Module 2 Flashcards
Define pharmacokinetics
the study of drug movement into the body
Pharmacokinetics is composed of which four basic processes?
ADME -
Absorption
Distribution
Metabolism
Excretion
Describe drug absorption
drug absorption is the movement of the drug from the site of administration into the blood
What determines how quickly the drug effect will occur?
the rate of absorption
What determines how intense the effect of the drug will be?
the amount of drug absorption
List the factors affecting absorption
1) Rate of Dissolution
2) Surface Area
3) Blood Flow
4) Lipid Solubility
5) pH Partitioning
6) Activity of Drug Transport Proteins
Define dissolution
dissolving in solution
Drugs must what before they can be absorbed?
dissolve
Drugs with a fast rate of dissolution will have what?
a faster onset of action than drugs with slow dissolution
What does a larger surface area mean (in relation to drug absorption)?
Faster drug absorption
Which has the greater surface, the stomach or the small intestine?
Small intestine
While the stomach has folds called rugae, the intestine has thousands of finger-like projections called villi. The villi that line the intestine make the surface area very large.
Describe blood flow
- Drug absorption is fastest in areas with high blood flow.
- Areas with a high blood flow maintain a concentration gradient which drives absorption.
- Areas with low blood flow do not maintain as great of a concentration gradient.
Exercise does what to blood flow?
increases blood flow and can increase drug absorption
Blood flow is what in heart failure, severe hypotension, hypothermia and circulatory shock?
decreased
What may be the greatest determinant in the absorption of a drug?
Surface area
Are lipophilic or hydrophilic drug absorbed more rapidly?
Lipophilic
* Lipophilic drugs are able to cross the cell membrane whereas hydrophilic drugs can’t
Describe pH partitioning and the effect it has on 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.
- Remember the effect of pH dependent ionization from Module 1!
Which type of drug transporters increase the absorption of drugs?
Uptake
Which type of drug transporters decrease the absorption of drugs?
Efflux
What are the 8 major routes of drug administration?
1) Oral (PO = per os which is latin for by mouth)
2) Sublingual
3) Transdermal
4) Rectal
5) Intravenous (IV)
6) Subcutaneous (SubQ or SC)
7) Intramuscular (IM)
8) Pulmonary
Routes of administration are often referred to as what?
enteral or parenteral
Describe enteral
routes of administration that involve the gastrointestinal tract
Describe parenteral
routes of administration that do not involve the gastrointestinal tract. In reality though, clinical practitioners consider parenteral to be routes of administration that include injections.
What is the most common method of drug administration?
oral
What are the advantages of oral drug administration?
safety, convenience, economical
What are the disadvantages of oral drug administration?
incomplete and variable absorption
Where would oral drug absorption be the greatest?
intestine
the intestine has a surface area over 200 m squared
What about drugs that are weak acids, wouldn’t they be better absorbed in the stomach?
- Based on the pH effects weakly acidic drugs should be better absorbed in the acidic environment of the stomach because they would unionized.
- However, the surface area of the stomach is small and the stomach is covered with a thick layer of mucous.
- Therefore the rate of drug absorption in the intestine will be greater than the stomach, even if the drug is ionized!
- The bottom line is for most drugs, oral absorption is greatest in the intestine.
Describe the pharmaceutical phase
- The pharmaceutical phase occurs after the patient swallows a tablet.
- It involves the disintegration of the tablet and the dissolution of the drug.
- If the drug does not completely disintegrate or does not go into solution, absorption is reduced.
Describe gastric emptying
- Gastric emptying is quite simply the movement of the stomach contents into the intestine.
- Since the rate of drug absorption is greater in the intestine, things that increase gastric emptying also increase the rate of drug absorption.
What are the modifiable factors that increase gastric emptying?
- Taking medications on an empty stomach
- Taking medications with cold water
- Lying down on the right side
- High osmolality feeing (tube feeding)
- Taking a pro-kinetic drug (a drug that increases GI motility)
What are the modifiable factors that decrease gastric emptying?
- High fat meal
- Heavy exercise
- Lying down on the left side
- Taking a drug that inhibits the vagus nerve (i.e., anticholinergic drugs)
What is an enteric coating?
Drugs with enteric coating are covered with a special coating that prevents their dissolution in the acidic environment of the stomach.
When are drugs with an enteric coating absorbed?
Once the drug passes into the more alkaline duodenum, the enteric coating dissolves and can be absorbed in the small intestine
What is bioavailability?
Bioavailability is the fraction of a dose of drug that reaches the systemic circulation unchanged.
What has a large influence on a drugs bioavailability?
drug formulation
Which drug formulations have the highest bioavailability?
Aqueous solutions and syrups, next suspension and chewable tablet
What is a suspension?
particles of drugs suspended in a liquid (it is not in solution, it is in suspension, so no disintegration phase associated with it)
What drug formulations have the lowest bioavailability?
Lowest: time release; second lowest: enteric coated tablets
What drug formulations have a mid bioavailability?
granules, capsules, compressed tablet (drug must disintegrate and dissolve before being absorbed)
What does it mean to administer a drug sublingually?
to place it under the tongue
Describe sublingual
- Involves placing a drug under the tongue.
- The drug dissolves and is absorbed across the oral mucosa.
- Venous drainage from the oral mucosa is to the superior vena cava. Superior vena cava takes blood to the heart.
- Drugs administered sublingually avoid first pass metabolism through the liver.
