AM - Side effects and Toxicity, Principles

Question 1

What are side effects of antibiotics?

Answer 1

• allergic reactions
• immediate hypersensitivity
• delayed hypersensitivity
• gastrintestinal side effects
• thrush
• liver toxicitiy
• renal toxicity
• neurological toxicity
• haemotological toxicity

Question 2

When can allergic reactions occur?

Answer 2

• 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

Question 3

What is immediate hypersensitivity?

Answer 3

• anaphylactic shock
• parenteral administration of the antibiotic
• IgE mediated occurs within minutes of admistration

Question 4

What is delayed hypersensitivity

Answer 4

• hours or days to develop, immune complex or cell mediated mechanism
• rashes, fever, serum sickness (T3)

Question 5

What is gastrointestinal side effects?

Answer 5

• nausea and vomiting are common

- diarrhoea associated with toxin production by clostridium difficile

Question 6

What Is thrush caused be

Answer 6

Therapy with penicillins or cephalosporins may be complicated by overgrowth of the yeast Candida albicans, resulting in oral and/or thrush

Question 7

What causes hepatotoxicity?

Answer 7

-Tetracyclin and the anti-tuberculous drugs isoniazid (INH) and rifampicin

Question 8

What causes renal toxicity?

Answer 8

• the kidney is the most important route of drug excretion

- most common with the aminogllycoside group (gentamicin, netilmicin, amikacin) or with vancomycin

Question 9

What is the most important route of drug excretion?

Answer 9

Kidney

Question 10

What are the types of neurological toxicity?

Answer 10

• Ototoxicity
• Optic neuropathy
• Peripheral neuropathy
• Encephalopathy and convulsions

Question 11

When does haematological toxicity occur?

Answer 11

• Toxic effect on the bone marrow
• results in selective depression of one cell line (neutropenia) or unselective depression of all bone marrow elements (pancytopenia)

Question 12

How to prevent adverse reactions

Answer 12

• 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

Question 13

What is therapeutic margin?

Answer 13

The difference between an effective and toxic dose

Question 14

Preventing adverse reactions- age

Answer 14

Certain drugs are contraindicated in children eg Ciprofloxacin is thought to affect developingcartilage

Question 15

What is safe in pregnancy?

Answer 15

penicillins, cephalosporins and the urinary antiseptic nitrofurantoin

Question 16

In hepatic insufficiency and renal insufficiency….

Answer 16

Doses of antibiotics should be decreased

Question 17

What must be considered when choosing a drug?

Answer 17

Spectrum of antimicrobial agent

Question 18

What happens when the organism causing infection is not known?

Answer 18

Empiral antimicrobial therapy may have to be commenced if urgent treatment is rewuired

Question 19

When is it necessary to used antimicrobials in combination?

Answer 19

• To cover mixed infection by more than one organism

- To minimise the development of resistant strains to any one agent

Question 20

When is combined antimicrobial agents used especially?

Answer 20

In the treatment of TB or HIV

Question 21

What are the three possible outcomes of combination?

Answer 21

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

Question 22

Example of combined antimicrobial agents?

Answer 22

• Penicillin and gentamicin in streptoccal infective endocartis
• Penicillin breaks down the streptococcal cell wall and allows gentamicin access to the ribosome

Question 23

What is the effect of two cidal drugs or two static drugs?

Answer 23

Additive or synergisitc

Question 24

What is the effect of one static and one cital drug?

Answer 24

Antagonism

Question 25

What are the two main reasons for monitoring serum levels of an antimicrobial?

Answer 25

• to ensure that therapeutic levels have been achieved

- to ensure that levels are not so high as to be toxic