Drug caveats with liver and kidney disease

Contraindications and Cautions with Liver and Kidney Disease (Drugs Are Detoxified)

Drug-drug interactions can occur by adding a drug that interferes with either the normal detoxification actions of the liver or with clearance via the kidney. However, the liver and kidneys should also figure into concerns for single drugs when either of them is compromised.

Drug-drug interactions occur in healthy patients because of clashes between different drugs, and single drug toxicity occurs in patients who are not healthy because of liver and/or kidney disease.

Drugs are cleared from the body by the enzymes of the liver changing them into substances that can be excreted by the kidneys via urine. The kidneys, besides partnering with the liver in this mission, can also primarily clear certain drugs on their own. The liver, to a lesser extent that the kidneys, can even clear some drugs on its own through excretion into bile that essentially transports these drugs into fecal matter, which of course eventually leaves the body. Therefore, problems with the liver and/or kidneys can be a challenge for physicians that are trying to treat an illness with medication. It becomes a delicate balancing act of managing drug toxicity with drug effectiveness.

What can cause impairment of liver function?

Over a thousand medications and herbal products have been implicated in drug-induced toxicity. Since these are only possible —remotely so, in some cases—and not probable causes of toxicity, a doctor must weigh the risks versus benefits of any drug that could theoretically impact a patient’s liver and even cause acute liver failure. If one were to survive acute liver failure beyond 26 weeks, the acute liver failure can then be deemed chronic liver failure. Besides drugs, there are other causes of liver damage and acute liver failure, including the following:

  • Alcoholism: It causes cirrhosis, which is fatty infiltration that replaces functional liver cells.
  • Infection: Hepatitis B, Hepatitis C, and herpes simplex can greatly damage the liver.
  • Drugs: A number of drugs can cause liver damage. Such drugs include the following:
    • Acetaminophen. This is the most common cause of acute liver failure.
    • Aspirin
    • NSAIDs
    • Oral antifungals (ketoconazole)
    • Anticonvulsants (valproic acid)
    • Antibiotics (tetracycline, amoxicillin, ciprofloxacin, nitrofurantoin, rifampin, and sulfonamides)
    • Monoamine oxidase inhibitors (MAOIs)
    • Statins
    • Tricyclic antidepressants (Triavil, Elavil)
    • Mushrooms, cocaine, MDMA (Ecstasy), methamphetamines, and other drugs of abuse
    • Thyroid medication (propylthiouracil—PTU)
    • Halothane (inhalant anesthetic)
  • Herbals: Like drugs, a number of herbs and herbal substances can cause liver damage. Such herbals include the following: 1
    • Herbalife
    • Ma Huang
    • Kava kava root
    • He Shon Wu
    • Chaparral leaf
    • Jin Bu Huan
    • Germander
    • Mistletoe
    • Skullcap
    • Alkaloids
    • Pennyroyal

The National Institute of Diabetes and Digestive and Kidney Diseases established the LiverTox website in collaboration with the National Library of Medicine to search for drugs and dietary supplements that can be toxic to the liver.

Because we cannot avoid every medication that has done anything to anyone at any time, lest we forbid all medicines altogether, the site also has a likelihood scale that can be used to label a drug’s likely risk of causing liver damage. The risks are listed from Category A, which are drugs that are known to cause liver injury, to Category E, which are drugs in which there is no evidence of them causing liver injury. Unknown medications are simply put into Category X until they more clearly understood.

What can cause impairment of kidney function?

Chronic kidney disease is when acute or diagnosed kidney disease continues for longer than three months. Things that can cause it include the following:

  • Diabetes;
  • Hypertension;
  • Urinary tract obstruction (stones);
  • Nephrotoxic drugs;
    • Certain antibiotics (gentamycin, tobramycin, amikacin, neomycin—usually IV drugs of the aminoglycoside class)
    • NSAIDs
    • Contrast material used in X-rays.

How is liver or kidney failure taken into account when selecting a particular medication?

A drug’s clearance property should be a primary consideration when prescribing a medicine. Certainly, if there are effective drugs that are only cleared by the kidneys, they can potentially cause liver failure. The opposite is true, as well. However, there is often the chance of a drug able to cause both liver and kidney disease and failure. Does this make using these medications prohibitively dangerous? Thankfully, the answer is no.

The administration of these drugs, however, must be carefully adjusted to take into account the potential for organ failure. This is the crucial thing. In the kidney, the ability to excrete drugs depends on urine flow, blood flow through the kidneys, and the condition of the kidney tissue. In the liver, its ability to prepare drugs for excretion via the kidneys or clear drugs on its own depends on liver function. In both cases, the solubility of drugs in water is a factor to take into account. Consider this:

  • The kidney and water-soluble drugs: These drugs are primarily excreted by the kidneys. They have to be both water-soluble and not bound to proteins in the blood, as drugs bound to proteins do not get filtered. Drugs primarily cleared by the kidneys must have their doses carefully monitored for toxicity when patients already have kidney damage.
  • The liver and water-insoluble drugs: These drugs have to be changed by the liver so that they can either be filtered by the kidneys as water-soluble versions of themselves or excreted into bile that eliminates said drugs via feces. Drugs primarily cleared by the liver must have their doses carefully monitored for toxicity when patients already have liver damage.

It goes in, it must come out

Medications that aren’t cleared effectively usually build up to toxic levels. Those trying to keep overall toxicity levels subtoxic (non-toxic) yet therapeutic have to take into account to what extent a drug is eliminated, where it is eliminated, and how fast it is eliminated in both healthy patients and liver- or kidney-compromised patients. This makes care for such compromised patients a dynamic interaction between the care-takers and the cared-for.