ANTIBIOTICS Flashcards
ANTIBIOTICS
Basic Structure of Penicillins?
Thiazolidine ring, which is attached to Beta-lactam ring and the Beta-lacatam ring is attached to Side chain
All the Pc derived from 6-APA method are all advantageous over PcG how???
Improved antibacterial activity
greater stability against Beta-lactamases
better pharmacokinetic properties
Are Pc bactericidal or bacteriostatic?
Bactericidal
MOA of Pc?
Function of the peptidoglycan component?
3 parts of Peptidoglycan?
Inhibit the development of the cell wall.
Peptidoglycan is a major component in the bacteria cell wall and it provides rigidity due to the cross linked structures. Cell wall is rigid structure and prevents the bacteria from brusting due to osmotic flow.
The 3 parts are N-Acetylglucosamine (NAG),
N-Acetylmuramic acid (NAM) and the cross linking of the 3rd AA (lys) of the pentapeptide (NAM) to the 4th AA (ala) of the opposite NAM by the 5 glycine aa.
lysine for G +ve and Meso-diaminopimelic acid for G - ve
Cross linking is done by transpeptidase (Pc inhibits this). Thus B-lactams inhibit the cross linking of peptidoglycans via inhibiting trranspeptidation and stimulation of autolysins that break down cell wall. this causes disruption of synthesis of the cell wall and promote its active destruction.
What are the narrow spectrum Pc?
Benzylpenicillin
Procaine penicillin
Benzathine penicillin
Phenoxymethlypenicillin
What are the narrow spectrum Pc with Anti-Staph?
Dicloxacillin and flucloxacillin
What are the moderate spectrum Pc?
Ampicillin and amoxicillin
What are the broad spectrum Pc?
Amoxicillin with Clavulanic acid
Piperacillin with Tazobactam
What are spectrum of activity of Pc?
highly active against Gram +ve (bacillus anthracis, clostridium perfringens)
some Gram - ve, spirochaetes and Actinomycetes
What is distribution of PcG?
Doesn’t enter the CSF when meninges are normal but when inflamed, Pc penetrates and is actively transported out, thus given with probenecid to prevent this.`
What are the indications for PcG?
Endocarditis, Syphilis, CAP, Aspiration Pneumonia, Meningitis and Septicaemia
Dosage for PcG?
0.6g - 1.2g (IV) every 4 - 6 hrs. not oral because acid destroys the PcG
Indications for procaine pencillins?
Respiratory tract infections, syphilis and cellulitis and erysipelas
dosage for procaine penicillins?
1g - 1.5g once daily and IM
Pk of procaine penicillins?
given IM and Absorbed slowly into circulation and hydrolysed into PcG and maintain conc upto 12 to 24 hrs
Pk for benzathine penicillins?
given IM and absorbed slowly into circulation and hydrolysed to PcG upto 4 weeks
Indications for Benzathine penicillins?
Prevention of rheumatic fever, which usually follows a streptococcus pyogenes
Early and Latent syphilis
Dosage for benzathine Pc?
0.9 - 1.8 g IM
Pk of PcV?
more stable in acidic medium (thus oral)
completely absorbed in the GIT
Rapid absorbed
Indications for PcV?
s.pyogenes tonsilitis/ pharyngitis or skin infections
prevention of rheumatic fever
gingivitis (with metronidazole)
Dosage for PcV?
250 to 500 mg every 6 to 8 hrs
Spectrum of dicloxacillin and flucloxacillin?
resistant to beta lactamase produced by staphylococci but no activity against MRSA
Pk of Dicloxacillin and Flucloxacillin?
absorption is reduced by presence of food in the stomach. only orally
Indications for dicloxacillin and flucloxacillin?
Pneumonia Osteomyelitis septicaemia endocarditis surgical prophylaxis staphylococcal skin infections
Adverse effects of dicloxacillin and flucloxacillin?
