Effects of Nutritional Status on Drugs
The presence of nutritional abnormalities may have an effect on drugs. Drug
dosages may need adjustment based on actual body weight for some drugs. Other
drugs may need to be dosed differently in obese, normal, and underweight patients,
based on actual, ideal, or an adjusted body weight corrected for lean body mass.
Somatic protein status may affect the dosing of medications that bind to somatic
protein.
Effects of Drugs on Nutritional Status
The converse effect may also be observed. Some drugs will have an effect on a
patient’s nutritional status. The mechanisms for these effects are varied and are
usually due to drug side effects. Medications may have direct effects on the gastrointestinal
tract (GIT), which can affect food ingestion. Nonsteroidal antiinflammatory
agents, commonly used to treat arthritis, including aspirin, can cause irritation
of the upper gastrointestinal mucosa and even cause ulcers. This can depress appetite
and produce weight loss. Chemotherapeutic agents used to treat cancer can affect
rapidly growing tissues, particularly the lining of the GIT. Nausea is a common side
effect and will interfere with eating. Some patients develop oral and esophageal
lesions that cause pain upon chewing and swallowing (odynophagia), which limits
oral intake. Antibiotics can suppress commensal bacteria, and this may result in
overgrowth of other organisms such as Candida albicans. Overgrowth in the GIT
may produce malabsorption and, subsequently, diarrhea. Overgrowth in the mouth
may result in candidiasis or thrush, which can reduce oral intake. Drug-related
dysgeusia may result in alteration of taste perceptions and avoidance of certain foods.
Many drugs reduce salivation and cause dryness of the mucus membranes. This may
also inhibit oral intake. Nausea, vomiting, diarrhea, and constipation are ubiquitous
side effects associated with most medications and even with placebo medications.
Again, oral intake of food may be reduced due to these effects.
Some drugs have a direct effect on digestion. Orlistat (Xenical®) interferes with
the digestion and subsequent absorption of fat intentionally to enhance weight loss.
Pancreatic enzymes enhance digestion for patients with limited amounts of digestive
enzymes. Several types of drugs interfere with hydrochloric acid production, but
none have demonstrated a significant effect on macronutrient absorption. Increasing
the gastric pH may affect absorption of weakly acidic drugs, as well as iron and
vitamin B12. Intrinsic factor requires an acidic pH to bind with vitamin B12. Without
the acidic pH, B12 deficiency can have an irreversible effect on brain function if
prolonged without treatment.
Some drugs have a direct effect on appetite. The amphetamines and their derivatives
were long used for weight loss. Unfortunately, side effects and transient results
for most patients have limited their usefulness. Sibutramine (Meridia®) has both an
appetite suppressing effect and a mild antidepressant effect and is approved by the
Food and Drug Administration (FDA) for weight loss. These drugs are discussed in
more detail in the Chapter 11, Obesity and Appetite Drugs, and Chapter 7, Gastrointestinal
and Metabolic Disorders and Drugs.
Dronabinol (Marinol®), also known as THC (from tetrahydracannabinols), the
active principle in cannabis, is also used as an appetite stimulant. Oxandrolone
(Oxandrin®) is an anabolic steroid approved for weight gain. Megesterol (Megace®),
a progestin used to treat certain types of cancer, is also indicated to enhance appetite.
Cyproheptadine (Periactin®) has been used to enhance appetite, although this is an
off-label use and not an FDA-approved indication.
Besides drugs specifically indicated to effect changes in appetite, some drugs may
affect appetite as a side effect. Several antidepressants have been observed to consistently
increase or decrease appetite. When these drugs are prescribed, their relative
side-effect profiles in relation to weight change may make one or another a preferred
agent for an individual who would benefit from an increase or decrease in weight.
