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Anti-microbes > Folate synthesis inhibitors > Flashcards

Folate synthesis inhibitors Flashcards

1
Q

What is the mechanism of action of sulfonamides?

A

Competitive inhibitor of dihydropteroate synthase, preventing the conversion of PABA to dihydropteroic acid

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2
Q

Why are mammalian cells insensitive to sulfonamides?

A

Mammalian cells require preformed folic acid and are hence not affected by the inhibition of the folic acid precursors

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3
Q

What are the 3 folate acid synthesis inhibitors?

A
  1. Sulfonamide
  2. Trimethoprim
  3. Cotrimoxazole
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4
Q

What is the route of administration of sulfonamides?

A

Oral

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5
Q

How are the sulfonamindes eliminated?

A

Metabolized in the liver and eliminated by the kidney

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6
Q

What are the clinical indications for cotrimoxazole?

A
  1. UTI
  2. Pneumocystis pneumonia caused by P. jiroveci
  3. MRSA infections
  4. RTI caused by H. influenzae, K. pneumoniae & Moraxella catarrhalis
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7
Q

What are the adverse effects of taking sulfonamides?

A
  1. Crystalluria
  2. Hypersensitivity
  3. Haematopoietic disturbances
  4. Kernicterus
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8
Q

What is the effect of sulfonamides on warfarin?

A

Sulfonamide potentiates warfarin by displacing it from its albumin binding sites, increasing plasma conc. of warfarin

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9
Q

How do sulfonamides cause kernicterus?

A

Sulfonamides displace bilirubin from binding sites on serum bilirubin, allowing the bilirubin to enter the CNS of the foetus as BBB not fully developed

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10
Q

Which group of individuals are sulfonamides contraindicated in?

A
  1. Pregnant women
  2. Neonates & children < 2mths old
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11
Q

What is the route of administration of trimethoprim?

A

Oral; good oral bioavailability

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12
Q

Does trimethoprim penetrate the CSF?

A

Yes

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13
Q

How is trimethoprim eliminated?

A

Primarily renal clearance

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14
Q

What is the mechanism of action of trimethoprim?

A

Trimethoprim inhibits drihydrofolate reductase, preventing the reduction of dihydrofolic acid to its active form tetrahydrofolic acid.

This decreases the availability of tetrahydrofolate cofactors required for amino acid, purine & pyramidine synthesis

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15
Q

Should trimethoprim be given during pregnancy?

A

No. Cat C in pregnancy

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16
Q

What are the adverse effects of taking trimethoprim?

A

Folic acid deficiency

17
Q

How to manage folic acid deficiency with trimethoprim?

A

Simultaneous administration of folinic acid

18
Q

What is the mechanism of action of cotrimoxazole?

A

Inhibition of 2 sequential steps in the synthesis of tetrahydrofolic acid results in synergistic antimicrobial activity

19
Q

What is the route of administration of cotrimoxazole?

A

Oral/IV

20
Q

Does cotrimoxazole penetrate the CSF?

A

Yes

21
Q

How is cotrimoxazole eliminated?

A

Renal clearance

22
Q

What are the adverse effects of taking cotrimoxazole?

A
  1. Hypersensitivity
  2. GI symptoms
  3. Haemolytic anaemia in G6PD deficient patients
  4. Hyperkalaemia
23
Q

What groups of individuals are cotrimoxazole contraindicated in?

A
  1. G6PD deficiency
  2. Infants < 2mths old
  3. Pregnant women
  4. Patients with folate deficiency
24
Q

What are the indications for trimethoprim?

A
  1. UTI
  2. Bacterial prostatitis
25
Q

What is the mechanism of action of nitrofurantoin?

A

Reduced by bacteria to highly active intermediate that inhibits various enzymes and disrupts the synthesis of proteins, DNA & RNA

26
Q

What is nitrofurantoin indicated in?

A

UTI caused by E. coli & Enterococci

27
Q

What is the route of administration of nitrofurantoin?

A

Oral

28
Q

How is nitrofurantoin eliminated?

A

Rapid clearance into the urine

29
Q

What are the adverse effects when taking nitrofurantoin?

A
  1. Colours urine brown
  2. Nausea, vomiting & diarrhoea
  3. Hypersensitivity
  4. Cholestatic jaundice & hepatotoxicity
  5. Patients with renal dysfunction may experience pulmonary & hepatic toxicities + peripheral neuropathies
  6. Leukopenia, haemolytic anaemia in G6PD deficient patients
30
Q

Which groups of individuals is nitrofurantoin contraindcated in?

A
  1. Renal dysfunction
  2. Pregnant women & infants due to risk of haemolytic anaemia

Anti-microbes (9 decks)

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