Increase in liver enzymes and bilirubin
flucloxacillin –> severe hepatic reactions
dicloxacillin –> interstital nephritis
Indications for Moderate spectrum Pc?
Chronic bronchitis CAP Otitis media Gonococcal infection Epididymo orchitis non-surgical prophylaxis of endocarditis acute cholecystitis
Pk for moderate spectrum Pc?
ampicillin–> only available as IV, 1 hr half life and low peak plasma conc
amoxicillin –> absorbed more rapidly and completely from GIT, high peak plasma conc (2 times)
dosage for moderate spectrum Pc?
ampicillin –> 500 mg - 1 g IV 4-6 hrs
amoxicillin –> 250 -500 mg every 8 hrs or 1 g bd
Indications for amoxicillin & clavulanic acid?
HAP PID UTI Epididymo orchitis Bites and fist injuries Otitis media sinusitis cholecystitis melioidosis
indications for piperacillin with tazobactam
Activity against pseudomonas aeruginosa
Resistance to Pc
Via destruction of AB by beta-lactamase enzymes - antibiotic cleaving.
beta-lactamases catalyse the hydrolysis of the beta lactam ring. thus breaking the ring structure (amide bond) and decrease in AB activity and no longer inhibit cell wall synthesis. penicillin to penicilloic acid by penicillinase.
ambler classification of beta lactamases
Class A: inhibited by clavulanic acid. Serine based (a, c ,d). Pc , ceph and monobactam Class b is zinc based Class c Class d Clavulanic acid doesn't inhibit b,c,d
How do B-lactamases inhibitors work?
The molecules inactivate b-lactamase enzymes because they have a similar structure of B-lactam ring as Pc. thus binds to B-lactamases and protects hydrolyzable penicillins from inactivation
Adverse effects of penicillins?
Hypersensitivity
Serum sickness: fever, lymphadenopathy, oedema and rash
SJS
Angioedema: swelling of face, tongue and lips
Allergic reaction
Monobactam drugs?
Spectrum?
Aztreonam (narrow spectrum)
Bactericidal
active against g-ve and aerobic g -ve (b-lactamase producing H.influenzae and pseudomonas spp
Indications for Aztreonam
Infections caused by G -ve aerobes
septicaemia
lower RTI
Pseudomonas Aeruginosa –> cystic fibrosis
people with severe hypersensitivity to Pc
MOA of Aztreonam
inhibits cell wall synthesis by binding to PBP-3 of G -ve
Carbapenems drugs?
Imipenem, Ertapenem and Meropenem
Broadest spectrum –> good activity against g +ve, g -ve & anaerobes
all are activity against staph aureus (no MRSA) and bacteroides fragilis
only Imipenem and meropenem is active against pseudomonas aeruginosa
ertapenem is inactive agianst p.aeruginosa and acinetobacter
Indications for ertapenem, imipenem and meropenem
ertapenem: community acquired infections
Imipenem & meropenem: UTI, Lower RTI and intre-abdominal infections
Meropenem as lower incidence of seizures thus tx for meningitis and melioidosis
Imipenem for nosocomal infections and life threatening multi resistant gram -ve infections
What the 1st generation cephalosorins and adverse effects
cefalexin (oral)
cefazolin (inj)
cefalotin (inj)
What the 2nd generation cephalosorins and adverse effects
Cefoxitin (inj) –> serum sickness like syndrome in children - cefuroxime is preferred
Cefaclor (oral)
Cefuroxime (oral)
What the 3rd generation cephalosorins and adverse effects
Cefotaxime (inj) -> life threatening arrhythmias with rapid infusion
Ceftriaxone (inj) -> pseudolithiasis & nephrolithiasis due to calcium ceftriaxone complex
ceftazidime (inj)
What the 4th generation cephalosorins
cefepime (inj)
Others for cephalosorins
ceftraoline (inj)
ceftobiprole
Antipseudomonal Cephalosorins
ceftazidime
ceftolozane with tazobactam
cefepime
Anti MRSA cephalosorins
Ceftaroline
Pk for cephalosporins
poor absorptions from GIT thus IV preferred
