Drug information provided by: Merative, Micromedex. Bactrim is a prescription medicine used to treat ear infections, urinary tract infections, bronchitis, traveler's diarrhea, shigellosis, and Pneumocystis jiroveci pneumonia. The efficacy of tricyclic antidepressants can decrease when coadministered with BACTRIM. If you're not disclosing your medical conditions to your tattoo artist prior to your session, what your tattoo artist doesn't know could seriously harm you. Gerontol. The hidden dangers of getting inked. Increased sulfamethoxazole blood levels may occur in patients who are also receiving indomethacin. BACTRIM is indicated in the treatment of enteritis caused by susceptible strains of Shigella flexneri and Shigella sonnei in adults and pediatric patients two months of age and older. Copyright: Merative US L.P. 1973, 2023. Do not use two doses at one time. Instruct patients to maintain an adequate fluid intake in order to prevent crystalluria and stone formation. It's a type of hemolytic anemia. Our team thoroughly researches and evaluates the recommendations we make on our site. Bactrim: For UTI, Uses, Dosage, Side Effects, Interactions - RxList Do not double doses. Make your tax-deductible gift and be a part of the cutting-edge research and care that's changing medicine. Information is for End User's use only and may not be sold, redistributed or otherwise used for commercial purposes. Low blood sodium levels: nausea, fatigue, headache, confusion, disoriented, hallucinations (seeing things that aren't real), seizures, unconsciousness. This site needs JavaScript to work properly. The trimethoprim component of BACTRIM may cause hyperkalemia when administered to patients with underlying disorders of potassium metabolism, with renal insufficiency or when given concomitantly with drugs known to induce hyperkalemia, such as angiotensin converting enzyme inhibitors. 2007 Nov;29(11):1061-4. doi: 10.1002/hed.20626. You should not take Bactrim if you are pregnant or breastfeeding. Store at room temperature (15C 30C or 59F 86F). This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. sores in the infected area, filled with pus or fluid. 2018;11(11):CD009435. There may be an increased risk of severe adverse reactions in elderly patients, particularly when complicating conditions exist, e.g., impaired kidney and/or liver function, or concomitant use of other drugs. If a dilution of 5 mL per 100 mL of 5% dextrose in water is desired, it should be used within 4 hours. To provide you with the most relevant and helpful information, and understand which 10. Common medications that may interact with Bactrim include: Note that this list is not all-inclusive and includes only common medications that may interact with Bactrim. Like other antibiotics, Bactrim can change the natural balance of bacteria present in your gut and may cause severe and persistent diarrhea, associated with a bacteria called. Signs and symptoms of overdosage reported with sulfonamides include anorexia, colic, nausea, vomiting, dizziness, headache, drowsiness and unconsciousness. MeSH Bactrim Side Effects: Common, Severe, Long Term - Drugs.com London NJ, Garg SJ, Moorthy RS, Cunningham ET. The Best Online Dermatologists to Treat Your Skin, Tattoo Placement 101: The Ultimate Guide, From Pain Level to Healing Time, Spironolactone for Acne: What You Need to Know Before Use. health information, we will treat all of that information as protected health As with any skin infection, in severe cases bacteria can enter your bloodstream and actually become life-threatening." Keep in mind, tattoo infections are usually deeper in the skin as the needle. health information, we will treat all of that information as protected health The amount of medicine that you take depends on the strength of the medicine. Tattoo-associated nontuberculous mycobacterial skin infections multiple states, 2011-2012. Sulfamethoxazole/trimethoprim: Uses, Side Effects & Dosage - GoodRx Mycobacterium fortuitum cutaneous infection from amateur tattoo. Copyright 2023 by RxList Inc. An Internet Brands company. PDF BACTRIM sulfamethoxazole and trimethoprim PEDIATRIC SUSPENSION DESCRIPTION How Long Does It Take a Tattoo to Fully Heal? Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances. Ramakrishnan K, et al. 30-mL Multiple-dose Vials, each 5 mL containing 80 mg trimethoprim (16 mg/mL) and 400 mg sulfamethoxazole (80 mg/mL) for infusion with 5% dextrose in water. If your dose is different, do not change it unless your doctor tells you to do so. To do so may increase the chance of side effects. Tell your doctor if you experience serious side effects of Bactrim including: BACTRIM (trimethoprim and sulfamethoxazole) injection, a sterile solution for intravenous infusion only, is a combination of sulfamethoxazole, a sulfonamide antimicrobial, and trimethoprim, a dihydrofolate reductase inhibitor antibacterial. To provide you with the most relevant and helpful information, and understand which Advertising revenue supports our not-for-profit mission. Clinical studies of BACTRIM did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Tattoo infection: Symptoms, treatment, and prevention - Medical News Today Common simple SSTIs include cellulitis, erysipelas, impetigo . BACTRIM is contraindicated in the following: BACTRIM is an antimicrobial drug [see Microbiology]. Cipro (ciprofloxacin) and Levaquin (levofloxacin) are two popular medications in this group. Bactrim belongs to the class of medicines known as antibiotics. The incidence of congenital abnormalities was 4.5% (3 of 66) in those who received placebo and 3.3% (4 of 120) in those receiving trimethoprim and sulfamethoxazole. Clinical signs, such as rash, sore throat, fever, arthralgia, cough, shortness of breath, pallor, purpura or jaundice may be early indications of serious reactions. Skin and Soft Tissue Infections | AAFP This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. 1999;45:209- 212. Trimethoprim alone was negative in in vitro reverse mutation bacterial assays and in in vitro chromosomal aberration assays with Chinese Hamster ovary or lung cells with or without S9 activation. Certain antibiotic, anti-inflammatory, and anti-malarial medications can trigger red blood cell breakdown. Can I Work Out With a New Piercing or Tattoo? J Infect Dis. While there are no large, prospective, well-controlled studies in pregnant women and their babies, some retrospective epidemiologic studies suggest an association between first trimester exposure to BACTRIM with an increased risk of congenital malformations, particularly neural tube defects, cardiovascular abnormalities, urinary tract defects, oral clefts, and club foot. 9. 7 Things You Should Avoid If You Have G6PD Deficiency - Verywell Health Receiving a tattoo adds more work to the immune system delaying the healing process for your body. Mycobacterium fortuitum-induced persistent parotitis: successful therapy with clarithromycin and ciprofloxacin. After diluting with 5% dextrose in water, the solution should not be refrigerated and should be used within 6 hours. Data sources include IBM Watson Micromedex (updated 1 May 2023), Cerner Multum (updated 17 Apr 2023), ASHP (updated 10 Apr 2023) and others. Local reaction, pain and slight irritation on intravenous (IV) administration are infrequent. Skipping doses could make your infection resistant to medication. Also, although an artist has the right to refuse service to a potential client based on health reasons, you also have the right to take your business elsewhere if you feel the artist was in error or being unfair. Removal may require special treatment in the clinic or hospital. Mayo Clinic College of Medicine and Science, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic School of Graduate Medical Education, Mayo Clinic School of Continuous Professional Development, Mayo Clinic on Incontinence - Mayo Clinic Press, NEW Mayo Clinic on High Blood Pressure - Mayo Clinic Press, Mayo Clinic on Hearing and Balance - Mayo Clinic Press, FREE Mayo Clinic Diet Assessment - Mayo Clinic Press, Mayo Clinic Health Letter - FREE book - Mayo Clinic Press, Financial Assistance Documents Minnesota, Sulfamethoxazole And Trimethoprim (Oral Route). However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. In vitro reverse mutation bacterial tests according to the standard protocol have not been performed with sulfamethoxazole and trimethoprim in combination. Make sure you ask your tattoo artist what ingredients their inks contain. The pharmacokinetics of sulfamethoxazole 800 mg and trimethoprim 160 mg were studied in six geriatric subjects (mean age: 78.6 years) and six young healthy subjects (mean age: 29.3 years) using a non-US approved formulation. (2012). doi:10.5863/1551-6776-22.6.471, Feghaly J, Al Hout AR, Mercieca Balbi M. Aspirin safety in glucose-6-phosphate