Книги фарма 2 / Bertram G. Katzung-Basic & Clinical Pharmacology(9th Edition)

Antidepressants, tricyclic.

Beta-blockade (especially with

-blocker

nonselective agents such as

effect:

propranolol) alters response to

Cimetidine: [P] Decreased

sympathomimetics with -agonist

metabolism of -blockers that are

activity (eg, epinephrine). Beta-

cleared primarily by the liver, eg,

blockers that undergo extensive

propranolol. Less effect (if any) on

first-pass metabolism may be

those cleared by the kidneys, eg,

affected by drugs capable of

atenolol, nadolol.

altering this process. Beta-blockers

-blocker

may reduce hepatic blood flow.

effect:

Enzyme inducers: [P] Barbiturates,

phenytoin, and rifampin may enhance

-blockers metabolism; other enzyme

inducers may produce similar effects.

Nonsteroidal anti-inflammatory

drugs: [P] Indomethacin reduces

antihypertensive response; other

prostaglandin inhibitors probably also

interact.

Effects of -blockers on other drugs:

Clonidine: [NE] Hypertensive

reaction if clonidine is withdrawn while

patient is taking propranolol.

Insulin: [P] Inhibition of glucose

recovery from hypoglycemia; inhibition

of symptoms of hypoglycemia (except

sweating); increased blood pressure

during hypoglycemia.

Lidocaine: [NE] Decreased clearance

of intravenous idocaine; increased

plasma lidocaine levels.

Prazosin: [P] Increased hypotensive

response to first dose of prazosin.

Sympathomimetics: [P] Increased

pressor response to epinephrine (and

possibly other sympathomimetics); this

is more likely to occur with nonspecific

-blockers.

Resins may bind with orally

Acetaminophen: [NE] Decreased

administered drugs in

gastrointestinal absorption of

gastrointestinal tract. Resins may

acetaminophen.

bind in gastrointestinal tract with

Digitalis glycosides: [NE] Decreased

drugs that undergo enterohepatic

gastrointestinal absorption of digitoxin

circulation, even if the latter are

(possibly also digoxin).

given parenterally.

Furosemide: [P] Decreased

gastrointestinal absorption of

furosemide.

Methotrexate: [NE] Reduced

gastrointestinal absorption of

methotrexate.

Mycophenolate: [P] Reduced

gastrointestinal absorption of

mycophenolate.

Thiazide diuretics: [P] Reduced

gastrointestinal absorption of thiazides.

Thyroid hormones: [P] Reduced

thyroid absorption.

See also Anticoagulants, oral.

Verapamil, diltiazem, and perhaps

Carbamazepine: [P] Decreased

nicardipine (but not nifedipine)

carbamazepine metabolism with

inhibit hepatic drug-metabolizing

diltiazem and verapamil; possible

enzymes. Metabolism of diltiazem,

increase in calcium channel blocker

nifedipine, verapamil, and probably

metabolism.

Cimetidine: [NP] Decreased

subject to induction and inhibition.

metabolism of calcium channel

blockers.

Cyclosporine: [P] Decreased

cyclosporine metabolism with

diltiazem, nicardipine, verapamil.

Phenytoin: [NE] Increased metabolism

of calcium channel blockers.

Rifampin: [P] Increased metabolism of

calcium channel blockers.

See also Azole antifungals,

Barbiturates, Theophylline.

Induction of hepatic microsomal

Cimetidine: [P] Decreased

drug-metabolizing enzymes.

carbamazepine metabolism.

Clarithromycin: [P] Decreased

metabolism, primarily by CYP3A4.

carbamazepine metabolism.

Corticosteroids: [P] Increased

corticosteroid metabolism.

Cyclosporine: [P] Increased

cyclosporine metabolism.

Danazol: [P] Decreased carbamazepine

metabolism.

Diltiazem: [P] Decreased

carbamazepine metabolism.

Doxycycline: [P] Increased doxycycline

metabolism.

Erythromycin: [NE] Decreased

carbamazepine metabolism.

Fluvoxamine: [NE] Decreased

carbamazepine metabolism.

Estrogens: [P] Increased estrogen

metabolism.

Haloperidol: [P] Increased haloperidol

metabolism.

Isoniazid: [P] Decreased

carbamazepine metabolism.

Nefazodone: [NE] Decreased

carbamazepine metabolism.

Propoxyphene: [HP] Decreased

carbamazepine metabolism.

Selective serotonin reuptake

inhibitors (SSRIs): [NE] Fluoxetine

and fluvoxamine decrease

carbamazepine metabolism.

Tacrolimus: [P] Increased tacrolimus

metabolism.