1st and 2 nd are not used for meningitis, poor csf
3rd and 4th are good csf penetration
spectrum for cephalosporins
1st excellent g +ve and modest g -ve
2nd better activity against g -ve
3rd activity against g +ve and enterobacteriaceae & pseudomonas aeruginosa
4th increased stability to hydrolysis by b-lactamases
Indications of 1st cephalosporins
all are used in staph & strep fx in Pc allergy people and UTI
addition cefazolin –> surgical prophylaxis
cefalexin –> epididymo orchitis
Indications for 2nd cephalosporins
cefaclor -> otitis media
RTI by H.influenzae
Sinusitis
Cefuroxime -> Otitis media
RTI by H. influenzae
Sinusitis
Gonococcal infection
Cefoxitin -> Alternative combination for surgical prophylaxis and anaerobic infections
indications for 3rd cephalosporins
Cefotaxime: empirical tx of bacterial meningitis
ceftraixone: used in Pc allergy and CI aminoglycosides
ceftazidime: tx of P.aeruginosa, melioidosis and empirical tx of sepsis in neutropenic or immunocompromised people
Indications for 4th cephalosporins
P.aeruginosa infections
empirical tx of sepsis in neutropenic or immunocompromised people
Fx caused by mo resistant to other cephalosporins
Pk for ceftaroline
ceftaroline fosamil is inactive produrg and is given IV and rapidly biotransformed into active ceftaroline by phosphatases
indication for ceftaroline
complicated skin and soft tissue infections
CAP
Adverse effects of cephalosporins
Neurotoxicity
bleeding
blood dyscrasias
Macrolides drugs
CARE
Clarithromycin
Azthromycin
Roxithromycin
Erythromycin
what drug is used against macrolide resistant strains
Telithromycin with is classified as Ketolides
MOA of Macrolides?
These are bacteriostatic AB
Inhibit protein synthesis by binding reversibly to the 23s rRNA of the 50s Subunit. theis inhibits translocation step so the AA residing at the A site fails to move to P site and this prevents the release of tRNA after the peptide bond formation.
Spectrum of Macrolides
LMS CMC
L.pneumophila M. pneumonia Streptococci (not staph) Clostridium perfringens moraxella catarrhalis chlamydia spp
Azithromycin and clarithromycin have enhanced activity against?
MAC
mycobacterium Avium Complex
Resistance of macrolides
due to expression of the erm genes modifying the ribosomal traget and drecrease the affinity of the AB occurs. this is due to erm enzyme or methylase enzyme catalyse mono or demethylation of a specific adenine residue in the 23s rRNA. thus methyl group hinder the MLSb binding site
Efflux via
mrsA in staph
mefA in strep
mefe in s.pneumonia
pk of erythromycin and distribution
the AB is inactivated by GI acid thus administrated with coated pellets that dissolve in duodenum.
food intake increase gi acid and decrease adsorption
Erythromycin ethly succinate is better in GI acid and less altered
all sites except brain and csf
pk of clarithromycin
rapidly absorded from GIT, can be given with or without food
has a long half life due the active metabolite
14-hydroxyclarithromycin
pk of azthromycin and distribution
rapidly absorded orally, should not be absorbed with food
all sites except brain and csf
high drug distribution thus prolonged t 1/2
Comparative info of macrolides
Erythromycin is the natural drug and all the others have increase bioavialablility, higher peak conc, longer t1/2 and improved tissue conc
Azthromycin and clarithromycin have high uptake in granule zone of polymorphonuclear neutrophils
all are immunomodulatory and anti-inflammatory effects of macrolides are used in cystic fibrosis (azthromycin in lung function)
macrolides are not active against p.aeruginosa but resduce biofilm production & virulence factors
Indications of macrolide drugs?
