Week 1 Flashcards
Definition of Pharmacokinetics
Derived from two Greek words: pharmkon (drug or poison) and kinesis (motion)
The study of drug movement throughout the body
4 Processes of Pharmacokinetics
- Absorption
- Distribution
- Metabolism
- Excretion
Pharmacokinetics does NOT include which of the following:
Absorption Distribution Metabolism Receptor activity Excretion
Receptor activity
The major barrier to the passage of drugs is?
the cell membrane (double-layer of phospholipids)
Three Ways to Cross a Cell Membrane
Channels or Pores
Na+ and K+ use channels (few drugs use)
Transport Systems
Very selective - drugs with a particular structure
Carries drug from one side to the other side
Some require energy, others do not
Direct Penetration of the Membrane
Most drugs use this method
Transmembrane protein which transports drugs out of cells Liver Kidney Placenta Intestine
Bile
Urine
Maternal Blood
Intestinal Lumen
Two types of Direct Penetration of the Membrane
-Lipophilic (Lipid soluble):Dissolves into lipid that composes the cell membrane and enters the cell
-Non-lipid soluble (Polar Molecules and Ions)
UNABLE to dissolve into membrane
Most drugs cross the cell membrane by:
- utilizing dedicated channels or pores.
- using selective transport systems.
- directly penetrating the cell membrane.
- diffusing between the cells.
- directly penetrating the cell membrane.
About Polar Molecules
- Uneven distribution of electrical charge
- No net charge
Number of protons = number of electrons - Dissolves well in water
- Have a net electrical charge
-Positive or negative charge
-Unable to cross cell membranes
-A few utilize channels: Na, K, Ca
Quaternary Ammonium Compounds
At least one nitrogen (N) N has four rather than 3 bonds --Carries a positive charge --Unable to cross most membranes Ex. Tubocurarine -Muscle relaxant
P-glycoprotein is a multidrug transporter found in the _________ and transfers drugs _____ the cells.
- cytoplasm, out of
- cytoplasm, into
- cell membrane, out of
- cell membrane, into
- cell membrane, out of
Definition of ionization
– Acid and Base
Process of when a base or acid become charged, the process
- An acid gives up a proton (H+) and becomes negatively charged
- A base accepts a proton (H+) and becomes positively charged.
About pH-Dependent Ionization
- The pH environment plays a role in cell membrane crossing
- Drugs exist as uncharged or charged (ionized) forms of weak bases or weak acids
- A weak base or weak acid carries a charge based on the pH of the environment
- –An acid will ionize in a basic (alkaline) environment
- —A base will ionize in an acidic environment
Example of pH-Dependent Ionization
Aspirin is a weak acid
- Does NOT ionize in the acidic stomach
- –May be absorbed in the stomach
- Does ionize in the basic intestines
- –Ionized forms are non-lipophilic
- –Unable to be absorbed in the intestines
Ion Trapping or pH Partitioning
If the pH gradient differs between 2 sides of a cell membrane
- -Acidic drugs gather on the basic (alkaline) side.
- -Basic drugs gather on the acidic side.
A drug accumulates on the side which most favors its ionization
–Ionized forms are non-lipophilic and unable to cross cell membranes
Acidic drugs are trapped on the ________ side of a pH gradient.
- acidic
- neutral
- basic (alkaline)
- Basic
Absorption
- Movement of drug from its administration site into the blood.
- Absorption rate determines onset of action.
- Amount absorbed determines intensity of effects.
Factors Affecting Absorption (first 3)
Rate of Dissolution
-The formulation that dissolves quickly has a faster onset of action.
Surface Area
- The larger the surface area, the faster the absorption.
- The small intestines have more surface area than the stomach (due to microvilli).
Blood Flow
- The higher the blood flow, the more rapid the absorption.
- Large diffusion gradient created.
Factors Affecting Absorption (last 3)
Lipid Solubility
- The higher the lipid solubility, the faster the absorption.
- Highly lipophilic drugs pass through cell membranes quickly.
pH Partitioning
-Absorption increases when pH partitioning causes drug molecules to ionize in the plasma rather than administration site.
