nates weak base drugs; alkaline urine (8.0) eliminates weak acid drugs. The pH of
urine can be altered to increase the elimination of certain drugs. For example, urine
can be made more alkaline by giving the patient sodium bicarbonate or made more
acidic by giving the patient high doses of vitamin C or ammonium chloride.
Kidney disease decreases the glomerular filtration rate (GFR) and thereby
reduces the quantity of drugs that can be eliminated by the kidneys. This can
result in drug toxicity. A similar effect can be caused by a decrease in bloodflow
to the kidneys.
Kidney function is tested by the creatinine clearance test. A decrease in GFR
causes an increase in creatinine in serum and a decrease in creatinine in urine.
The results of the creatinine clearance test vary with age and whenever there is
decreased muscle mass.
In some situations, it is important to reduce the excretion of a drug to prolong
the drug’s therapeutic effect, such as with penicillin. Giving the patient another
drug, such as Probenecid, blocks excretion of penicillin.
Drugs can be excreted artificially through the use of dialysis, which is a com-
mon treatment in certain drug overdoses. Drugs that are excreted by the kidneys
can be eliminated using hemodialysis. These drugs include stimulants, depres-
sants, and some non-narcotic analgesics.
Drugs that are metabolized by the liver are secreted into bile and then passed
through the intestines and eliminated in feces. During this process, the blood-
stream might reabsorb fat-soluble drugs and return them to the liver where they are
metabolized and eliminated by the kidneys. This is called the enterohepatic cycle.
The lungs eliminate drugs that are intact and not metabolites such as gases
and anesthetic drugs. The rate at which these drugs are eliminated corresponds
to the respiratory rate. Some drugs, such as ethyl alcohol and paraldehyde, are
excreted at multiple sites. A small amount is excreted by the lungs and the rest
by the liver and the kidneys. Volatile drugs such as anesthetics and drugs that are
metabolized to CO 2 and H 2 0, are excreted through the lungs.
Sweat and salivary glands are not a major route of drug elimination because
elimination depends on the diffusion of lipid-soluble drugs through the epithe-
lial cells of the glands. However, side effects of drugs, such as rashes and skin
reactions, can be seen at these sites. Some intravenously administered drugs are
excreted into saliva and cause the patient to taste the drug. Eventually, drugs that
are excreted into saliva are swallowed, reabsorbed, and eliminated in urine.
Many drugs or their metabolites are excreted in mammary glands. These
include narcotics such as morphine and codeine. Diuretics and barbiturates,
which are weak acids, are less concentrated in breast milk. However, even
small amounts of drugs can accumulate causing an undesirable effect on an
infant receiving breast milk.(^32) CHAPTER 2 Drug Action and Drug Interactions