Trimepthoprim

Question 1

What are five indications?

Answer 1

1.acute lower urinary tract infections -men and non-pregnant women

2. prophylaxisod recurrent UTI
3. Acne vulgaris
4. prostatitis
5. co-trimoxazole- treat and prevent pneumocytis pneumonia in immune suppression.

Question 2

What is the spectrum of activity of trimethoprim?

Answer 2

Has broad activity against many gram positive and gram negative bacteria however this is limited y resistance.

Question 3

What is the mechanism of action?

Answer 3

Inhibits bacterial folate synthesis slowing bacterial growth

Question 4

What is bacterias mechanism of resistance against trimethoprim?

Answer 4

Reduced intracellular abx accumulation and reduced sensitivity of target enzymes.

Question 5

Why should trimethoprim be given alongside sulphonamides?

Answer 5

Combination with sulphonamide extends spectrum to include activity against fungus
‘ pneumocystis jirovecii’

when with sulfamethazole as co-trimaxazole it extends the spectrum to include activity against the fungus.

Especially as its increasingly resistance.

Question 6

What are important side effects?

Answer 6

-GI upset and skin rash
-anaphylaxis

Due to it being a folate antagonist it can cause Haematopoeisis:
-megablastic anemia
-leukopenia
-thrombocytopenia
-hyperkalaeamia and elevation of plasma concentration

Question 7

Who should not be prescribed trimethoprim

Answer 7

Women in first trimester pregnancy as it is a folate antagonist

Question 8

When should trimethoprim be prescribed with caution?

Answer 8

Patients with folate deficiency who are more susceptible to haematological effects

Renal impairment (dose reduction - excreted unchanged into urine

Question 9

What group of people are more susceptible to adverse reactions?

Answer 9

Neonates

elderly

HIV

Question 10

What are important interactions and why?

Answer 10

-Potassium-elevating drugs

-folate antagonists (methotrexate)

-drugs that increase folate metabolism -phenytoin(increases risk of haematological effects)

• Warfarin
  trimethoprim can enhance the anticoagulant effects by killing gut flora that synthesises vitamin K

Question 11

What are dosages of different indications?

Answer 11

acute UTI- the usual dosage 200mg BD

Prophylaxis of recurrent UTI-
100mg ON

Pneumocystis -(co-trimoxazole) weight based dose
120mg/kg per day, oral or IV in 2-4 divided doses

pneumocysitis prophylaxis- (co-trimoxazole)
960mg orally three times a week

Question 12

How should IV be given and why?

Answer 12

Diluted immediately before use (to prevent crystallisation)

in 125-500ml saline or glucose infused over 60- 90 minutes.

Question 13

What are monitoring requirements for acute treatment ?

Answer 13

Monitor for improvement in symptoms
inflammatory markers
sterile urine on culture test

Question 14

What are monitoring requirements for long term treatment?

Answer 14

FBC- check for haematological effects
Inflammatory markers

Question 15

How would you manage a patient showing signs of haemotological effects?

Answer 15

replace folate

or

stop antibiotic

Question 16

Why may the efficacy of trimethoprim be reduced in UTIs

Answer 16

Trimethoprim treatment can cause a small reversible rise in serum creatinine concentrations, without reducing the glomerular filtration rate.

Trimethoprim and creatinine compete for secretion by the renal tubules.

In renal impairment, increased serum creatinine concentrations compete with trimethoprim for secretion into the urinary tract, potentially reducing efficacy against UTIs.

Question 17

What are side effects of co-trimoaxazole?

Answer 17

SJS toxic epidermal necrolysis, photosensitivity