Download PowerPoint 簡報

CH 19
FOOD-DRUG INTERACTIONS
Food-drug interactions can
- Alter the intended response to the
medication
- Cause drug toxicity
- Alter the normal nutritional status.
I. Pharmacologic Aspects of Food-Drug
Interactions
Two types:
1. Pharmacodynamic interactions
- affect the pharmacologic action of the
drug
2. Pharmacokinetic interactions
- affect the movement of the drug into,
around, or out of the body
1. Pharmacodynamics:
- Studying the biochemical and physiologic
effects of a drug
- Mechanism of action of a drug: binding of
the drug mol. to receptor, enzyme, or ion
channel→ physiologic response.
*Agonist: Enhance normal metabolism and
physiologic function
*Antagonist: Attenuate normal metabolism
and physiologic function
2. Pharmacokinetics – the study of the time course
of a drug in the body, including absorption ,
distribution, metabolism (biotransformation),
excretion.
(1) Absorption – from the adm. Site to blood
stream
a. route of administration
iv: intravenous
im: intramuscular
ip: intraperitoneal
Sc: subcutaneous
b. the chemistry of the drug and its ability to cross
biologic membranes
c. the rate of gastric emptying and GI movement
d. the quality of the product formulation.
(2) Distribution – drug leaves the systemic
circulation and travels to various regions
of the body,
- the drug’s chemistry and ability to cross
biologic membranes.
- the rate and extent of blood flow
- bound form or unbound fraction
(3) Biotransformation (metabolism) of
drugs: major in the liver.
- cytochrome P-450 enzyme system
(Fig 12-2, p311), substances ↑or↓ this
enzyme system may change the rate
or extent of drug metabolism.
(4) Excretion:
- Renal excretion: Glomerular
filtration or tubular secretion
Ex. Urinary pH – affect tubular reabsorption
- Bile or other body fluid, lesser
extent.
II. Risk factors for Drug-Nutrient
Interactions
1. Drug-induced malnutrition – most
commonly during long-term
treatment for chronic disease
2. Existing malnutrition places people
at risk for drug-nutrient interactions
3. Specific nutrient deficiencies can
affect drug metabolism by
influencing the MFOS
4. Body composition - drug response
Pharmacogenomics – Genetically
determined variations that are revealed
solely by the effects of drugs.
Ex.(1) Slow acetylators: lower levels of the
hepatic enzyme acetyl transferase →
(a) INH (isoniazid) user: ↑risk of pyridoxine
def.
(b) phenelzine (MAO inhibitor) user: ↑risk of
HTN if ingest foods high in tyramine (Box
19-2)
(2) G6PD deficiency: X-chromosome-linked
def. of G6PD in RBC
- Fava beans or pollen can cause acute
hemolysis
III. EFFECT OF FOOD ON DRUG
THERAPY
1. Effect on Drug Absorption: The
presence of food and nutrients in
the stomach or GI lumen →↓drug
abs.
Ex.: abs. of Fe may be ↓50% when
taken with food
- Mechanisms
(1) Rate of the gastric empty
(2) Chelation – drugs and divalent or
trivalent cations
(3) Adsorption
(4) GI pH
2. Medication and Enteral Nutrition
Interactions
- Liquid medication mixed with enteral
feeding formulas
(1) cause granulation and gel formation
(2) Emulsion breakage
3. Drug Distribution
low serum Alb. →↑unbound
fraction drug →↑risk for adverse
effects from highly proteinbound drugs
Ex.: Anticoagulant - warfarin,
anticonvulsant - phenytoin
4. Effect on Drug Metabolism
- Enzymes in GI & liver – account for a
large portion of the drug meta.
(1) Hi-protein, Lo-CHO diet →↑the hepatic
metabolism of theophylline (antiasthma
drug)
(2) Substance found in grapefruit can inhibit
the intestinal metabolism of drugs →↑drug
in the circulation →↑toxicity.
(3) Competition between food and drugs
with hepatic enzymes →↑drug in the
circulation →↑toxicity
5. Effect on Drug Excretion
- Food and drugs can alter the reabsorption of drugs from the renal
tubule
(1) Low Na intake or dehydration→↓Na
re-absorption, →↓Li re-absorption.
(2) Urinary pH changed →change the
amount of drug existing in the
nonionic state →↓drug re-absorption,
IV. Effects of Drugs on Food and
Nutrition
1. Nutrient absorption (Appendix 34)
(1) Chelation: tetracycline – Ca (or
other divalent or trivalent ions)
(2) Adsorption: Cholestyramine – fat
soluble vitamins
(3) Hi Mineral oil →↓fat soluble
vitamins
(4) Influencing the transit time in the gut.