Showing posts with label Drug Interactions: Basic Concepts. Show all posts
Showing posts with label Drug Interactions: Basic Concepts. Show all posts
Monday, September 19, 2011
Types and Mechanisms of Drug–Drug and Drug–Nutrient Interactions
Now that basic information about pharmaceutics, pharmacokinetics, and pharmacodynamics
has been presented, drug interactions can be appreciated. The types
of interactions that can occur include potentiation, inhibition, alteration of absorption,
direct chemical interaction, alteration of metabolism, alteration of distribution,
competition at the site of action, and alteration of elimination.
Potentiation can be additive or synergistic and refers to an increase in the effect
of one drug as a result of a second drug or nutrient. The increased pain relief
experienced when acetaminophen is combined with a narcotic (Tylenol #3®, Vicodin
®, Lortabs®) illustrates a positive example of this effect. Adding bananas, potatoes,
and other foods rich in potassium to the diet at the same time a patient is taking a
prescribed potassium supplement (e.g., Kaon-Cl®) would cause an additive
food–nutrient effect with a therapeutic purpose.
Inhibition refers to the decrease of effect when two substances have opposite
effects on a process. The decreased anticoagulant effect of warfarin (Coumadin®)
seen when vitamin K intake is increased is a negative example of this type of
interaction. Warfarin therapy frequently requires adjustment because of such inhibition,
especially when patients suddenly increase their intake of green leafy vegetables
rich in vitamin K. This is a real hazard for patients who are avid gardeners and whose
vitamin K intake can vary drastically from season to season. Caffeine, a nonnutritive
food constituent, may oppose the pharmacological effect of tranquilizers.
Decreased absorption of nonheme iron from food is seen when antacids are
taken on a chronic basis with iron-containing foods. This may result in iron deficiency
anemia with its characteristic microcytic, hypochromic, red blood cells.
Grapefruit juice will increase the bioavailability of cyclosporine (Sandimmune®).
This will decrease the potential for organ rejection by recipients of organ transplants,
but may also increase the potential for cyclosporine toxicity. Deliberate ingestion
of grapefruit to decrease cytosporine doses is not advised due to the unpredictable
nature of this interaction.
An example of a direct chemical interaction is the reaction between dextrose
and amino acids in parenteral nutrition. This is the same reaction seen when meats
are cooked and is known as the Maillard reaction. The substrates involved tend to
reduce sugars and amino acids, and these factors limit the storage time for parenteral
nutrition solutions. The reaction results in a darkening of the solution.
Alterations of metabolism may also occur. This generally occurs in the liver but
may also be peripheral. Many enzymes responsible for drug metabolism are part of
the cytochrome P-450 family. St. John’s Wort induces an increase in the activity of
one P-450 isoform termed CYP 3A4. This can result in decreased levels of cyclosporine,
indinavir, and oral contraceptives. This drug interaction with St. John’s Wort
demonstrates the potential for herbal products to participate in significant herb-drug
interactions when used in combinations with conventional medications.
Alterations of distribution may occur when drugs are protein-bound. Binding to
protein will generally reduce the amount of free drug. Decreased amounts of free
drug may decrease the activity of the drug and also decrease the metabolism and
elimination of the drug. In this type of interaction, one substance that is bound
displaces another bound substance from a binding site. The effect, if any, may be
transient because the increased effect of the free drug may be countered by increased
metabolism and excretion of the free drug. Some significance is possible if the
second agent is taken on an intermittent basis. A nontransient example of this is the
need to adjust measured serum total calcium levels based on serum albumin levels.
Only ionized Ca++ is physiologically active. Most clinicians do not have rapid access
to ionized calcium levels; total serum calcium levels are commonly available.
Because each gram of albumin in the bloodstream will bind with approximately 0.8
mg of calcium, serum with a lower than normal albumin concentration will have a
lower amount of bound calcium. This will result in a lower total calcium level, even
if the ionized (unbound) calcium is normal. Many clinicians calculate the corrected
calcium level by subtracting the patient’s albumin level from either 4.0 g/dL (midpoint
of normal range) or 3.5 g/dL (low normal albumin), then multiplying this by
0.8 mg/g, and adding this factor to the total serum calcium.
