Skip to content

Sulfonamides, Trimetophrim and Quinolones

  • by

Recorded lecture about Sulfonamides, Trimetophrim and Quinolones for my students of Pharmacology and Toxicology at the University of Santo Tomas. This was uploaded for my academic purposes only. If you plan to use this as stated otherwise, please contact the uploader.

Hello glass frit a our topics are sulfonamides trimethoprim and quinolones our lecture outline is as follows we will discuss and by folly drugs and then after it we will discuss dna gyrase inhibitors to guide us with our discussion today we’re gonna have two cases so for the first case a thirty year old male patient developed painful urination for the past eight days

Past medical history revealed that patient may have allergies to on recalled rugs due to the community quarantine he opted to self-medicate with a metal rim sulfamethoxazole the code is tpms mx after taking two doses of tpms mx patient started to develop multiple skin and mucosal lesions as shown in the picture what happened to this patient the second case is a 25

Year old woman present to you with three the history of painful urination and flank pain she also had fever chills and body weakness past medical history revealed she had four episodes of uti in the past year and was lead with pmps mx for all those four episodes by her mod urinalysis revealed many bacteria in four plus four nitrates urine culture was also requested

What is the empiric antibiotic of choice for this patient so for our first topic we’ll discuss on phone amides one of the oldest antibiotics that we know and still use today soulful drugs are one of the earliest successful antibiotics every develop it was introduced by gerardo mach in 1935 was initially marketed as prone to sell it is structurally similar to the

Amino benzoic acid or fava very important for the formation of folic acid and eventually being a physical chemical and pharmacological properties are produced by attaching substituents to the middle group or the amino group of the sulfa malad needed being one of the most inexpensive antibiotics to be reserved for the night let’s discuss the mechanism of action

Of some ornaments but before we go there let’s discuss how important folly for bacteria gives you money and other mammals can get folly from exogenous sources like food on the other hand some bacterium must rely on endogenous sources like baba making it essential for purine synthesis and eventually dn dna synthesis therefore this is the one that we utilize for

This drug inhibits the hybrid trait synthase and foley production is haunted this drug is bacteriostatic when given alone it inhibits both gram positive just as staphylococcus wishing gram negative enteric bacteria such as a coli klebsiella pneumoniae salmonella shigella enterobacter nocardia chlamydia trachomatis and some protozoa on the other hand we catch are

Stimulated to grow with this drug it has productivity against an aerobics and so the manas originals are is spiritually resistant to also follow miles it is usually given in combination with trimethoprim or pyrimethamine please take note though that some bacteria depends on exogenous sources of folate therefore they are not affected by this rod resistance patterns

And sulfonamides are generally attributed to some rotations in those bakhtiar resulting in the following overproduction of the substrate which is your pa be a member through production of a folic acid synthesizing enzyme that has low affinity for sulfonamides and 3 the lately we discovered for impaired permeability to dissolve our mind and recently antibiotic a

Flux is another mechanism where assistance pattern is attributed in this causing pharmacokinetics it’s best to describe them in groups now the first group is your oral absorbable second is her oral not absorbable in the last are your topical oral absorbable sulfonamides are absorbed from the stomach and small intestine and that’s why distribution including the

Cns la santé and the fetus protein binding varies from 20 percent to 90 percent it undergoes metabolism in the liver and excreted in the urine therefore requires adjustments in renal failure ever since the inception of this drug bhakti resistance continues to increase together with dearth i made the cream therefore limiting their use in the clinical setting many

Strains on our system later meningococcal new methoxide chapter fox i staphylococci anyone a fox in the plane makes it is frequently used in combination with try mentally and only commercially available in some countries as a combination trimethoprim sulfamethoxazole is the drug of choice for pneumocystis jaribg previously this was called pneumocystis carrying in

