Streptomycin

An adverse effect of this medicine is ototoxicity. It can result in permanent hearing loss.

Chemical desciptions:

Unites States National Library of Medicine: PubChem
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=19649

Snippet: Absorption, Distribution and Excretion

  • STREPTOMYCIN IS DISTRIBUTED INTO MOST BODY TISSUES & FLUIDS EXCEPT THE BRAIN. SUBSTANTIAL AMOUNTS OF THE DRUG ARE FOUND IN PLEURAL FLUID AND TUBERCULOSIS CAVITIES AND SMALL AMOUNTS ARE EXCRETED IN SALIVA AND SWEAT.
  • Because of their polar nature, the aminoglycosides are largely excluded from most cells, from the central nervous system, and from the eye. Except for streptomycin, there is negligible binding of aminoglycosides to plasma albumin. The apparent volume of distribution of these drugs is 25% of lean body weight and approximates the volume of extracellular fluid.
  • As would be expected, concentrations of aminoglycosides in secretions and tissues are low. High concentrations are found only in the renal cortex and in the endolymph and perilymph of the inner ear; this may contribute to the nephrotoxicity and ototoxicity caused by these drugs. Concentrations in the bile approach 30% of those found in plasma as a result of active hepatic secretion, but this represents a very minor excretory route for the aminoglycosides. Penetration into respiratory secretions is poor. Diffusion into pleural and synovial fluid is relatively slow, but concentrations that approximate those in the plasma may be achieved after repeated administration. Inflammation increases the penetration of aminoglycosides into peritoneal and pericardial cavities.
  • Administration of aminoglycosides to women late in pregnancy may result in accumulation of drug in fetal plasma and amniotic fluid.
  • The aminoglycosides are excreted almost entirely by glomerular liberation, and concentrations in the urine of 50 to 200 ug/ml are achieved. A large fraction of a parenterally administered dose is excreted unchanged during the first 24 hours, with most of this appearing in the first 12 hours.
  • All of the aminoglycosides are absorbed rapidly from intramuscular sites of injection. Peak concentrations in plasma occur after 30 to 90 minutes and are similar to those observed 30 minutes after completion of an intravenous infusion of an equal dose over a 30 minute period. In critically ill patients, especially those in shock, absorption of drug may be reduced from intramuscular sites because of poor perfusion.
  • The aminoglycosides are highly polar cations; they are thus very poorly absorbed from the gastrointestinal tract. Less than 1% of a dose is absorbed following either oral or rectal administration. The drugs are not inactivated in the intestine, and they are eliminated quantitatively in the feces. … However, long-term oral or rectal administration may result in accumulation of aminoglycosides to toxic concentrations is patients with renal impairment. Instillation of these drugs into body cavities with serosal surfaces may result in rapid absorption and unexpected toxicity. Similarly, intoxication my occur when aminoglycosides are applied topically for long periods to large wounds, burns, or cutaneous ulcers, particularity if there is renal insufficiency.

 

Adverse effects:

A list of published research on the adverse effects of Streptomycin

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed&term=%22Streptomycin%2fadverse%20effects%22[Mesh%20Terms%3anoexp

Snippet:
BACKGROUND:
The paucity of effective anti-tuberculosis drugs often justifies rechallenge with first-line drugs following adverse drug reactions (ADR) to eliminate the offending drug from the regimen. Rechallenge is usually performed under cover of drugs the patient has not been exposed to previously. The occurrence of hypersensitivity reactions to both the first-line and cover drugs poses a therapeutic dilemma and makes it difficult to identify the offending drug(s).
OBJECTIVE:
To characterise multiple drug hypersensitivity (MDH) in five human immunodeficiency virus (HIV) infected patients with previous tuberculosis (TB) associated ADR.
DESIGN:
The series is part of an ongoing randomised controlled trial assessing rechallenge dosing following TB-associated cutaneous ADR.
RESULTS:
The MDH was secondary to both first- and second-line anti-tuberculosis drugs. Itch, oedema, eosinophilia and fever were the most common features of MDH. Acute peripheral neuropathy associated with ethionamide, streptomycin (SM) and/or ofloxacin (OFX), to our knowledge not previously described in relation to MDH and these drugs, occurred in two patients. SM and OFX were associated with the most reactions. One patient had morphologically different reactions, namely Stevens Johnson syndrome/toxic epidermal necrolysis overlap and drug hypersensitivity syndrome, respectively to isoniazid and SM.
CONCLUSION:
In a description of MDH in five HIV-TB co-infected patients, including acute peripheral neuropathy, SM and OFX were the most common offending drugs.