Theophylline: [NE] Increased

theophylline metabolism.

Troleandomycin: [P] Decreased

carbamazepine metabolism.

Verapamil: [P] Decreased

carbamazepine metabolism.

See also Anticoagulants, oral;

Antidepressants, tricyclic; Azole

antifungals; Calcium channel blockers.

Inhibits hepatic drug-metabolizing

Phenytoin: [P] Decreased phenytoin

enzymes.

metabolism.

Sulfonylurea hypoglycemics: [P]

Decreased sulfonylurea metabolism.

See also Anticoagulants, oral.

Inhibits hepatic microsomal drug-

Benzodiazepines: [P] Decreased

metabolizing enzymes. (Ranitidine,

metabolism of alprazolam,

famotidine, and nizatidine do not

chlordiazepoxide, diazepam,

appear to do so.) May inhibit the

halazepam, prazepam, and clorazepate

renal tubular secretion of weak

but not oxazepam, lorazepam, or

bases. Purportedly reduces hepatic

temazepam.

blood flow, thus reducing first-pass

Carmustine: [NE] Increased bone

metabolism of highly extracted

marrow suppression.

drugs. (However, the ability of

Ketoconazole: [NE] Decreased

cimetidine to affect hepatic blood

gastrointestinal absorption of

ketoconazole due to increased pH in

gut; other H2 blockers and proton pump

inhibitors would be expected to have

the same effect.

Itraconazole: [NE] Decreased

gastrointestinal absorption of

itraconazole due to increased pH in gut;

other H2-receptor antagonists and

proton pump inhibitors would be

expected to have the same effect.

Lidocaine: [P] Decreased metabolism

of lidocaine; increased serum lidocaine.

Phenytoin: [NE] Decreased phenytoin

metabolism; increased serum phenytoin.

Procainamide: [P] Decreased renal

excretion of procainamide; increased

serum procainamide levels. Similar

effect with ranitidine but smaller.

Quinidine: [P] Decreased metabolism

of quinidine; increased serum quinidine

levels.

Theophylline: [P] Decreased

theophylline metabolism; increased

plasma theophylline.

See also Anticoagulants, oral;

Antidepressants, tricyclic; Beta-

adrenoceptor blockers; Calcium channel

blockers, Carbamazepine.

Susceptible to inhibition of

Clarithromycin: [NP] Decreased

metabolism by CYP3A4 inhibitors.

metabolism of cisapride; possible

High cisapride serum

ventricular arrhythmia.

Cyclosporine: [NE] Decreased

ventricular arrhythmias.

metabolism of cisapride; possible

ventricular arrhythmia.

Erythromycin: [NP] Decreased

metabolism of cisapride; possible

ventricular arrhythmia.

Fluconazole: [NE] Decreased

metabolism of cisapride; possible

ventricular arrhythmia.

Itraconazole: [NP] Decreased

metabolism of cisapride; possible

ventricular arrhythmia.

Ketoconazole: [NP] Decreased

metabolism of cisapride; possible

ventricular arrhythmia.

Nefazodone: [NP] Possible decreased

metabolism of cisapride by CYP3A4;

possible ventricular arrhythmia.

Ritonavir: [NE] Decreased metabolism

of cisapride; possible ventricular

arrhythmia.

Selective serotonin reuptake

inhibitors (SSRIs): [NP] Fluvoxamine

inhibits CYP3A4 and probably

decreases cisapride metabolism;

possible ventricular arrhythmia.

Metabolism inducible. Susceptible

Aminoglycosides: [NE] Possible

to inhibition of metabolism by

additive nephrotoxicity.

Amphotericin B: [NE] Possible

sirolimus appear to have similar

additive nephrotoxicity.

interactions.)

Androgens: [NE] Increased serum

cyclosporine.

Barbiturates: [P] Increased

cyclosporine metabolism.

Carbamazepine: [P] Increased

cyclosporine metabolism.

Clarithromycin: [P] Decreased

cyclosporine metabolism.

Diltiazem: [NE] Decreased

cyclosporine metabolism.

Erythromycin: [NE] Decreased

cyclosporine metabolism.

Lovastatin: [NE] Myopathy and

rhabdomyolysis noted in patients taking

lovastatin and cyclosporine.

Nefazodone: [P] Decreased

cyclosporine metabolism.

Phenytoin: [NE] Increased

cyclosporine metabolism.

Pimozide: [NE] Decreased pimozide

metabolism.

Rifampin: [P] Increased cyclosporine

metabolism.

Ritonavir: [P] Decreased cyclosporine

metabolism.

