winter 3 Flashcards
1
Q
Sulfonamides MOA
Trimethoprim MOA
A
- sulfonamide MOA- inhibit dihydropteroate synthase stoping conversion of PABA–> dihydropteroic acid,
- TMP MOA- a diaminopyrimidine- inhibits DHFR enzyme stopping DHF-> THF, 100,000x more sensativte to bacteria DHFRf
- both stop folate production, and inhibiting DNA production
- each is static on own but tidal when used together, 1:5 TRI to SMX ratio-> 1:20 ration in serum
- Sulfonamides penetrate in to most body fluids, and can cross into CNS and cross the placenta, TMP penetrates CNS better b/c lipophilicity
- t1/2 both = 10-12 hr, tmp excreted in urine-> dose adjust in renal disease
2
Q
Sulfonamide and Trimethoprim adverse effects
A
- sulfonamide low solubility–> crystal urea(prevent with 1200ml output/day), redox potential-> hemolytic anemia in G-6PD deficiency pts
- anti folate drugs in general-> can lead to anemia from bone marrow suppression (esp in aids/cancer pts)
- both-skin hypersensitivity(^ inHIV pts), NV and GI distress
- allergy also to other sulfa drugs( sulfonureas, diuretics, and diazoxide)
- TRI- hyperK(via blocking Na abs in distal nephron), inhibit human folate in malnurished pts
- PREGNANCY- category D- early in preg-> inhibit human DHFR, late preg can displace bilirubin-> neurotoxic kernicterus, in milk-> don’t use in G-6PD infant nursing
- but use in preg when benefit>risk - P. jirovecii pneumo treat/prophylax and toxoplasma prophylaxis
- displace phenytoin, warfarin, sulfonylureas
3
Q
Sulfonamide and Trimethoprim USES
A
- lower UTI- TRi penetrates prostate, G- like E. coli, proteus, klebsiella, enterobacter, morganella
- RESP pathogens- strep pneumo, h flu, moraxella, P. jirovecii, high rate of pneumococcal resistance
- GI- E coli, salmonella, VIbrio cholera, NOT for shigella
_some MRSA are sensitive to it
-Listeria, yersinia pestis, nocardia, Toxoplasma gondii, pneumocystis
- resistance mutations to DHFR or dihydropteroate synthase, Pseudomonas use efflux pumps, Bacteroides, MTB, Treponema palladium, Campylobacter, penicillin resistant pneumococcus, rickettsiae
- enterococcus faecalis is auxotrophic for folic acid
4
Q
Silver Sulfoadiazine
A
- also mafenide, and sulfacetamide
- standard treatment for the infection of burns because of the very little absorption into the body and limiting the toxicities,
- ophthalmological ointments for chlamydia trachoma conjunctivitis
5
Q
aminoglycosides pharmacokinetics
A
- MOA- inhibit bacterial protein synthesis bind to 30S unit
- polar drugs effecting pharmicokinetics–> poor oral absorption, whole dose out in feces, so give IV(30-60 min drip) or IM
- dont penetrate cell well, little entrance into eye or CNS
- form complex w/ b lactam ABx-> administer separately
- cross G- outer membrane thru poron, cross inner membrane via O2 dependent active transport(not effective in low pH and anderobic infections), B lactase enhance transport–> synergistic killing effect
- NOT metabolized, cleared via filtration, dose adjust in renal failure(t.5 in healthy=2-3, in renal disease 24-48 hrs)
6
Q
aminoglycosides pharmacodynamics
A
- inhibit bacterial protein synthesis by irreversibly binding to 30S subunit, and are bactericidal(dose dependent)
- blocks initiation of protein synthesis
- blocks movement of ribosome-> breakup of 70S subunit
- mRNA misreading-> mutant proteins that kill the cell( even at [ ] below MIC
7
Q
aminoglycosides toxicities
A
-Ototoxic CNVIII damage(acumulate in the endo and perilymph-> distraction of vestibular and cochlear hair cells) strepto>amika=genta=tobra, ^ risk w/loop diuretics and vancomycin, in elderly, dehydrate, and long term use