Toxicity:

A list of published research on the adverse effects of Streptomycin

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed&term=%22Streptomycin%2ftoxicity%22[Mesh%20Terms%3anoexp

Snippet:
OBJECTIVE:
To investigate the outcome of cochlear implantation (CI) in patients deafened by ototoxic drugs and to compare this, with the outcome of CI in sudden sensorineural hearing loss (SSNHL) with a similar duration of deafness.
METHODS:
The Manchester Auditory Implant Centre database was reviewed to identify patients who were implanted to rehabilitate profound sensorineural hearing loss resulting from treatment with ototoxic agents and patients with SSNHL group. A retrospective case note review of selected patients was carried out. Primary outcome measure was post-implantation Bamford-Kowal-Bench (BKB) score in quiet in both the groups. Secondary outcome measure was any significant complications following implantation.
RESULTS:
We identified 14 patients in the ototoxic group, which were matched with 13 patients in the SSNHL group. The post-operative BKB score in the ototoxic group ranged from 33 to 100% (median score 91%). One patient had bilateral CI. One patient required explantation following an infection. The post-operative BKB score in the SSNHL group ranged from 16 to 100% (median score 88%). One patient in this group could not be tested using this method as they did not have open set speech discrimination. Two patients in this group had bilateral CI. The data were analysed using Mann-Whitney U test. There was no statistically significant difference in the BKB scores in the two groups of patients (P value -0.983).
CONCLUSION:
Patients with profound hearing loss secondary to ototoxic agents can be rehabilitated successfully with CI. The outcomes may be variable and may be dependent on the underlying pathology for which the ototoxic agents were prescribed.

Poisoning:

A list of published research on the adverse effects of Streptomycin

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed&term=%22Streptomycin%2fpoisoning%22[Mesh%20Terms%3anoexp

Snippet:
Many studies have sought to document ototoxic damage and to study repair and regeneration of mammalian vestibular sensory epithelia. However, linear density analysis of the sensory cells or use of methods that focus on detection of actin in the stereocilia and cuticular plates at the reticular lamina detect only the disappearance of “hair cells” as defined by a narrow set of criteria. The research presented here focuses on the effects of two ototoxic drugs (gentamicin and streptomycin). We used light microscopic analysis of semithin sections to observe changes in the distribution of sensory and supporting cell nuclei and to elucidate other, previously undetected, morphological changes that occurred within the vestibular epithelia. Age-matched untreated and vehicle-treated controls showed that the gerbil posterior crista is asymmetrical on either side of the septum cruciatum; the longer end is taller and narrower than the shorter end. In cross sections taken throughout the length of each posterior crista, the thickness of the sensory epithelium along the sides (peripheral zone) is greater than at the apex (central zone). In tissue sections of the sensory epithelium, the ratio of sensory cell nuclei to support cell nuclei is slightly over 1:1.5 in all regions except the septum cruciatum where most sensory cells are absent and supporting cells predominate. In tissue sections from the most damaged drug-treated specimens, there was a decrease in the linear density of nuclei in the sensory cell layer, with a compensatory increase in the linear density of nuclei in the support cell layer of the sensory epithelia. In these specimens, linear density of total nuclei/tissue section remained the same. In these regions, the width of the epithelium became up to 50% thinner. The ratio of sensory to supporting cell nuclei changed to 1:6. Drug exposure led additionally to a decrease in length of the cristas, but there was not a linear relationship between the change in length of the crista and length of the septum cruciatum in these shorter cristas. In drug-treated cristas, other changes included a decrease in calculated surface area and volume of the epithelia. Thus, while linear density measurements of sensory cell nuclei provide an indication of damage, there are additional anatomic changes to the cristas and caution is advised with regard to interpreting changes as “loss” of cells.

Streptomycin injection product info:

http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=abd1f64e-4283-4370-aae8-3666316aa36e

Snippet: “To reduce the development of drug-resistant bacteria and maintain the effectiveness of streptomycin and other antibacterial drugs, streptomycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.”

ADVERSE REACTIONS:

The following reactions are common with Streptomycin: vestibular ototoxicity (nausea, vomiting, and vertigo); paresthesia of face; rash; fever; urticaria; angioneurotic edema; and eosinophilia.

The following reactions are less frequent: cochlear ototoxicity (deafness); exfoliative dermatitis; anaphylaxis; azotemia; leucopenia; thrombocytopenia; pancytopenia; hemolytic anemia; muscular weakness; and amblyopia…Although streptomycin is the least nephrotoxic of the aminoglycosides, nephrotoxicity does occur rarely.

“THE NEUROTOXICITY OF STREPTOMYCIN CAN RESULT IN RESPIRATORY PARALYSIS FROM NEUROMUSCULAR BLOCKAGE, ESPECIALLY WHEN THE DRUG IS GIVEN SOON AFTER THE USE OF ANESTHESIA OR MUSCLE RELAXANTS.”

Source: Dailymed