- In order to be absorbed drugs must be lipophilic and uncharged.
What does the transdermal route of administration involve?
Involves a drug penetrating the barrier layer of the skin
Describe transdermal
- Not all drugs penetrate the skin.
- The epidermis provides a lipid barrier, therefore drugs must be lipophilic enough to penetrate the skin.
- Drugs must also be relatively hydrophilic in order to dissolve in the extracellular fluid.
- Ideal transdermal preparations have some degree of lipophilicity and some degree of hydrophilicity and are usually small (< 600 Da) molecules.
Transdermal drugs are typically administered as what?
patches, ointments, sprays, and lotions
How does one avoid tolerance when dealing with transdermal drug preparations?
Tolerance may develop unless drug-free period’s are enforced. Typically patches are removed for 6 – 10 hours per day to avoid tolerance.
What is one of the advantages of the transdermal route of administration?
Transdermal administration provides constant plasma drug levels with minimal peaks and troughs.
What factors affect transdermal absorption?
1) Thickness of the skin – Transdermal absorption is inversely proportional to skin thickness.
2) Hydration – Transdermal absorption is increased when the skin is well hydrated.
3) Hair follicles – Provide routes for drugs to bypass the barrier function of the epidermis. In general the greater the number of hair follicles, the greater the transdermal absorption is.
4) Application Area – The greater the application area, the greater the transdermal absorption.
5) Integrity of the barrier – In conditions such as psoriasis, burned or abraded skin, transdermal absorption is increased.
When is the rectal route of administration particularly useful?
When the patient is unconscious or vomiting
Define suppository
a solid medical preparation in a roughly conical or cylindrical shape, designed to be inserted into the rectum or vagina to dissolve.
What are the major disadvantages of the rectal route of administration?
- Incomplete rectal absorption
- Some drugs may actually irritate the rectal mucosa
Approximately 50% of rectally administered drugs bypass what?
the liver (an important site for drug metabolism)
How is a rectal suppository administered?
Administration: The drug is inserted into the rectum as a suppository. The suppository dissolves and the drug crosses the rectal mucosa into the blood.
What is a common route of administration for hospital settings?
Intravenous (IV)
Describe intravenous (IV)
Drug is injected directly into a peripheral vein.
What are the most commonly used veins when administering IV?
Most commonly used veins are those on the back of the hand or the median cubital vein at the elbow although any visible vein may be used.
Define bolus
An IV bolus is a single dose administered over a short time period.
How can intravenous drugs be given?
As a bolus or by an IV drip
How is an IV drip medication administered?
In an IV drip a drug is administered under continuous infusion over a prolonged period. Drugs are typically diluted in a “vehicle” such as saline in an IV bag.
What are the advantages of the IV route of administration?
- No barriers to absorption, bioavailability is 100%.
- Allows precise control of the drug dosage and duration of action.
- Allows administration of poorly soluble drugs that must be diluted in a large volume.
- Allows the injection of drugs that are irritants (i.e. many chemotherapeutic drugs) as they can be injected slowly so they are diluted in the blood.
What are the disadvantages of the IV route of administration?
- Expensive, invasive and inconvenient.
- Drug cannot be removed once injected.
- Risk of infection and fluid overload.
- Risk of injecting wrong formulation (IM formulation sometimes injected IV by accident).
Describe the subcutaneous route of administration
- Drug is injected beneath the skin into the subcutaneous tissue.
- Irritant drugs must not be injected subcutaneously as this will cause severe pain and/or tissue sloughing.
What is the only barrier to absorption when administering a drug subcutaneously
The only barrier to absorption is the capillary wall.
Describe intramuscular (IM) parenteral route of administration
drug is injected directly into muscle tissue
What are the advantages to the IM route of administration?
- Can be used for poorly soluble drugs.
- Can use it to administer depot preparations (preparations in which the drug is absorbed slowly over time).
What are the disadvantages to the IM route of administration?
- Pain/discomfort
- May cause local tissue and/or nerve damage if the injection is done improperly.
What are the primary determinants of rate of absorption with the IM route of administration?
The primary determinants of rate of absorption are blood flow and water solubility.
What are the primary determinants of rate of absorption with the subcutaneous route of administration?
The primary determinants of rate of absorption are blood flow and water solubility.
How is absorption determined with the IM route of administration?
Absorption is determined by the ability of the drug to pass through fenestrations in the capillary wall.
List the factors affecting intramuscular absorption
- Blood flow is different depending on which muscle is used for injection. In general blood flow is deltoid > vastus lateralis> gluteal.
- Exercise increases blood flow and may therefore increase absorption for IM drugs.
- Blood flow may be decreased in heart failure, severe hypotension and hypothermia.
What are the advantages of the pulmonary route of administration?
- Absorption is very rapid (almost instantaneous) due to the large surface area of the lung.
- In the case of pulmonary disease (i.e. asthma), the drug is delivered to its site of action which is a major advantage.
Describe the pulmonary route of administration
Gaseous and volatile drugs inhaled and absorbed into the blood through the pulmonary epithelium (such as with an inhaler)
What is a commonly used class of drugs that are administered by the pulmonary route of administration (aside from drugs administered by inhaler)
general anaesthetics used in surgery are also commonly administered by the pulmonary route of administration
What can bioavailability be influenced by?
1) Drug formulation
2) Route of Administration
3) Degree of Metabolism
