Week 1 (23 questions) Flashcards
ADME
Describe each
Absorption- when the drug is released from the formulation//administration site and enters the bloodstream
Distribution- the movement once it is in the bloodstream
Metabolism- the body using the drug and giving off a byproduct
Excretion- getting rid of the by product
ABSORPTION
fastest to slowest absorption
Fastest to slowest absorption:
Oral disintegration, buccal tablets, and oral soluble wafers
Liquids, elixirs, and syrups
Suspension solutions
Powders
Capsules
Tablets
Coated tablets
Enteric-coated tablets (broken down not in stomach but in intestines)
ORAL
What can influence ORAL drug BIOAVAILABILITY?
The most common of all routes
Most drugs are ABSORBED in stomach or small intestine
pH of the GI tract (Absorption)
Co-Administration w/ Drugs or Meals(Absorption)
Drug Formulation/Pharmaceutics(Absorption)
P-Glycoproteins(Absorption)
First Pass Effect (Metabolism)
EXAMPLES OF ORAL DOSAGE FORMS (most common route):
Oral Liquids/Suspensions
Already in dissolved form and thus absorbed quickly
Sometimes called IR= Immediate Release
In general, you should SHAKE an ORAL suspension (powder will go to the bottom)
EXAMPLES OF ORAL DOSAGE FORMS (most common route):
Enteric Coated Tablets
Whereis drug absorbed?
and why?
Extra coating on the outside prevents drug from being broken down by the acidic pH of the stomach
Drug is not absorbed until they reach the small intestine (higher pH)
Commonly made to PROTECT the gastric mucosa from irritation
Famous Example: Enteric Coated Aspirin (EC)
EXAMPLES OF ORAL DOSAGE FORMS (most common route):
Extended Release/Sustained Release Tablets
Release drug over a prolonged period
Abbreviations => SR, SA, CR, XL, XT, ER, and more
Oral Drug Bioavailability Influences:
1.pH of the GI Tract (ABSORPTION)
Some drugs need an acidic environment (may prefer the stomach)
Some drugs need a basic environment (may prefer the intestines)
Factors that influence pH of the GI Tract:
Time of day (pH can fluctuate throughout the day)
With or without food
Medications (Tums®)
Lifespan (neonates, geriatrics)
Diseases/Conditions
- Co-Administration with Drugs or Meals (ABSORPTION)
Co-Administration with Drugs or Meals (ABSORPTION)
Can be GOOD or BAD!
A) Certain drugs may adhere to one another, others may change the pH of the GI tract
B) Food alters pH of the GI tract and transit time
Example : Doxycycline (a Tetracycline Antibiotic)
Avoid administering with other medications (like Tums®). Calcium carbonate (Tums®) will bind to the doxycycline and prevent the body from absorbing the antibiotic
- Pharmaceutics (ABSORPTION)
Different formulations will have different dissolution rates
Liquid vs. Enteric Coated vs. Extended-Release Tablet
- P-Glycoproteins (ABSORPTION)
Part of our “defense system”
Located in essentials areas of body
Blood Brain Barrier, GI Tract
Sometimes called “Anti-absorption pumps” or Efflux Pumps designed to pump out xenobiotics (toxins, drugs)
Net Result= Less absorption of oral drugs into the general circulation
P-glycoprotein Inhibition
In the past several years, we have discovered that certain drugs and foods may block/prevent normal P-glycoprotein function
Famous example of P-Glycoprotein Inhibitor:
Grapefruit and Grapefruit Juice (Pomelo too)
Real World Example:
There is a cholesterol lowering drug class commonly known as “Statins”
“Statins” have a risk of rhabdomyolysis or rapid muscle breakdown (risk increases based on dosage)
If you take Atorvastatin and drink Grapefruit Juice, the Grapefruit Juice inhibits the P-glycoproteins, allowing the body to absorb more Atorvastatin than anticipated= increased risk for toxicity
Best to tell patients to avoid grapefruit while taking certain medications
- First Pass Effect (METABOLISM)
Oral drugs are the only route subjected to what’s known as the “First Pass Effect”.
- Drug is swallowed,
- Goes to GI tract
- Gets absorbed into GI mucosa
- The gastric/intestinal mucosal blood flow goes to portal vein
- Portal Vein carries the blood to the Liver
- Liver metabolizes drugs (FIRST PASS EFFECT)
- Metabolized drug reaches general blood circulation
Enteral Routes
The drug is absorbed into the systemic circulation through the GI tract
The Enteral route has variable Bioavailability
Parenteral Routes
Non-GI-Tract administration, aka injections
The drug is absorbed into the systemic circulation
Intravenous: 100%: Blood stream
Intramuscular/Subcutaneous/ Intradermal:
Variable: Depends on location
Epidural: Variable: Epidural space around the spinal cord
DISTRIBUTION
Permeability of the Cell Membrane
Lipid Soluble vs Water Soluble
Blood Brain Barrier, Placenta
Lipid Soluble
Easily distribute into fatty tissues where they may store or concentrate
Have the potential to cross the Blood Brain Barrier (BBB) and the Placenta
Water Soluble
Typically remain in highly vascularized spaces and can easily leave the body via elimination (urine!)
DISTRIBUTION
PROTEIN BINDING
most common blood protein?
Albumin is the most common blood proteiN
Some drugs preferentially bind to protein/albumin
Called “highly bound drugs“
DISTRIBUTION
Bound drug vs Free Drug
Free drug (active)
Drug is not bound to albumin
can distribute into extravascular tissue to its intended target
Bound drug (inactive)
Stuck to albumin, stays in the bloodstream
Cannot get to extravascular space and reach intended target
DISTRIBUTION
Give an example of a highly protein bound drug
Famous Example of a highly protein bound drug= PHENYTOIN
10% Free, 90% bound