Gastric Emptying
- Some drugs are designed to be absorbed only in the intestine
- Delayed gastric emptying may delay absorption by minutes to hours
Routes of Administration
- Enteral (via the GI tract)- oral or rectal
- Parenteral (outside the GI tract)
- -Intravenous
- -Subcutaneous
- -Intramuscular
Local vs. Systemic Effects
Local
-Effects seen in area of administration only
Systemic
- Effects seen in other areas besides the site of administration
- Drug absorbed from site of administration and distributed to other parts of the body
Intravenous Absorption
No barriers to absorption with this method of delivery
Instantaneous complete absorption
Multiple advantages
- -Hallmark – Rapid onset
- -Control over amount of drug delivered
- -Ability to deliver large fluid volumes
- -Ability to give irritating drugs
Intravenous Absorption, Disadvantages
Irreversible
- –Give slowly IV push over at least 1 min
- –Reaches brain in 15 seconds
- –Infusing slowly allows stopping medication and preventing dangerous reactions
Fluid overload
—Monitor IV rate of infusion
Infection risk
—Avoid drug contamination
Embolism risk – blockage of vessel distant to site of administration
- –Clots due to RBC destruction from hypertonic or hypotonic solutions
- –Incompletely dissolved drugs
High cost, difficulty, inconveniences
Intramuscular Absorption
Only barrier to absorption is the capillary wall
- –Large spaces in between the capillary wall cells
- –Drug passes through these spaces with ease
Rate of absorption
- –Rapid absorption of water-soluble drugs (10-30 minutes)
- –Increased rate of absorption if high blood flow
Intramuscular Absorption
- Advantages and Disadvantages
Advantages
- Administration of poorly soluble drugs
- Administration of depot preparations
- –Preparations designed to be absorbed over time
- –Less injections
Disadvantage
- Discomfort and inconvenience
- Very painful injections
- Local tissue injury
- Nerve damage if improperly administered
Subcutaneous Absorption
SC administration is almost identical to IM injection
- -Passes readily between spaces between capillary wall cells
- -Water-soluble drugs absorbed rapidly
- -Increased absorption with increased blood flow
No significant barriers to absorption
Subcutaneous Absorption
- Advantages and Disadvantages
Advantages
- -Suitable for poorly-soluble drugs
- -Depot preparations
Disadvantages
- -Discomfort
- -Inconvenience
- -Potential for tissue injury
The advantages of intramuscular absorption include:
- instantaneous, complete absorption.
- administration of poorly soluble drugs.
- convenience of administration.
Answer 2. administration of poorly soluble drugs
Oral Absorption
PO abbreviation stands for per os, a Latin phrase meaning by way of the mouth
Absorbed by the stomach or intestines
Oral Absorption- Three barriers to absorption exist for this route:
Epithelial cell membranes that lines the GI tract
Capillary cell membranes
P-glycoprotein
- -In intestinal epithelial cell membranes
- -Transports drug back into intestinal lumen
Factors influencing oral absorption
(highly variable)
- Solubility and stability of drug
- Gastric and intestinal pH
- Gastric emptying time
- Food in gut
- Coadministration of other drugs and herbals
- Special coatings on drug preparations
The rate of absorption may be increased by:
- smaller surface areas.
- lower blood flow.
- lower lipid solubility.
- ionization of the drug at the site of administration.
- formulations which dissolve quickly.
- delayed gastric emptying.
answer 5
Drug Movement
All drugs taken orally must go through the liver
–Except drugs absorbed by the oral mucosa or distal segment of the rectum
Some drugs reenter GI tract
- -Enterohepatic circulation (reabsorption from the bille)
- -Excreted in stools
Oral Absorption
- Advantages and Disadvantages
Advantages
- -Easy, convenient, inexpensive to administer
- -Safer than injection
- -No risk of fluid overload, infection, or embolism
- -Reversible by giving activated charcoal to soak up drug
Disadvantages
- Highly variable absorption
- Inactivation
- –Digestive enzymes
- –Liver enzymes with first-pass effect
- –Inactivated by other medications, foods, herbals
- Difficulty swallowing or unwillingness to take medication
Oral versus Parenteral
Oral administration is usually preferred
Parenteral administration is necessary when:
- Require rapid onset of action.
- Need tightly controlled plasma levels.
- Drugs are destroyed by gastric acid.
- Drugs can cause severe local injury.
- Drugs cannot cross cell membranes.
- Need prolonged effects of drug (ex. depot preparation).
- Unable/unwilling to take oral drugs.
Drug Terminology
Chemically Equivalent
—Same amount of identical compound (drug)
Bioavailability
- –Same drug AND
- –Same rate and extent of absorption
Preparations of Oral Drugs (Tablets)
Tablets
- Compressed mixture
- –Drug-Active ingredients
- –Binders
- –Fillers
- –Dyes
- Differ in bioavailability as to onset and intensity of effects
Preparations of Oral Drugs (Enteric-coated)
Enteric-coated
Dissolve in intestines
- –Absorption depends on rate of gastric emptying
- –Some may fail to dissolve
- –Do NOT crush!
Protection
- —Drug from acid and pepsin
- –Stomach from gastric discomfort
Coatings of fatty acids, waxes, shellac
Preparations of Oral Drugs (sustained release)
Sustained-release
Capsules filled with variable time-release spheres
- –Each sphere releases drug at different times
- –Maintains steady release of drug
- –Do NOT crush!
Permits longer times between administration
Potential for variable absorption
High cost
Additional Routes of Administration
Topical
–Local treatment of skin, eyes, ears, nose, mouth, vagina
Transdermal - skin
Inhalation - lungs
Suppositories - rectal or vaginal
Injections into specific sites
Which oral formulation may be crushed?
- Immediate-release tablets
- Sustained-release tablets
- Enteric-coated tablets
Answer 1. Immediate-release tablets
