Aminoglycoside

Aminoglycosides cause non-oliguric renal failure. Penicillin causes proliferative glomerulonephritis with vasculitis. Ampicillin causes interstitial nephritis.

Deafness

Gentamycin

Use of Streptomycin along with competitive non depolarizing blockers like d-tubocurarine can potentiate its action and produce prolonged apnea.

It acts by reducing the release of acetylcholine from the prejunctional nerve endings by competing with calcium.

Therefore streptomycin should not be used with d-tubocurarine.

Administration of penicillin along with aminoglycoside does not increase the risk of aminoglycoside renal toxicity.

Aminoglycosides are highly effective against gram negative bacteria whereas penicillins are effective against gram positive bacteria.

Penicillins also increase the bactericidal activity of aminoglycosides.

Combination of penicillins/cephalosporins and aminoglycosides is the treatment of choice for pseudomonas infections.

Ref: The Spinal Cord Injured Patient By Bok Y. Lee, 2nd Edition, Page 82

Streptomycin is a tuberculocidal drug which is less effective than isoziazid or rifampicin.  It is less commonly used as an antitubercular drug due to potential for nephrotoxicity and ototoxicity. It acts only on extracellular bacilli. It penetrates the tubercular cavities, but do not cross the CSF and has poor action in acidic medium.

Common side effects of anti tubercular drugs:

• Isoniazid: Peripheral neuritis, hepatitis.
• Rifampin: Hepatitis, respiratory syndrome, cutaneous syndrome, flu syndrome, orange red colured body secretions.
• Pyrazinamide: Hepatotoxicity, arthralgia, flushing, loss of diabetes control.
• Ethambutol: Loss of colour vision or visual acuity, hyperuricemia.

Nonoliguric AKI (i.e. Without a significant reduction in urine volume) accompanies 10-30% of courses of aminoglycoside antibiotics, even when plasma levels are in the therapeutic range. Aminoglycosides are freely filtered across the glomerulus and then accumulate within the renal cortex, where concentrations can greatly exceed those of the plasma. AKI typically manifests after 5-7 days of therapy and can present even after the drug has been discontinued. Hypomagnesemia is a common finding.

Ans. is ‘a’ i.e., Enterococcus faecalis

“Unlike streptococci, enterococci are not reliably killed by penicillin or ampicillin alone. Because of synergistic action of Penicillin and aminoglycoside against enterococci combination therapy is recommended “.

Ans. is ‘a’ i.e., Streptomycin; ‘b’ i.e., Tetracycline

Ans. is ‘a’ i.e., Doxycycline; ‘b’ i.e., Streptomycin

A i.e. Streptomycin

Ans. is `a’ i.e., Concentration dependent lytic effect

Concentration dependent effect

o The outcome is related to the peak antibiotic concentration achieved at the site of infection in relation to the minimum inhibitory concentration.

o The killing effect of a drug is high when ratio of peak concentration to MIC is more.

o These drugs produce a prolonged inhibitory effect on bacterial multiplication (post antibiotic effect) which suppresses growth until the next dose is given.

o So, these drugs produce better action when used as a large single dose as compared to same daily dose divided into 2-3 times.

o Example – Aminoglycosides, quinolones.

Time-dependent effect

o Concentration should be kept above the MIC for a high proportion of the time between each dose, i.e. action depends on the length of time the concentration remains above the MIC.

o Examples are —> Macrolides & fi-lactams.

Ans. is ‘c’ i.e., Streptomycin

Ans. is ‘b’ i.e., Gentamycin

o For most of the infection of pseudomonas, treatment of choice is the combination of an antipseudomonal t3-lactam and an aminoglycoside.

Ans. is ‘b’ i.e., Gycoside

o Streptomycin is an amino-glycoside i.e. amino group is linked to aminosugar by glycoside bond.

Ans. is ‘a’ i.e., Inhibition of translation

o Streptomycin inhibit protein synthesis (translation).

Ans. is ‘a’ i.e., Inhibition of protein synthesis

Ans. is ‘c’ i.e., Framycetin

o Systemic aminoglycosides – Streptomycin, Amikacin, Gentamycin, Sisomicin, Kanamycin, Netilmicin.

o Topical aminoglycosides – Neomycin, Framycetin.

Ans. is ‘c’ i.e., Amikacin

Amikacin has widest spectrum of activity amongst aminoglycosides as it has resistance to bacterial aminoglycoside inactivating enzymes.

Ans. is ‘c’ i.e., Amikacin

Ans. is ‘b’ i.e., Amikacin

Ans. is ‘b’ i.e., Outer hair cells of basal turn

o Aminoglycosides affect exclusively outer hair cells, particularly of basal coil of cochlea.

Ans. is ‘c’ i.e., Ototoxicity

Ans. is ‘a’ i.e., are bacteriostatic

o Aminoglycosides are bactericidal antibiotics.

o They are distributed only extracellularly so the volume of distribution is nearly equal to the extracellular fluid volume. o They are not metabolized, they are excreted unchanged in urine.

o Aminoglycosides (streptomycin) should be avoided during pregnancy as they are teratogenic.

Ans. is ‘b’ i.e., Streptomycin

“Streptomycin is one of the most vestibulotoxic drug”.

Ans. is ‘d’ i.e., Streptomycin

o All aminoglycosides reduce Ach release from the motor nerve endings. They interfere with mobilization of centrally located synaptic vesicles to fuse with the terminal membrane (probably by antagonizing Ca2+) as well as decrease the sensitivity of the muscle end plates to Ach.

