Lecture 3 Flashcards
ADME
Absorption
Distribution
Metabolism
Excretion
Study of how a body influences a drug
Pharmacokinetics
________ is a breakdown of the processes which affect a drug molecule
ADME
The movement of a drug from the site of administration into the bloodstream
Drugs enter the bloodstream for the purpose of traveling to their target tissues
Absorption
Administration route
Cell membrane permeability
Drug formulation
Physiology: gastric emptying, surface area, temperature
Factors that affect Absorption
non-invasive, good for repeated dosing, safety
Subject to first-pass metabolism
Prodrugs
Absorption: ORAL ROUTE
Intravenous: rapid
Subcutaneous: slower
Intramuscular: larger volumes, slow-release formulas
Routes: Parenteral Routes
Localized
Mucous membranes? Rapid uptake
Routes: Topical
Sustained release
Can be irritating
Routes: Transdermal
Rapid, efficient
Initial localization to pulmonary system
Routes: Inhaled
When it goes into the stomach first and then the liver it’s called
First pass
How much of the drug gets absorbed
Usually described as a percentage
Oral? IV?
Bioavailability
Two drugs that have the same bioavailability and same concentration of active ingredient
Bioequivalents (generic vs brand)
Drug molecules can cross a barrier passively or actively
Active transport
Passive diffusion
Movement across membranes
- molecule size
- lipophinicity
- drug ionization
Membrane permeability
Smaller drugs are absorbed faster than larger drugs
Molecule size
Lipophilic = increased absorption
Lipophilicity
Want drugs to be neutral when they are absorbed, not ionized
A basic drug in an acidic environment will not absorb well
An acidic drug in a basic environment will not absorb well
Drug ionization
Drugs are designed and formulated with the pH of the enteral environment in mind
Weakly acidic drugs are meant to be absorbed in the stomach
Likewise, weakly basic drugs are meant to be absorbed in the intestine (alkaline environment)
Think: neutral is better than ionized, and the pH of the environment surrounding the drug molecule impacts it’s charge
How do we know whether a drug is intended for stomach or intestinal absorption?
Ionization
Coatings
Buffered medications
Hydrogels
Sustained v. controlled release
Absorption: drug formulation
Enteric coating (“EC”)
Prevents drug from dissolving in stomach
Enteric coated tabs absorb in the intestine
Therefore, we do not EVER crush or dissolve an enteric coated tab prior to administration! (no GT tubes, no pudding)
Coatings
Drug contains ions to decrease gastric acidity
Buffered Medication
drug released over period of time
Controlled release
drug released at a constant rate over time
Sustained release (“SR”)
high dose intended to release over extended period.
Crushing, chewing, splitting or opening immediately releases the entire dose
Extended-release (“XR”) formulations
_________ drugs cannot be administered PO
Example: InsulinProtein would be digested by the stomach and rendered useless. That is why we inject insulin.
Protein-based
some drugs may have unpleasant effect on oral cavity (bitter taste, stain teeth, irritate mucosa). Any drug with an oral cavity effect may have a more palatable alternative (e.g: sweetened liquid) so ask pharmacy!
Other considerations for crushing
Gastric emptying
Blood flow
Surface area
Body temperature
Psysiologic and other factors that affect absorpotion
Fatty foods delay emptying
Some drugs can decrease motility
Nursing implication for this?
Gastric emptying
Increased blood flow = increased absorption
Blood flow
Can affect topicals
Body Temperature
Transport of a drug by the bloodstream to its site of action
Distribution
Blood flow to target tissue
Drug solubility (lipophilic/hydophobic)
Drug-Protein binding
Special physiologic barriers
Blood-Brain Barrier
Fetal circulation
Factors affecting distribution
More blood flow = more drug reaching target tissue
Drugs distribute first to areas with ++ blood supply
Blood Flow to target tissue
Lipid-soluble cross cell membranes more readily
Drugs in their active form are usually lipophilic
Question for thinking! – equal amounts of lipid-soluble drug and water-soluble drug – which one will have higher plasma concentration?
Solubility
Drugs will bind to proteins in the bloodstream (albumin)
Only unbound drug molecules can freely distribute – “active”
low albumin levels = risk for toxicity
Drug-protein binding
two medications that are highly protein-bound may “compete” for binding sites on the albumin.
Protein binding site competition
Creates more free, unbound drug = unpredictable drug response
This is called a ______ interaction
drug-drug
when the presence of one drug decreases or increases the action of another drug administered concurrently
Drug to Drug Interaction