Part of our assignment in which we have to make a paperwork and presentation of a few sub-topics (hepatotoxicity, renal toxicity, neurotoxicity, skeletal-muscle-toxicity) under the topic of Drug-induced Toxicity.
Paperwork can be found in: http://www.slideshare.net/annisahayatunnufus/druginduced-toxicity-liver-kidney-nervous-system-muscle-54844837
Students of Bachelor of Pharmacy
Management & Science University
6. 2
3
4
1C. Prevention
Recognition and rapid discontinuation of
agent
Patient with risk factors should not
receive hepatotoxic agents if & when
alternative agents are available
Monthly monitoring liver
DRUG-INDUCED HEPATOTOXICITY
6/19
7. 3
4
1
2A. Introduction & Mechanism
Mechanism?
1. Altered intraglomerular hemodynamics 2. Tubular cell toxicity
3. Inflammation 4. Crystal nephropathy
5. Rhabdomyolysis 6. Thrombotic microan-giopathy
One of the most common kidney problems & occurs
when the body is exposed to a drug or toxin that
causes damage to the kidneys.
kidney damage occurs unable to rid of excess urine + wastes in the
body blood electrolytes (ie. K & Mg) elevated
Nephrotoxicity?
DRUG-INDUCED RENAL TOXICITY
7/19
9. 3
4
1
9/19
2B. Drugs That Cause (Ex: Aminoglycocides)
DRUG-INDUCED RENAL TOXICITY
Concentrated in renal cortex and
proximal tubular cells
AMG bind to lysosomes with
formation of myeloid bodies
Release of AMG interferes
phosphatidyl-inositol pathway.
Clinical Features:
Proximal tubular dysfunction, glycosuria, hypokalemia, hypomagnesemia
Mechanism:
10. 3
4
1
10/19
2E. Prevention
Lowest dose Shortest course of
therapy
Avoid giving
nephrotoxic drugs
concurrently
Make interval between
aminoglycoside courses
as long as possible
Patients on
aminoglycoside should
be monitored
Use aminoglycosides as
an once daily dose
rather than divided
dose
DRUG-INDUCED RENAL TOXICITY
11. 2
4
1
11/19
3A. Introduction
Drug-induced neurotoxicity most often
associated with the use of cancer
chemotherapeutic agents
Peripheral neuropathy has been associated
with:
In most cases, neurotoxicity manifests in the
peripheral nerves, but the central nervous
system may be affected as well.
Vinca Alkaloids
• Vinchristine
• Vinblastine
Platinum
Compounds
• Cisplatin
Taxanes
• Paclitaxel
DRUG-INDUCED NEUROTOXICITY
12. 2
4
1
12/19
3B. Example by Vinca Alkaloids
Originally to treat…
• leukemia
• lymphomas
• sarcomas
• brain tumors
How does it induce
neuropathy?
Disruption of microtubules within axons & interference with axonal
transport neuropathy of sensory & motor fibers Virtually all
patients have some degree of neuropathy The clinical features
resemble those of other axonal neuropathies (ex: diabetic
neuropathies)
• Loss of ankle jerks
• Profound
weakness
• Neuropathies
• Abdominal pain
• Constipation
• Impotence
• Postural hypotension
• Retinal damage
• Night blindness
• Jaw and parotid
pain.
DRUG-INDUCED NEUROTOXICITY
17. 2
3
1
17/19
4C. Clinical Presentations
• Muscles of patients with rhabdomyolysis may be tender,
stiff, or weak.
• However, most patients with drug-induced rhabdomyolysis
do not complain of swelling or tenderness at the time of
admission. They may develop a “second wave phenomenon”
in which a delayed increase in fascial compartment pressure
causes compression neuropathies, swelling, and tenderness.
• Compartment syndromes in drug-induced rhabdomyolysis
usually occur secondary to prolonged immobilization or
coma, which can result in contractures and amputations.
• Acute cardiomyopathy can present from direct toxic
effects of drugs on the cardiac muscle.
DRUG-INDUCED SKELETAL MUSCLE TOXICITY
18. 2
3
1
18/19
4D. Prevention
• Use the lowest dose possible, avoid or minimize concomitant risk factors,
and monitor carefully for onset of symptoms when drugs known to cause
myopathy cannot be avoided
• Moderate amounts of exercise and physical activity (extremely vigorous or
prolonged periods of exercise may increase the risk for drug-induced
myopathies)
• Avoid combining drugs when each has a risk of myopathy, when possible
(ex: statin + fibrates or statin + cyclosporine)
• Consider genetic screening when drug-induced myopathy occurs
DRUG-INDUCED SKELETAL MUSCLE TOXICITY
• Consider measuring a baseline creatine kinase in patients with multiple risk
factors of causing myopathy
• Educate patients regarding signs and symptoms:
discoloured urine
Weakness in addition to pain
Symptoms in more than one muscle system
Editor's Notes
Nephrotoxicity can be temporary with a temporary elevation of lab values (BUN and/or creatinine). If these levels are elevated, these may be due to a temporary condition such as dehydration or you may be developing renal (kidney failure). If the cause of the increased BUN and/or creatinine levels is determined early, and your healthcare provider implements the appropriate intervention, permanent kidney problems may be avoided.
The neuropathy cause by vinca alkaloids and taxanes is directly related to their primary mechanism of action, microtubule disruption. In peripheral nerves, microtubule disruption is thought to result in altered axonal trafficking and both sensory and motor neuropathy. Platinum- containing compounds may have direct toxic effects on peripheral nerves.