An example of competition at the site of action is best illustrated by the effect
of naloxone (Narcan®) on narcotics. Naloxone reverses the effects of narcotics at a
receptor site. This can be useful after surgery to reverse the effects of intraoperative
narcotics. Naloxone is also useful in the treatment of narcotic overdoses. Caution is
needed if an individual is dependent on narcotic drugs because naloxone can cause
withdrawal symptoms. This interaction is further modified by drug metabolism.
Naloxone is eliminated faster than the narcotics that it affects. It is, therefore,
necessary to monitor a patient who has received a narcotic overdose even after he
appears to have recovered. The naloxone may wear off, and then the narcotic effect
will recur.
Renal excretion may also be involved in interactions between drugs and nutrients.
The classic example is the effect of most diuretics (e.g., loop diuretics and
thiazide diuretics) on potassium. These diuretics result in increased loss of potassium
in the urine. This may require pharmacological or nutritional supplementation of
potassium intake.
Drug Interaction Risk Factors and the Unknown
By now, the potential for unexpected effects as a result of interactions between
a drug and other drugs or foods has been well established. The risk of having drug
interactions will be increased as the number of medications taken by an individual
increases. This also implies a greater risk for the elderly and the chronically ill, as
they will be using more medications than the general population. Risks also increase
when a patient’s regimen originates from multiple prescribers. Filling all prescriptions
in a single pharmacy may decrease the risk of undetected interactions.
The method for getting new drugs approved has increased in efficiency in recent
years. Drug studies done to seek approval of a new agent are often done on “ideal”
populations, that is, individuals with a single ailment. This highlights the effect of
the drug being studied. As a result, few subjects are taking other medications. Once
the drug is approved, it is used by a less select group of patients. As a result, the
full extent of drug interaction potential may be only recognized after the drug is
widely available. In addition, medical practice is highly individualized and managed
based on specific patient response. This may delay or prevent recognition of interactions.
Taking a thorough medical, drug, and nutritional history from patients when
they seek medical attention may help identify drug–drug and drug–nutrient interactions.
has been presented, drug interactions can be appreciated. The types
of interactions that can occur include potentiation, inhibition, alteration of absorption,
direct chemical interaction, alteration of metabolism, alteration of distribution,
competition at the site of action, and alteration of elimination.
Potentiation can be additive or synergistic and refers to an increase in the effect
of one drug as a result of a second drug or nutrient. The increased pain relief
experienced when acetaminophen is combined with a narcotic (Tylenol #3®, Vicodin
®, Lortabs®) illustrates a positive example of this effect. Adding bananas, potatoes,
and other foods rich in potassium to the diet at the same time a patient is taking a
prescribed potassium supplement (e.g., Kaon-Cl®) would cause an additive
food–nutrient effect with a therapeutic purpose.
Inhibition refers to the decrease of effect when two substances have opposite
effects on a process. The decreased anticoagulant effect of warfarin (Coumadin®)
seen when vitamin K intake is increased is a negative example of this type of
interaction. Warfarin therapy frequently requires adjustment because of such inhibition,
especially when patients suddenly increase their intake of green leafy vegetables
rich in vitamin K. This is a real hazard for patients who are avid gardeners and whose
vitamin K intake can vary drastically from season to season. Caffeine, a nonnutritive
food constituent, may oppose the pharmacological effect of tranquilizers.
Decreased absorption of nonheme iron from food is seen when antacids are
taken on a chronic basis with iron-containing foods. This may result in iron deficiency
anemia with its characteristic microcytic, hypochromic, red blood cells.
Grapefruit juice will increase the bioavailability of cyclosporine (Sandimmune®).
This will decrease the potential for organ rejection by recipients of organ transplants,
but may also increase the potential for cyclosporine toxicity. Deliberate ingestion
of grapefruit to decrease cytosporine doses is not advised due to the unpredictable
nature of this interaction.