dehydrogenase deficiency patients with acute coronary syndrome undergoing percutaneous coronary intervention. You may be having an allergic reaction to the ink. Simple infections confined to the skin and underlying superficial soft tissues generally respond well to outpatient management. This is one of the major risks you should be aware of before getting a new piercing or tattoo. Bactrim may also be prescribed to children over 2 months old, and the dosage is based on the childs weight. Nov 1973;128 (Suppl): S657-S663. No adverse effects on fertility or general reproductive performance were observed in rats given oral dosages as high as 350 mg/kg/day sulfamethoxazole plus 70 mg/kg/day trimethoprim, doses roughly two times the recommended human daily dose on a body surface area basis. Most infections can be treated within a week with antibiotics. Peritoneal dialysis is not effective and hemodialysis is only moderately effective in eliminating trimethoprim and sulfamethoxazole. ! Make your tax-deductible gift and be a part of the cutting-edge research and care that's changing medicine. We'll discuss why. BACTRIM-induced thrombocytopenia may be an immune-mediated disorder. Avoid use of BACTRIM in patients with impaired renal or hepatic function, in those with possible folate deficiency (e.g., the elderly, chronic alcoholics, patients receiving anticonvulsant therapy, patients with malabsorption syndrome, and patients in malnutrition states) and in those with severe allergies or bronchial asthma. She has been an amateur artist as a hobby since grade school, and served a 12 month tattoo apprenticeship in a tattoo studio. You should also avoid "quinolone" antibiotics. Drinking extra water will help to prevent some unwanted effects (eg, crystals in the urine). We comply with the HONcode standard for trustworthy health information. Last updated on Oct 18, 2021. Generic name: sulfamethoxazole and trimethoprim [SUL-fa-meth-OX-a-zole-and-trye-METH-oh-prim] Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. Skin and soft tissue infections. The mean renal clearance of trimethoprim was significantly lower in geriatric subjects compared with young adult subjects (19 mL/h/kg vs. 55 mL/h/kg). Nu-Cotrimox Septa Pediatric Septra Pediatric Suspension Descriptions Sulfamethoxazole and trimethoprim combination is used to treat infections including urinary tract infections, middle ear infections (otitis media), bronchitis, traveler's diarrhea, and shigellosis (bacillary dysentery). Children 2 months of age and olderDose is based on body size and must be determined by your doctor. Keenan M. (2015). Tattoos are also becoming less controversial in the workplace in many industries. the unsubscribe link in the e-mail. All rights reserved. Bactrim is a combination antibiotic used to treat infections such as those affecting the ear, urinary tract, lungs, or gastrointestinal tract. other information we have about you. Not all possible drug interactions are listed here. The following infusion systems have been tested and found satisfactory: unit-dose glass containers; unit-dose polyvinyl chloride and polyolefin containers. Around 4 in 10 Americans now have one or more tattoos. Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available. Weighing 8 kg1 teaspoonful (5 mL) 4 times a day for 14 to 21 days. Margassery S, Bastani B. Bactrim Prices, Coupons & Savings Tips - GoodRx Minor bumps and rashes can usually be managed at home with antibacterial ointment, proper cleaning, and rest. (twice a day). Hypersensitivity and Other Fatal Reactions [see, Hepatitis (including cholestatic jaundice and hepatic necrosis), Elevation of serum transaminase and bilirubin, Sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides) and oral hypoglycemic agents (cross-sensitivity may exist with these agents), Diuresis and hypoglycemia (have occurred in patients receiving sulfonamides), Known hypersensitivity to trimethoprim or sulfonamides [see, History of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulfonamides [see, Patients with documented megaloblastic anemia due to folate deficiency [see, Pediatric patients less than two months of age [see, Severe renal insufficiency when renal function status cannot be monitored [see, Concomitant administration with dofetilide. AIDS patients may not tolerate or respond to BACTRIM in the same manner as non-AIDS patients. Localized cutaneous infections in immunocompetent individuals due to rapidly growing mycobacteria. Additional adverse reactions included gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. J Pediatr Pharmacol Ther. Children 2 months of age and olderDose is based on body weight and must be determined by your doctor. Monitor patients for hematologic toxicity. . 