donator
base: proton acceptor

Question 14

is an ionized acid or base more or less likely to be absorbed?

Answer 14

• less likely: affects drug’s ability to permeate biological membranes and exert its effect
• ionized drugs are surrounded by water molecules that increase hydrophilicity and prevent it from diffusing through lipid bilayers

Question 15

why is a drug that is a weak acid absorbed in the stomach?

Answer 15

• stomach has low pH, very acidic: more protons
• weak acid will not donate proton in very acidic environement; therefore it stays protonated, non-ionized which means it is more lipid soluble and rapidly absorbed

Question 16

why is a weakly acid drug not absorbed in the intestine?

Answer 16

• intestine has high pH; few floating protons
• weak acid will donate H and become unprotonated (A-) and ionized therefore not readily absorbed

Question 17

why won’t a weakly basic drug be absorbed in the stomach?

Answer 17

• stomach has low pH, lots of protons
• weak base (B) is a proton acceptor and accepts a proton to become (BH+) which is ionized and therefore not readily absorbed

Question 18

why is a weakly basic drub absorbed in the intestine

Answer 18

• intestine has a high pH, few floating protons
• weak base is predominately unprotonated (B) which is non-ionzed, more lipid soluble and rapidly absorbed

Question 19

how does ion trapping work to increase the elimiation of drugs

Answer 19

1. can trap a weakly basic drug in an acidic medium or a weakly acidic drug in a basic medium because both in scenarios, the drug will become ionized and will accumulate in that environment
2. ex: urine can be made basic (sodium bicarbonate or acetazolamid) so that acidic drugs will be trapped and excreted

Question 20

what is the pka

Answer 20

pH at which the amount of ionized vs. non-ionized forms of a drug are equal

Question 21

if pH < pKa, what form of acids and bases will dominate?

Answer 21

Protonated

• acid will be non-ionized (HA)
• base will be ionized (BH+)

Question 22

if pH>pKa, what form of acid and base will dominate?

Answer 22

• unprotonated form
• acid will be ionized (A-)
• base will be non-ionized (B)

Question 23

what is the henderson-hasselbalch equation

Answer 23

pH - pKa = log (A-)/HA

• for an acid
• A-: ionized
• HA: non-ionized

Question 24

ex: weak acid in acidic environment

• pKa=5.4
• pH= 4.4
• what is the ratio of ionized/non-ionized

Answer 24

• pH < pKA therefore weak acid will be protonated (nonionized)
• pH-pKa = log (A-/HA)
• OR 4.4 to 5.4 is 1 degree of difference which is 10x difference in proportion
• A-/HA = 1 ionized / 10 non-ionized

Question 25

ex: weak acid in basic environment

• pKa = 4.4
• pH = 7.4
• what is the proportion of ionized/non-ionized drug?

Answer 25

• pH > pkA therefore weak acid will be deprotonated (A-) and ionized
• 7.4-4.4 = 3
• 3 = 1000
• A-/HA = 1000 ionized / 1 non-ionized

Question 26

Ex: weak base in an acidic environment

• pKa= 5.4
• pH = 3.4

Answer 26

• pKa > pH therefore weak base will be protonated (BH+) and ionized
• 3.4-5.4 = [2]
• 2=100
• 1 non-ionized / 100 ionized

Question 27

• weak base in basic environment
• pKa = 4.4
• pH = 8.4
• ionized/ non-ionized ?

Answer 27

• pH > pKa therefore weak base will not be protonated (B) and be nonionized
• 8.4-4.4 = 4
• 4=10,000
• 1 ionized / 10,000 non-ionized