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interactions
Introduction to Drug Interactions
Antibiotic Drug Interactions
Anticoagulant Drug Interactions
Antidiabetic Drug Interactions
Antihypertensive Drug Interactions
Antipsychotic Drug Interactions
Cardiac Drug Interactions
Diuretic Drug Interactions
NonSteroidal anti-inflammatory Drug Interactions
Oral Contraceptive Drug Interactions
Mechanisms of Drug Interactions Drugs
DRUGS & DRUG INTERACTIONS
Introduction to Drug Interactions
1. Types of drug interactions:
a. Addition (1 + 1 = 2): The response elicited by combined drugs is equal to
the combined responses of the individual drugs
b. Synergism (1 + 1 = 3): The response elicited by combined drugs is greater
than the combined responses of the individual drugs:
c. Potentiation (0 + 1 = 2): A drug which has no effect enhances the effect
of a second drug
d. Antagonism (1 + 1 = 0): A drug inhibits the effect of another drug
4. Quinolones with:
a. Multivalent cations (antacids): Effect is decreased effects of the
quinolones, mechanism is chelation binding decreases the GI absorption
b. Theophylline: Effect is increased theophylline toxicity, mechanism is
inhibition of hepatic metabolism of theophylline
c. Carafate: Effect is decreased effects of quinolones, mechanism is chelation
binding decreases GI absorption
d. Caffeine: Effect is increased effect of caffeine
5. Miscellaneous antibiotics:
a. Penicillins (ampicillin) with allopurinol: Effect is markedly increased rate of
ampicillin retention and induced skin rash, mechanism is unknown
b. Metronidazole with alcohol: Effect is a disulfiram-like reaction, mechanism
is metronidazole inhibits aldehyde dehydrogenase
2. Sulfonylureas with:
a. Alcohol: Effect is hypoglycemia and disulfiram-like reactions, mechanism is
decrease elimination and altered metabolism involving aldehyde
dehydrogenase
b. Anticoagulants: Effect is hypoglycemia, mechanism is inhibition of hepatic
metabolism of sulfonylureas
c. MAO inhibitors: Effect is hypoglycemia, mechanism is unknown
d. NSAIDS: Effect is hypoglycemia, mechanism is protein binding
displacement
e. Sulfinpyrazone: Effect is hypoglycemia, mechanism is inhibition of hepatic
metabolysm of sulfonylureas
f. Thiazide diuretics: Effect is hyperglycemia, mechanism is thiazide diuretics
decrease insulin secretion
2. Lithium with:
a. Iodide salts: Effect is hypothyroidism or goiter, mechanism is
pharmacologic synergism
b. Thiazide diuretics: Effect is increased lithium toxicity, mechanism is
decreased lithium renal clearance
c. NSAIDS: Effect is increased lithium toxicity, mechanism is decreased
lithium renal clearance
3. Phenothiazines with:
a. Meperidine: Effect is excessive hypotension and sedation, mechanism is
pharmacologic synergism
b. Anticholinergics: Effect is decreased effect of phenothiazines, mechanism
is accelerated metabolism of phenothiazines
2. Digoxin with:
a. Diuretics: Effect is electrolyte disturbances predispose to digitalis-induced
arrhythmias, mechanism is increased loss of potassium affects cardiac
muscle action
b. Verapamil: Effect is increased digoxin toxicity, mechanism is additive
effects
c. Erythromycin: Effect is increased digoxin toxicity in about 10% of patients,
mechanism is in about 10% of patients, digoxin is metabolized by GI bacteria
d. Tetracycline: Effect is the same as above, mechanism is the same as
above
e. Quinidine: Effect is increased digoxin toxicity, mechanism is reduced renal
and biliary clearance of digoxin
f. Quinine: Effect is same as above, mechanism is same as above
4. Spironolactone with:
a. Salicylates: Effect is blockage of spironolactone-induced diuresis,
mechanism is blockage of the renal tubular secretion
b. Acceleration of metabolism:
i. Phenobarbital accelerates the metabolism of coumadin, anticoagulants,
steroids, and griseofulvin.
Note* Patients on anticoagulants and barbiturates must be carefully
monitored when the barbiturate is discontinued, as prolonged 4.
hemorrhage can result.
