Hepatoxicity (damage to the liver)

Hepatoxicity (damage to the liver) manifestations include:

1. hepatitis, jaundice, elevated liver enzyme levels, and fatty infiltration of the liver

2. hepatic anatomy and function both contribute to the high susceptibility of the liver to toxicants

Nephrotoxicity (damage to kidneys) signs & symptoms:

1. decreased urinary output

2. elevated blood urea nitrogen

3. increased serum creatinine

4. electrolyte imbalances

5. renal function contributes to development of nephrotoxicity

Ototoxicity (damage to 8^th cranial nerve) signs & symptoms:

1. tinnitus

2. sensorineural hearing loss

3. light-headedness, vertigo, a spinning sensation from a seated position, nausea and vomiting

Drug Interactions

1. drug interactions occur when one drug (drug "A")is affected in some way by

   another drug (drug "B"), a food, or some other substance taken concurrently

2. drug interactions may be beneficial or adverse, intended or unintended

3. drug interactions may take place in any phase of pharmacokinetics, absorption, distribution, metabolism, or excretion

Drug Interactions affecting absorption

1. drug absorption is often decreased because of drug interactions

2. if a drug binds with another substance in the GI tract, less of the drug is available to be absorbed

3. drug absorption may be increased as a result of a drug interaction or the presence of food in the GI tract

4. a less acidic environment decreases ionization of drugs that are basic, which promotes absorption of these drugs

Drug Interactions affecting metabolism

1. grapefruit juice is also known to inhibit CYP3A4

2. some herbs and botanicals may also affect the CYP3A4 enzyme, such as St John's Wort

3. alcohol & nicotine alter the metabolism of some drugs

Drug Interactions affecting Pharamacodynamics

1. drugs that act in different ways or at different receptors can interact in several ways

2. they may create an additive effect, a synergistic effect, a potentiated effect, or antagonistic effect

Additive Effect

1. Drug A + Drug B = 2 (1+1=2)

2. beneficial: (codeine combined with tylenol provides better pain control than either alone

3. harmful: alcohol taken with salicylates (aspirin) increases risk for GI bleeding; morphine taken with alcohol = CNS depression, can be fatal

Potentiated Effect

1. ½ (drug A) + (drug B) = 2

2. beneficial – antiemetic drug hydroxyzine combined with morphine increases the pain-relieving ability of the morphine without increasing the dose of the morphine

Antagonistic Effect

1. Drug A + Drug B – 0 (1+1=0)

2. beneficial – heparin and protamine sulfate (a heparin antagonist) form an ionic bond that lacks any anticoagulant activity. *antidote

Drug Incompatibilities (chemical incompatibilities between drugs change both the drug's structure and its pharmacologic properties)

1. beneficial – heparin & protamine sulfate

2. harmful – combining multivitamins & antibiotics in the same IV solution changes the solution's pH and inactivates the antibiotic (precipitates out)

Drug Incompatibilities (physical incompatibilities occur when two drugs are mixed together)

harmful

1. Phenytoin (dilantin) and a diluent containing dextrose produce a cloudy white precipitate (should only mix dilantin with normal saline)

2. this kind of reaction usually interferes with pharmacologic activity of one or both drugs

Implications for Nursing Management – health team must ensure a beneficial outcome by:

1. maximizing therapeutic effects

2. minimizing adverse effects & drug interactions

3. providing appropriate drug education for the patient & family