- tinnitus-> hearing loss (Amika, Kana, netil,Neo)
- Vestibular tox->vertigo ataxia,loss of balance, Genta,strepto, tobra
- NEPHROTOXICITY-in prox tubule and is reversible, monitor w/ creatinine serum level every 2-3 day, Genta, tobra, neo
- ^ risk w/^ doses, coda w/ vanco or cephalosporin, prexisting renal fail, elderly and dehydtrate pts
- NEUROmuscular blockade-weakness and resp paralysis, blockage of Ach release and post synapse activity, treat w/ Ach as inhibitor (neostigmine/edrophonium) and IV Ca
- drug levels routinly obtained in pts b/c of ^ toxic effects
8
Q
Bacterial resistance to aminoglycosides
A
- production of bacterial enzymes that phosphorylate, adenylate, or acetylate the drugs-> not allowing binding to the 30S subunit, on plasmid and spread via conjugation
- problem in hospital setting
- Amikacin, netilmicin are most resistant to these enzymes, these are useful in gentamicin resistant G- bacteria
- important in entercoccal endocarditis
- inability to penetrate the cell wall(less problem clin) , mutation in the 30S subunit to decrease binding
9
Q
antibacterial spectrum of aminoglycosides
A
- USED TO TREAT SYSTEMIC INFECTIONS FROM G- ENTERICS (SPESIS)
- IN COMBO W/CELL WALL INHIBITORS TO TREAT BACTERIAL ENDOCARDITIS
- G+ baceria- limited activity alone, used in combo w/ ABx that inhibit cell wall synthesis to have synergistic effects,
- good for S. aureus and epidermidis, Strep pneuma and pyogenes are highly resistant, Genta and strepta use w penicillin and amoxicillin for synergistic effect on enterococci and viridens group strep
- G- Bacteria-best activity against G- enterics, E coli Klebsiella pneumo, Proteus
–Genta Tobra, Netil, Amikacin have Pseudomonas activity
- NOT ACTIVE AGAINST ANAEROBES(b/c transported in tobacteria via O2 dependent manner)
- no fungal or virus
10
Q
streptomycin
A
aminoglycoside
- inhibit bacterial protein synthesis by irreversibly binding to 30S subunit
- less G- activity b/c of resistance->limited colin use
- uses- in combo w/ penicillin for Bacterial endocarditis (gentamicin is preferred but some resistant to it are sensitive to street), 2nd line in combo for MDR MTB,yersinia and francisella IM in combo w/ tetracycline
- adverse RXN- allergic skin rash, pain at injection, OTOTOXICITY, irreversible associated w/ vertigo and loss of balance, in pts using for >2wks, defenses of child if used in preg
11
Q
Gentamicin
A
aminoglycoside
-inhibit bacterial protein synthesis by irreversibly binding to 30S subunit
-first choice b/c of low cost
-USE- G- infections from Pseudomonas, enterobacter, klebsiella, serratia
UTI in combo w/ B lactam ABx(initial broad spec coverage) switched to less tox ABx if susceptible infection(TMP-SMX), G- pneumoniaI as initial empirical therapy HAP(Not for CAP)
- in combo w/ penicillin for bacterial endocarditis(better than amika or tobra),
- G- sepsis, for pseudomonas use genta in combo w/ ticarcillin or piperacillin(anti pseudomonal penicillins)
- adverse effects- nephrotox and ototox( trough [>2ug/ml]
12
Q
Tobramycin
A
aminoglycoside
-inhibit bacterial protein synthesis by irreversibly binding to 30S subunit,
- same spec of activity as gentamicin
- better pseudomonal coverage than gentamicin and use in sepsis, osteomyelitis and pneumonia from this bug
- orphan drug status for pseudomonal bronchopulm infections in Cistic fibrosis pts
- less effective against enterococci, E faecium
- TOX- nephrotoxicity and ototoxicity
13
Q
Amikacin
A
aminoglycoside
