Drug Toxicity

How drug toxicity happens

Every medicine has a range of blood levels where it works. Below the range it does little; above it, side effects turn into toxicity. For most drugs this window is wide. For narrow therapeutic index drugs, the toxic level is only slightly above the effective level, so small changes in how the body handles the drug matter.

Toxicity at a normal dose usually happens for one of these reasons:

• Reduced kidney function: many drugs leave the body in urine. Acute kidney injury, chronic kidney disease or simple dehydration lets them accumulate. Lithium, digoxin, metformin, gabapentin and some antibiotics are typical.
• Liver disease: the liver breaks down most other medicines.
• Drug interactions: one drug can block the enzymes that clear another. For example, some antibiotics and antifungals raise levels of warfarin, statins and certain heart drugs; NSAIDs, diuretics and ACE inhibitors raise lithium levels.
• Older age: lower kidney function, less muscle and body water, and more medicines overall. See polypharmacy.
• Illness: vomiting, diarrhea, fever or not eating can rapidly change drug levels and blood salts.
• Dosing errors: taking a dose twice, confusing brands and generics, or measuring liquid medicine incorrectly.

Medicines most often linked to toxicity

Blood pressure medicine toxicity

Antihypertensive drug poisoning usually causes low blood pressure and a slow heart rate, with dizziness, fainting, tiredness and cold, clammy skin. Beta-blockers and calcium channel blockers are the most dangerous in overdose and can also cause high blood sugar (calcium channel blockers) or low blood sugar (beta-blockers, especially in children). Clonidine causes drowsiness, small pupils and slow breathing. Even one adult tablet can harm a toddler. Toxicity can also build up at regular doses when kidney function falls or another blood pressure drug is added. See blood pressure medication overdose for first aid and treatment.

Drug combinations that cause toxicity

Some combinations produce toxic effects even when each drug level is normal. Serotonin syndrome, from combining antidepressants with other serotonin-raising drugs such as tramadol, triptans or linezolid, causes agitation, sweating, muscle twitching and fever. Combining opioids with benzodiazepines, gabapentinoids or alcohol depresses breathing.

Symptoms

Toxicity often starts with vague symptoms, which is why it is missed:

• nausea, vomiting, diarrhea and loss of appetite
• drowsiness, confusion or unusual behavior, especially in older adults
• dizziness, unsteadiness and falls
• tremor, twitching or slurred speech
• palpitations, slow or irregular heartbeat
• bleeding or bruising
• ringing in the ears or changes in vision

Diagnosis

A doctor will ask exactly which medicines you take, including over-the-counter medicines and supplements, any recent changes, and when the last dose was taken. Bringing all your medicine bottles helps. Tests may include:

• Drug levels: blood tests for lithium, digoxin, phenytoin, carbamazepine, valproate, theophylline, vancomycin, aminoglycosides, acetaminophen and salicylate. Timing matters, so the time of the last dose is recorded.
• INR for warfarin.
• Kidney and liver function, sodium, potassium and blood sugar.
• ECG for heart-active drugs.

Regular therapeutic drug monitoring, meaning scheduled blood level tests, is part of routine care for lithium, some antiseizure drugs and certain antibiotics.

Treatment

• Stopping or reducing the drug is often enough for mild toxicity.
• Fluids and correcting salts such as potassium and sodium.
• Activated charcoal within a few hours of a large overdose of some drugs, in hospital.
• Antidotes: acetylcysteine for acetaminophen, vitamin K and clotting factors for warfarin, digoxin-specific antibody fragments for digoxin, naloxone for opioids, and glucagon, calcium and high-dose insulin therapy for beta-blocker or calcium channel blocker poisoning.
• Dialysis removes some drugs quickly, including lithium, salicylates, metformin and theophylline, in severe cases.
• Heart monitoring for drugs that affect rhythm.

Preventing drug toxicity

• Keep an updated list of every medicine and supplement, and show it to each doctor and pharmacist.
• Use one pharmacy where possible, so interactions are flagged.
• Keep scheduled blood tests for monitored drugs.
• Ask your doctor for a "sick day" plan. Some medicines, such as diuretics, ACE inhibitors, metformin and lithium, may need pausing during vomiting, diarrhea or dehydration. Do not stop any medicine without advice.
• Avoid NSAIDs such as ibuprofen if you take lithium, or have kidney or heart problems, unless your doctor agrees.
• Use a pill organizer and store medicines out of children's reach.

Accidental and intentional overdoses, including first aid steps, are covered under medication poisoning.

Frequently asked questions

What are the signs of drug toxicity?

Common signs are nausea, vomiting, loss of appetite, drowsiness, confusion, dizziness, tremor, unsteadiness and changes in heart rhythm. Some drugs cause specific signs, such as yellow vision with digoxin, ringing in the ears with aspirin or bleeding with warfarin. Older adults may show only new confusion or falls.

Can you get drug toxicity from a normal dose?

Yes. A normal dose can become toxic when kidney or liver function falls, when another medicine slows how the drug is cleared, or during dehydration from vomiting, diarrhea or heat. This is most common with narrow-margin drugs such as lithium, digoxin and some antiseizure medicines.

What happens if you take too much blood pressure medicine?

Too much blood pressure medicine can cause dizziness, fainting, a slow heartbeat, confusion and, in severe cases, shock. Beta-blockers and calcium channel blockers are the most dangerous. Call Poison Control or 911 straight away, even if the person feels fine, because effects can be delayed with extended-release tablets.

What is a narrow therapeutic index drug?

It is a medicine whose effective dose is close to its toxic dose. Small changes in dose or blood level can cause harm or failure of treatment. Examples include lithium, warfarin, digoxin, phenytoin, carbamazepine, theophylline and tacrolimus. These drugs often need regular blood tests.

How long does drug toxicity last?

It depends on the drug and on kidney and liver function. Mild toxicity often settles within a day or two after a dose is held. Long-acting drugs and extended-release tablets can cause effects for several days. Some damage, such as liver injury or hearing loss, can be permanent.