Pharmacokinetics Acid/Base Metabolism

Question 1

True/False: Ionization causes the drug to be repelled from protein portions of the drug with similar charges.

Answer 1

True. Ionization can cause problems with how things bind.

Question 2

ionized/nonionized cross lipid barrier?

Answer 2

nonionized.

Question 3

Metabolism takes a _____ drug and makes it ______.

Answer 3

lipophilic, hydrophilic

Question 4

nonionized/ionized more likely to undergo metabolism?

Answer 4

nonionized

Question 5

nonionized/ionized more likely to be renally eliminated?

Answer 5

ionized

Question 6

The pKa corresponds to the _______

Answer 6

pH at which 50% of the drug is ionized and 50% is nonionized.

Question 7

Examples of weak acids include:

Answer 7

sodium thiopental, sodium nitroprusside, Na+, Mg++ and Ca++, weak acids form salts with positively charged ions.

Question 8

Examples of weak bases include:

Answer 8

morphine sulfate, lidocaine hydrochloride. Cl-, SO-2, weak bases form salts with negatively charged ions.

Question 9

Acids like to _______ protons.

Bases like to ________ protons.

Answer 9

acids=donate

bases=accept

Question 10

Acidic drug + basic solution=more ______ form of drug.

Answer 10

ionized, acid wants to donate and base wants to accept

Question 11

Acidic drug + acidic solution=more _______ form of the drug.

Answer 11

nonionized, acidic drug wants to donate and so does acid solution, no one to accept, remains neutral

Question 12

Weak acids become more nonionized as pH ______ in the body.

Answer 12

falls, drug pKa 9.4 to body 7.4=more nonionized

Question 13

The ______ the pKa of a weak acid the greater the amount of drug in nonionized form.

Answer 13

higher. 2 acidic drugs at same solution pH, higher pKa is more nonionized

Question 14

Basic drug + acidic solution=more _______form of the drug.

Answer 14

ionized.

Question 15

Basic drug + basic solution= more_______ form of the drug.

Answer 15

nonionized.

Question 16

Weak bases become more nonionized as the pH ______ in the body.

Answer 16

increases. drug pKa 2.6 to body 7.4=more nonionized

Question 17

The ______ the pKa of a weak base the greater the amount of drug in the nonionized form.

Answer 17

lower. 2 basic drugs at same solution pH, lower pKa is more nonionized.

Question 18

True/False: NMBD aren’t an acid or a base.

Answer 18

True.

Question 19

Define biotransformation

Answer 19

The conversion of the parent drug into secondary molecules.

Question 20

End products of biotransformation are usually active/inactive? and water/lipid? soluble to be excreted by the kidneys/liver.

Answer 20

inactive; water soluble

Question 21

What 2 things influence biotransformation?

Answer 21

intrinsic rate of metabolism (genetics, enzyme induction); concentration of drug at metabolism site.

Question 22

What are the types of reactions in Phase I, Modification?

Answer 22

Oxidation, reduction, hydrolysis

Question 23

What does Phase I reaction do?

Answer 23

convert a parent drug into more polar metabolites

Question 24

Oxidation involves loss/gain of electrons?

Answer 24

loss. OIL-RIG, oxidation loses; catalyzed by cyto P-450.

Question 25

Reduction involves loss/gain of electrons?

Answer 25

gain. OIL-RIG, reduction gain, catalyzed by cyto P-450

Question 26

How does hydrolysis work?

Answer 26

breaks compound into two parts by adding water: non-specific esterases and pseudocholinesterase. occurs outside liver (GI tract, plasma)

Question 27

Give examples of drugs metabolized by hydrolysis.

Answer 27

remifentanil, succs, esmolol, ester local anesthetics

Question 28

What type of reaction is Phase II?

Answer 28

Conjugation

Question 29

Define conjugation.

Answer 29

Couples parent drug or phase I metabolite with endogenous substrate to form a HIGHLY POLAR, HIGHER MOLECULAR WEIGHT (WATER SOLUBLE) end product that can be eliminated in the urine.

Question 30

Name 3 kinds of Phase II reactions.

Answer 30

Glucuronidation (glucuronosyl transferases) *most common in anesthesia; sulfonation (sulftransferases); Acetylation (N-acetyltransferases, NAT)

Question 31

What do Cytochrome-450 Inducers do?

Answer 31

increase clearance and reduce half-lives of drugs also metabolized by the enzyme. Example anticonvulsants

Question 32

What do Cytochrome-450 Inhibitors do?

Answer 32

decrease clearance and increase half-lives of drugs also metabolized by the enzyme.

Question 33

Name some drugs the CPY 3A4 metabolizes.

Answer 33

fentanyl, alfentanil, sufentanil, methadone, lidocaine, ropivacaine, bupivacaine, midazolam, diazepam

Question 34

Name CPY 3A4 Inducers.

Answer 34

Ethanol, carbamazepine, rifampin, st. john's wart, tamoxifen, barbiturates.

Question 35

Name CPY 3A4 Inhibitors.

Answer 35

ketoconazole, fluconazole, cimetidine, erythromycin, grapefruit juice, SSRI

Question 36

What drugs does CYP 2D6 metabolize?

Answer 36

codeine, morphine, oxycodone, hydrocodone, zofran

Question 37

Name CYP-2D6 Inducers.

Answer 37

phenytoin, carbamazepine, dexamethasone

Question 38

Name CYP-2D6 Inhibitors.

Answer 38

Isoniazid, SSRIs, quinidine