6. and transmitted securely. Primaquine is a medicine used to treat or prevent malaria. For specific information regarding susceptibility test interpretive criteria, and associated test methods and quality control standards recognized by FDA for this drug, please see https://www.fda.gov/STIC. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. Please enable it to take advantage of the complete set of features! Treatment failure and excess mortality were observed when BACTRIM was used concomitantly with leucovorin for the treatment of HIV positive patients with Pneumocystis jirovecii pneumonia in a randomized placebo controlled trial.4 Avoid coadministration of BACTRIM and leucovorin during treatment of Pneumocystis jirovecii pneumonia. 11. And, unfortunately, it wouldn't be the artist's fault. J. Nephrol. Drug-induced uveitis. Symptom relief is often seen within 3 days of starting treatment. For this reason, experts recommend screening for the condition before using rasburicase. (2016). Your tattooist makes thousands of tiny puncture wounds on your skin so that ink can be inserted. sore throat. G6PD is an inherited form of hemolytic anemia that can cause damage to your red blood cells. information highlighted below and resubmit the form. When administered at high doses as for the treatment of P. jirovecii pneumonia and concomitantly with other products that contain propylene glycol, hyperosmolarity with anion gap metabolic acidosis, including lactic acidosis can occur. Following repeated intravenous administration of the same dose at 8-hour intervals, the mean plasma concentrations just prior to and immediately after each infusion at steady state were 5.6 0.6 g/mL and 8.8 0.9 g/mL for trimethoprim and 70.6 7.3 g/mL and 105.6 10.9 g/mL for sulfamethoxazole. 2003;289(16):2120-2127. Learning how to choose a good tattoo artist and take care of your tattoo are crucial to making sure that your tattoo heals well, doesnt get infected, and looks the way you want it to. This content does not have an Arabic version. Would you like email updates of new search results? If they didnt provide you with clear guidelines afterward, give them a call. 7. Marinella MA. In in vitro and in vivo tests in animal species, sulfamethoxazole/trimethoprim did not damage chromosomes. Take Bactrim exactly as prescribed by your doctor. Amber Yates, MD, is a board-certified pediatric hematologist and a practicing physician at Baylor College of Medicine. Do NOT administer BACTRIM intramuscularly. Pyrexia, hematuria and crystalluria may be noted. Additional monitoring of blood glucose may be warranted. doctor said i should try for 7 days if i can but 6 if it looks healed could work. Symptoms of a tattoo infection include: a rash . Tattoos and infection: Think before you ink. This interaction should be kept in mind when BACTRIM is given to patients already on anticoagulant therapy, and the coagulation time should be reassessed. Tattoos are an increasingly common sight. We recommend trimethoprim-sulfamethoxazole (TMP-SMX) as the treatment of choice for PCP of any severity in patients without HIV . High dosage of trimethoprim, as used in patients with P. jirovecii pneumonia, induces a progressive but reversible increase of serum potassium concentrations in a substantial number of patients. Sulfamethoxazole alone was positive in an in vitro reverse mutation bacterial assay and in in vitro micronucleus assays using cultured human lymphocytes. Yes, Bactrim DS contains sulfamethoxazole and trimethoprim. Advise pregnant women of the potential harm of BACTRIM to the fetus (see Clinical Considerations). Medicines that interact with Bactrim may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Bactrim. By rejecting non-essential cookies, Reddit may still use certain cookies to ensure the proper functionality of our platform. include protected health information. If an infection isnt treated soon enough or cant be treated properly because the bacteria have become resistant to an antibiotic, abscesses can result. All rights reserved. If signs of bone marrow depression occur, the patient should be