Drug interactions reducing risk

CYP enzymes are induced, resulting in reduced plasma drug levels. Alternatively, CYP enzymes could also undergo mechanism-based inhibition, whereby a CYP enzyme can be completely inactivated by covalent bonding to a component of the herb. Furthermore, botanicals can elicit a biphasic cellular response, whereby CYP activity may be inhibited initially, followed by induction after prolonged incubation or repeated administration. Such factors would need to be considered in future studies in order to establish the true risk of ginseng in herb-drug interactions. 

Another practical example of a pharmacokinetic drug interaction concerns the incidence of seizures in patients given a standard (300 mg/ day) dose of clozapine. Should the patient be given an SSRI antidepressant (such as fluoxetine, fluvoxamine, sertraline or paroxetine) concurrently then the clearance of clozapine could be reduced by up to 50%, an effect which would be comparable with a doubling of the dose. This could lead to a threefold increase in the risk of the patient suffering a seizure. 

Isosorbide Dinitrate Hydralazine (BiDil) [Antianginal, Antihypertensive/Vasodilator, Nitrate] Uses HF in African Amer-icans improve survival functional status, prolong time between hospitalizations Action Relaxes vascular smooth muscle peripheral vasodilator Dose Initially 1 tab tid PO (if not tol ated reduce to 1/2 tab tid), titrate >3-5 d as tolerated Max 2 tabs tid Caution [C, /-] recent MI, syncope, hypovolemia, hypotension, hep impair Contra For children, concomitant use w/ PDE5 inhibitors (sildenafil) Disp Tabs SE HA, dizziness, orthostatic hypotension, sinusitis, GI distress, tach, paresthesia, amblyopia Interactions t Risk of severe hypotension W/ antihypertensives, ASA, CCBs, MAOIs, phenothiazides, sildenafil, tadalafil, vardenafil, EtOH X pressor response Wf i -1- effects W7 NSAIDs EMS Use ASA, antihypertensives and CCBs w/ caution, may t hypotension concurrent Viagra-type drug use can lead to profound hypotension concurrent EtOH use can t effects OD May cause N/V, profound hypotension, skin flushing, HA from ICP, bradycardia, confusion, and circulatory collapse activated charcoal may be effective, epi use is contraindicated... 

Cadieux Rf. Antidepressant drug interactions in the elderly. Understanding the P-450 system is half the battle in reducing risks. Postgrad Med i999d06 23i-240, 245. 

Drug interactions Proleukin may affect central nervous system function. Therefore interactions could occur following concomitant administration of psychotropic drugs. Concurrent administration of drugs possessing nephrotoxic, myelotoxic, cardiotoxic, or hepatotoxic effects with Proleukin may increase toxicity in these organ systems. Reduced kidney and liver function secondary to Proleukin treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs. Beta-blockers and other antihypertensives may potentiate the hypotension seen with Proleukin. 

Three randomized clinical trials support the efficacy of bupropion in ADHD. The first used doses up to 6 mg/kg (98) the other two used doses of 100 to 300 mg per day in equally divided daily doses spaced at least 6 hours apart ( 99, 100). The concern with bupropion is its seizure risk, which requires that its daily dose stay below 450 mg per day in adults (i.e., approximately 6.5 mg/kg). Virtually no work has been done to determine the plasma concentrations of bupropion and its three active metabolites in children and adolescents. Hence, it is unknown whether a limit of 6.5 mg per kg is also appropriate for children. No data exist as to whether children are more or less sensitive to bupropion in terms of seizure risk at the same drug concentration. Also, little is known about pharmacokinetic drug-drug interactions that could reduce the clearance of bupropion. For these reasons, cautious dosing is advised when prescribing bupropion for children on other medications that can reduce oxidative drug metabolism (see Chapter 3 and Chapter 7 for more details). 

Leibovitch ER, Deamer RL, Sanderson LA. Food-drug interactions careful drug selection and patient counseling can reduce the risk in older patients. Geriatrics. 2004 59 19-22, 32-33. 

ED and vascular disease commonly coexist. They share the same risk factors and endothelial dysfunction is the common denominator. ED may develop in an otherwise asymptomatic male and be an important predictor of subsequent acute or chronic cardiac events. ED may therefore offer an opportunity for risk assessment and therapeutic intervention to reduce the chance of a subsequent cardiac presentation. Cardiac patients with ED need a careful assessment to judge the safety of sexual activity and suitability for ED treatment. Properly assessed and counselled patients can safely enjoy sexual activity. ED therapy with phosphodiesterase type five inhibitors is safe and effective providing the patient and partner are advised on their use and the importance of avoiding drug interactions, especially with nitrates. 

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