Drug Absorption

Question 1

Most therapeutic drugs have a molecular weight between what?

Answer 1

100 to 1000 MW

Question 2

What is the difference between pharmacokinetics and pharmacodynamics?

Answer 2

Pharamcokinetics: how your body reacts to a drug (ADME: absorption, distrubution, metabolism, and elimination)

Pharmacodynamics: how the drug reactions in your body: receptor binding, drug efficacy, drug potency, toxicity

Question 3

What are some physicochemical factors in transferring drugs across the membrane?

Answer 3

-molecular size/structure features, degree of ionization, relative lipid solubility, binding to serum and tissue proteins

Question 4

What are the major passive and active transport mechanisms for drugs?

Answer 4

passive: paracellular transport, diffusion
active: facilitated diffusion, endo/exocytosis, drug transporters

Question 5

What is p-glycoprotein? What gene codes for it?

Answer 5

• a protein localized in the enterocyte that limits the oral absorption of transported drugs by exporting contents back into lumen after they enter via passive diffusion
• coded by multidrug resistance-1 gene (MDR1)

Question 6

What is the most important barrier to drug permeation?

Answer 6

Lipid diffusion because of the large number of lipid barrier that separate compartments in the body

Question 7

Weak acids ____ protons. Weak bases ____ protons

Answer 7

• acids donate (loss)

- bases accept (gain)

Question 8

What is the relationship of charge and permeability of drugs?

Answer 8

-non-ionized (non-charged) molecules are lipid soluble and can diffuse while ionized (charged) molecules can’t

Question 9

Define pKa. What is the Henderson-Hasselbach equation?

Answer 9

• pKa: the pH at which half the drug (weak acid or base electrolyte) is in its ionized form
• log (protonated form)/(unprotonated form= pKa-pH

Question 10

Define absorption. What is it characterized by?

Answer 10

• uptake of a compound from the site of admin into the systemic circulation (plasma)
• characterized by absorption rate constant and absorption half-life

Question 11

What is the rate of absorption? What does it influence?

Answer 11

• the amount of time for a drug to reach an effective plasma concentration (a level where it works in the body)
• affects Cmax (peak plasma concentration) and Tmax (time to reach Cmax)

Question 12

What are some common extravascular routes of administration? Characteristics?

Answer 12

• oral, intramuscular, subcutaneous, intradermal, transdermal,inhalation, rectal
• requires absorption, may have drug loss, bioavailability very important

Question 13

When is drug absorption said to be zero order? first-order/

Answer 13

zero order: rate is independent of the amount of drug still in the gut (determined by the rate of gastric emptying or a controlled release drug formulation)
-first order: when dose is dissolved in GI fluids and thus proportional to GI concentration

Question 14

What is the issue with absorption is a drug is too hydrophilic or too lipophilic? Give examples of each

Answer 14

• too hydrophilic (atenolol) can’t cross plasma membrane

- too lipophilic (acyclovir): drug not soluble enough to cross the water layer adjacent to the cell

Question 15

What is the issue with drinking grapefruit juice with certain medication?

Answer 15

grapefruit juice inhibits P-glycoprotein, which leads to increased drug absorption

Question 16

What is sustained release of a medication? Most common form? Other forms?

Answer 16

• prolonged therapeutic effect by continuously releasing medication over an extended perio of time.
• most common: enteric coating
• others: spansules, slow core release tabletes, mutlilayer, repeat action tablets, liquid products, ion exchange resins, and transdermal systems

Question 17

What are some important characteristics of intravascular administration?

Answer 17

-no absorption, no drug loss, 100% bioabailability

Question 18

What are some determinants of absorption?

Answer 18

-disintegration, dissolution, molecular size, degree of ionixation

Question 19

Give examples of weak acids and weak base medications? What is the only strong acid medication?

Answer 19

• acids (aspirin, barbiturates)
• base (noepi, epi)
• HCL

Question 20

Describe the different absorptive surfaces from taking an oral medication? give time frames? Relevant examples. best pH to absorb in stomach?

Answer 20

1. buccal/sublingual: 1-2 mins (Nitroglycerin for MI)
2. stomach/gastric pouch: 20 mins. pH= 3-3.5 (normally 1-2)
3. small intestine: 30-90 minutes. promoted by water and inhibited by food. primary absorptive surface

Question 21

What is important about all drugs that are absorbed in the stomach or small intestines?

Answer 21

they will go through first pass effect (by liver)

Question 22

What types of administration avoid first pass?

Answer 22

rectal, buccal/sublingual, IV/infusion

Question 23

Define the following administration forms and give examples: intrathecal, intradermal, intramuscular, subcutaneous, topical, transdermal, inhalation, eye and eye, intranasal, intrasynovial

Answer 23

• intrathecal: injection into CSF to get to CNS
• intradermal: injection into dermal layer (local anesthesia)
• intramuscular: into muscle (used for irritating drugs, drugs not absorbed by oral route, rate of absorption can change by heat, cold, or exercise, risk of local infection or damange to nerve or vasculature
• subcutaneous: under the skin: absorption is slower than IV or IM (insulin/heparin)
• topical: on the skin
• transdermal: patch (fentanyl, nitroglycerin, scopolamin, hormones)
• inhalation: get absorption due to lungs being huge (local and systemic effects occur in this route)
• eye/ear: topically: can lead to systemic toxicity
• intranasal: local/systemic effects
• intrasynovial: into joint space

Question 24

Define bioavailability. Describe for IV and oral medication

Answer 24

Bioavailability: fraction of administered rug that reaches systemic circulation unchanged

• IV: 100% or 1
• Oral: less than 100% due to incomplete absorption and first pass metabolism

Question 25

What is the first pass effect? What is hepatic extraction ratio and what does it mean for dosing?

Answer 25

drugs taken orally metabolize (breakdown) before absorption or before they reach circulation (occurs w/ GI and liver)

• hepatic extraction ratio: how much drug is lost to the liver.
• example: morphine is .067, so 1-0.67= .33 so bioavailability of morphine is 33% orally (30 mg orally equals 10 mg IV)