Module 2 Flashcards
Study of drug movement in the body.
Pharmacokinetics
Movement of the drug from the site of administration into the blood.
Absorption
What does the rate of absorption determine?
What does the amount of drug absorption determine?
Rate of absorption - determines onset of action (i.e. how quickly the drug effect will occur)
Amount absorbed –> determines intensity of the drug effect
What are the different factors affecting absorption?
Rate of dissolution Surface area Blood flow Lipid solubility pH partitioning Activity of drug transport proteins
Dissolving in solution
Dissolution
How is an orally administered tablet dissolved?
The orally administered drug dissolves into the gastric fluid, and can then be absorbed
How does dissolution rate affect onset of action?
Drugs with a faster dissolution rate will have a faster onset of action.
What is the major determinant of drug absorption?
Surface area
How is surface area related to drug absorption?
The higher the surface area, the greater the drug absorption
What increases surface area in the stomach?
What increases surface area in the small intestine?
The stomach has folds called rugae
The small intestine has projections called villi (and microvilli)
How does blood flow drive absorption?
Areas with high blood flow maintain a concentration gradient, driving absorption
How does exercise affect blood flow?
What pathologies decrease blood flow?
Exercise increases blood flow
Blood flow is decreased in heart failure, severe hypotension, hypothermia and circulatory shock
How does lipid solubility affect absorption?
Lipid soluble drugs are absorbed more rapidly than water soluble drugs.
How does pH partitioning affect drug absorption?
Drug absorption is greater when there’s a difference between the pH at the site of administration and the blood, such that the drug is ionized in the blood
How can drug transport proteins increase drug absorption? Decrease?
Uptake transporters increase drug absorption; efflux transporters decrease drug absorptoin
What are the 8 major routes of drug administration?
Oral, rectal, sublingual, transdermal, IV, SC, IM, pulmonaryh
What is the most important and most common route of administration?
PO = per os = oral
Routes of administration that involve the GI tract
enteral
Routes of administration that do not involve the GI tract.
Parenteral
Place the 8 major routes of administration into groups based on whether they are enteral, parenteral or other.
Enteral - oral, rectal
Parenteral - IV, SC, IM
Other - pulmonary, transdermal, sublingual
What are the advantages of oral administration?
Safe, convenient, economic
What are the disadvantages of oral administration.
incomplete and variable absorption
Drug absorption is higher in the _______ than in the _______.
Intestine > stomach
Why are acidic drugs still better absorbed in the small intestine?
Due to the stomach’s small surface area and it being coated with mucus
When does the pharmaceutical phase occur?
Occurs after a patient swallows a tablet
What are the phases of the pharmaceutical phase?
Disintegration phase and dissolution phase
Describe the disintegration and dissolution phases.
Tablet disintegrates into granules, then to smaller particles in the disintegration phase.
Then, in the dissolution phase, smaller particles dissolve in gastric fluid, so it is completely in solution.
Movement of the stomach contents into the intestine.
Gastric emptying
How would increased gastric emptying affect absorption?
Since more absorption occurs in the small intestine, increasing gastric emptying would increase drug absorption
What factors increase gastric emptying?
Taking meds on an empty stomach Taking medications with cold water Lying on the RIGHT side (since the stomach is on the upper left side) High osmolarity feeding (tube feeding) Taking a prokinetic drug
What is a prokinetic drug?
A drug that increases GI motility
What factors decrease gastric emptying?
High fat meals
Heavy exercise
Lying on the left side
Taking a drug that inhibits the vagus nerve
What drug type would inhibit the vagus nerve?
Anticholinergics
Drugs covered with a special coating that prevents their disintegration/dissolution in the acidic environment of the stomach.
Enteric coating
How does an enteric coating work?
Enteric coating prevents dissolution/disintegration of a drug in the stomach acid; it then dissolves in the more alkaline duodenum, and is absorbed.
What is the purpose of enteric coating?
Used if a drug is destroyed by stomach acidity or is an irritant to the stomach lining
Fraction of the dose of a drug that reaches the systemic circulation unchanged
Bioavailability
What is bioavailability influenced by?
Drug formulation
Route of administration
Degree of metabolism (liver)
Provide the order, in terms of decreasing bioavailability for orally administered drugs.
Aqueous solution –> syrup –> Suspension –> Chewable tablets –> granules –> Capsules –> compressed tablet –> enteric coated tablet –> time release capsules
(ASS CGC CET)
How does a drug in an aqueous solution or syrup affect bioavailability?
Liquid solution, so no disintegration or dissolution phase
How does a drug in suspension affect bioavailability?
No disintegration phase
How does chewing a tablet affect bioavailability?
Chewing gets around the disintegratoin phase and facilitates dissolution
How does enteric coated or time-released drugs affect bioavailability?
Disentegration phase is appreciably slower
Describe absorption of sublingual drugs
Drug placed under dongue, absorbed across oral mucosa into the blood, drains through the superior vena cava to the heart.
First pass metabolism is avoided.
In order to be absorbed sublingually, what drug quality does there need to be?
Lipophilic (and uncharged)
What drugs are typically given sublingually?
Drugs that act on the heart
What is the ideal formulation for transdermal drugs?
Need to be lipophilic enough to cross the epidermis (lipid barrier) and hydrophillic enough to dissolve in the extracellular fluid; they are also usually small - <600 Da
What are the different transdermal formulations?
Ointments, patches, sprays, lotions
Describe the plasma levels of transdermal preparations.
Constant plasma drug levels with minimal peaks and troughs
How does tolerance play a role in transdermal administration?
Tolerance may develop unless drug-free periods are enforced, so patches are typically removed for 6-10 hours per day to avoid tolerance
What factors affect the rate of transdermal absorption?
Skin thickness Hydration Hair follicles Application area Integrity of the skin barrier
How does skin thickness affect transdermal absorption?
inversely proportional to drug absorption
How does hydration affect transdermal absorption?
transdermal absorption is increased when the skin is well hydrated
How do hair follicles affect transdermal absorption?
Hair follicles provide routes to bypass the lipid barrier of the skin - in general, the greater the number of hair follicles, the greater the drug absorption
How does application area affect transdermal absorption?
the greater the area, the greater the absorption
How does integrity of the barrier affect transdermal absorption?
In conditions such as psoriasis, skin burns or abraded skin, drug absorption is increased