St. John's wort: [NE] Increased

cyclosporine metabolism.

Verapamil: [NE] Decreased

cyclosporine metabolism.

See also Azole antifungals,

Barbiturates; Calcium channel

blockers.

Digoxin susceptible to inhibition of

Drugs that may increase digitalis

gastrointestinal absorption.

effect:

Amiodarone: [P] Reduced renal

by drug-induced electrolyte

digoxin excretion leads to increased

imbalance (eg, hypokalemia).

plasma digoxin concentrations.

Digitoxin metabolism inducible.

Clarithromycin: [NE] Reduced renal

Renal excretion of digoxin

susceptible to inhibition.

excretion of digoxin.

Diltiazem: [P] Increased plasma

digoxin (usually 20–30%) due to

reduced renal and nonrenal clearance.

Erythromycin: [NE] Reduced renal

excretion of digoxin.

Itraconazole: [NE] Reduced renal

excretion of digoxin.

Potassium-depleting drugs: [P]

Increased likelihood of digitalis

toxicity.

Propafenone: [P] Increased plasma

digoxin levels.

Quinidine: [HP] Reduced digoxin

excretion; displacement of digoxin from

tissue binding sites; digitoxin may also

be affected.

Spironolactone: [NE] Decreased renal

digoxin excretion and interference with

some serum digoxin assays.

Verapamil: [P] Increased plasma

digoxin levels.

Drugs that may decrease digitalis

effect:

Kaolin-pectin: [P] Decreased

gastrointestinal digoxin absorption.

Penicillamine: [NE] Decreased

plasma digoxin.

Rifampin: [NE] Increased metabolism

of digitoxin and possibly digoxin.

Sulfasalazine: [NE] Decreased

gastrointestinal digoxin absorption.

See also Antacids; Azole antifungals;

Bile acid-binding resins.

Inhibits hepatic microsomal drug-

Benzodiazepines: [P] Decreased

metabolizing enzymes. Inhibits

metabolism of chlordiazepoxide and

aldehyde dehydrogenase.

diazepam but not lorazepam and

oxazepam.

Metronidazole: [NE] Confusion and

psychoses reported in patients receiving

this combination; mechanisms

unknown.

Phenytoin: [P] Decreased phenytoin

metabolism.

See also Alcohol; Anticoagulants, oral.

Metabolism inducible.

Ampicillin: [NP] Interruption of

Enterohepatic circulation of

enterohepatic circulation of estrogen;

estrogen may be interrupted by

possible reduction in oral contraceptive

alteration in bowel flora (eg, due to

efficacy. Some other oral antibiotics

antibiotics).

may have a similar effect.

Corticosteroids: [P] Decreased

metabolism of corticosteroids leading to

increased corticosteroid effect.

Diazepam: [NE] Decreased diazepam

metabolism.

Griseofulvin: [NE] Possible inhibition

of oral contraceptive efficacy;

mechanism unknown.

Phenytoin: [NP] Increased estrogen

metabolism; possible reduction in oral

contraceptive efficacy.

Primidone: [NP] Increased estrogen

metabolism; possible reduction in oral

contraceptive efficacy.

Rifabutin: [NP] Increased estrogen

metabolism; possible reduction in oral

contraceptive efficacy.

Rifampin: [NP] Increased estrogen

metabolism; possible reduction in oral

contraceptive efficacy.

St. John's wort: [NE] Increased

estrogen metabolism; possible reduction

in oral contraceptive efficacy.

See also Barbiturates; Carbamazepine.

Lovastatin, simvastatin, and, to a

Clarithromycin: [P] Decreased statin

lesser extent, atorvastatin are

metabolism.

lesser extent, atorvastatin are

Diltiazem: [NE] Decreased statin

susceptible to CYP3A4 inducers;

metabolism.

increased risk of additive myopathy

Cyclosporine: [P] Decreased statin

risk with other drugs that can cause

metabolism.

myopathy.

Erythromycin: [P] Decreased statin

metabolism.

Gemfibrozil: [NP] Increased plasma

lovastatin and simvastatin.

Nefazodone: [NE] Decreased statin

metabolism.

Ritonavir: [NE] Decreased statin

metabolism.

Verapamil: [NE] Decreased statin

metabolism.

See also Azole antifungals.

Binds with drugs in gastrointestinal

Methyldopa: [NE] Decreased

tract, reducing absorption.

methyldopa absorption.

Quinolones: [P] Decreased absorption

of ciprofloxacin.

Tetracyclines: [P] Decreased

absorption of tetracyclines; decreased

efficacy of iron.

Thyroid hormones: [P] Decreased