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Phenytoin: phenytoin is one of those drugs that is an inducer on its own so you don’t typically think about it being affected by inducers or inhibitors. It can, with rifampin, you can have near – or you can have therapeutic failure of phenytoin because it will be metabolized away so quickly that the serum concentrations will be diminished. Also with inhibition, any of those drugs that I have listed there can result in significant increases. For example fluoxetine can result in 100 to 200% increases in serum concentration of phenytoin. So it’s something you need to pay attention to and make dosage adjustments.
Terfenadine and astemizole: I’m sure all of you have heard and seen all of the information on this. Received many “Dear Dr.” letters about it. As far as induction, the use of a drug that induces liver enzymes is not a problem with these agents. The place that we get in trouble is with drugs that inhibit liver enzymes. I will make the comment that loratadine, which is the other non-sedating antihistamine, is inhibited. The metabolism of it is inhibited by all of these drugs. The difference is the parent compound does not have cardiotoxic properties. So it is an option in this situation. But all of these drugs that I have listed there can result in syncopal episodes, torsades have been reported and there also have been deaths reported. In this situation grapefruit juice actually down there at the bottom, has resulted in Q-t prolongation. So there actually hasn’t been a fatality reported but there’s been some things suggesting that it could be a problem. Cheap propecia 5 mg.
Theophylline is affected both by inducers and inhibitors resulting in changes in serum concentrations, necessitating both or either dosage increases or decreases. Warfarin also is one of those drugs that can be significantly affected resulting in potential problems, potentially significant problems, for the patient. So close monitoring is needed. The one that I will point out, that I’ve actually seen problems happen with, is the trimethoprim sulfamethoxazole inhibiting the metabolism of warfarin and resulting in bleeding. I guess the situation that I saw it most in was in patients who were … postpartum patients, who had had problems with DVT. They were put on warfarin for short term and then they would call in and they would say, “I have typical symptoms of a UTI” and then Bactrim would be called in without remembering that the patient was on warfarin. We have had a couple … I‘ve seen a couple of situations where the patient actually has had problems with bleeding in that situation.
We’ll move on now and get out of the metabolism area and we’ll talk about altered excretion. Diuretics basically increase sodium resorption and lithium always follows sodium in the kidney. If you wonder about lithium, just think about what happens to sodium and that’s what happens to lithium. When a patient takes a diuretic we have increase in sodium re-absorption, so you also have increased lithium re-absorption with increases in lithium serum concentrations happening. Also, with non-steroidal antiinflammatory agents, this is an example of indomethacin. This is a kind of confusing slide. The top curve here with the open circles is urinary lithium levels. The bottom line is plasma lithium levels, and this center section that is kind of striped is the time period that the patients received indomethacin. So if we look here at the time they began taking indomethacin, plasma lithium levels rose that directly correspond to urinary lithium excretion going down. When the indomethacin was discontinued the urinary excretion went up and the plasm lithium levels came back down corresponding to that. It appears as though sulindac is a non-steroidal that does not have affects on the prostaglandins in the kidney. So it appears as though it does not – Clinoril or sulindac would not have this affect on serum lithium levels. But all the other non-steroidals will have this effect to varying degrees. So you would want to monitor lithium levels in those patients who you end up putting on a non-steroidal as chronic therapy. If they are taking it occasionally, it’s not a problem. But if they are taking it chronically it can be. Canadian viagra.

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Cisapride with induction: there really are not any clinically significant type side effects that need to be concerned about when a drug that induces liver enzymes is induced simultaneously. However, when drugs that inhibit cisapride’s metabolism are administered – drugs like ketoconazole, itraconazole, fluconazole, metronidazole, erythromycin and clarithromycin – a reaction very similar to those with the non-sedating antihistamines occurs, with potential for ventricular tachycardia and ventricular fibrillation. There have also been some reports of death as a result of this interaction. So this is one that you obviously want to keep in mind and try to avoid. There’s been some in vitro speculation, no case reports, but there has been some speculation because of the way cisapride is metabolized that these drugs could have some problems associated with their use. Human Growth Hormone pharmacy.
Cyclosporine: we worry about the use of things like phenytoin, carbamazepine, Phenobarbital, also rifampin in a patient that’s receiving cyclosporine and the potential for increasing it’s metabolism to the point that an inadequate immunosuppressive response would be seen, necessitating dosage increases of cyclosporine. Now we have used drugs to inhibit cyclosporine’s metabolism on purpose, because cyclosporine is such an expensive drug and it’s kind of nice if you can make it hang around longer and you can use lower dosages. So sometimes we do use that combination, or some of the combinations intentionally for that purpose. To try to decrease the amount of cyclosporine that needs to be taken.
With the oral contraceptives and estrogens, all of the anticonvulsants – with the exception of sodium valproate and the newer ones, lamotrigine and gabapentin – will induce the metabolism of the oral contraceptives for all practical purposes making them ineffective. There was one study that looked at a patient who was receiving phenytoin and they administered Ortho-Novum 150 – which isn’t even available anymore – to the patient and they had non-detectable estradiol levels. It took up to the equivalent of Ortho-Novum 1-100 before estradiol levels were such that the patient would not become pregnant. So the use of a different form other than oral contraceptives is suggested in those patients. Also rifampin and griseofulvin can have similar effects. Under inhibition, I have not affected. What I mean by non-affected is that contraception will still be achieved. That does not mean that the patient may not complain of some type of side effects, like maybe increased nausea. May complain of breast tenderness and those sorts of things. So you may see exacerbation of side effects but you will not see decreased efficacy of the therapy. Viagra online pharmacy.
The HMG-CoA reductase inhibitors, primarily lovastatin – although it can happen with all of them – the big problem is with inhibition. If we inhibit its metabolism through itraconazole or erythromycin we can end up with problems with increases in creatine kinase, with the progression on to rhabdomyolyses and those type of problems.
The protease inhibitors: one problem that we run into it with it is in a patient receiving rifampin of the treatment of TB, and TB is becoming a bigger problem with our AIDS population and they need to be treated for tuberculosis. The CDC has actually published a report with their recommendations of how to treat patients in this situation. Because rifampin can cause sub-therapeutic levels of the protease inhibitors and we know that part of the reason for resistance to the protease inhibitors is sub-therapeutic levels. The last thing we want to do is treat the patient for TB and then make their protease inhibitors ineffective, or for them to develop resistance to that. So if you ever have the need, the CDC does have very specific recommendations. Also with inhibition, if the patient needs fluconazole or ketoconazole, dosage decreases of the protease inhibitors may be needed.