53. understanding medication interaction

8/12/2019 53. Understanding Medication Interaction

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282 Understanding Medication Interaction11. Pickett P, Masand P, Murray GB: Psychostimulant treatment of geriatric d12. SpencerT, et al: Pharmacotherapy of attention-deficit hyperactivity disorde13. Woods SW, Tesar GE, Murray GB, Cassem NH: Psychostimulant treatm

medical illness. J Geriatr Psychiatry Neurol 3 3):146-151, 1990.Child Adolesc Psychiatry 35:409-432, 1996.ondary to medical illness. J Clin Psychiatry 47:12-15, 1986.

53 UN DERSTAN DING MEDIINTERACTIONSDee Opp, R.Ph., BCPP nd Lyle Laird, Phccv

1. Why are drug interactions important to consider?To maximize therapeutic outcome and minimize adverse side effederstand how a drug works, how it is metabolized, and what side effecthe medication. When you consider a new medication for use, you mboth dynamicallyand kinetically with other medications. For exampclonidine for hypertension, and a tricyclic antidepressant TCA) is beiprescriber should know that the TCA could antagonize the alpha-2 ago

and negate its antihypertensive effects. This is an example of a pharmait is important to have an understanding of the mechanisms of action oone is likely to antagonize or block the therapeutic effect of another.In many therapeutic regimens, physicians are faced with using mameliorate symptoms. All combinations need to be assessed for the prenamic interactions.2. What are the mechanismsof psychotropic medication metaboMost of the psychotropic medications are metabolized by a proce

lism. This type of metabolism is carried out hepatically by a group tochrome P450 CYP450) mixed oxidase system. CYP450 enzymesinto more water-soluble metabolites, which then are more easily excr


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Understanding Medication Interactionsvolume of distributionof another. If on e medication like warfarin isother highly protein-bound medication is added (e.g., valproic acid ointeract via a competition for albumin-binding sites, resulting in a risnents of on e of the medications in the blood. If the medication freed from this interaction is warfarin, the patient could be at risk for bleedinWith carbam azepine, after the initial increase in blood levels and INbinding displacement, metaboliceffects will occur due to the enzym e inticonvulsant. Warfarin will then be m etabolized more read ily, and IN R von the other hand can initially bum p INR values and m ay continue to incinhibition of warfarins main route of metabolism (the CY P45 0 isoenzy

Excretion is another mode of interaction and occurs when one medcretion of another. For example, nonsteroidal antiinflamm atory drugs (Nsynthesis, which is responsible for normal renal function. If NSAIDs (elithium, on e could observe a 30 or higher increase in lithium levels. peutic index, such a consequence could result in lithium toxicity. Othelithium disposition in this w ay are the so-called ACE inhibitors and thiaMechanisms o Drug Interactions

PHARMACOKINETIC PHARMACOAbsorptionDistribution Duplication in effect or anmedicationsMetabolism (includes the ability of medica-Excretion

Side effects common withcomplicate other mediions to induce or inhibit P 450 soenzymes)

4. How do patient specific factors play a role in predicting clinicinteractions?Age, gender, race, and co-morbid m edical conditions can com plicaplays an important role in how we choose medications and dose themmore easily toxic on water-soluble medications or medications with Hence, lithium should be prescribed in lower doses in a geriatric patiThese lower than expected doses can readily result in therapeutic blooquire closer monitoring. Liver function can be decreased in the elderly


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284 Understanding M edication Interact ionkidney impairm ent. In this exam ple, the renally comp romised indivchance of becom ing lithium toxic. Similarly, patients with severe liveare more likely to becom e toxic on m any medications, since the majopatic function fo r effective elimination from the body.

5. When assessing patient medication regimens what are twometabolic interaction?There are two drug interaction m echanism s that are crucial to detewill interact. Induction is the propensity of certain subs tances to inzymes in the liver. For example, phenytoin (relying o n CY P45 0 1A2carbamazep ine (relying on 2C 9, 3A4 ), and phenobarbital (relying o3A4) are enzyme-inducing antiepileptics. When these medications artion of certain subfamilies of isozymes in the liver. Th is enzyme inductential when the inducer m edication itself reaches steady-state cond iteach inducer) and adequate time has elapsed for the new production ofinstance, takes at least 2 weeks to see an induction effect. Other indomeprazole (1A2), nicotine I A2), rifampin (2C9, 2C19, 3A 4), ritonavbital 1 A2, 2C9, 3A4).Once m ore enzym es ar e produc ed, they metabolize substrates mocreased levels of the substrate com pared to the pre-induction period. effects of the substrate drugs, their doses need to be increased. The opis discontinued from a patients regimen, necessitating a reduction in ication to avoid potential toxicity. This type of interaction may take aducer is completely eliminated f rom the body. An exa mple is the discfrom a regimen that includes haloperidol. O nce induction has subsidelevels could place the client at greater risk of adverse drug effects.In contrast to induction, inhibition can occu r and is usually cofrom one substrate having greater affinity for an isozyme in the liverexample, erythromycin is an effective inhibitor of the 3A 4 isozyme. Iferythromycin, the metabolism of cisapride is effectively impaired, rebility of cardiac toxicity, such as Torsades d e pointes, f rom the cisapmedications can be greatly increased by the concomitant administrathibit CYP450 isozymes. Inhibition can b e immed iate, but is dose depeinhibitor, the more likely the interaction with other substrates (medicseen after one dose, but does not reach full effect until the inhibitor ha


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Understanding Medication InteractionsHence when used concomitantly with medications metabolized by thapride, nortriptyline, some antipsychotic medications) significant toxicWith complex, m ulti-medication regimens it may be prudent to cocist or pharmacologist to understand the relative risks with differentarise with side effects. Keeping track of trends in side effec ts (e.g., timmedication may provide clues to these drug interactions. Educating about these risks (including risks with over-the-counter and nontraditiring with other prescribers are essential in providing safe, effective phThe following table is not complete, but provides a guideline to astions (see next page).8 How do psychiatrists minimize adverse effects secondary to drAs a rule of thumb, it is pruden t to add only one medication at a timedifficult to d o given the enorm ous num ber of variables with any given ptioner to observe which m edication is working w hile minimizing chanceLikew ise, it is advisable to titrate dosages of only one m edication

dosage has been max imized for an adequate period of time but the pating, consider the possibility of a drug-drug interaction com plicatingyourself ad ding m edications to treat side effects, always ask yourselfanother medication is warranted before the addition.Con sider antidepressan t-induced sleep disturbance. If a patient bcomplaining of sleeplessness, evaluate drug-induced reasons f or this ogiene issues before the addition of a sleep medication. The reason maytime of administration of a medication. For example, fluoxetine, buprnot be given at bedtime secondary to the risk of activation and insommedication is prevented which in turn decreases the likelihood of drug

BIBLIOGRAPHY1. Anderson G: A mechanistic approach to antiepileptic drug interactions. Ann2. Evans WE , Schentag JJ , Jusko WJ: Applied Pharmacokinetics, 3rd ed. 3. Jefferson J: Drug interactions-Friend or foe? J Clin Psychiatry 5 9(s up pl44. Michalets EL : Update: Clinically significant cytochrome P-450 drug interac5 Shen W Th e metabolism of psychoactive d rugs: A review o f enzy matic b

Therapeutics, Inc. , 1992.

112, 1998.Biol Psychiatry 41:814-826, 1997.


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53. understanding medication interaction

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