The most common cause of pneumonia in patients with needs toxoplasmosis the one that you get from ingesting raw meat or from cats now and then now hardly uses so for clinical uses for oral absorbable engagements sulfadiazine t-shirts will combine with pyrimethamine as a first-line agent for acute toxoplasmosis sulfa dachshund has pyrimethamine marketed as funds

In a deal is only available in some countries it’s a second line anti malarial so now let’s go to the clinical uses of non-absorbable agents opus allison is used for ulcerative colitis and titus and other inflammatory bowel diseases silver sulfadiazine an ointment is given for burn wounds for the prevention of infection please take note that men with deep burn

Patients we don’t give antibiotics right away so we give up something to prevent that infection in the back of this patient to your left is the ointment no it’s a white substance it’s given generously on areas of affectations muffin audacity are also used to spread wounds but it can cause metabolic acidosis and we don’t like that in burn patients based on recent

Evidence as strong containing sulfonamide moiety having common close allergenicity potential changing the paradigm about this drug the most common adverse effect or reaction of these drugs are fever skin rashes x+ dermatitis photosensitivity or taqueria nausea vomiting diarrhea and urinary tract problem presenting with crystal maria a materia and even obstruction

At neutral or acid ph uncommon but tears and potentially fatal side effect of sulfonamides are steven johnson syndrome the others are stomatitis conjunctivitis or try this in maputo ethics river disturbances hepatitis psychosis and polyarteritis nodosa now we can answer case 1 3 dear old male patient we develop painful here in the nation for the past 3 days

Past medical history revealed that the patient may have allergies to unruh called drug to the dominate quarantine ‘i opted to self-medicate with trimethoprim sulfamethoxazole or tpms mx after taking two doses this patient started to develop multiple skin and mucosal lesions what happened to this patient basically this patient develop what evolvers even johnson

Syndrome marked by multiple skin and the postal additions as you can see in the picture now let’s go to trimethoprim as the mechanism of fashion’s of trimethoprim by metaframe selectively inhibits the material the hydro folic acid we de deus complimenting the action of your sulfonamides so this is a bacteriostatic when given alone this is how yield information

By methoprene or some sulfamethoxazole when given alone is bacteriostatic of b however when you give them as a combination therapy they are back there inside so the maple dupree resistance are also attributed to mutations now and these mutations produces reduce soil permeability overproduction of dihydrofolate reductase s production of an altered reductase would

Reduce drug binding now let’s go to pharmacokinetics given orally alone or in combination well absorbed from the gut well distributed even in the cns it is mortal lipid soluble than sulfamethoxazole and therefore has larger volumes of distribution it is excreted in the urine and requires three no those adjustments crematorium concentrates in the prostatic fluid

In vaginal fluid better pbt then some antibiotics in those areas so trimethoprim or al is given for acute uti first effects of trimethoprim because of its mode of action produces megaloblastic and email leukopenia and going new low side uppy mia in some subsets of patients no remember these diseases are caused by your folate inhibition so it’s important to avoid

Them in patients with problems with those trimethoprim in a bit secretion of creatinine access digital rena few people resulting in mild elevation of blood create a clinician must know to differentiate the pea this is secondary to trimethoprim or other modalities here are some generalities of retirement of him sulfamethoxazole combination therapy the synergistic

Combination of these folate antagonist blocks purine production and nucleic acid synthesis again making them very bactericidal tpms mx is a drug of choice for pneumocystis reserve ichi previously known as a picker ni pneumonia in aids patient toxoplasmosis and no heart disease ibd mps mx is an agent of choice for moderate to severe pneumocystis pneumonia alternative

For infections from mdr strains of enterobacter in say raffia shigellosis typhoid and the preferred alternative therapy for this theory i monocytogenes patients with aids and pneumocystis pneumonia have a particularly high frequency of untoward reaction to this drug now let’s go to your fluoroquinolones the most famous of these drugs are your zip to floss the