given leucovorin 5 to 15 mg daily until normal hematopoiesis is restored. You should also see a doctor if you experience uncomfortable itching around the tattooed area or if the area is oozing pus or fluid. Let the area air-dry for a few minutes. Moh R, et al. It is a white to light yellow, odorless, bitter compound with a molecular weight of 290.3 and the following structural formula: Sulfamethoxazole is N1-(5-methyl-3-isoxazolyl) sulfanilamide. Many people with G6PD deficiency don't experience any symptoms at all on a daily basis. The formulation of N 4-hydroxy metabolite is mediated via CYP2C9. Avoid use of BACTRIM in the treatment of streptococcal pharyngitis. It seemed to be missing beats and stopping at times. Pneumocystis jirovecii Pneumonia (1.1) Shigellosis (1.2) Aquaphor is a skin care staple for many people who have dry, chapped skin or lips. information is beneficial, we may combine your email and website usage information with How long does it take for a boil to heal while taking Bactrim? * A total daily dose of 10 to 15 mg/kg was sufficient in 10 adult patients with normal renal function in a published literature. If you miss a dose of this medicine, take it as soon as possible. Weighing 80 kilograms (kg)10 teaspoonfuls (50 milliliters (mL)) or 5 tablets (or 2 DS tablets) 4 times a day for 14 to 21 days. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. can i start back and finish 4 days? Before getting a tattoo, find out if youre allergic to any ingredients in tattoo ink. Diagnosis and treatment can be difficult without clinical suspicion. May lower blood sugar levels in people without diabetes. However, if you have G6PD deficiency, your body makes a smaller amount of G6PD, which can lead to anemia. Clinical studies have documented that patients with group A -hemolytic streptococcal tonsillopharyngitis have a greater incidence of bacteriologic failure when treated with BACTRIM than do those patients treated with penicillin, as evidenced by failure to eradicate this organism from the tonsillopharyngeal area. 2001;14(5):410-414. Even treatment with recommended doses may cause hyperkalemia when trimethoprim is administered to patients with underlying disorders of potassium metabolism, with renal insufficiency, or if drugs known to induce hyperkalemia are given concomitantly. If you stop taking this medicine too soon, your symptoms may return. Anecdotally, some people have reported unusual skin reactions to tattoos when they were on antibiotics. Trimethoprim is metabolized in vitro to 11 different metabolites, of which, five are glutathione adducts and six are oxidative metabolites, including the major metabolites, 1-and 3-oxides and the 3-and 4-hydroxy derivatives. Mayo Clinic College of Medicine and Science, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic School of Graduate Medical Education, Mayo Clinic School of Continuous Professional Development, Mayo Clinic on Incontinence - Mayo Clinic Press, NEW Mayo Clinic on High Blood Pressure - Mayo Clinic Press, Mayo Clinic on Hearing and Balance - Mayo Clinic Press, FREE Mayo Clinic Diet Assessment - Mayo Clinic Press, Mayo Clinic Health Letter - FREE book - Mayo Clinic Press, Financial Assistance Documents Minnesota, Sulfamethoxazole And Trimethoprim (Oral Route). Concurrent administration is contraindicated, Elevated plasma concentrations of dofetilide have been reported following concurrent administration of trimethoprim and dofetilide. Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Accessibility BACTRIM (sulfamethoxazole and trimethoprim) is a synthetic antibacterial combination product available in a pediatric suspension for oral administration, with each teaspoonful (5 mL) containing. Getting a tattoo from a person or a shop that doesnt properly clean their tools or provide you with instructions for keeping your fresh tattoo clean can lead to skin conditions, infections, or other health problems. Oral isotretinoin for acne. privacy practices. Side Effects of Bactrim (Trimethoprim and Sulfamethoxazole - RxList (2012). May interact with several other drugs including thiazides, warfarin, phenytoin, leucovorin, methotrexate, digoxin, and medications for diabetes. A tattoo blowout looks like your tattoo is bleeding or blurry outside the lines. In those instances where fluid restriction is desirable, each 5 mL may be added to 75 mL of 5% dextrose in water. Severe skin reactions, generalized bone marrow suppression [see WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS], a specific decrease in platelets (with or without purpura), and hyperkalemia are the most frequently reported severe adverse reactions in elderly patients. pain, tenderness, or swelling of the foot or leg. Was taking bactrim ds for 6 days for skin infection. The "DS" form means double strength. C. difficile produces toxins A and B which contribute to the development of CDAD. Bookshelf We include products we think are useful for our readers. Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. You may need more frequent check-ups or medical tests if you also use medicine to treat depression, diabetes, seizures, or HIV. There have been reports of marked but reversible nephrotoxicity with coadministration of BACTRIM and cyclosporine in renal transplant recipients. Keep from freezing. However, keep in mind that it may be difficult to know what exactly is in tattoo inks as they arent regulated in any way. The dose of this medicine will be different for different patients. (875 mg orally every 12 hours) plus either doxycycline (100 mg orally twice daily) or trimethoprim-sulfamethoxazole (TMP-SMX; one to two double-strength . They can let you know whether the medications are safe to take with G6PD deficiency. Follow all directions on your prescription label and read all medication guides or instruction sheets. The good news? Mar 1979;15:447-451. Non-tuberculous mycobacterium skin infections after tattooing in healthy individuals: A systematic review of case reports. Suvanasuthi S, Wongpraparut C, Pattanaprichakul P, Bunyaratavej S. Nagore E, Ramos P, Botella-Estrada R, Ramos-Nguez JA, Sanmartn O, Castejn P. Acta Derm Venereol. Persistent, sometimes itchy, and painful bumps in your tattoo may be signs of an atypical mycobacterial infection. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors. Drug-induced thrombocytopenia is a rare but serious adverse reaction to sulfonamide antibiotics like Bactrim/Septra. This medicine is also used to prevent or treat Pneumocystis jiroveci pneumonia or Pneumocystis carinii pneumonia (PCP), a very serious kind of pneumonia. If a significant blood dyscrasia or jaundice occurs, specific therapy should be instituted for these complications. Under these circumstances the solution should be mixed just prior to use and should be administered within 2 hours. What drugs should be avoided with a sulfa allergy? J Ophthalmic Inflamm Infect. If youre experiencing an infection, treatment depends on the cause. You may opt-out of email communications at any time by clicking on Unable to load your collection due to an error, Unable to load your delegates due to an error. This ointment gets its moisturizing powers mainly from petrolatum, lanolin, and glycerin. These effects are reversible by folinic acid therapy. Complete blood counts should be done frequently in patients receiving BACTRIM. Increased digoxin blood levels can occur with concomitant BACTRIM therapy, especially in elderly patients. Revised: Jul 2020. EMPIRIC ANTIBIOTIC GUIDELINES FOR SKIN AND SOFT TISSUE INFECTIONS IN PATIENTS ON PEDIATRIC SERVICES This guideline is designed to provide guidance in pediatric patients with a primary skin and soft tissue infection (SSTI). doi:10.1136/adc.85.5.411. Should not be used in pregnant or lactating women or babies less than two months old. Adjunctive folinic acid with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death. The gasping syndrome is characterized by central nervous system depression, metabolic acidosis, and gasping respirations. All rights reserved. ive missed three doses. Other over-the-counter pain relievers like acetaminophen or ibuprofen don't cause issues with G6PD. PPD is used in hair dye because it is a permanent dye that gives a natural look, and the dyed hair can also be shampooed or permed without losing its colour. They both are antibiotics used to treat a variety of bacterial infections. Bactrim is available as a generic under the name sulfamethoxazole/trimethoprim. (2012). Created for people with ongoing healthcare needs but benefits everyone. Prescription drugs for acne can cause skin to be hyper-sensitive. Quinolones, including Cipro and Levaquin. Probably not. A 34-year-old active duty marine male with no sign Dont feel shy about asking the parlor about how they sterilize their instruments and meet safety standards. Clin Pharmacol Ther.