Drug Resistance, Sulfonamides, Trimethoprin Flashcards
Needs to be used with Dihydropteroate Synthase (DHPS) in folate biosynthesis to make 7,8-Dihydropteroate.
pABA
Folate (FH4) is made from this crucial molecule.
7,8-Dihydropteroate
These drugs competitively inhibit PABA.
Sulfonamides
Sulfonamides are a type of _______.
Anti-folate.
MOA of Sulfonamides.
Competitively inhibit pABA, which is needed for folate synthesis.
These drugs decrease the Dihydropteroate precursor.
Sulfonamides
Mammals and folates.
Mammals cannot make folic acid, so they have to get it in the diet.
These anti-folate drugs have a free para-amino acid.
Sulfonamides
Sulfonamides bacteriocidal or static?
Static.
Delayed bacteriostatic effect.
Concentrated in the urine, and effective in aerobic Gram + and -.
Sulfonamides
Folate is used for what kind of metabolism?
One-carbon unit transfer reactions
Converts dUMP to dTMP
Thymidylate cycle
Part of the Folate pathway and makes dTMP
Thymidylate cycle
These are needed in order for the Thymidylate cycle to work
Folate derivatives
Folate synthesis inhibitor.
Trimethoprim
A folic acid analog that inhibits folate synthesis by blocking DHFR (Dihydrofolic Reductase).
Trimethoprim
How do microbes prevent microbial disease?
Create an inhospitable environment by lowering the pH.
Host microbes make these, which insert into the cell walls of bad bacteria to create pores and cause cell death.
Colicins
What is a microbial disease?
An overpopulation of microbes that colonize sterile zones, and a small number of them are pathogenic.
How does microbial disease occur?
Exposure through ingestion, inhalation, or a wound, or thru a superinfection.
How do microbes cause disease?
1) Through tissue invasion and immune over-response.
2) Make exo and endotoxins (LPS).
Anti-microbial proteins found in body fluids that defend against bad bacteria.
Defensins.
Using a single drug to treat a disease.
Monotherapy.
This therapy uses microbes to kill bad bacteria without harming the host.
Antimicrobial therapy.
Bacterial shape and how they stain is known as bacterial ________.
Taxonomy
These antimicrobial drugs are most used by general dentists.
Attack cell wall and protein synthesis.
What does the gram stain tell you?
Thickness and composition of the cell wall.
Bacteriostatic or cidal drugs recommended if you are immunocompromised?
CIDAL!
A lack of antimicrobial effect at the highest drug concentration that’s tolerable to the host.
Drug resistance.
When a protective substance, like pus, prevents the antibiotic from getting to the site of infection.
Escape
Escape in the oral cavity.
Biofilm
There’s a pre-existing mechanism in the bacteria that makes it naturally resistant to the drug.
Intrinsic/Natural resistance.
When species that used to be sensitive to a drug are no longer sensitive to it.
Acquired resistance.
Acquired drug resistance can be _______ or ________.
Chromosomal; Extrachromosomal
Ways that bacteria can spread acquired drug resistance extrachromosomally.
Transformation
Transduction
Conjugation
Chromosomal spread of resistance is through ______.
Replication
Interfere with the normal metabolism within cells.
Antimetabolites
What do bacteria use to make DNA?
Folate derivatives.
These inhibit folate metabolism in bacteria to stop DNA synthesis.
Anti-folates.
Can either inhibit a reaction or incorporate into the DNA as an analog and disrupt the metabolism.
Anti-metabolites.
Synthetic antibiotics bc they’re man-made structural analogs.
Anti-folates
These two things are needed to make 7,8-Dihydropteroate synthase.
pABA and Dihydropteroate Synthase
Create a delayed bacteriostatic effect.
Sulfonamides
Has a free para-amino group.
Sulfonamides
This is needed to convert dUMP to dTMP in the Thymidylate cycle so that bacteria can make nucleotides.
Folate
Inihibits DHFR
Trimethoprim (TMP)
Folate analogue that inhibits DHFR
Trimethoprim
Analogue of dTMP
TMP (Trimethoprim)
Converts 7,8-Dihydrofolate to Folate.
DHFR
Bacteriostatic and NOT delayed.
Trimethoprim
Rationale for blocking the folate synthesis pathway at two steps rather than just one.
1) Decreased chance of drug resistance.
2) Has a greater effect at stopping bacterial replication if two steps are blocked rather than one.
These drugs concentrate in the urine, so they’re used to treat UTI’s and p. cervicii pneumonia.
Sulfonamides + Trimethoprim
Adverse event of Sulfonamides + Trimethoprim when used to treat p. cervicii pneumonia (PCP).
Increased CNS effects
Oral manifestation of folate deficiency.
Chronic ulcers.
Folate deficiency is commonly seen in:
- Chronic alcoholics
- Elderly
- People with Folate malabsorption
