Flashcards in CPTP 3.10 Pharmacology of Antimicrobials 1 Deck (49)
How are the cephalosporins used?
As a second choice agent for many infections
Describe the pharmacokinetics of cephalosporins, with regard to distribution and excretion.
• Diffuse into all tissues but not CSF (unless inflamed like with penicillins)
What can be used to treat bacterial meningitis?
What must be considered for patients with renal disease?
Penicillin clearance is reduced in people with renal disease, so it may be better to use cephalosporins for these patients (still mostly excreted through kidney tho)
What are the adverse effects of cephalosporins?
• Shares sensitivity with penicillin
• Antibiotic associated colitis
• Hepatitis and jaundice
• Blood disorders (aplastic ones like with chemotherapy)
How is folate acquired by humans and bacteria?
• No pathways for synthesis
• No pathways for absorption
How do bacteria synthesise DNA? (Pathway)
(IMG 6) By biosynthesising folate:
• Dihydropteroate synthase
• Dihydrofolate reductase
What class of antibiotics inhibits the metabolic pathways involving folate? What enzyme does this class act on? It it bacteriostatic or bacteriocidal?
Sulphonamides (act on Dihydropteroate synthase)
Bacteriostatic, as it prevents DNA replication
What is PABA? What is it used for by bacteria?
Essential in bacterial folate synthesis and subsequent production of pyrimidines and purines for DNA synthesis
Name an analogue of folate. What enzyme is it used to antagonise
Trimethoprim (note, this does act on the folate pathway but is not a sulphonamide because it does not act on Dihydropteroate synthase)
BACTERIAL Dihydrofolate reductase (but not human)
What gives trimethoprim its selective toxicity? (i.e. acts on bacteria but not humans) What other drug works on the same enzyme and what is it used for?
Bacterial dihydrofolate reductase has a higher affinity for trimethoprim than for folate
Human dihydrofolate reductase has a higher affinity for folate than for trimethoprim
Methotrexate is also DHFR inhibitor, used in chemotherapy. In this case, HUMAN pyrimidine and purine synthesis is inhibited, to prevent mitosis of cancer cells (form of chemo)
What are the routes of administration of the antibiotics affecting folate pathways? What type of antibiotic are each of these?
Trimethoprim - oral
Co-trimoxazole - Parenteral
What is co-trimoxazole a combination of?
Trimethoprim (not a sulfonamide, DHPR)
Sulfamethoxazole (sulphonamide, DHFR)
What is the distribution and excretion of the drugs affecting folate pathways?
• Good diffusion and passes the blood-brain barrier
How could sulphonamides be used for burns victims?
What are the contraindications of sulphonamides (and similar folate-affecting compounds i.e. trimethoprim)?
Pregnancy, because these drugs can cross the placenta (NTDs from no folate)
Neonates (as it causes bilirubin displacement causing brain damage)
So whats the deal with trimethoprim, it's kind of confusing?
It can be considered a sulphonamide because it affects the same pathway, but it technically isn't one because it affects a different enzyme.
What are sulphonamides (and trimethoprim) typically used to treat?
• Simple UTIs
• Respiratory tract infections
• Immunocompromised patients:
> T. gondii
> P. jirovecil