Alteration of Electrolytes:
a. Hypokalemia may be caused by long term usage of digoxin, thiazide, and
furosemide diuretics, and corticosteroids.
b. Hyperkalemia may result from ACE inhibitors
Drugs
1. Topical antibacterials:
a. Muprocyn (Bactroban®): Effective against gram (+) cocci
b. Iodochloroquine (1 % cream/ointment): Effective against gram (+) and (-)
organisms
c. Gentamycin (Garamycin®): An aminoglycoside effective against gram (+)
and (-) organisms
d. Chloramphenicol (Chloromycetin®): Effective against gram (+) and gram
(-) organisms. Blood dyscrasias have been reported
2. Topical antiseptics:
a. Povidone-lodine (Betadine): Antibacterial and antifungal scrub
b. Chlorhexidine (Hibiclens: Antibacterial and antifungal, and nonallergenic
c. Hexachlorophene (Phisohex: Antibacterial and antifungal, a neurotoxin
(especially in infants)
d. Benzalkonium Cl (Zephiran Chloride®): A quaternary ammonium
compound. Antifungal and antibacterial depending on the concentration
e. Dakin's Solution (sodium hypochlorite): Active ingredient of commercial
liquid bleaches
5. Adrenocorticosterolds:
a. Control mechanism: Corticotropin (ACTH) released from the anterior
pituitary stimulates the adrenal cortex to secrete glucocorticoids (cortisol)
and other corticosteroids. The release of ACTH is affected by corticotropin
releasing factor (CRF) from the hypothalamus. ACTH and CRF are subject to
negative feedback inhibition by cortisol/glucocorticoids. ACTH is at its highest
level in the early morning
b. Actions/Side effects of glucorticoids: Any dose of glucocorticoids may exert
a physiologic (replacement) or pharmacologic (anti-inflammatory,
immunosuppressive) effect. Adverse effects can result from too rapid
withdrawal, manifesting as acute renal insufficiency. Glucocorticoids inhibit
the early and the late phases of the inflammatory response. The physiologic
antagonism of histamine, prostaglandin, and kinin-induced vasodilation
occurs. There is an inhibition of prostaglandin and leukotriene synthesis. Also,
leukocyte adherence, chemotaxis, and bacteriocidal/fungicidal activities are
reduced. An inhibition of interleukin1 and T-cell lymphokine release occurs:
i. Hepatic gluconeogenesis/glycogen deposition
ii. Suppression of the HPA axis (after 5-7 days of high dose therapy)
iii. Decrease resistance to infection (signs of infection may be masked)
iv. Possibility of perforation in patients with peptic ulceration or
inflammatory bowel -disease
v. Myopathy: characterized by weakness of proximal muscles of the arms and
legs (tendon rupture)
vi. Osteoporosis (postmenopausal females are at greatest risk), fractures,
aseptic necrosis of the femoral head
vii. Fluid and electrolyte imbalances (sodium and water retention,
hypokalemia)
viii. May increase blood pressure and exacerbate K+ sensitive arrhythmias
ix. Exacerbation of diabetes mellitus
x. Impaired wound healing and skin fragility
xi. Increased frequency of subcapsular cataracts or glaucoma
xii. With high doses, psychologic disturbances (steroid psychosis) may
occur
c. Agents:
i. Short-acting:
Betamethasone sodium phosphate: Celestone®,
Dexamethasone sodium phosphate: Decadron®, Hexadrol®
ii. Long-acting:
Hydrocortisone:
Dexamethasone acetate: Decadron-LA®
Triamcinolone acetonide: Kenalog®
Methylprednisolone acetate: Depo-Medrol®
iii. Mixtures:
Betamethasone acetate and phosphate: Celestone Soluspan®
NOTE* In diabetics using probenecid, a false positive test may result for
urinary glucose using Clinitest® reagents may be observed ii.
