Why does cimetidine potentiate opiates

Effects: Raised desipramine levels by up to a factor of two. Mechanism: Unknown mechanism not seen with other tricyclic antidepressants. Other tricyclic antidepressants Status of interaction: Theoretical. Effects: Enhanced sedative effect which is dose dependent.

Disulfiram Status of interaction: Avoid in combination with methadone formulations containing alcohol check with manufacturer. Effects: Very unpleasant reaction to alcohol which can be dangerous. Mechanism: Disulfiram inhibits metabolism of alcohol allowing metabolites to build up. Erythromycin Status of interaction: In theory should interact but not been studied.

Effects: Increase in methadone levels. Mechanism: Decreased methadone metabolism. Fluconazole In theory the same as ketoconazole. Fluoxetine and sertraline Status of interaction: Clinically important. Effects: Raised methadone levels but not as significant as for fluvoxamine. Fluvoxamine Status of interaction: Clinically important. Effects: Raised plasma methadone levels. Grapefruit juice Status of interaction: Should interact in theory and there have been several anecdotal reports.

Effects: Raised methadone levels. Indinavir Status of interaction: Clinically important. Ketoconazole Status of interaction: Clinically important. Mechanism: Decreased methadone levels. MAOI including selegiline and moclobemide Status of interaction: Severe with pethedine though unlikely with methadone and has never been described. Effects: CNS excitation. Hypotension or respiratory depression. Mechanism: Unclear, avoid the combination if possible. Meprobamate Status of interaction: Clinically important.

Effects: Enhanced sedative and respiratory depressant effect. Naltrexone Top of page Status of interaction: Clinically important. Effects: Blocks effect of methadone long acting.

Mechanism: Opioid antagonist — competes for opiate receptors. Naloxone Status of interaction: Clinically important. Diltiazem Cardizem , although a substrate for CYP3A4 metabolism, does not show a substantial increase in serum concentrations due to grapefruit juice consumption. Otherwise, patients may be at an increased risk of such side effects as orthostatic hypotension. The phosphodiesterase inhibitors, sildenafil Viagra , vardenafil Levitra , and tadalafil Cialis , used for erectile dysfunction, can also increase blood levels with concurrent use of grapefruit juice, but this interaction is unpredictable.

While the clinical effects of the interaction are less pronounced than other classes of drugs, patients may have a slightly higher risk of adverse reactions, such as priapism, hypotension, and visual disturbances. Diazepam Valium , temazepam Restoril , and midazolam Versed are interacting agents of the benzodiazepine class that have increased concentrations and central nervous system depressant effects with grapefruit juice.

Grapefruit juice doubles the oral systemic effects of budesonide Entocort , increasing the risk of the already prevalent glucocorticoid effects. Another potentially significant grapefruit juice interaction is with the immunosuppressant tacrolimus Prograf. This drug is often used following organ transplantation. Due to the ability of grapefruit juice to inhibit the metabolism of tacrolimus, the manufacturer recommends avoiding the use of grapefruit juice during therapy.

Caffeine Not only do foods affect the metabolism of drugs, but also in some cases, drugs interact with and alter the metabolism of food additives, such as caffeine. While it is appropriate to consider caffeine as a drug itself, rather than a food additive, some patients may disregard the fact that a high content of caffeine is found in coffee, tea, soft drinks, and other "energy" foods and beverages. Many common drugs interfere with the metabolism of caffeine, resulting in an increase in caffeine blood levels.

Consumption of caffeinated beverages late at night in combination with these medications may result in sleepless nights. In addition, this may enhance caffeine's diuretic effect. Ciprofloxacin inhibits the metabolism of caffeine, resulting in increased effects of caffeine. Cimetidine also increases caffeine levels, thus a different H 2 antagonist e. Oral contraceptives and prednisone also increase caffeine levels due to the inhibition of caffeine metabolism.

In contrast to caffeine and grapefruit juice, the use of dairy products containing calcium may cause a chemical interaction, not a metabolic interaction. The calcium ion chelates with the drug and may decrease its absorption. Most pharmacists are familiar with the typical antacid and dairy product interactions. However, an increasing number of foods is being fortified with calcium. Orange juice, bread, and other foods enriched with calcium can result in the same type of interactions seen with calcium-containing antacids and dairy products.

Patients should be monitored for decreased therapeutic effects of oral quinolones if administered with oral calcium supplements. Bisphosphonates alendronate, risedronate, and ibandronate have low bioavailability, and little drug is absorbed when given with any type of food or beverage other than water; this is especially problematic with dairy products.

Levels of cefuroxime, a cephalosporin antibiotic, are decreased when taken with dairy products. In addition, methotrexate levels are decreased with the consumption of milk-rich foods.

