7-27 General Principles of Pharmacology Flashcards
Definition of pharmacology?
Pharmacology - the study of the actions, effects, and disposition (or fate) of drugs in the body. Other related disciples include toxicology
Definition of drug?
Drug = any chemical. Limiting this definition is seldom useful. Medically, any agent used in the treatment or prevention of disease, or prevention of pregnancy.
Definition of pharmacodynamics?
Pharmacodynamics - the study of drug effects and their mechanisms of action. (The study of what drugs do to you).
Definition of pharmacokinetics?
Pharmacokinetics - quantitative descriptions of the time course of drug and metabolite concentrations in plasma, tissue and urine: i.e., drug fate (the study of what your body does to drugs).
Definition of pharmacotherapeutics?
Pharmacotherapeutics (Clinical Pharmacology) - The application of drugs in the prevention, treatment or diagnosis of disease and their use in purposeful alteration of normal functions
Definition of drug action?
Drug Action: Drugs cause changes at the molecular level by interacting with biological macromolecules, i.e., they have a molecular mechanism of action.
Action = biochemical event.
Example: a certain drug blocks a Na+/K+ - ATPase on the cell membrane which ultimately leads to a change in Ca++ flux.
Definition of drug effect?
Drug Effect: Most often, the clinical practitioner is more concerned with the effect of a drug on the body, i.e., a change in a physiological function.
Effect = physiological event.
Example: a certain drug increases the contractility of the heart. Often, we can describe the effects (both bad and good) of a drug in detail, but have incomplete information to describe its molecular mechanism of action.
What is a therapeutic window?
a “window” or range of plasma drug concentration, not too little and not too much drug, to obtain optimal therapeutic effects
What is the MEC?
Minimum Effective Concentration
In plasma or other tissue, fluid, or compartment
What does the dose have to do with the effectiveness of a drug? In a basic sense, how does changing the dose change the effect of the drug?
Dose: The actions and effects of drugs are dose-dependent.
- There is some dose below which no effect is observed
- There is some dose above which no greater effect is observed
- There is a dose‑response relationship
- There is a threshold concentration of drug or minimum effective concentration (MEC) in the plasma or other tissue fluid or compartment.
There is a maximum tolerated concentration of drug above which toxicity occurs.
What must a physician do in order to achieve the therapeutic window for a drug? What 4 factors will make this up?
A key goal of therapy is to choose the right drug for each individual patient, and to administer the drug in the correct quantity (dose) over the correct dosing interval. To achieve this goal the clinician must understand the factors that determine:
Absorption of the drug.
Distribution of the drug throughout the tissues.
Elimination of the drug from the body.
Drug action and effect.
Why are onset and termination important events in a graph of a therapeutic window?
Indicate start and end point of desired therapeutic range
Major objective of drug therapy is to keep plasma conc. above this range
What limits percutaneous administration of drugs?
keratinous nature of skin severely limits absorption
What is transdermal/percutaneous delivery good for treating?
- Used to treat dermatological conditions or to deliver slow, sustained systemic absorption.
- Transdermal patches or via creams and ointments (percutaneous) - some drugs delivered through skin patches, e.g., nicotine for smoking cessation, scopolamine for motion sickness, nitroglycerin for angina.
How would you describe percutaneous absorption of drugs? What kinds of drugs do well with this delivery system? What other local routes are similar?
1.Absorption is slow and sustained.
Lipid soluble drugs, e.g., steroids, penetrate skin much more readily than water soluble drugs.
2.Other local routes would include eyedrops, nasal sprays, etc.
How many enteral routes are there? What are they? What does enteral mean?
. Enteral - means via the gastrointestinal tract.
- Sublingual (SL)
- Oral (per os or PO)
- Rectal (rect)
How would you describe the absorption rate of SL administration? Why?
· Warm moist environment for rapid drug dissolution
· Rich blood flow, close to mucosal surface
· More rapid absorption than oral
What are the advantages of SL administration? Disadvantages?
· The unpleasant taste of most drugs limits usefulness of sublingual approach.
· Drug absorbed from sublingual sites is not carried directly to the liver and thus no “first pass” metabolism occurs. Compare this to oral administration.
What is the most common route of administration?
PO - oral
What are the barriers to oral administration? Where are most enteral drugs absorbed?
Barriers to Absorption
After swallowing, the drug may be absorbed from the stomach and the intestine, but the extent of absorption from the intestine is more significant for most drugs.
· Two barriers for drug to cross are
1) epithelial cells - because of tight junctions between cells, drug molecules must diffuse through these cells.
2) capillary wall.
What affects the absorption pattern of most orally administered drugs?
Absorption Pattern
· The rate and extent of absorption is high variable among patients because of differences in:
1) gastric and intestinal pH
2) gastric emptying time
3) presence or absence of food
4) coadministration of other drugs
What are the advantages of PO for drugs?