all are tx for Pc and Ceph allergy and pertussis
Azthromycin: chlamydial infections and CAP and MAC
Clarithromycin: better against MAC
no meningitis
adverse effects of macrolides
E: GI SE
Only for C and E : increase in QT interval & cause torsade de ppointes
candidal infection
hypersensitivity
SJS
psychiatric distrubance
Drug interactions for macrolides
atorvastatin:
clarithromycin will increase the conc of atorvastatin and risk of myopathy
What are the tetracycline drugs? and broad or narrow spectrum? and bacteriostatic or bactericidal
Doxycycline
minocycline
tetracycline
broad spectrum
bactericidal at high conc but usually bacteriostatic
MOA of tetracyclines
inhibit the protein systhesis by binding to the 30s subunit and blocking the tRNA (aminoacyl tRNA) from binding to the A site
Spectrum for tetracycline
wide range of aerobic & anaerobic g+ve and g-ve (staph and strep)
what drug is used to mo that is resistance to Tc?
Tigecycline
Indications of tetracyclines
RTI (doxycycline –> CAP)
Skin and soft tissue infections -> MRSA
Acne (inihibition of propionibacteria)
intra-abdominal infections
STD (chlamydia trachomatis)
Minocycline: leprosy
Pk of Tc
tetracycline poorly absorbed form GIT,
effected by food, di or trivalent cations, dairy product, antacids, Fe and Zn supplements
doxycycline and minocycline less affected by GI acid and orally absorbed
Resistance of tetracyclines
efflux by tetK
ribosomal protection by tetM
Enzymatic inactivation of Tc
Adverse effects of Tc
Tooth discolouration (in children , tetracycline calcium orthophosphate complex causes this)
reduced bone growth (calcification)
vestibular toxicity - minocycline
CDAD
what are the glycopeptide drugs
Vancomycin and teicoplanin
MOA of glycopeptides? bacteriostatic or bactericidal
Inhibit the call wall synthesis or elongation by binding to the 2 D-alanine residue of the free carboxy end of the pentapeptide. the binding sterically hinders the elongation of the peptidoglycan backbone.
bactericidal
Spectrum for Glycopeptides
G +ve only (narrow)
MRSA
staph aureus
Strep (PPV)
Resistance to glycopeptides
is a result of the alteration of d-alanyl-d-alanine to d-lactacte or d-serine.
Van A: d-lactate and both are resistant
Van B: teicoplanin as be used and d-lactate
Van C: non-transferable, constitutive, low level resistance to vancomycin and d-serine
Van D: non trasferable, resistance to vancomycin and reduced effect by teicoplanin, constitutive and d-lactate
Van E,G &L
Pk of glycopeptides
both IV, vancomycin is widely distributed (csf) and teicoplanin as high plasma protein bound
Indications for glycopeptides
MRSA, MRSE (multi resistant s. epidermidis) Pc allergy CDAD prophylaxis in endocarditis in Pc hypersensitive surgical prophylaxis in implantation
Adverse Effects for glycopeptides
Red man syndrome
usually due to infusion being given too quickly. thus having a direct effect of vancomycin on the mast cells & basophihls. degraulation of mast cells cause release of histamine . Sx include fever, chills, itch, hypotension
management via slow infusion rate (>60 mins) and antihistamine (promethazine)
Precautions for glycopeptides
allergy to vacomycin or teicoplanin
thrombocytopenia during Tx
Hearing impairment (increase of ototoxicity)
renal impairment (nephrotoxicity –> ototoxicity)
What are the drug AB under aminoglycosides
Parenteral (Amikacin , Gentamicin , Streptomycin & Tobramycin)
Oral ( Neomycin )
Topical ( Framycetin)
MOA of aminoglycosides and stages of uptake and how does it interfere with protein synthesis?
inhibits protein synthesis by binding irreversibly to the 30 s Subunit causing cell membrane damage –> cell death.
