Drug Absorption Flashcards
Most therapeutic drugs have a molecular weight between what?
100 to 1000 MW
What is the difference between pharmacokinetics and pharmacodynamics?
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
What are some physicochemical factors in transferring drugs across the membrane?
-molecular size/structure features, degree of ionization, relative lipid solubility, binding to serum and tissue proteins
What are the major passive and active transport mechanisms for drugs?
passive: paracellular transport, diffusion
active: facilitated diffusion, endo/exocytosis, drug transporters
What is p-glycoprotein? What gene codes for it?
- 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)
What is the most important barrier to drug permeation?
Lipid diffusion because of the large number of lipid barrier that separate compartments in the body
Weak acids ____ protons. Weak bases ____ protons
- acids donate (loss)
- bases accept (gain)
What is the relationship of charge and permeability of drugs?
-non-ionized (non-charged) molecules are lipid soluble and can diffuse while ionized (charged) molecules can’t
Define pKa. What is the Henderson-Hasselbach equation?
- 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
Define absorption. What is it characterized by?
- uptake of a compound from the site of admin into the systemic circulation (plasma)
- characterized by absorption rate constant and absorption half-life
What is the rate of absorption? What does it influence?
- 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)
What are some common extravascular routes of administration? Characteristics?
- oral, intramuscular, subcutaneous, intradermal, transdermal,inhalation, rectal
- requires absorption, may have drug loss, bioavailability very important
When is drug absorption said to be zero order? first-order/
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
What is the issue with absorption is a drug is too hydrophilic or too lipophilic? Give examples of each
- too hydrophilic (atenolol) can’t cross plasma membrane
- too lipophilic (acyclovir): drug not soluble enough to cross the water layer adjacent to the cell
What is the issue with drinking grapefruit juice with certain medication?
grapefruit juice inhibits P-glycoprotein, which leads to increased drug absorption
What is sustained release of a medication? Most common form? Other forms?
- 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
What are some important characteristics of intravascular administration?
-no absorption, no drug loss, 100% bioabailability
What are some determinants of absorption?
-disintegration, dissolution, molecular size, degree of ionixation
Give examples of weak acids and weak base medications? What is the only strong acid medication?
- acids (aspirin, barbiturates)
- base (noepi, epi)
- HCL
Describe the different absorptive surfaces from taking an oral medication? give time frames? Relevant examples. best pH to absorb in stomach?
- buccal/sublingual: 1-2 mins (Nitroglycerin for MI)
- stomach/gastric pouch: 20 mins. pH= 3-3.5 (normally 1-2)
- small intestine: 30-90 minutes. promoted by water and inhibited by food. primary absorptive surface
What is important about all drugs that are absorbed in the stomach or small intestines?
they will go through first pass effect (by liver)
What types of administration avoid first pass?
rectal, buccal/sublingual, IV/infusion
Define the following administration forms and give examples: intrathecal, intradermal, intramuscular, subcutaneous, topical, transdermal, inhalation, eye and eye, intranasal, intrasynovial
- 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
Define bioavailability. Describe for IV and oral medication
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
What is the first pass effect? What is hepatic extraction ratio and what does it mean for dosing?
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)