Advantages
By far, oral is the most used route of administration
Convenient for both patient and clinician
Safe, because drug recall is possible by vomiting or lavage
Inexpensive
What are the disadvantages of PO for drugs?
In general, slow absorption (for water soluble drugs especially)
Variability between patients and at different times for same patient.
Some drugs, e.g., penicillin G, are inactivated in GI tract.
First-pass metabolism by the liver inactivates a significant proportion of many drugs. This is a major source of variability.
Requires conscious, cooperative patient.
G.I. irritation can occur
Why is first-pass metabolism such an important concept?
Inactivates a significant proportion of many drugs, and is a major source of variability of drugs
What is the advantage of rectal administration of a drug?
a suppository may be used when the oral route is not feasible, e.g., vomiting patient.
What does parenteral mean?
Parenteral = non-oral routes of administration
What are the major types of parenteral administration?
IV
Intra-arterial injection
Subcu injection - SQ
IM
Percutaneous
Inhalation
Intranasal
What are the advantages of IV delivery? How would you describe absorption?
No barriers to absorption; drug placed directly into the venous system.
Rapid onset and subsequent control of drug concentration is possible.
Large fluid volumes can be delivered.
What are the disadvantages of IV drug delivery?
Unsuitable for non-aqueous solution.
Disadvantages include high cost, difficulty, inconvenience, irreversibility (no recall of drug is possible once injected), possible fluid overload, infection, embolism
What is intra-arterial injection used for?
Mostly used for diagnostic procedures
How would you describe absorption for SQ? How does this affect the action of a drug?
Lower blood flow in SQ regions leads to slower absorption of drug.
Slower absorption allows for sustained action.
Time course of absorption dictated by blood flow and drug solubility.
What kinds of drugs are good for SQ injections?
Allows injection of drugs poorly soluble in water and depot preparations.
Most all protein drugs (antibodies for example) must be given SQ or IV
Examples: insulin for diabetes; epinephrine for emergencies.
What are the disadvantages of SQ injection?
Drawbacks include discomfort, inconvenience, and potential for injury.
What are the barriers to absorption with IM?
Only barrier to absorption is capillary wall with large spaces between cells (fenestrations), so drugs pass with ease into the blood stream.
What is the time course of absorption for IM?
Time course of absorption is dictated primarily by water solubility of the drug and blood flow to the site of injection.
Generally, high blood flow in muscle.
Drugs that are highly soluble in water will be absorbed rapidly (10 - 30 minutes) whereas drugs that are poorly soluble in water will be absorbed more slowly
What kinds of drugs is IM partcularly useful for?
IM allows injection of oily or particulate matter, depot preparations, or drugs poorly absorbed or intolerable orally.
Example: benzathine penicillin G, a depot preparation of penicillin, can release effective amounts of penicillin for a month or more after a single IM injection.
Penicillin G itself would be absorbed and excreted in less than one day.
What are the disadvantages of IM?
Pain and inconvenience
What drugs is the inhalation route good for?
For localized application of drug to the lungs. Systemic absorption of drug is intended to be limited so as to minimize systemic side effects.
Examples include: corticosteroids and albuterol for the treatment of asthma or COPD, anesthetic agents.
What factors affect absorption in the lungs? What medical applications use this route of administration?
Very large surface area for drug absorption.
Particle size and technique very important.
Especially important in therapy of respiratory diseases.
Inhalation for anesthesia.
What is the intranasal route used for?
7.Intranasal
Used to treat upper respiratory tract, e.g., rhinitis.
Significant amount of drug swallowed.
What are some other routes of administration not discussed?
7.Other routes of administration:
vaginal suppositories, intraocular, epidural (regional anesthesia), intrathecal (CNS infections, pain, tumors), intraperitoneal, intra-articular (treat afflicted joint or synovium).
What is the definition of absorption?
Absorption definition: the movement of a drug from its site of administration into the blood.
What is the difference between rate and extent of absorption?
The rate of absorption determines how soon effects will begin.
The amount (extent) of absorption helps determine how intense the effects will be.
Name 7 factors that influence drug absorption.
- Rate of drug dissolution
- Concentration of the drug
- Blood flow
- Size of the surface absorbing it
- Lipid solubility
- pH
- Condition of absorbing surface
Why does drug dissolution rate affect drug absorption?
Rate of Drug Dissolution - before a drug can be absorbed it must first be dissolved. Drug formulations that allow rapid dissolution have a faster onset than drug formulated for slow dissolution.
Drug that is dissolved, i.e., free in solution and not bound to protein (or food, etc) is free to diffuse across epithelial cells and capillary walls
How does the physical form of a drug affect the rate of dissolution?
· The dosage form (physicochemical state) affects the rate of dissolution.
a. Many drugs can exist as a free acid or base, or salt
b. Particle size - the smaller the size the faster it dissolves.
c. Solid vs. liquid forms (compare tablets vs. capsules vs. suspensions, etc.)
d. Sustained release or prolonged action forms are prevalent