Protein-Rich Foods. Protein-rich foods can interfere with or potentiate the absorption of various medications. Consuming a meal high in protein and taking propranolol concurrently can increase the beta-blocker's bioavailability.

The amounts addicts are ingesting to feed their habits can cause cardiac arrhythmia or death. The U. Food and Drug Administration issued a warning on June 7 after a recent study by toxicology experts showed an uptick in loperamide abuse. He is the lead author of the loperamide research report.

His remarks were aired in a National Public Radio interview in May. Addiction is not just a personal problem or a family problem. The mechanisms of this interaction are antiplatelet effect and gastric mucosal damage, because most NSAIDs do not produce a hypothrombinemic response. When given to or withdrawn from patients maintained on warfarin, NSAIDs may actually alter anticoagulant control as a result of changes in the amount of circulating warfarin released from plasma albumin binding sites.

One retrospective study found that the risk of hemorrhagic peptic ulcers was 13 times greater in patients older than 65 years who were taking NSAIDs and warfarin than in patients of the same age who were taking neither drug. Patients also should be informed about the risk of bleeding associated with combined warfarin and NSAID therapy.

Fluoroquinolone antibiotics are useful in the management of infections caused by a variety of pathogens. Several agents can substantially reduce the absorption of fluoroquinolones, thereby causing treatment failure.

Divalent cations calcium and magnesium and trivalent cations aluminum and ferrous sulfate can form insoluble complexes in the gut if they are taken concurrently with fluoroquinolones. Common products containing divalent or trivalent cations are listed in Table 2. Studies have shown that the absorption of fluoroqinolones is reduced by 60 to 75 percent when these antibiotics are administered concomitantly with divalent or trivalent cations.

If withholding therapy is not feasible, the fluoroquinolone and cation product should be administered at least two hours apart preferably four hours apart. Carbamazepine Tegretol , phenobarbital and phenytoin Dilantin are commonly prescribed for the management of epilepsy and other disorders. These agents are eliminated through hepatic metabolism. Thus, their effects may be potentiated by drugs that inhibit cytochrome P hepatic metabolism, such as macrolide antibiotics, cimetidine Tagamet and fluconazole Diflucan.

Agents that inhibit cytochrome P metabolism or depend on cytochrome P for metabolism substrate 13 are listed in Table 3. Combining a cytochrome P inhibitor with a substrate can potentiate the pharmacologic effects of the substrate. Paroxetine Paxil. Sertraline Zoloft. Perphenazine Trilafon. Venlafaxine Effexor. Clarithromycin Biaxin. Fluvoxamine Luvox. Grapefruit juice. Itraconazole Sporanox. Ketoconazole Nizoral.

Lovastatin Mevacor. Nefazodone Serzone. Specific data support interactions between the following drugs: erythromycin and carbamazepine; cimetidine and carbamazepine or phenytoin; fluconazole and phenytoin; and rifampin and phenytoin.

Serum antiepileptic drug levels should be monitored in patients who receive any of these combinations. Lithium therapy is useful for indications ranging from bipolar disorder to migraine headaches, but several interactions must be considered.

As a result, serum lithium levels increase secondary to enhanced reabsorption. If coadministration is necessary, the dosage of lithium should be reduced by 50 percent when a diuretic or an NSAID is added. Signs or symptoms of lithium toxicity involve the central nervous system drowsiness, confusion, hand tremor, blurred vision, vertigo and seizures , gastrointestinal tract nausea and vomiting and cardiovascular system arrhythmias and widening of the QRS complex.

Rifampin can increase the activity of hepatic enzymes involved in the metabolism of exogenous estrogens. Concomitant use of rifampin and oral contraceptive pills can lead to breakthrough bleeding and an increased risk of pregnancy. The interaction between oral contraceptives and other antibiotics is controversial in that no definitive studies have demonstrated contraceptive failure from such combinations.

A recent retrospective study of patients who were taking an oral contraceptive and an antibiotic showed a small but insignificant increase in the risk of pregnancy.

One proposed mechanism is interruption of the enterohepatic circulation of estrogen as a result of reduced bacterial hydrolysis in the gastrointestinal tract. A variety of antibiotics have been implicated. The failure of oral contraception may be suggested by breakthrough bleeding. A reasonable recommendation is to remind patients that the baseline failure rate for oral contraceptives is approximately one pregnancy per woman years i.

Although insufficient evidence is available to make a firm conclusion, it appears possible that oral contraception may fail while patients are taking an antibiotic. Thus, patients should be encouraged to consider using an alternative method of contraception for the duration of the cycle. Troglitazone Rezulin has been reported to reduce the plasma concentrations of oral contraceptives by 30 percent through an unknown mechanism. Potentially fatal interactions can occur with coadministration of cisapride Propulsid and other drugs.