Diffuse throught eh porin in outer membrane of G-ve bacteria & enter the periplasmic space.
transported across cytoplasmic membrane via the oxygen dependent process. once inside the cytoplasm bings to the 30s Subunit irreversibly.
interferes with protein synthesis via:
- blocks the formation of the initiation complex
- blocks further translation of protein and produces premature protein
- incorporation of incorrect amino acid
Resistance of aminoglycosides?
Antibiotic substituting enzyme , resistance is due to transferable plasmid mediated enzymes that modify the amino groups (N-acelytransferase) (AAC) and OH group (O-adenyltransferase (ANT) and O-phosphotransferase (APH)
What drug is given if the strains are resistant to Aminoglycoside?
Amikacin
Spectrum for Aminoglycoside? gentamicin activity?
SPACE MP Serratia Pseudomonas Actineobacter Citrobacter Enterobacteriaceas Morganella Providencia
Gentamicin is usedin hosptial acquired G-ve infections
Adverse effects for aminoglycosides
Ototoxicity: caused by auditory and vestibular dysfunction due to the drug accumulation in the perilymph and endolymph. thus causing damage to sensory cells
Nephrotoxicity: Due to the accumulation and retention in the brush border cells of PCT. the drug alters the structure and function of the PCT cells causing decrease in excretion and thus leads to ototoxicity
Nueromuscular blockade
Theory of once daily dosage for aminoglycosides
- Concentration Dependent Killing
- Concentration Dependent Post-Antibiotic Effect
- First Exposure Effect - Selection of resistant mutants less likely
- Less Nephrotoxicity - Renal accumulation & nephrotoxicity reduced
- Uptake into the Ear Reduced
- Efficacy Maintained
Indications of aminoglycosides
Cystic fibrosis
What are the lincosamide drugs?
clindamycin
lincomycin
MOA of lincosamides?
inhibits protein synthesis by interfering with the formation of initiation complexes and translocation reactions
Spectrum for Lincosamides
G+ve (SSV) - Strep pyogenes - strep pneumonia -viridans strep Anaerobic (BCF) -bacteroides fragilis -Clostridium difficle -Fusobacteria spp
NO GRAM -ve
Indications for lincosamides
Alternative in people with allergy to Pc and Cep
Adverse effects for lincosamides
Clostridium difficile-associated disease
Mild to severe diarrhoea
o May have 5-20 watery bowel movements per day
• Malaise, anorexia, nausea
• Dehydration, fever (30-50% of patients)
• Abdominal pain & cramping
• Colitis, toxic megacolon
Treatment: Metronidazole 400mg tds for 10 days
Drugs that are part of Streptogramins
Quinupristin 30% and dalfopristin 70%
MOA of Streptogramins
Inhibit protein synthesis, binding to 50s Subunit
- Dalfopristin interfers with polypeptide chain formation
- Quinupristin inhibits elongation of proteins
Indications for streptogramins
MRSA or VREF
Adverse effect for sterptogramins
Infusion related events
CDAD
Hepatitis
Linezolid MOA
Inhibits protein synthesis by binding to the p-site of the 50s Subunit and prevents the formation of initiation complex
Spectrum for Linezolid
Aerobic and G +ve only
Indications for linezolid
VRE and MRSA
serious g +ve infections
Interesting about linezolid
linezolid is a weak reversible nonselective mono amine oxidase inhibitor. thus interaction with adrenergics causes hypertension and avoid foods rich with tyramine
when given with serotonergic drugs may cause serotonin syndrome => confusion and restlessness
MOA of Chloramphenicol
Broad spectrum
inhibits the protein synthesis by binding to the 50s Subunit of the p-site thus preventing the transpeptidation reaction NOT THE TRANSLOCATION
Spectrum of Chloramphenicol
gram +ve => staph aureus, strep
gram - ve => but no pseudomonas activity
Indications for Chloramphenicol
Reserved for meningitis and others that resistant to other drugs
Adverse effect for chloramphenicol
Grey baby syndrome:
sx such as refusal to suck, rapid respiration and loose green stools.