Sulfinpyrazone (Anturane): similar to probenecid in action
c. Xanthine oxidase inhibitors:
i. Allopurinol (Zyloprim): Inhibits xanthine oxidase which converts xanthine
into uric acid. This drug is contraindicated in an acute attack (acts as a
competitive inhibitor of the enzyme)
d. NSAIDs: Used for symptomatic relief of acute gouty arthritis
7. NSAIDs:
a. Actions:
i. Analgesia
ii. Anti-inflammatory
iii. Antipyresis
iv. Gastric symptoms
v. Inhibition of platelet aggregation (reversible)
vi. Exacerbation of symptoms of aspirin-intolerant patients
vii. Other: CNS symptoms, hepatic injury with elevation of serum
transaminase, cutaneous reactions
b. Indications:
i. Arthritis
ii. Tendonitis
iii. Soft-tissue inflammation
iv. Mild to moderate pain
c. Groups:
i. Salicylates:
Diflunisal (Dolobid®)
ii. Propionic acids:
Ibuprofen (Motrin®)
iii. Acetates:
Naproxen (Naprosyn®/Anaprox®)
Fenoprofen (Nalfon®)
Ketoprofen (Orudis®)
Etodolac (Lodine®)
Flurbiprofen (Ansaid®)
iv. Pyrole acetic acids:
Indomethacin Indocin®)
Sulindac (Clinoril®)
Tolmetin (Tolectin®)
Nabumetone (Relafen®)
v. Oxicams:
Piroxicam (Feldene®)
vi. Phenylacetic acids
iclofenac (Voltaren®)
vii. Pyrazoles:
Phenylbutazone (Butazolidin®)
viii. Fenamates:
Meclofenamic acid (Meclomen®)
8. Laxatives/Antidiarrheals:
a. Laxatives: Are used for the treatment of constipation secondary to the use
of opiate analgesics for postoperative pain relief. Are classified by differences
in mechanism (active or passive), intensity of effect, and time to the onset of
action
i. Passive (24-72 hours): Metamucil®, Colace®, Chronulac®
ii. Active (6-8 hours): Ex-lax®, Senokot®, Dulcolax®
iii. Saline cathartics (30 minutes-3 hours): Magnesium citrate, Milk of
Magnesia®)
iv. Suppositories (15 minutes-1 hour): Glycerin, Dulcolax
b. Antidiarrheals should not be used for the treatment of acute diarrhea
associated with broad-spectrum antibiotics because of possible exacerbation
of pseudomembranous colitis
i. Passive (non-opiate): Kaopectate®, Pepto-Bismol®
ii. Opiates and others (decrease GI motility): Lomotil®, Imodium®
9. Muscle relaxants: Decrease skeletal muscle tone for use in acute muscle
spasms. Can be used after muscle or tendon transfer. All agents cause a
degree of sedation or CNS dysfunction. Most agents are combined with
acetominophen or aspirin
a. Centrally acting agents:
i. Metaxalone (Skelaxin®): contraindicated in patients prone to hemolytic
anemia
ii. Carisoprodol (Soma®): Contraindicated in acute intermittent porphyria
iii. Cyclobenzaprine (Flexeril®): Contraindicated in patients who have cardiac
pathologies or those receiving MAO inhibitors
iv. Orphenadrine (Norflex®): Contraindicated in glaucoma or prostatic
hypertrophy
v. Chlorzoxazone (Paraflex®)
b. Indications:
I. Adjunct in the treatment of pruritus and allergic reactions ii. Nocturnal leg
cramps
iii. As local anesthesia in patients allergic to amides and ester-linked
compounds
iv. Perioperative medication
16. Anxineytics (Sedative-Hypnotics): Benzodiazepines
a. Major effects:
i. Anxiolytic action (that is distinguished from the effects of reduced
conscious excitability)
ii. Sedation/sleep induction
iii. Skeletal muscle relaxation
iv. Anticonvulsant action
v. Antiemetic effect
b. Indications:
i. Perioperatively, for the relief of anxiety
Valium®- 10 mg PO or IM
Ativan®-0.05 mg/kg IM up to 4 mg
Librium®- 50-100 mg PO or IM 1 hour before surgery
ii. Conscious sedation
iii. Sleep induction:
Dalmane®- 15-30 mg
Restoril®- 15-30 mg
Halcion®- .25-.5 mg
Ativan®- 2-4 mg
iv. Skeletal muscle relaxation:
Valium®- 5-10 mg 3-4 times daily
v. Termination of acute seizures
Valium®- 5-10 mg IV, repeated every 10-15 minutes prn, or 2-3 mg IV
repeated every 5 minutes
c. Precautions:
i. Contraindicated in acute narrow angle glaucoma
ii. IV administration may result in apnea or hypotension