Cisapride has been associated with prolongation of the QT interval, torsades de pointes, syncope, cardiac arrest and sudden death. The primary agents contraindicated for use with cisapride are certain macrolide antibiotics erythromycin and clarithromycin , certain antifungal agents fluconazole, itraconazole [Sporanox] and ketoconazole [Nizoral] , one antidepressant drug nefazodone [Serzone] and certain protease inhibitors indinavir [Crixivan] and ritonavir [Norvir].

Most data on cisapride interactions are derived from case reports. However, current prescribing information warns against the coadministration of cisapride and any medications known to prolong the QT interval, such as class IA or III antiarrhythmic drugs, tricyclic antidepressants, erythromycin, clarithromycin and phenothiazines.

Sildenafil Viagra is the first oral medication labeled by the U. Food and Drug Administration for the treatment of erectile dysfunction. Through inhibition of phosphodiesterase type 5, sildenafil enhances the effects of nitric oxide, potentiating penile erection after sexual arousal. Therefore, patients with erectile dysfunction are often taking other medications.

Sildenafil therapy is absolutely contraindicated in patients who are taking any form of nitrates, because of the potentiation of nitrate hypotensive effects. Sildenafil is primarily metabolized in the liver by cytochrome P 3A4. Drugs that inhibit this enzyme, including erythromycin, cimetidine, ketoconazole and itraconazole, may increase plasma sildenafil concentrations.

Sildenafil therapy should be initiated in the lowest dosage 25 mg in patients who are also taking a cytochrome P 3A4 inhibitor. The benefits of lowering cholesterol levels for the primary and secondary prevention of coronary artery disease have been well established. Most evidence supports using drugs that inhibit 3-hydroxymethylglutaryl—coenzyme A HMG-CoA reductase in the liver, which is the main site of cholesterol synthesis.

These drugs are metabolized through the cytochrome P pathway. Concomitant use of statins and erythromycin, itraconazole, niacin or gemfibrozil Lopid can cause toxicity that manifests as elevated serum transaminase levels, myopathy, rhabdomyolysis and acute renal failure. However, the risk of toxicity increases when statins are coadministered with certain drugs.

Because this risk may be dose-dependent, the dosage should be limited to the equivalent of 20 mg of lovastatin per day when any statin is given in combination with an interacting drug. In many patients, HMG-CoA reductase inhibitors fail to lower triglyceride cholesterol levels to a desirable range. Although concomitant use of gemfibrozil or niacin with an HMG-CoA reductase inhibitor may appear clinically appropriate, these combinations have been associated with a 2 to 5 percent increase in the risk of myopathy.

If either combination is used, patients should be alert for muscle pain, tenderness or weakness. Creatine kinase levels should be measured if these symptoms occur. Lovastatin may potentiate the effects of warfarin by displacing the drug from plasma protein binding sites or inhibiting hepatic metabolism of the drug.

Although potentiation of warfarin by lovastatin has been reported in at least 10 patients, controlled trials in large numbers of patients are needed to discern the clinical importance of this effect. Over the past 15 years, selective serotonin reuptake inhibitors SSRIs have become the most commonly used antidepressant drugs.

These agents are generally well tolerated and have a more favorable side effect profile than tricyclic antidepressants. Concurrent use of SSRIs with agents metabolized by this pathway can result in increased serum concentrations of these agents. Patients already being treated with a tricyclic antidepressant may experience significant increases in plasma antidepressant concentrations and possibly antidepressant toxicity when fluoxetine Prozac is added. When concomitant use of an SSRI and a tricyclic antidepressant is required, the patient should be monitored for anticholinergic excess.

Conservative dosing of the tricyclic antidepressant should also be considered. Isolated case reports suggest that coadministration of fluoxetine and selegiline Eldepryl may result in mania and hypertension. The causal mechanism has not been established. However, selegiline is thought to produce additive serotoninergic effects, because serotonin is metabolized by MAO-A.

The prescribing information for selegiline recommends that the drug not be used with SSRIs. The concomitant use of fluoxetine and non-selective MAO inhibitors has resulted in the serotonin syndrome, which is characterized by anxiety, agitation, confusion, hyperreflexia, myoclonus, diaphoresis and hyperthermia. Several cases of serious or fatal reactions have occurred when tranylcypromine Parnate was used with fluoxetine. Reports of serotonin syndrome in association with tramadol and SSRI coadministration appear in the literature.

At least one case report has described incoherence attributable to the combination of an SSRI and St. John's wort extract of the Hypericum perforatum plant.

John's wort is mediated through inhibition of serotonin uptake or MAO antagonism.