AM - Side effects and Toxicity, Principles Flashcards
What are side effects of antibiotics?
- allergic reactions
- immediate hypersensitivity
- delayed hypersensitivity
- gastrintestinal side effects
- thrush
- liver toxicitiy
- renal toxicity
- neurological toxicity
- haemotological toxicity
When can allergic reactions occur?
- in any antimicrobial, but is commonly associated with the B-lactam
- true penicillin sensitivity is rare
- 10% of truly penicillin allergic patients are allergic to cephalosporins
What is immediate hypersensitivity?
- anaphylactic shock
- parenteral administration of the antibiotic
- IgE mediated occurs within minutes of admistration
What is delayed hypersensitivity
- hours or days to develop, immune complex or cell mediated mechanism
- rashes, fever, serum sickness (T3)
What is gastrointestinal side effects?
- nausea and vomiting are common
- diarrhoea associated with toxin production by clostridium difficile
What Is thrush caused be
Therapy with penicillins or cephalosporins may be complicated by overgrowth of the yeast Candida albicans, resulting in oral and/or thrush
What causes hepatotoxicity?
-Tetracyclin and the anti-tuberculous drugs isoniazid (INH) and rifampicin
What causes renal toxicity?
- the kidney is the most important route of drug excretion
- most common with the aminogllycoside group (gentamicin, netilmicin, amikacin) or with vancomycin
What is the most important route of drug excretion?
Kidney
What are the types of neurological toxicity?
- Ototoxicity
- Optic neuropathy
- Peripheral neuropathy
- Encephalopathy and convulsions
When does haematological toxicity occur?
- Toxic effect on the bone marrow
- results in selective depression of one cell line (neutropenia) or unselective depression of all bone marrow elements (pancytopenia)
How to prevent adverse reactions
- Antimicrobials should be used only when absolute necsasary and in the minimum dose and duration necessary to achieve efficacy
- Care should be taken when administering antimicrobials to extremes of age, pregnant women and patients with liver or renal insufficiency
- Antimicrobiasl with a low therapeutic margin should be monitored to ensure maximal efficacy and minimal toxicity
What is therapeutic margin?
The difference between an effective and toxic dose
Preventing adverse reactions- age
Certain drugs are contraindicated in children eg Ciprofloxacin is thought to affect developingcartilage
What is safe in pregnancy?
penicillins, cephalosporins and the urinary antiseptic nitrofurantoin
In hepatic insufficiency and renal insufficiency….
Doses of antibiotics should be decreased
What must be considered when choosing a drug?
Spectrum of antimicrobial agent
What happens when the organism causing infection is not known?
Empiral antimicrobial therapy may have to be commenced if urgent treatment is rewuired
When is it necessary to used antimicrobials in combination?
- To cover mixed infection by more than one organism
- To minimise the development of resistant strains to any one agent
When is combined antimicrobial agents used especially?
In the treatment of TB or HIV
What are the three possible outcomes of combination?
Additive
Antagonistic
-Their combined effect is less than the sum of their individual contributions
Synergistic
-Their combined effect is greater than the sum of their individual contributions
Example of combined antimicrobial agents?
- Penicillin and gentamicin in streptoccal infective endocartis
- Penicillin breaks down the streptococcal cell wall and allows gentamicin access to the ribosome
What is the effect of two cidal drugs or two static drugs?
Additive or synergisitc
What is the effect of one static and one cital drug?
Antagonism
What are the two main reasons for monitoring serum levels of an antimicrobial?
- to ensure that therapeutic levels have been achieved
- to ensure that levels are not so high as to be toxic
