Renal Disease

Renal insufficiency results from a functional loss of nephrons. Although generally transient and reversible as in acute renal failure, the loss may be permanent and lead to dialysis in chronic renal failure.

Table 30-1. Medication use in hepatic disease

Medication class

Impact of hepatic disease on drug dosing

Potential drug effect on liver function

Antidepressants

Antipsychotics

Mood stabilizers

ADHD medication treatments

Antidepressants that are metabolized by phase I hepatic oxidative metabolism require an approximately 50% dosage reduction.

Doses of bupropion should not exceed 75 mg/day in patients with cirrhosis.

Trazodone requires dosage reduction due to prolonged clearance of trazodone in patients with hepatic disease.

Atypical antipsychotics that are metabolized by phase I hepatic oxidative metabolism require dosage reduction.

Anxiolytics/hypnotics

Benzodiazepine half-lives are increased in hepatic disease.

Lorazepam, oxazepam, and temazepam require no dosage adjustment in hepatic disease because they are metabolized by phase II hepatic oxidative metabolism.

Zaleplon and zolpidem require dosage reduction.

Carbamazepine, divalproex, lamotrigine, and topiramate require dosage reduction and close monitoring.

No dosage adjustment is required for gabapentin or lithium.

Atomoxetine requires 25%-50% reduction in dosage.

TCAs may exacerbate hepatic encephalopathy by anticholinergic action.

Nefazodone use is contraindicated in hepatic disease.

Minor elevations in transaminases are common and usually benign.

Sertraline's short half-life and less potent inhibition of CYP 2D6 make it the preferred SSRI in hepatic disease.

Chlorpromazine is associated with intrahepatic cholestasis and obstructive hepatic disease.

Low-potency drugs may precipitate hepatic encephalopathy in patients with cirrhosis.

Discontinue clozapine in patients with marked transaminase elevations or jaundice.

Avoid use of benzodiazepines in patients at risk of hepatic encephalopathy.

Divalproex sodium is associated with hepatic failure in 1 in 40,000 cases.

Carbamazepine is associated with hepatitis.

Carbamazepine and valproic acid are contraindicated in patients with preexisting hepatic disease.

Note. ADHD = attention-deficit/hyperactivity disorder; CYP = cytochrome P450; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant. Source. Beliles 2000b; Jacobson 2002; Robinson and Owen 2005.

The pharmacodynamic effects of renal failure include increased receptor activation, whereas phar-macokinetic effects include delayed drug clearance (Beliles 2000b). Renal insufficiency may result in decreased drug absorption from the small intestine due to the gastric-alkalinizing effects of increased ammonia levels that develop in the presence of excess urea. Renal insufficiency may increase the volume of distribution of water-soluble or protein-bound drugs with a consequent reduction in plasma levels. Plasma protein binding may be reduced in nephrotic syndrome as a result of decreases in albumin. Displacement of highly protein-bound drugs may result in increased availability of these drugs for renal filtration and excretion. Renal insufficiency may also be associated with decreased firstpass metabolism and influence hepatic clearance due to cytochrome P450 inhibition (Dreisbach and Lertora 2003; Michaud et al. 2005). Renal excretion or clearance is reduced in renal failure and is significant for drugs that are cleared primarily by renal excretion. Renal blood flow may be altered by changes in glomerular vasculature, severe dehydration, and conditions affecting other organ systems (e.g., cirrhosis).

In general, initial dosages of medications should be reduced or dosing intervals lengthened in patients with renal failure (see Table 30-2). However, with the exception of lithium and gabapentin, psy-chotropic medications do not require significant dosing adjustments in patients with renal failure (Levy 1990). Nevertheless, it is important to monitor serum concentrations in renal insufficiency, particularly for medications with a narrow therapeutic index. Lithium may be given to renal transplant recipients; however, cyclosporin may elevate serum lithium levels by decreasing lithium excretion, necessitating a dosage adjustment. Patients with renal failure and those on dialysis appear to be more sensitive to TCA side effects, possibly due to the accumulation of hydroxylated tricyclic metabolites (Lieb-erman et al. 1985).

Eliminating Stress and Anxiety From Your Life

Eliminating Stress and Anxiety From Your Life

It seems like you hear it all the time from nearly every one you know I'm SO stressed out!? Pressures abound in this world today. Those pressures cause stress and anxiety, and often we are ill-equipped to deal with those stressors that trigger anxiety and other feelings that can make us sick. Literally, sick.

Get My Free Ebook


Post a comment