Lecture 3 part 2 Flashcards
What are the sites of site drug interaction ?
Therefore, the kidney and the liver are very important sites of potential drug interactions. Some drugs are able to reduce or increase the metabolism of other drugs by the liver or their elimination by the kidney
Site of absorption During distribution At receptor or target organ Metabolism Enzyme inhibition Enzyme induction excretion
Risk Factors for Drug
Interactions
High Risk Patients
Elderly, young, very sick, multiple disease
Multiple drug therapy
Renal, liver impairment
High Risk Drugs
Narrow therapeutic index drugs
Recognised enzyme inhibitors or inducers
Some drugs with a low
therapeutic index
Lithium Digoxin
Carbamazepine Cyclosporin
Phenytoin Phenobarbitone
Theophylline (Aminophylline) Warfarin
Food Drug interaction
Food-Drug Interaction
Drug-nutrient interaction: the result of the
action between a drug and a nutrient that
would not happen with the nutrient or the
drug alone
Food-drug interaction: a broad term that
includes drug-nutrient interactions and the
effect of a medication on nutritional status
For example, a drug that causes chronic
nausea or mouth pain may result in poor
intake and weight loss
A drug-food interaction occurs when your food and medicine interfere with one another.
Therapeutic Importance
Therapeutically important interactions are those that: Alter the intended response to the medication Cause drug toxicity Alter normal nutritional status
Patients at Risk for FoodNutrient Interactions
Patient with chronic disease Elderly Fetus Infant Pregnant woman Malnourished patient Allergies or intolerances
Malnutrition Effect on Drugs
Low albumin levels can make drugs more potent by
increasing availability to tissues
–Lower doses often recommended for persons
with low albumin
–Warfarin and phenytoin are highly protein
bound in blood; ↓ albumin can result in poor seizure
control (phenytoin) or hemorrhage (warfarin)
nBody composition: obese or elderly persons have a
higher ratio of adipose tissue; fat soluble drugs may
accumulate in the body ↑ risk of toxicity
Food/Nutrient Effects on
Drugs
Absorption
–Presence of food and nutrients in
intestinal tract may affect absorption of
drug
–Antiosteoporosis drugs Fosamax or
Actonel: absorption negligible if given with
food; ↓ 60% with coffee or orange juice
Absorption of iron from supplements ↓↓ 50% when taken with food Best absorbed when taken with 8 oz of water on empty stomach Food may ↓↓ GI upset If take with food, avoid bran, eggs, fiber supplements, tea, coffee, dairy products, calcium supplements
Metabolism - Food nurtinet effect on drug
Metabolism
Changes in diet may alter drug action
Theophylline: a high protein, low CHO diet can
enhance clearance of this and other drugs
Grapefruit/juice: inhibits the intestinal metabolism
(cytochrome P-450 3A4 enzyme) of numerous drugs
(calcium channel blockers, HMG CoA inhibitors, antianxiety agents) enhancing their effects and
increasing risk of toxicity; may interfere with the
absorption of other drugs
Grapejuice on Metabolism
Grapefruit Inhibits Metabolism of
Many Drugs
Inactivates metabolizing intestinal enzyme
resulting in enhanced activity and possible
toxicity
Effect persists for 72 hours so it is not
helpful to separate the drug and the
grapefruit
Many hospitals and health care centers
have taken grapefruit products off the
menu entirely
in which it inhibits the first-pass metabolism of the CYP 3A4 substrates leading to an increase in Cmax and area under the concentration time curve (AUC).
Grapefruit juice acts by inhibiting presystemic drug metabolism mediated by CYP3A isoforms in the small bowel. The interaction appears particularly relevant for medications with at least a doubling of plasma drug concentration or with a steep concentration-response relationship or a narrow therapeutic index.
Drugs known to interact with
grapefruit juice
Anti-hypertensives (filodipine, nifedipine, imodipine,
nicardipine, isradipine)
Immunosuppressants (cyclosporine, tacrolimus)
Antihistamines (astemizole)
Protease inhibitors (saquinavir)
Lipid-Lowering Drugs (atorvastatin, lovastatin,
simvastatin)
Anti-anxiety, anti-depressants (buspirone,
diazepam, midazolam, triazolam, zaleplon,
carbamazepine, clomipramine, trazodone
Food/Nutrient Effects on Drugs - EXCRETION
Excretion
—Patients on low sodium diets will reabsorb
more lithium along with sodium; patients on
high sodium diets will excrete more lithium
and need higher doses
—Urinary pH: some diets, particularly
extreme diets, may affect urinary pH,
which affects resorption of acidic and
basic medications
Food/Nutrient Effects on Drug
Action: MAOIs
Monoamine oxidase inhibitor
It occurs naturally in the body, and it’s found in certain foods. Medications called monoamine oxidase inhibitors (MAOIs) block monoamine oxidase, which is an enzyme that breaks down excess tyramine in the body. Blocking this enzyme helps relieve depression.
Monoamine oxidase inhibitors (MAOI)
interact with pressor agents in foods
(tyramine, dopamine, histamine)
Pressors are generally deaminated rapidly
by MAO; MAOIs prevent the breakdown of
tyramine and other pressors
Significant intake of high-tyramine foods
(aged cheeses, cured meats) by pts on
MAOIs can precipitate hypertensive crisis
Food/Nutrient Effects on Drug
Action: Caffeine
Caffeine can cause insomnia, nervousness and restlessness, stomach irritation, nausea and vomiting, increased heart rate and respiration, and other side effects
Increases adverse effects of stimulants
such as amphetamines, methylphenidate,
theophylline, causing nervousness, tremor,
insomnia
Counters the antianxiety effect of
tranquilizers
Food/Nutrient Effects on Drug
Action: Warfarin
Warfarin can help to prevent dangerous blood clots. It works by slowing the production of clotting factors, which the body makes by using vitamin K from food. …
High levels of alcohol may affect the metabolism of warfarin and increase the risk of major bleeding
Warfarin (anticoagulant) acts by preventing the
conversion of vitamin K to a usable form
Ingestion of vitamin K in usable form will allow
production of more clotting factors, making the
drug less effective
Pts must achieve a balance or steady state between
dose of drug and consumption of vitamin K;
recommend steady intake of K
Other foods with anticlotting qualities may also
have an effect (garlic, onions, vitamin E in large
amounts, and ginseng)