Ex.: cathartic agents and laxatives
(5) Changing GI environment. (pH)
Ex.- Cimetidine→ ↓ HCl secretion
& Intrinsic factor→ ↓Vit. B-12 abs.
- Antacids: ↑pH & chelating
minerals, ∴ ↓Ca, Fe, Mg & Zn abs.
(6) Damage the intestinal mucosa.
Ex.: chemotherapeutic agents, NSAIDS,
long-term antibiotic therapy.
(7) Affect intestinal transport mech.
2. Nutrient Metabolism –
- Drugs →↓or ↑nutrient metabolism
Ex.:
(1) phenobarbital and phenytoin
(anticonvulsants) → ↑Vit. D, K and folic
acid meta.
(2) INH (anti-tuberculosis): blocks the
conversion of pyridoxine → PLP
(3) MTX: a folic acid antagonist →↓folate to
be active form →megaloblastic anemia
3. Nutrient Excretion
(1) Interfering with nutrient reabsorption
a. Diuretics (furosemide, ethacrynic
acid, triamterene) →↑excretion of Ca, K,
Mg, Zn etc.
thiazide: →↑excretion of Na
b. Chemotheraputic agents →
hypomagnesemia
V. MODIFICATION OF DRUG ACTION BY
FOOD AND NUTRIENTS
1. Substances enhance drug effects
(1) MAOI and pressor agents (Box 19-2)
* Biologically active amines
a. the psychoactive amines
(neuotransmitters) – norepinephrine and
dopamine
b. the vasoactive amines – tyramine,
serotonin & histamine
monoamine & diamine oxidase
Amines→ → → → → → → deamination
Presence of the unoxidized pressor
amines causes constriction of blood
vessels and HTN→ Symptoms
(2) Caffeine - ↑the adverse effects of
stimulant drugs
(3) Warfarin ( an oral anticoagulant) →
↓hepatic production of 4 vit. Kdependent clotting factors.
*Dong Quai- contains coumarin-like
substance
*Ginseng - contains a platelet inhibitor.
2. Alcohol
(1) ethanol combined with CNSdepressant→ excessive drowsiness,
incoordination and other signs of
CNS depression
(2) Mucosal irritant – with aspirin or
other NSAIDs→↑risk of GI ulceration
(3) →↑risk of hepatic toxicity
(4) Inhibit gluconeogenesis, →↑prolong
a hypoglycemic episode
(5) ethanol+disulfiram →↑risk of lifethreatening reaction
VI. Effects of drugs on Nutritional Status
Drugs
1. Oral, Taste, and Smell (Box 19-3)
- ↓Food intake
(1) alteration in taste sensation (dysgeusia)
(2) ↓taste sensation (hypogeusia)
(3) an unpleasant aftertaste
* Mechanisms?
- alter the turnover of taste cells
- interfere with transduction mech.
- Alter neurotransmitters in the CNS
(4) Inflammation of the mucous membranes
(mucositis)
- Stomatitis (mouth inflammation)
- glossitis (tongue inflammation)
- Cheilitis (lip inflammation and cracking)
(5)↓secretions → dry mouth→ dental caries
and loss of teeth, gum disease, stomatitis
and glossitis.
2. Gastrointestinal Effects
(1) GI irritation and ulceration – NSAIDs
(2) Severe nausea and vomiting –
Antineoplastic drugs → nausea nd
vomiting
(3) Changes in bowel function →
constipation or diarrhea (↓peristalsis)
(4) Destruction of intestinal bacteria (Box
19-6)
(5) Inhibit intestinal enzymes – DM drugs
→undigested CHO →diarrhea,
flatulence, cramping etc.
3. Appetite Changes
• Suppress appetite (Box 19-7)→wt.
changes, nutritional imbalance, and
growth retardation in kids.
- Side effects of stimulant drugs
a. HTN
b. interfere with the ability or desire to eat
(2) Stimulate appetite (Box 19-8) )→wt. gains
4. Organ System Toxicity
- hepatotoxicity, nephrotoxicity,
pulmonary toxicity, neurotoxicity,
ototoxicity, ocular toxicity,
pancreatitis, cardiotoxicity etc.
Ex. Hepatotoxicity→ hepatitis, jaudice,
hepatomegaly, liver failure etc.
5. Glucose levels
- Hypoglycemia or hyperglycemia
(Box 19-9)
VII. EXCIPIENTS AND FOOD-DRUG
INTERACTIONS
- An excipients ( inactive ingredients) is
added to drug formulations for its action
as a buffer, binder, filler, diluent,
disintegrate, glidant, flavoring, dye,
preservative, suspending agent, or
coating.
VIII. MEDICAL NUTRITION THERAPY (MNT)
1. Prospective – All MNT offered when the
pt. first starts a drug
2. Retrospective – evaluation of symptoms
to determine whether medical problems
might be the result of food-drug
interactions.