An example of a direct chemical interaction is the reaction between dextrose
and amino acids in parenteral nutrition. This is the same reaction seen when meats
are cooked and is known as the Maillard reaction. The substrates involved tend to
reduce sugars and amino acids, and these factors limit the storage time for parenteral
nutrition solutions. The reaction results in a darkening of the solution.
Alterations of metabolism may also occur. This generally occurs in the liver but
may also be peripheral. Many enzymes responsible for drug metabolism are part of
the cytochrome P-450 family. St. John’s Wort induces an increase in the activity of
one P-450 isoform termed CYP 3A4. This can result in decreased levels of cyclosporine,
indinavir, and oral contraceptives. This drug interaction with St. John’s Wort
demonstrates the potential for herbal products to participate in significant herb-drug
interactions when used in combinations with conventional medications.
Alterations of distribution may occur when drugs are protein-bound. Binding to
protein will generally reduce the amount of free drug. Decreased amounts of free
drug may decrease the activity of the drug and also decrease the metabolism and
elimination of the drug. In this type of interaction, one substance that is bound
displaces another bound substance from a binding site. The effect, if any, may be
transient because the increased effect of the free drug may be countered by increased
metabolism and excretion of the free drug. Some significance is possible if the
second agent is taken on an intermittent basis. A nontransient example of this is the
need to adjust measured serum total calcium levels based on serum albumin levels.
Only ionized Ca++ is physiologically active. Most clinicians do not have rapid access
to ionized calcium levels; total serum calcium levels are commonly available.
Because each gram of albumin in the bloodstream will bind with approximately 0.8
mg of calcium, serum with a lower than normal albumin concentration will have a
lower amount of bound calcium. This will result in a lower total calcium level, even
if the ionized (unbound) calcium is normal. Many clinicians calculate the corrected
calcium level by subtracting the patient’s albumin level from either 4.0 g/dL (midpoint
of normal range) or 3.5 g/dL (low normal albumin), then multiplying this by
0.8 mg/g, and adding this factor to the total serum calcium.
An example of competition at the site of action is best illustrated by the effect
of naloxone (Narcan®) on narcotics. Naloxone reverses the effects of narcotics at a
receptor site. This can be useful after surgery to reverse the effects of intraoperative
narcotics. Naloxone is also useful in the treatment of narcotic overdoses. Caution is
needed if an individual is dependent on narcotic drugs because naloxone can cause
withdrawal symptoms. This interaction is further modified by drug metabolism.
Naloxone is eliminated faster than the narcotics that it affects. It is, therefore,
necessary to monitor a patient who has received a narcotic overdose even after he
appears to have recovered. The naloxone may wear off, and then the narcotic effect
will recur.
Renal excretion may also be involved in interactions between drugs and nutrients.
The classic example is the effect of most diuretics (e.g., loop diuretics and
thiazide diuretics) on potassium. These diuretics result in increased loss of potassium
in the urine. This may require pharmacological or nutritional supplementation of
potassium intake.
Drug Interaction Risk Factors and the Unknown
By now, the potential for unexpected effects as a result of interactions between
a drug and other drugs or foods has been well established. The risk of having drug
interactions will be increased as the number of medications taken by an individual
increases. This also implies a greater risk for the elderly and the chronically ill, as
they will be using more medications than the general population. Risks also increase
when a patient’s regimen originates from multiple prescribers. Filling all prescriptions
in a single pharmacy may decrease the risk of undetected interactions.
The method for getting new drugs approved has increased in efficiency in recent
years. Drug studies done to seek approval of a new agent are often done on “ideal”
populations, that is, individuals with a single ailment. This highlights the effect of
the drug being studied. As a result, few subjects are taking other medications. Once
the drug is approved, it is used by a less select group of patients. As a result, the
full extent of drug interaction potential may be only recognized after the drug is
widely available. In addition, medical practice is highly individualized and managed
based on specific patient response. This may delay or prevent recognition of interactions.
Taking a thorough medical, drug, and nutritional history from patients when
they seek medical attention may help identify drug–drug and drug–nutrient interactions.
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