- inhibit bacterial protein synthesis by irreversibly binding to 30S subunit, derivative of kanamycin
- broadest spectrum of the aminoglycosides b/c resistant to the enzymes that inhibit genta and tobra
- G- bacteria- proteus, pseudomonas, enterobacter, serratia
- bad against G+ bacteria, but does have activity against streptomycin resistant MTB
- USES-serious nosocomial G- infections resistant to genta and tobra, should NOT be used in endocarditis
- TOX- nephro and ototoxicity( oto is more common
14
Q
Fluoroquinolones drugs, MOA, kinetics
A
Ciprofloxacin
levofloxacin
moxifloxacin
- target and inhibit bacterial DNA gyrase and topoisomerase IV, these enzymes fix supercoiling that occurs in DNA replication-> inhibition of replication(cidal), gyrase more in G- and topoisomerase more in G+
- addition of Fluorine improved lipid solubility, accumulation in bacteria, and affinity for DNA
- good oral abs, inhibited by poly cations(Ca, Mg, Al, Fe, Zn) supplements
- wide distribution to exceed serum [ ] in Mphage, PMN, kidney, urine, prostate, lung, stool, bile
- not used in CNS infection, t1/2 mostly 3-10 hrs
- cleared by renal mech–> dose adjust
- moxifloxacin met in liver-> caution in liver fail
15
Q
Fluoroquinolone Theraputic uses
A
- target and inhibit bacterial DNA gyrase and topoisomerase IV, these enzymes fix supercoiling that occurs in DNA replication-> inhibition of replication(cidal)
- UTI and prostatitis(e coli most common for both), useful in Chlamydia and haemophilus ducreyi chancre
- no use- N. gonorrhea(ceftriaxone instead) or trepomona palladium, preg category C
- diarrheas from Salmonella, shigella, and e coli
- only class w/ oral form for pseudomonas(cipro)
- levo and moxi(resp fluoros) to treat CAP, cipro
- bone joint and soft tissue infections, osteomyelitis and diabetes foot infections
- M. avium in AIDS pts, francisella and anthrax
16
Q
Ciprofloxacin
A
- fluoroquinolone
- UTI and prostatitis( coli most common for both), useful in Chlamydia and haemophilus ducreyi chancre
- oral dose pseudomonas in cistic fibrosis pts
- diarrheas from Salmonella, shigella, and e coli
- bone joint and soft tissue infections, osteomyelitis and diabetes foot infections
- M. avium in AIDS pts, francisella and anthrax
17
Q
levofloxacin
A
respiratory fluoroquinolone-target and inhibit bacterial DNA gyrase and topoisomerase IV, these enzymes fix supercoiling that occurs in DNA replication-> inhibition of replication(cidal)
- pneumonia causeing- s. pyogenes S aureus, mycoplasm, and legionella, prominent( but not 1st line)role in CAP,
- UTI and prostatitis( coli most common for both), useful in Chlamydia and haemophilus ducreyi chancre
- diarrheas from Salmonella, shigella, and e coli
- bone joint and soft tissue infections, osteomyelitis and diabetes foot infections
- M. avium in AIDS pts, francisella and anthrax
18
Q
moxifloxacin
A
respiratory fluoroquinolone-target and inhibit bacterial DNA gyrase and topoisomerase IV, these enzymes fix supercoiling that occurs in DNA replication-> inhibition of replication(cidal)
- pneumonia causeing- s. pyogenes S aureus, mycoplasm, and legionella, prominent( but not 1st line)role in CAP,
- reported w/ high rate of adverse effects
- BEST CHOICE of class for anaerobics for complicated intra abdominal infections on par w/ pipercillin/amox
- UTI and prostatitis( coli most common for both), useful in Chlamydia and haemophilus ducreyi chancre
- diarrheas from Salmonella, shigella, and e coli
- bone joint and soft tissue infections, osteomyelitis and diabetes foot infections
- M. avium in AIDS pts, francisella and anthrax
19
Q