due to deficiency of glucuronyl transferase and inadequate renal excertion
Resistance to chloramphenicol
Drug modifying enzyme (Ab substituting) -> chloramphenicol acetyl transferase
Sodium fusidate MOA
Inhibits protein synthesis by preventing the translocation of the peptide subunit
Spectrum for sodium fusidate
G +ve only —> Staph and MRSA
NO G -ve
Indications for sodium fusidate
Staph infections –> osteomyelitis and burns
Adverse effections for sodium fusidate
leucopenia
thrombocytopenia
MOA of Mupirocin
AB conatin a structure similar to isoleucine. thus competes with isoleucine for binding to to isoleucine transfer RNA synthetase and prevent the formation of isoleucyl transfer RNA thus prevent the Isoleucine incoporation in proteins
Spectrum for mupirocin
G +ve and selected g -ve strep and MRSA
Indications for mupirocin
Mild impetigo
small skin lesions
nasal carriage of staph
Lipopeptides drugs
Daptomycin
MOA of daptomycin
Bactericidal activity by distrupting the plasma membrane without entering the cytoplasm. the acyl tail portion inserts into the plasma membrane in presence of Ca 2+ causing depolarisation of the membrane –> efflux of K+ ions (essential for DNA, RNA and protein synthesis) lead to cell death. leaves a ghost shell behind
Indication of Daptomycin
Stap, MRSA
only G +ve
Adverse effects and precautions
CDAD
multi-organ hypersensitivity syndrome
Myopathy is the precaution
MOA of peptides
Acts like cationic detergents that interacts with phospholipids and disrupts the structure of the cell membrane
Indications for peptides or polymyxins
G -ve only
Pseudomonas aeruginosa in cystic fibrosis
Gramicidin is a peptides that is active against gram +ve not g -ve and highly toxic to liver and kidneys
Adverse effects for peptides
Nephrotoxicity and neurotoxicity
MOA of Sulfonamides
Sulfonamides are structural analogues and competitive antagonists of para-aminobenzoic acid (PABA), this prevents bacterial utilisation of PABA for the synthesis of FOLIC acid. Sulfonamides have a higher affinity for the bacterial enzyme dihydropteroate synthase (DHPS) thus prevents PABA into incorporation into dihydropteroic acid.
Drugs for sulfonamides?
Sulfamethoxazole is orally taken and Crystalluria is possible
Silver sulfadiazine is used to reduce microbial colonization and incidence of infections from burns
MOA of trimethroprim
This Ab is a potent and selective competitve inhibitor of dihydrofolate reductase. this enzyme reduces dihydrofolic acid to tetrahydrofolic acid and inhibits the folate production
Indication and contraindications for trimethroprim
Empirical treatment for uncomplicated lower UTI
Epididymo orchitis
Prostatitis
CI: Megaloblastic anaemia and hyperkalaemia
Indications for sulfamethoxazole with trimethoprim
MRSA
Shigellosis
Melioidosis
PK, adverse effects for sulfamethoxazole with trimethoprim
20:1 ratio (800 mg : 160 mg bd
Crystalluria and hyperkalaemia nad thromocytopenia
Drugs for Quinolones
COMN
Ciprofloxacin
Ofloxacin
Moxifloxacin
Norfloxacin
MOA for Quinolones
Inhibit bacterial DNA synthesis by blocking DNA gyrase (topoisomerase 2) and iopoisomerase 4. these 2 enzymes are involved in DNA synthesis and DNA replication.
Topoismerase 2 is involved in the replication, transcription and repair of bacterial DNA. In the DNA replication the double helical DNA is separated to all DNA polymerase to read. but separation results in supercoiling of the DNA in front of the point of separation. the DNA gyrase introduces negative supercoils to allow DNA synthesis to continue.