Same level of locks the same the earliest drug under this group is rain and indexof acid used for me ti however this drug wasn’t able to produce systemic concentrations then after this intently chlorinated derivatives were made like a ciprofloxacin and level fluxes in this were originally developed because of their gram-negative arabic coverage the piece take note

That they also have gram-positive coverage as well and these drugs are generally back there is a little to your left are the structures of non-addictive acid and their variations in the other fluoroquinolones the mechanism of action of fluoroquinolones is that it knocks bacterial dna synthesis by inhibiting bacterial topoisomerase – which is also a dna gyrase in

Topoisomerase for inhibition of the dna gyrase prevents the rexall oxygen of positively super coiled dna that is required for your normal transcription resistant organisms appear in about every tender seven if that is nine population of the bacteria especially notable among staphylococci p aeruginosa and zarate immerse essence mutation in depend on binding region

Of the target enzyme or a change in permeability is the very accepted model of resistance a trains in fluoroquinolones so now let’s go to pharmacokinetics it is well absorbed orally distributed widely long half-lives of levofloxacin j my flock the same and moxifloxacin permits once a day to see impaired absorption when combined with antacids de valence intraoral

Billion cat ions therefore it should be taken two hours before or four hours after taking any of the antacids divalent or trivalent at ions most are really excreted requiring low you know those adjustment except for moxifloxacin so now let’s go to the clinical uses of fluoroquinolones it’s used primarily for urinary tract infection including those costs types

Of the mona’s original so unlike the previous drug that we’ll discuss which has resistance patterning against pseudomonas aeruginosa bacterial diarrhea caused by shigella salmonella toxic e coli campylobacter the shoes bones and joints infections intra-abdominal infections and respiratory tract infections except for the drug nerf laxus in ciprofloxacin is a drug

Of choice for prophylaxis and treatments of anthrax caused by bacillus and tracy’s going to cook all infections but because of the high rates of resistance in the u.s. it’s no longer used their alternative to chlamydia traitors or cervicitis specifically here levofloxacin and also flocks of sin this is a second line agent for your micro bacterial infections men in

Your quick ocala carriers prophylaxis for bacterial infections in neutropenic cancer patients it’s acceptable for those cases as well respiratory fluoroquinolones are your levofloxacin je my flocks the same and moxifloxacin therefore they can use in cases of here the known adverse effects of the reckoning loss the most common are nausea vomiting and diarrhea

Occasionally patients develop headache dizziness insomnia skin rash or abnormal liver-function tests photosensitivity specifically for drugs roma fluxes in and for fluxus in qt interval prolongation in gotham zoo blocks the same levofloxacin jamie flocks a scene in moxifloxacin so therefore patient suffering for it yeah should be warned been using this drug

Hyperglycemia when given alone or hypoglycemia when given with oral hypoglycemic agents is observed for ngati flocks aslam this drug may damage growing cartilage and cause arthropathy therefore it is not recommended but may be used for patients below eating in seoul it should be avoided in pregnancy unless it cannot be treated by alternative drugs temporary to

Permanent for penelope is also common and the new reverse effect discovered in this firm so now let’s answer case to a 25 year old female rape 10% steve with a three day history of painful urination and family she also had fever chills and body weakness past medical history revealed she had four episodes of uti in the past year and was detailed by the dmv xmx

By her body urinalysis revealed many bacteria in four plus four nitrates urine culture was also requested as the clinician of this patient what is the empiric antibiotic choice for this the answer is you shifted fluoroquinolones and we used ciprofloxacin to be given twice a day for seven days you should instruct the patient to watch out for other side effects of

These drugs and repeat the urinalysis after seven weeks you so for any questions or concerns or any discussions that you need to do you may reach me at my email address listed there and my twitter account don’t hesitate to ask restaurants because for me that’s very important so i hope you’re all staying safe and healthy goodbye glass you

Transcribed from video
Sulfonamides, Trimetophrim and Quinolones By Doc Karl