resistance to fluoroquinolone
A
-develop quickly and confers resistance to all
- most rapid from plasmid factors,
- quinolone resistance proteins(Qnr)- protect bacterial gyrase
- aminoglycoside acetyltrasnferase can act on cipro conferring resistance to both
- 3rd plasmid- efflux pumps
- chromosomal pont mutations to binding site
- cross resistance is common- enterobacter and klebsiella resistant to both quinolone and B lactase
- no use in MRSA-resistance is wide spread
20
Q
Fluoroquinolone adverse effect and interactions
A
- most serious-QT prolongation, hypoglycemia, immune hemolytic anemia, hepato tox, photo tox,
- moxifolxacin - reported w/ high rate of adverse effects
- GI-are most common-NVD, most common cause of C difficile, an especially toxic strain
- 10% CNS- headache, dizzy, other like hallucination or seizure are rare- caused by displacing GABA from receptor, enhanced by theophylline or NSAIDS
- black box 1- achilles tendon rupture in elderly, steroid pts, and organ transplants
- blackbox 2-exacerbation of myasthenia gravis
- category C preg- meta acidosis and hemolytic anemia
- rash 2%,
- caution w/ QT prolonging drugs-SRI, TRIcyclic AD, diuretics, anti psychotics
21
Q
Vancomycin
A
- Inhibits Bacterial cell wall synthesis
- poor oral abs, IV arm
- wide distribution and penetrates CNS w/ inflammed meninges, 90% renal excretion, dose adjust in failure
- MOA- binds to D-alanyl-D-alanine of peptidoglycan pentapeptide-> inhibit PG formation and is bactericidal
- resistance via alteration cell wall precursors so vance can’t bind as well, ex: DaDa replaced w/D-alanyl-D lactase/serine
- USE- G+ bac, active against MSSA and MRSA, s epidermitis, strep, corny bacteria, C dif and C. perfringes
- G- bac: NO ACTIVITY
- anaerobes: only clostridium- not used against others
- clinical- serious staph infections(sepsis and endocarditis), G+ in pts allergic to penicillins and cephalosporons( enterococcus endocarditis-vanco w/aminoglcosides), dhrea from C diff and GI bugs, staph meningitis w/3rd cephalo
- tox-ototox and nephrotox(rare) more common in combo w/ ahminoglycosides, RED MAN- arm to fast-> His release
22
Q
Clindamycin
A
- MOA- binds to 50S subunit and inhibits protein synthesis
- well abs orally, t.5=2.9 metabolized and excreted mostly in bile, dose adjust in hepatic failure- Bacterio static
- widely distributed inbody, not in CNS even w/ inflammation of meninges, GOOD entry into Abscesses
- resistance- mutation to 50S subunit to prevent binding, methylase modification of binding site, enzymatic inhibition of ABx, bugs resistant to clindamycin are also resistant to erythromycin
- USES- G+ bac- most staph aureus strains(some MRSA), s. pneuma, but ENTEROCOCCI are resistant, NO G- USE, active against G+ and G- anaerobes, including b. fragilis and C. perfringens
- used to treat abscesses( not in brain), prophylactic use for dental procedures prevent endocarditis, alternative to cephalosporins and penicillin allergic pts, P, Jiroveci and toxo in AIDS pts
- tox-ND, skin rash, pseudomembranous colitis- C dif
23
Q
Nitrofurantoin
A
- MOA- not well understood- reduced forms damage DNA, static and cidal
- rapid oral abs, rapid met and excretion by filtration and renal secretion(not used in renal fail) so fast that systemic effects not seen, more active at urine ph of 5.5- administer with acidifying agent
- Uses-many G- and G+, pseudomonas and proteus are resistant
- clinical-used to treat UTI and prophylaxis of frequent UTI, Ecoli resistant to TMP-SMA and Fluroquinolones
