Sulfanomides Flashcards
Sulfanomides are absolutely selectively toxic, why?
they block organisms that synthesize folic acid and humans do not synthesize folic acid
what enzyme do sulfanomides block and reaction does this enzyme catalyze?
pteroate synthetase, this enzyme normally catalyzes the reaction of PABA+pteridine to become pteroic acid(folic acid)
what are the list of enzymes involved in the process of converting PABA+pteridine into Purines, Amino acids, and Thymidines?
- pteroate synthetase 2. Dihydrofolate synthetase 3. Dihydrofolate reductase
how is tetrahydrafolate and dihydrofolate formed?
it is the conversion from dihydrofolate to tetrahydrofolate via the dihydrofolate reductase
dihydrofolate is formed via the synthesis of pteroic acid(folic acid)+glutamic acid using dihydrofolate synthetase
what are the structural requirements for the sulfanomide molecule? List 5
- N4 must be a free amino group with no attachments
- The amino groups must be in the para position
- the only active ring structure allowed is the benzene ring. All others must be inactive.
- Substitutions on the benzene ring reduce its activity
- Substitutions are allowed on the N1 compound but it must be heterocyclic increasing the SO2’s electronegativity.
What are the three resistance mechanisms of sulfanomides?
- Decreased uptake of sulfonamide(which is the most common)
- Decrease the affinity for pteroate synthetase
- Increase the concentration of PABA to overcome the competitive inhibition of sulfonamides
List all of the representative sulfonamides?
Triple Sulfa: sulfadiazine, sulfamerazine, sulfamethazine
Sulfisoxazole
Sulfamethoxazole
Sulfacetamide
Silver Sulfadiazine
Sulfasalazine
Sulfadoxine+pyrimethamine
Sulfadiazine+pyrimethamine
prophylaxis of burn patients, little or no pain
silver sulfadiazine
how is sulfasalazine activated?
split by intestinal flora to yield 5-amino-salicylate and sulfapyridine
usually administered as fixed-ratio combination with trimethoprim
sulfamethoxazole
highest urine solubility, short acting, most commonly used single sulfa
sulfisoxazole
what is the upside with using triple sulfa
single dosage contianing equal amounts of sulfa; reduces indent of cystatturia
chloroquine-resistant falciparum malaria. High incidence of drematits
sulfadoxine+pyrimethamine
treatment of toxoplasmosis
sulfadiazine + pyrimithanine
which sulfanomide has the longest half-life
sulfadoxine-it treats chloroquin resistant plasmodium falciprum
What does our body do to sulfanomides and how does it affect its solubility?
N-Acetylates it however, it is not that much water soluble first with this. Our body also conjugates it with glucoronic acid
what are some of the adverse effects including the serious rare conditions of sulfonamides?
you can get drug allergy such as rashes, eosinophilia, drug fever
can get steven johnson’s syndrome
renal toxicity because of crystullaria(not being able to dissolve in water)
can also get displacement of bilirubin(deposits on axons and kills them) in a complication called kernicterus
drug interactions occur
if patient is G6PDH deficient they can get hemolytic anemia
what drug interaction does sulfanomides have?
with oral anticoagulants, uricosuric, and severe reactions with methotrexate
Displaces these drugs from albumin or decrease their clearance
trimethoprim is a competitive inhibitor of what?
dihydrofolate reductase
the enzyme that catalyzes the DHF to THF then eventually to purines, thymidines, and amino acids
Trimethoprim and sulfonamides have what type of effect? Also what should you avoid with trimethoprim?
Sulfonamides and trimethoprim are synergistic.
You should avoid giving pregnant women trimethoprim because of the need of folic acid between the child and the mother.
what are three advantages to this synergy between TMP-SMZ?
potency
increased spectrum
decreased resistance
what are the therapeutic uses for Sulfonamides by theirselves
UTIs(mainly from e-coli)
Norcadiosis
Chlamydia Infection (trachomatis)
what are the therapeutic uses for the synergist drugs TMP and SMZ and pyrimethamine
UTI
Respiratory and ear Infections (strep pneumonia and H influenzae)
Shigella and Salmonella
Pneumocystis jiroveci pneumonia
toxoplasmosis and plasmodial infections
what are some of the structure features of fluoroquinolones
- Positions 2,3, 4 are inviolate
- The fluorine at position 6 confers resistance
- x=can be C or N
- if there is a halogen on positon 8 you get phototoxicity
- R7 is nitrogen containing saturated ring
What are some of the resistant mechanisms against fluoroquinolones? 2 ways
Point mutation on the DNA gyrase
and actively pumping the drug out of the organism
what organisms actively pump the fluoroquinolones out?