Quinolones ihibit nicking and closing of DNA gyrase activity
Topoismerase 4 is important in separating the daughter DNA copies during cell division
Quinolones block the decatenating activity of topoismerase 4
Spectrum for 4 generation of quinolones
1st -> Modearte g -ve and minimal systemic distribution
2nd-> expanded g -ve activity and limited g+ve (ciprofloxacin & norfloxacin)
3rd -> expanded G -ve and improved G +ve converage
4th-> maintain G-ve and improved G+ve (moxifloxacin)
Ciprofloxacin for Pseudomonas aeruginomas
Absorption, Distribution and Elimination of quinolones
Absorded well after oral administration. food doesn’t impair absorption but chelate with cations. dairy products, antacidsd, Fe and Zn supplement
Distribution t1/2 is 4-5 hrs and high volume of distribution
Elimination: most by kidney but moxifloxacin is by liver
Indications for quinolones
Ciprofloxacillin (PUSSPOET) pertusis UTI Salmonella shigellosis pseudonomas aeruginomas otitis media epididmyo Orchitis Typoid
Norfloxacillin (SPUD) Shigellosis pseudomonas aeruginomas UTI Diahorrea
Moxifloxacillin (CCAST) Chronic bronchitis CAP Anaerobic Bacteria Soft skin infections multi drug resistant TB
Adverse effects in quinolones and precautions
Tendon rupture -Over 60 years -Use of corticosteroid Organ transplant Renal impairment rheumatoid arthritis
Precautions: neurological (seizures) and cardiovascular
MOA of fidaxomicin
inhibits bacterial transcription by binding to RNA polymerase, a large enzyme that consists of 5 subunits and fidaxomicin inhibits sigma subunit
Spectrum, indications and adverse effects for fidaxomicin
Narrow spectrum. Activity against c.difficle, staphylococci and enterococci
Poorl absorded from GIT
Indicated for Clostridium Difficile infection
ADR : Hypersensitivity
Nitrofurantoin MOA
by suspectible MO it is reduced to form a reactive intermediate that will inhibit enzyme that is required for DNA/RNA/Protein synthesis
Spectrum and indications for Nitrofurantoin
and adverse effects
active against urinary pathogens
indicated for lower UTI
Drowsiness and allergic skin reactions
MOA of Hexamine Hippurate
In kidney Hexamine hippurate dissociates to hippuric acid + hexamine
(methenamine)
◦ Methenamine is a urinary tract antiseptic & prodrug Is hydrolysed in acidic pH to ammonia & formaldehyde, which is bactericidal against G+ve & G-ve mo
Indications and spectrum for Hexamine hippurate
Prophylaxis of chronic or recurrent lower UTIs
Active against G+ve & G-ve bacteria
Pk for hexamine hippurate
Readily absorbed orally
Mainly excreted unchanged in the urine
The decomposition reaction is fairly slow
Methenamine is distributed throughout body fluids but no decomposition of the drug occurs at pH 7.4 ∴ systemic toxicity should
not occur
CI for hexamine hippurate
Severe dehydration
Gout
Hepatic insufficiency
drugs under nitroimidazoles
Metronidazole
Tinidazole
MOA of nitroimidazoles
Both drugs are prodrugs, removes electrons from ferredoxin (ferredoxins donate electron -> highly reactive nitro radical is produced and this damages DNA) causing the nitro group of the drug to be reduced. the reduced intermediate is highly reactive and binds to DNA which undergoes Strand breakage
Spectrum for nitroimidazoles
Anaerobic (BCF)
Protozoa (Trichomonas vaginalis and gradnerella vaginalis)
resistance for nitroimidazoles
Metabolic changes and increased O2 levels results in poor penetration and reduced activity
Indication for nitroimidazoles
CDAD
bacterial vaginosis
Tinidazole (protozoal infection)
Adverse effects for nitroimidazoles
furry tongue slossitis stomatitis SJS Headache