- Tox- GI upset=anorexia NV, rare hemolytic anemia, headache, demylination, pulm fibrosis, shronic hepatitis (rare but serious), contraindicated in renal failure cautious in preg
24
Q
Polymyxin B sulfate
A
- cidal Abx by interacting with cell membrane phospholipids and disrupting cell membrane permeability and causing leakage of intracellular components
- resistance from inability to pass through cell wall
- restricted to susceptible G- bac. enterobacter, ecoli, klebsiella, h flu, acinetobacter, pseudomonas
- topical treat of eye, skin, MM, ear wound and burn infections, IV therapy for drug resistant G- pneumonia, IV or IM for G- septicemia and UTI, Intra thecal for Meningitis, combo w/ neomycin to irregate bladder to prevent infection from indwelling catheters
- TOX-neurotoxicity, nephrotoxicity, reserve use to when less toxic Abx are no longer available for use
25
Metronidazole
- MOA-reduction of drug to compounds that bind to intracell macromolecules, bactericidal effect
- a nitroimidazole, good oral abs,IV, rectal or topical vag gel
- Mide distrubution include CNS and abscesses, met in live excrete via kidney
- not good for G+or G- aerobes, GOOD ACTIVITY against anaerobes including clindamycin resistant B. fragilis
- CLIN-anaerobic infections (soft tissue, brain abscess, intra AB, pelvic inflame) pseudomembranous colitis from C diff, H pylori
- TOX-carcinogenic potential, present intreats milk and crosses placenta->NO USE in PREG, disulfiram like interaction w/ EtOH
26
Bacitracin
- inhibits cell wall formation via inhibiting lipids that carry PG to the site of cell wall formation, no cross resistance
- ophthalmic and dermatologic ointment( not used parenteral b/c nephrotox)
- similar activity to PCN, activity to G+ cocci and rods, and G- Neisseria, H flu, and spirochete treponema palladium
- USES-topical wounds to eradicate mixed microbes, eye infections
- TOX-SERIOUS nephrotox w/ parenteral use-> renal failure due to tubular and glomerular necrosis, rare hypersensitivity from topical use
27
Quinupristin/dalfopristin
- Streptogamin ABx combo- Q is group B, D is group A
- MOA- like macrolides- inhibit protein synthesis by binding to 50S subunit, each binds to different site on subunit
- resistance- modification of Q bind site, enzyme destruction or efflux of D
- IV for bacteremia and life threat vanco resistant entercoccus faecium and complicated skin infections from s aureus and s progenies
- activity to MRSA and MSSA, PSSP and PRSP
- used when E faecium, strep or staph infections resistant to other ABx, or allergy to other ABx
- erethyma/pain at injection site, arthralgia/myalgia, CYP3A4 inhibition
28
Linezolid
- MOA-binding 50S subunit-> prevent 70S initiation complex
- oral and parenteral adm
- cidal to strep static to many others
- resistance- entero and streptococci via point mutation at 23S rRNA of 50S subunit
- spec activity-vanco resistant E. Facacium,HAP/CAP from S. aureus and PSSP, skin infection from MRSA and MR S pyogenes
- TOX-NVD, Thrombocytopenia-monitor platelet count in treatment >2 weeks, reversible inhibitor to monoamine oxidase( co adm w/ tyramine foods-> HTN), avoid in PKU pts, can lead to C diff
29
Daptomycin
- [ ]dependent killing effect by binding and depolarizing cell membranes-> loss of Mem potential->K efflux->death
- use only IV, t.5=8-9 hrs, 80% excreted in urine-> dose adjust if creatine clear is below 30
- cidal for aerobic, facultative , and anaerobic G+
- skin and skin structure infection s from MSSA MRSA, hemolytic strep , and vanco resistance B faecalis
30
first line drugs for TB
Isoniazid
Ethambutol
Rifampin
pyrazinamide
31
