What do tetracyclines do?
Bind to small subunit of ribosome Interfere with tRNA binding (block attachment of tRNA to ribosome) meds = doxycycline and minocycline
What do aminoglycosides do?
Bind to small subunit of ribosome Bend mRNA and cause misread of codon; blocks initiation and ribosome formation Drug ex: tobramycin and gentamicin
What do macrolides do?
Bind to large subunit of ribosome Block translocation Drugs: Clarithromycin, erythromycin and azithromycin
What do lincosamides do?
Bind to large subunit of ribosome Blocks peptide bond formation and translocation Drugs: clindamycin and lincomycin
What do Oxazolidinones do?
Bind large subunit of ribosome Interferes with initiation and ribosome formation Drugs: linezoild
What do amphenicols do?
Bind large subunit of ribosome Block peptide bond formation drug: chloramphenicol
What is job of B-lactam antibiotics?
They inhibit (block) transpeptidase enzymes so crosslinking cant occur
What are some examples of B-lactams ?
1. penicillins - Amox, Penicillin V 2. Cephalosporins - Cephalexin 3. Monobactams 4. Carbapenems
How does the inhibition of Transpeptidase by penicillin work?
The pocket of the bacteria that needs to be linked together by the side groups of penicillin such that hydrolysis by water cant happen. This makes transpeptidase being irreversibly inhibited, leading to no crosslinking to cell death
What does a bacteria do to have drug resistance?
The bacteria produces production of a B-lactamase enzyme which chemically degrades (destroys) the B-lactam drug
What are ways we have overcome the bacterial drug resistance ?
We targeted the B-lactamase enzyme Augmentin is a combo of B-lactam antibiotic and clavulanic acid -- The clavulanic acids acts as an irreversible inhibitor of B-lactamase to prevent the cleavage and inactivation of the amoxicillin
What are Antimetabolites?
They are compounds that resemble and interfere with something required for metabolism
What are some examples of antimetabolites?
5-fluorouracil and capecitabine which resemble dUMP and inhibit thymidylate synthase 6-mercaptopurine, an analog of hypoxanthine (leads to xanthine) Allopurinol - a substrate and then inhibitor xanthine oxidase
What are antifolates?
These resemble a portion of tetrahydrofolate
What are some examples of antifolates?
Aminopterin, methotrexate, and trimethoprim which inhibit dihydrofloate reductase Sulfa antibiotics which block the synthesis of folic acid
How does allopurinol and febuxostat treat gout?
Remember Xanthine oxidase carries out the last two steps in the formation of uric acid 1. Allopurinol and febuxostat inhibit xanthine oxidase 2. if you inhibit xanthine oxidase it will decrease the amount of uric acid in the system
What specifically does allopurinol do to xanthine oxidase?
It makes oxypurinol (adds an oxygen) which inhibits the use of the enzyme
How does 5-Fluorouracil and capecitabine (prodrug) inhibit dTMP synthesis?
They act as suicide inhibitors and covalently bind to and irreversibly inhibits thymidylatye synthase **adds a F which can not be taken off
How does Aminopterin Methotrexate and Trimethoprim stop dTMP synthesis?
It inhibits dihydrofolate reducatse **remeber this creates the 5, 10 methylene thing that is used in order to convert dUMP to dTMP
How does bactrim (trimethoprim + sulfamethoxazole) stop dTMP synthesis?
It inhibits both folic acid synthesis and dihydrofolate reductase
What two enzymes are used in the salvaging nucleosides?
Deoxycytidine kinase Thymidine kinase **these are very specific and add the first phosphate to recover the nucleoside **they only work on cytidosine and thyosine
How does Acyclovir and Valacyclovir work as antivirals?
They resemble guanosine which means they act like nucleoside reverse transcriptase inhibitors (NRTIs) *it gets phosphorylated and activated then gets incorporated into viral DNA which stops it ably to replicate and it dies **Important to know this only slows down infection and eases symptoms, you body still needs to deal with it