Exam 1: Pharmacokinetics Flashcards

Question

Intramuscular Route

Answer 1

* Site can serve as depot for slow delivery of drug * Not all of the drug absorbed instantly so get slow release * Depends on blood flow * Ex. exercising or anxiety ⇒ inc. blood flow ⇒ inc. delivery * Large volumes often feasible * Self-admin possible

Answer 2

* Absorption depends on lipid solubility of drug or vehicle * Can be irritants * Can get slow absorption

Answer 3

* Technically a topical application * Usually see local affect with little systemic absorption * Ex. bronchodilators * With anesthesia, can finely control depth of anesthesia

Answer 4

* Admin of drug to CSF * Used to produce slelective spinal blockade

Answer 5

The movement of a drug from systemic circulation to other tissues.

Answer 6

The process of removing a drug from the systemic circulation by excretion or metabolism.

Answer 7

Body acts as a single compartment. k_a ⇒ rate of absorption k_e ⇒ rate of elimination Assume instantaneous delivery and distribution ⇒ k_a = ∞

Answer 8

_Proportional to drug concentration:_ k_e = elimination rate constant Given in concentration per unit time e.g. (mg/ml)/hr

Answer 9

Follows a single exponential time course. C₀ ⇒ concentration at t = 0

Answer 10

Time it takes for the concentration at any one time to get to 50% of that value.

Answer 11

The _volume_ needed to account for the amount of a drug that _reaches the plasma_ for a given amount of drug introduced. Commonly normalized to body weight ⇒ l/kg

Answer 12

Drugs that accumulate in the tissue or fat have unrealistic V_d because majority is not in the plasma.

Answer 13

0.2-0.35 L/kg

Answer 14

Relates the rate of elimination to the plasma concentration. Units of amount of drug per unit time e.g. mg/hr

Answer 15

Absorption slow enough to measure. k_a ≠ ∞ k_e can still be determined from the late decay phase. Cannot extrapolate t=0 to get C₀.

Answer 16

AUC ⇒ area under the concentration-time curve (For single exponential decay, AUC = k_e/C₀)

Answer 17

Dose needed to maintain a steady-stant concentration (C_ss). Deliver rate = Elimination rate k_a = k_e

Answer 18

4-5 half lives

Answer 19

**Central compartment** ⇒ plasma **Peripheral compartment** ⇒ tissues that are in rapid equilibrium with the plasma It takes time for a drug to be evenly distributed throughout the body. Drug concentration falls more rapidly during **distribution phase** than during **elimination phase**.

Answer 20

Half-life of a drug is determined from the **slow phase**. V_d and CL can also be determined.

Answer 21

Need to maintain a therapeutic level: * **Constant infusion** * **Infrequent large doses** * Goes above toxic levels * Dips below therapeutic levels * **Frequent small doses** * Takes time to reach therapeutic levels * Steady state concentration stays between toxic and therapeutic levels ⇒ 'safe zone'

Answer 22

**Active, lipophiic molecules ⇒ less active, polar molecules** _Two broad categories:_ Phase I reactions Phase II reactions

Answer 23

Parent drug ⇒ more polar metabolite via introduction/unmasking of a **polar functional group** (-OH, -NH₂, -SH) * **↑ polarity ⇒ ↑ water solubility** * **∆ pharmacological activity** * Usually means reduction or loss of activity * Some are inactive drugs converted to active metabolites ⇒ **prodrugs** * Some are non-toxic compounds ⇒ toxic compounds

Answer 24

Enalapril ⇒ Enalaprilat (inactive "prodrug" ⇒ active) By de-esterification.

Answer 25

* Used as a pesticide * Converted to toxic intermediates via phase I reactions by desulfuration * Birds & mammals able to convert these to non-toxic substances via phase IL reactions * Insects are not

Answer 26

Phase I reaction ⇒ add polar group **Phase II reaction** ⇒ conjugate to endogenous polar substrates * Glucuronic acid * Sulfuric acid * Acetic acid * Glycine **Produces highly polar compounds w/ high water solubility** ⇒ **increases excretion** Almost all conjugated products are **inactive**.

Answer 27

Liver is 1° site of biotransformation Most phase I reactions catalyzed by SER enzymes ⇒ **microsomes**

Answer 28

Two play key roles in phase I reactions: **Cytochrome p450** ("CYP") ⇒ oxidases **NADPH-cytochrome P450 reductase**

Answer 29

Repeated administration of some substances ⇒ **inc. levels of CYP isoform that metabolizes compound** **Results in acceleration of metabolism of all substrates for that isoform** Ex. Barbiturates ↑ [CYP2C9] ⇒ ↑ warfarin metabolism

Answer 30

**Some substrates can inhibit CYPs via:** * **Competitive inhibition** * Ex. Erythromycin & Terfenadine both metabolized by CYP3A4 * **Covalent modification of enyme** * Usually attacks heme moiety

Answer 31

renal & biliary

Answer 32

Major site of excretion. _3 transport mechanisms involved:_ 1. **Glomerular filtration** * Factors that ∆ GFR ⇒ ∆ CL * % bound to plasma proteins ⇒ ∆ CL 2. **Active tubular secretion** * Non-selective organic cation/anion transporters can move some compounds 3. **Passive tubular absorption** * H₂O reabsorption ⇒ ↑ [Drug] * Only uncharged drugs can be reabsorbed * pH of urine ∆ CL

Answer 33

* Must undergo conjugation in the liver first * Products frequently excreted into biliary tract ⇒ bowel * **May be excreted** * Bowel flora can _cleave off conjugate_ * Drug may be reabsorbed if lipid-soluble ⇒ **enterohepatic recirculation**

Answer 34

Genetic differences ⇒ ∆ rate of drug metabolism * ∆ expression levels of enzyme * ∆ enzymatic activity

Answer 35

* **Slow acetylators** * ↓ [enzyme] * ↑ plasma levels of drug * AR trait seen in 50% of blacks and whites in US & Europheans living @ high altitude * **Fast acetylators** * Usually Asians and Inuits

Answer 36

* CYP2D6 metabolizes many medications * Flecanide, Metoprolol, Fluoxetine, Imipramine * Genetic polymorphisms * Gene duplication ⇒ ultrarapid metabolizers * Null nutation ⇒ poor metabolizers * Exam ratio of debrisoquin : 4-hydroxydrisoquin in urine * Determine activity of CYP2D6 * Ratio \< 0.1 ⇒ ultrarapid * Ratio \> 10 ⇒ poor * Compound is inert in the body

Answer 37

* TPMT metabolizes thiopurine drugs * Patients w/ low or absent TPMT activity @ inc. risk for drug induced bone marrow toxicity * Test for abnormal TPMT\*3A allele before treatment

Answer 38

* **Liver function** * Hepatitis * Cirrhosis * **Hepatic blood flow** * Affects "flow-limited" metabolism drugs most * Metabolism so fast that it is limited by rate of delivery to liver * Ex. Amitriptyline & imiprimine

Answer 39

Generally, **very old and very young** more sensitive to drugs. _Can be due to many factors:_ * Renal clearance * Body fat content * End-organ responsiveness * Drug metabolism * **Reduced rate of hepatic metabolism ⇒ most significant determinant**

Exam 1: Pharmacokinetics Flashcards

(71 cards)