| Antiprotozoal drugs: quinine |
Quinine is a rapidly acting blood schizonticide used to treat falciparum malaria.
Quinine has also been used as a muscle relaxant. However, as it has limited benefits and high risks due to hypersensitivity reactions its use for this indication is rarely justified.
Hypersensitivity reactions include angioedema, intravascular haemolysis and pancytopenia (particularly thrombocytopenia). Hypersensitivity or dose accumulation may lead to cinchonism (tinnitus, impaired hearing, headache, gastrointestinal disturbances, visual disturbances). Other adverse effects include urticaria, fever, rash, dyspnoea, and haemolytic anaemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Aminoglycosides
Aminoglycosides provide effective bactericidal activity against:
Common aminoglycosides
Aminoglycosides currently in use include:
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amikacin sulfate
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gentamicin sulfate
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kanamycin sulfate
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neomycin sulfate
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paromomycin sulfate
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streptomycin sulfate
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tobramycin sulfate.
Pharmacokinetics (how drugs circulate)
Because aminoglycosides are absorbed poorly from the GI tract, they’re usually given parenterally. After I.V. or I.M. administration, aminoglycoside absorption is rapid and complete.
Distribution
Aminoglycosides are distributed widely in extracellular fluid. They readily cross the placental barrier, but don’t cross the blood-brain barrier.
Metabolism and excretion
Aminoglycosides aren’t metabolized. They’re excreted primarily unchanged by the kidneys.
Pharmacodynamics (how drugs act)
Aminoglycosides act as bactericidal drugs (remember, this means they kill bacteria) against susceptible organisms by binding to the bacterium’s 30S subunit, a specific ribosome in the microorganism, thereby interrupting protein synthesis and causing the bacterium to die.
Rising resistance
Bacterial resistance to aminoglycosides may be related to:
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failure of the drug to cross the cell membrane
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altered binding to ribosomes
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destruction of the drug by bacterial enzymes.
One-two punch
Some gram-positive enterococci resist aminoglycoside transport across the cell membrane. When penicillin is used with aminoglycoside therapy, the cell wall is altered, allowing the aminoglycoside to penetrate the bacterial cell.
Pharmacotherapeutics (how drugs are used)
Aminoglycosides are most useful in treating:
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infections caused by gram-negative bacilli
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serious nosocomial (hospital-acquired) infections, such as gram-negative bacteremia (abnormal presence of microorganisms in the bloodstream), peritonitis (inflammation of the peritoneum, the membrane that lines the abdominal cavity), and pneumonia, in critically ill patients
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urinary tract infections (UTIs) caused by enteric bacilli that are resistant to less toxic antibiotics, such as penicillins and cephalosporins
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infections of the central nervous system (CNS) and the eye (treated with local instillation).
Works well with others
Aminoglycosides are used in combination with penicillins to treat gram-positive organisms, such as staphylococcal or enterococcal
infections. Combination therapy increases the drugs’ effectiveness.
Inactive duty
Aminoglycosides are inactive against anaerobic bacteria.
Role call
Individual aminoglycosides may have their own particular usefulness:
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Streptomycin is active against many strains of mycobacteria, including Mycobacterium tuberculosis, and against the gram-positive bacteria Nocardia and Erysipelothrix.
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Amikacin, gentamicin, and tobramycin are active against Acinetobacter, Citrobacter, Enterobacter, Klebsiella, Proteus (indole-positive and indole-negative), Providencia, Serratia, Escherichia coli, and Pseudomonas aeruginosa.
Drug interactions
Carbenicillin and ticarcillin reduce the effects of amikacin, gentamicin, kanamycin, neomycin, streptomycin, and tobramycin. This is especially true if the penicillin and aminoglycoside are mixed in the same container or I.V. line.
Putting up a blockade
Amikacin, gentamicin, kanamycin, neomycin, streptomycin, and tobramycin administered with neuromuscular blockers increase neuromuscular blockade, resulting in increased muscle relaxation and respiratory distress.
Kidney punch
Toxicity to the kidneys may result in renal failure; toxicity to the neurologic system results in peripheral neuropathy with numbness and tingling of the extremities. The risk of renal toxicity also increases when amikacin, gentamicin, kanamycin, or tobramycin is taken with cyclosporine, amphotericin B, or acyclovir.
What? Say that again…
The symptoms of ototoxicity (damage to the ear) caused by aminoglycosides may be masked by antiemetic drugs. Loop diuretics taken with aminoglycosides increase the risk of ototoxicity. Hearing loss may occur in varying degrees and may be irreversible.