Mycobacterium, Staph aureus, Pseudomonas Arginosum
Out of the fluoroquinolones, which one has non renal elimination and which one can penetrate the CSF
Moxifloxacin has non-renal elimination and levofloxacin is the only fluoroquinolone that can penetrate the CSF
which fluoroquinolone has the longest half life and which has the shortest
Moxifloxacin has the longest at 10 hours. Ciprofloxacin is at 3-4 hours. Levofloxacin is at 5 hours.
what are some of the adverse effects in taking fluoroquinolones?
GI effects(most common)
May have some CNS effects like dizziness, agitation and headache
May also have some rash (pruritis)
tendonitis
arthropathy(not sure yet only in animal models)
crystallurias
QT elongation
beware of drug interactions
what happens with cystic fibrosis patients and fluoroquinolones?
Fluoroquinolones are used as a substitute for aminoglycosides in Cystic fibrosis patients who get a lot of pulmonary infections; the activity by the oral route is the advantage when treating chronic reinfections in cystic fibrosis
what drug interaction causes tendonitis in patients taking fluoroquinolones
fluoroquinolones and corticosteroids
fluoroquinolones cause crystalluria in what environment
in akaline pH
which fluroquinolones cause QTc prolongation
Levo and moxi
What are the three drug interactions that fluoroquinolones can have?
Do not mix with antacids because it reduces the oral absorption
can form chelates with magnesium, aluminum, iron and zinc which creates a large impermeable molecule
cipro and levo cause a reduced metabolism of warfarin and theophylline
which types of fluoroquinolones can have a patient presentation with the person feeling agitated or excessive bleeding?
levofloxacin and ciprofloxacins interaction with warfarin and theolyphins
list all the things that can reduce the absorption of fluoroquinolones
antacids
chelate forming
sulcrate which is the coating for the stomach(GI tract)
what are fluoroquinolones treated against
UTIs caused by E.coli, pseudomonas aeruginosa, Proteus and K. pnuemonia
Prostatitis because it can penetrate the prostate tissue
STDs with N. gonorrhea
GI problems such as infection via sigella , and salmonella
Respiratory problems: #1 for community acquired pneumonia due to H. influenza
Used for multidrug resistant TB
used to treat bone infections because of its ability to penetrate
which fluoroquinolone is useful to treat against penicillnase producing strep pneumoniae
trovafloxacin
which fluoroquinolone can be used as prophylaxis for pulmonary anthrax
ciprofloxacin
moxifloxacin is unique in that it has
non-renal elimination and it is used to treat against anaerobic bacteria
describe the structure and what treatment methanamine is used against
it is used to treat UTI
what is the active form of methamine and what are its disadvantages?
formaldehyde; it takes a long time to dissociate in water, takes 3 hours to reach 90% of its equilibrium, its pH dependent (prefers acid)
what are the adverse effects of taking methenamine
GI symptoms
bladder irritation at high doses
contraindicated for hepatic insufficiency because of ammonia production
contraindicated for renal insufficiency because of crystalluria
drug interaction with formaldehyde and sulfas produce an insoluble product
what is an improtant drug interaction that could cause adverse effects in usage of methenamine
with sulfas because the formaldehyde and sulfas produce an insoluble product
Explain the structure and list 3 attributes of the UTI treatment drug nitrofurantoin
- bacteriostatic(ecoli UTi infections)
- Rapidly excreted
- Resistance rarely develops
what are the adverse effects of nitrofurantoin
NVD
fever, chills, allergic pneumonitis(elderly)
Neurological: vertigo, headche, nystagmus
High dose-polyneuropathy of motor and sensory nerves
Hemolytic anemia in G-6-PDH deficient
Colors urine brown
what do you use for the discomfort of UTIs and when do you use it?
Use it early and it is an analgesic
what is the color of urine when the patient is taking nitrofurantoin vs phenazopyridine
Nitrofurantoin-brown
Phenazopyridine-orange red
which UTI treatment can be used in pregnancy with no harm
fosfomycin
what is the mechanism of action of fosfomycin and what is its structure?
Inhibitor of pyruval transferase which is important in the assembly of the muramic acid monomer of the peptidoglycan cell wall