Ans. is ‘a’ i.e., Streptomycin

o Amongst the first line antitubercular drugs, streptomycin causes ototoxicity.

Ans. is ‘c’ i.e., Streptomycin

o Streptomycin is an aminoglycoside antibiotic contraindicated in pregnancy due to risk of fetal ototoxicity. o Recommended treatment in pregnancy is (2HRZ + 4HR) for 6 months by WHO and British Thoracic Society. o Ethambutol can be added during late but not early pregnancy.

o In India, treatment for pregnant women is 2HRE + 7 HR (Total 9 months).

Ans. is ‘a’ i.e., Streptomycin; ‘b’ i.e., Pyrazinamide

Antitubercular drugs used in children

First line drugs : Isoniazid, Rifampicin, Ethambutol, Streptomycin, Pyrazinamide

Second line drugs : Cycloserine, Ethionamide, PAS, Capreomycin, Kanamycin

Other drugs : Quinolones —> Ofloxacin, Rifamycin, Amikacin, Imipenem, Ampicillin

Ans. is ‘a’ i.e., Streptomycin; ‘b’ i.e., Ethionamide; ‘c’ i.e., Ethambutol

A i.e. Granuloma venerum

Answer is A (Aminoglycoside toxicity):

Oliguric phase of ATN is asociated with Hyponatremia and not hypernatremia

Hyponatremia results from expansion of ECF volume due to dimnished water excretion and excessive administration of free water (volume overload)

Ans. B: Streptomycin+Ethambutol

Hepatitis is a major side effect of isoniazid, pyrazinamide and rifampicin.

In case hepatitis develops, all these drugs should be stopped and S+E may be started or continued.

When the reaction clears, the above drug is added one by one to identify the culprit, which should never be used again, while the others found safe should be continued.

It is best to avoid Pyrazinamide in patients who once developed hepatitis.

Ans. B: Ototoxicity

The side effects of streptomycin include fever, hives, rashes, nausea and vomiting.

Less common side effects include paresthesia of the face (Bell’s Palsy), anaphylaxis, exfoliative dermatitis, “lazy eye,” low white blood cell count, low platelet count, muscle weakness and angioneurotic edema.

Dangerous side effects include injury to the kidneys (nephrotoxicity), and nerve damage that can result in deafness (ototoxicity).

Ans. D: Poor absorption

Like all aminoglycosides, when gentamicin is given orally, it is not systemically active. This is because it is not absorbed to any appreciable extent from the small intestine. It is administered intravenously, intramuscularly or topically to treat infections.

Common properties of aminoglycoside antibiotics

• Distribute extracellularly, do not penetrate brain/ CSF
• Act by interfering with bacterial protein synthesis.
• Completely eliminated unchanged in the urine by glomerular filtration.
• Narrow margin of safety.
• Bactericidal and more active at alkaline pH.
• Ototoxicity and nephrotoxic

Ans. C: Streptomycin

Streptomycin stops bacterial growth by hurting cell membranes and inhibiting protein synthesis. Specifically, it binds to the 16S rRNA of the bacterial ribosome, interfering with the binding of formyl-methionyl-tRNA to the 30S subunit. This prevents initiation of protein synthesis. Streptomycin cannot be given orally, but must be administered by regular intramuscular injection.

Uses

• Tuberculosis in combination with other anti-TB drugs. It is not the first line treatment.
• Plague (Yersinia pestis) has historically been treated with it as the first line treatment.
• Infective endocarditis caused by enterococcus when the organism is not sensitive to Gentamicin
• Tularemia

Ans. C: Gentamycin

Drugs whose dosage are affected in mild renal insufficiency (GFR 20-50 mL/ min or serum creatinine 150-300 micromol/L) are: ACE inhibitors, Aminoglycosides, chlorpropamide, digoxin, fibrates, lithium and zidovudine

Ans. is ‘a’ i.e., Gentamycin

• Gentamycin is the most commonly used of the aminoglycosides. It produces vestibular toxicity and irreversible hearing loss.
• Clarithromycin is known to produce reversible hearing loss.

Ans. is ‘a’ i.e., High dose OD

Authortities recommend giving a single total daily dose regime for aminoglycosides for patients with normal renal function. This is based on the following considerations:

1) Aminoglycosides exert concentration dependent bactericidal action and a long post antibiotic effect, therefore higher plasma concentrations attained after the single daily dose will be equally or more effective than the divided doses.

2) With the single daily dose the plasma concentration will remain subthreshold for ototoxicity and nephrotoxicity for a longer period each day allowing washout of the drug from the endolymph and renal cortex, thus decreasing the toxic effects.

Ans. is ‘c’ i.e., Steptomycin

• Streptomycin is an aminoglycoside antibiotic contraindicated in pregnancy due to risk of fetal ototoxicity. 
• Recommended treatment in pregnancy is (2HRZ + 4HR) for 6 months by WHO and British Thoracic Society.
• Ethambutol can be added during late but not early pregnancy.
• In India, treatment for pregnant women is 21-IRE + 7 HR (Total 9 months).

Ans. is ‘a’ i.e., Gentamycin

• Intravitreal aminoglycosides (gentamycin, amikacin) are a reported cause of macular toxicity.
• Aminoglycosides induced macular toxicity is thought to be partially due to the gravity-induced settling of drugs on the macula in supine position.
• This may result in a higher concentration of drug locally at the macula.