Sulfonamides
distinguish between sulfonamide functional group and sulfonamide pharmacophore
why is this important for patient counseling
sulfonamide functional group is different than antibiotic class
pharmacophore= minimum structure required to get any pharmacological activity
patients who have sulfa allergy can't take certain drugs like chlorthalidone, HCTZ, lasix, Celebrex, tolbutamide, zonisamide
why are tetracyclines good antibiotics
how can you tell if an antibiotic is a tetracycline
broad spectrum
has 4 annulated 6 member rings
10 ; Tigecycline
describe difference in gram -/+ cell wall
what is MOA of this group
gram+ only has one big layer and b-lactamase is produced outside the cell and must be regenerated more often
Penicillins stop the cell wall crosslinking NAG-NAM is not able to bind to another because penicillin looks like D-Ala-D-Ala-- this causes PBP to bind to penicillin instead of making the cross link and it is permanently inhibited-- cell wall is defective
what is important about C7 in cephalosporins
it needs to be a good leaving group
which carbons are essential in the SAR for quinolones
which Carbon is better if the R group is kept small
3 and 4
2
what is the main mechanism of resistance a bacteria has against sulfonamides
make more PABA
describe a hyclate
monohydochloride hemithanolate hemihydrate
HCL 1/2C2H5OH 1/2H2O
compare Pen G to Pen V
what is special about methicillin
Pen V
-more acid stable=oral; similar spectrum, less potent; similar sensitivity to b-lactamase and allergenicity; longer D of A
methicillin contains a bulky r chain group that causes steric hindrance and shields the lactam from hydrolysis-- both ortho positions are filled= increased stability
what happens if the double bond moves to the 3,4 spot instead of the normal 2,3
greatly reduced activity-- not in conjugation for leaving group
at physiological pH what does a quinolone look like
= neutrals
If the pH of urine is < the pKa for a sulfonamide functional group, will the drug have good water solubility?
what are ways to help dissolve sulfonamides in urine?
no
1. increase fluids
2. raise urine pH
3. use sulfa drug with lower pKa value
4. mix sulfas to reach the total dose needed
describe the MOA of tetracyclines
hinders translation when making proteins
binds to 30s subunit to stop anticodons from being able to join
describe characteristics of carbenicillin
derivative of Pen G
very broad-- most broad of all
large doses are not good for patients with cardiac issues because it comes as a salt -- sodium form
what is the MOA for cephalosporins
bactericidal
similar to penicillins
bind to PBP
causes cell lysis
what are side effects of fluroquinolones
joint and bone degradation
photosensitivity
what happens if a functional group is added to N4?
what happens if a functional group is added to N1?
for N1, can both H's be substituted?
N4 substitution results in activity loss-- unless pro drug
N1-- withdrawing group= more acidic= more activity
sulfone maintains activity
amide decreases activity
Both H's can't be substituted unless it is going to be a prodrug
what C's can be changed and keep or increase activity
what happens if 11a is alkylated
do you want a hydroxy group at C6?
5, 5a, 6, 7, 9
activity is abolished
no-- makes more likely for degradation to occur
what are the degradation products of acid and base breakdown-- names
Acid: penilloaldehyde & D-penicillamine
Base: penilloic acid
describe issues that can happen with tetrazolethiomethyl leaving group in cephalosporins
good leaving group
-- causes hemorrhages-clots
-- makes it easier to become alcoholics
topo II= gram -
topo IV= +
Describe MOA for sulfonamide and trimethoprim
name enzyme
what does sulfonamide look like and how does it inhibit
is sulfamethoxazole or trimethoprim more potent
Both drugs work to stop the pathway that makes folic acid
Folic acid is necessary pathway to make nucleic acids-- DNA and RNA
Sulfa= competitively inhibit dihydropteroate synthase by looking similar to PABA
Trimethoprim selectively inhibits dihydrofolate reductase-- selective for bacteria over human by 100,000X
Trimethoprim is more potent-- mixes are 5:1
what can the acid degradation of tetracyclines cause if someone take out of data medicine
acid: 4-epitetracycline, anhydrotetracycline, anhydro-4-tetracycline
base: lactone
old medicine can cause a Fanconi like syndrome that hurts the kidneys
how are acylureidopenicillins taken
what are beta-lactamase inhibitors
name the drug that is in combo with impenem and why there has to be another drug with it
IM or IV
drugs that are given to help with efficacy -- stop the breakdown of beta-lactamase which will stop b-lactams from being able to do their jobs
Cilastatin sodium goes with imipenem because imipenem is broken down by renal dehydrogenase 1-- cilastatin is an inhibitor of this enzyme
when cephalosporins are metabolized what does it form?
is this active or inactive?
lactone is formed as leaving group
no longer looks like amino acid structure needed to bind to PBP
inactive
for gram negative bacteria what is the relationship between log P and uptake
for gram negative bacteria what is the relationship between log P and uptake
inverse
direct