Trimethoprim

Question 1

What does trimethoprim target in bacterial cells?

Answer 1

DNA synthesis (folate inhibitor)

Question 2

How does trimethoprim work?

Answer 2

Inhibits dihydrofolate reductase so the bacterial cell does not make as much folate required for DNA synthesis.
Bacterial cells cannot use external sources of folate therefore inhabiting folate production reduces the amount of DNA the bacterial cell can make = BACTERIOSTATIC

Question 3

Is Trimethoprim bactericidal or bacteriostatic?

Answer 3

Bacteriostatic

Question 4

What other antibiotic can trimethoprim be added to to make it bactericidal?

Answer 4

Sulfonamides e.g. sulfamethaoxazole = CO-TRIMOXAZOLE

Question 5

How does Co- trimoxazole work?

Answer 5

Sulfamethaoxazole is also a folate inhibitor at a different stage of folate metabolism.
Adding sulfamethazoxazole with trimethoprim therefore completely inhibits folate synthesis and therefore DNA synthesis making it BACTERIOCIDAL

Question 6

What side effect does co-trimoxazole have more than trimethoprim?

Answer 6

hypersensitivity reactions (anaphylactic, erythema multiform and drug fever)

Question 7

What form does trimethoprim and co-trimoxazole come in?

Answer 7

Trimethoprim: Oral only

Co-trimoxazole: Oral and IV

Question 8

What is trimethoprim and co-trimoxazole commonly used for?

Answer 8

1. UTI: first line choice for UTI (nitrofurantoin and amoxicillin second)
2. Pneumocystic pneumonia: Co-trimoxazole for those who are immunosuppressed due to HIV

Question 9

What spectrum does trimethoprim have?

Answer 9

Broad spectrum against gram positive and gram negative but mostly eneterbacteria e.g. E.coli
- A lot of resistance now though

Question 10

What bacteria is trimethoprim particularly useful for?

Answer 10

Enterobacteria e.g. e.coli

Question 11

What are the contra-indications of using trimethoprim?

Answer 11

Pregnancy

• folate needed in pregnancy
• can cause CV defects and cleft lip

Question 12

When should trimethoprim be used with caution?

Answer 12

1. Folate deficiency (susceptible to haematological effects)
2. Renal Impairment (excreted unchanged in urine)
3. Neonates, elderly and HIV (susceptible to haematological effects)
4. Blood Disorders (adverse haemotological effects)

Question 13

What are the common interactions with trimethoprim?

Answer 13

1. Potassium elevating drugs (ARBS and ACEi increase risk of hyperkalaemia)
2. Folate Antagonists e.g. Methorexate (increase risk of haem affects)
3. Drugs that increase folate metabolism e.g. Phenytoin (increase risk of haem affects)
4. Warfarin (increases anticoagulation effects by killing bacteria responsible for Vit K production)

Question 14

What are the common side effects of using trimethoprim?

Answer 14

1. GI Upset (nausea, vom and sore mouth)
2. Hyperkalemia
3. Rash (3-7%)
4. Hypersensitivity reasctions in co-trimoaxzole (anaphylactic, erythema multiforme and drug fever)
5. Haemotological effects (megaloblastic anaemia, thrombocytopenia and leucopenia)
6. Increase in serum plasma creationine concentration

Question 15

How is trimethoprim elimiated?

Answer 15

Metabolised by liver

Excreted almost unchanged in urine

Question 16

Why is trimethoprim not as effective in those with renal impairment?

Answer 16

Trimethoprim competitively competes with creatinine secretion by renal tubules
Because of this trimethoprim increases creatine concentrations reversibly with no reduction in GFR
In renal failure creatine wins the competition so not as much trimethoprim is secreted into urinary tract