GENERAL PRINCIPLES OF DRUG ACTION

...for tablet / capsules

 Pharmaceutic
 Pharmacokinetics
 Pharmacodynamics
...for parenteral drugs
 Pharmacokinetics
 Pharmacodynamics
I. Pharmaceutic Phase (drug dissolution)
 disintegration. breakdown of a tablet into smaller particles
 dissolution. dissolving of the smaller particles in the GI fluid before absorption
- rate of dissolution. the time it takes the drug to disintegrate and to dissolve
- excipients (fillers & inert substances). allow the drug to take on a particular size and shape and
to enhance drug dissolution
- drugs in acidic fluids with a pH of 1 or 2 are disintegrated and absorbed faster rather than in
alkaline fluids
- alkaline drugs would become ionized and have difficulty crossing cell membrane barriers
- very young and older adults have less gastric acidity
- enteric-coated drugs resist disintegration in the gastric acid of the stomach, until the drug
reaches the alkaline environment of the small intestine
- enteric-coated tablets or capsules and sustained-release (beaded) capsules should not be
crushed ; crushing would alter the place and time of absorption of the drug
- food in the GI tract may interfere with the dissolution of certain drugs, however, it serves as a
protectants necessary to dilute the drug concentration, avoiding irritation in the gastric mucosa
II. Pharmacokinetic Phase (drug action). study of how medications enter the body, reach their
site of action, metabolize, and exit the body
a. absorption. process by which a drug passes into the bloodstream
i. factors affecting drug absorption
1. route of administration
 correct form of the drug must be given by the route intended
 some drugs are absorbed by tissues before they reach the stomach
(nitroglycerin administered sublingually) ; however, if swallowed,
the drug will undergo on a first-pass effect (hepatic first pass) by the
liver, where it will be destroyed. This requires higher oral doses in
order to achieve the appropriate effect
 IV ministration is the route of choice for rapid action
 rectum ministration is used only when other routes are unavailable
or when the intended action is localized to the rectum or sigmoid
colon
 skin medications have slow absorption
  medications placed on mucous membranes and respiratory airways
are quickly absorbed
 oral medications have slow overall rate of absorption, and absorbed
mainly in small intestine through the action of the extensive mucosal
villi ; reduced villi equates decreased absorption
2. ability of the medication to dissolve
 body absorbs liquid solutions and suspensions more readily than
tablets or capsules
 some drugs intended to be absorbed slowly are suspended in low-
solubility medium (oil)
 medications that are basic are not absorbed before reaching the
small intestine
 acid medium in the stomach which vary according to the time of the
day, foods ingested, use of antacid medications, and the age of the
client
 protein-based drugs such as insulin and growth hormones are
destroyed in the small intestine by digestive enzymes
3. blood flow to the site of administration
 application of heat increases blood flow to the area, thus absorption
is accelerated
 injection of an epinephrine (vasoconstrictor) can slow absorption of
other drugs
 poor circulation to the stomach as a result of shock, vasoconstrictor
drugs, or disease hampers absorption
 exercise can decrease blood flow by causing more blood to flow to
the peripheral muscle, thereby decreasing blood circulation to the
GI tract
4. body surface area
 when a medication comes in contact with a large surface area, the
medication is absorbed at a faster rate
 majority of medications are absorbed in the small intestine rather
than the stomach
5. lipid solubility of a medication
 GI membrane is composed mostly of lipid and protein, so drugs that
are lipid soluble pass rapidly '
 large particles pass through the cell membrane if they are
nonionized
 highly-lipid soluble medications easily cross the cell membrane and
are absorbed quickly
 foods can delay the dissolution of some drugs as well as their
passage into the small intestine ; food can also combine with
molecules of certain drugs, thereby preventing their absorption
through the change in molecular structure that have occurred
 pain, stress, and foods that are solid, hot, or high in fat can slow
gastric emptying time, so the drug remains in the stomach longer
 calcium carbonate and many of the antifungals need an acidic
environment to achieve greater drug absorption, thus food can
stimulate the production of gastric acid
 drugs that are lipid-soluble and nonionized are absorbed faster that
water-soluble and ionized drugs
 6. ability of the drug to enter the membrane
 water-soluble drugs need a carrier, either enzyme or protein, to
pass through the membrane
 weak acid drugs (aspirin) are less ionized in stomach, passing the
lining of the stomach easily and rapidly
 an infant's gastric secretions have a higher pH (alkaline) than those
of adults, thus infants can absorb more penicillin
ii. processes
1. passive
 occurs mostly by diffusion (movement from higher conc. To lower
conc.) ; drug doesn't require energy
2. active
 requires a carrier such as an enzyme or protein to move the drug
against a concentration gradient ; energy is required
3. pinocytosis
 a process by which cells carry a drug across their membrane by
engulfing the drug particles
iii. bioavailabity. the percentage of the administered drug dose that reaches the
systemic circulation ; for the oral route of drug administration, bioavailability occurs
after absorption and first-pass metabolism ; the percentage of bioavailability for the
oral route is always less than 100%, but for the IV route it is 100%
1. factors that alter bioavailability
 the drug form
 route of administration
 GI mucosa and motility
 food and other drugs
 changes in liver metabolism caused by liver dysfunction or
inadequate hepatic blood flow
b. distribution. transportation of a drug from its site of absorption to its site of action ; process
by which the drug becomes available to body fluids and body tissues
i. factors affecting drug distribution
1. circulation
 how fast it reaches the site depends on the vascularity of the
various tissues and organs
 conditions that limit blood flow or blood perfusion (congestive heart
failure) inhibit the distribution of a medication
2. membrane permeability
 medication has to pass through all of the organ's tissues and
biological membranes
 blood-brain barrier allows only fat-soluble medications ; cns
infections often require treatment with antibiotics injected directly
into the subarachnoid space in the spinal cord
 placental membrane also has a non-selective barriers to
medications
3. protein binding
 the degree to which medications bind to serum proteins such as
albumin affects medication distribution
 unbound or "free" medication is the active form of the medication
 drugs bound to proteins cannot leave the systemic circulation to get
to the site of action
  when two highly protein-bound drugs are given concurrently, and
when a low serum protein level decreases (older adults
experiencing from hypoalbuminemia and patients with liver or
kidney disease and malnourished) the number of protein-binding
sites and can cause an increase in the amount of free drug in the
plasma, drug toxicity may then result... a decreased drug dose is
needed as there is not as much protein circulated for the drug to
bind to
 clients who are old, who have liver disease and malnutrition have a
decrease in albumin in the bloodstream. consequently, they are at
risk for an increase in medication activity and/or toxicity
 most anticonvulsants bind primarily to albumin ; some basic drugs
such as antidysrhythmics (e.g., lidocaine, quinidine) bind mostly to
globulins
ii. volume of drug distribution (Vd) is dependent on drug dose and its concentration
in the body ; drugs with a larger volume of drug distribution have a longer half-life
and stay in the body longer
iii. nurse's additional responsibilities in administering medications
1. checking the protein-binding percentage of all drugs
2. check the patient’s plasma protein and albumin levels, because a decrease
in plasma protein (albumin) decreases protein-binding sites
3. check for abscesses, exudates, body glands, and tumors for it may hinder
drug distribution ; antibiotics do not distribute well at abscess and exudate
sites
4. check which drugs may cross into breast milk before administering to a
lactating patient
c. metabolism (biotransformation). how the body chemically modifies the drug
d. excretion (elimination). how the body gets rid of the drug.
III. Pharmacodynamics. study of the effects of drugs in the