drugs for treating leprosy
Dapsone
Clofazimine
rifampin
32
principles of TB therapy
- therapy must consist of 2 or more drugs that Tb is sensitive to
- treatment must continue 3-6 months after sputum becomes negative
- drugs work only during replication, TB obligate aerobe, effected by the pH of its environment
- recommended 6 months of INH, rifampin, and pyrazinamide ( 1st 2 mo) and INH and rifampin for final 4
- resistance- 3 variables, history of prior anti TB therapy, country of origin , and duration of residence in US
- single drug therapy is only in preventative therapy, INH for 9 months( also 2mo of combo rifampin and pyrazinamide)
33
short course chemotherapy for TB
6-9 months in US
- initial phase of INH, rifampin, pyrazinamide, and ethambutol daily for 2 months
-continuous phase- INH and rifampin (daily, 2x/wk, or 3x/wk) for 4 months
34
goal of leprosy chemotherapy
broad objectives
1. render the pt noninfectious
2. prevent further bacterial multiplication
3. avoid or treat reactions
- paucibacillary treatment- Sulfone Sensative- dapsone(3-5y), rifampin(6mo), SR- clofazimine and rifampin
- multibacillary- SS-dapsone(10y-indefinate) rifampin(3y), SR-clofazimine(indefinate) rifampin(3y)
35
INH- Isoniazid
- hydrazide of isonicotinic acid
- interferes w/ mycolic acid biosynthesis, bactericidal in rapidly dividing bacteria
- excreted in the urine w/in 24hrs as acetylated or hydrolyzed nisonicotinic acid(slow android acylators)
- Adverse rxn- peripheral neuropathy from increased excretion of pyridoxine
- Hepatitis- Major effect more communion the slow acetylators, pts should be monitored peridically serum transaminase levels
36
Rifampin
- derivative of rifamycin B, for TB and leprosy
- inihbits bacterial RNA synthesis- binding to B subunit of DNA dependant RNA polymerase, does not inhibit mammalian RNA Polymerase
- resistance w/ mono therapy, met in liver and excrete in urine(33%) and bile (66%)
- inhbits most G+ and some G-, most active during cell multiplication
- ADVERSE RXN- GI disturbance, NV , hepatitis, red-orange color in urine salivia and sweat w/long term use
- Potent activator of P450 system-> decreased t1/2 of many drugs
37
Ethambutol
-MOA- unknown- inhibits incorporation of mycolic acid into the mycobacterium cell wall, rapid abs from GI tract
- Adverse RXN- MOST SIG- dose related ocular toxicity, reversible vision changes -> retrobulbar neuritis and loss of green red discrimination
- should be stopped immediately
- oral adm w/ rifampin and INH in TB chemotherapy
38
Pyrazinamide
-pyrazine analogue of nicotinamide
- MOA- unknown-exhibits bactericidal activity at acidic pH, hydralized to pyrazinoic acid which has anti TB activity
- good GI abs
- adverse RXN- hepatotox is main SE, all pts treated w/ this should have LFT before beginning and throughout treat
- nongouty polyarthralgia- drug causes hyperuricemia
- important in short term multi drug therapy of TB
39
Clofazimine
- red colored compound
- MOA- binding of drug to mycobacterial DNA to inhibit growth, cidal for M. leprosy
- Very long t.5=70days, slowly excreted in urine
- TOX- discoloration of the skin- first reddish-> mahogany brown, will clear after discontinuation
- GI- most serious effects- NVD at higher doses
-used for lepromatous leprosy
40
Dapsone
-sulfone analogue of p-aminobenzoic acid
- MOA- inhibits folic acid synthesis (similar to sulfonamides by inhibiting dihydropteroate synthase)
- bacteriostatic for M leprae, T.5=10-50 hours, acetylated inlayer and excreted in urine
-TOX-usually mild, but can cause hemolytic anemia(CBC should be performed frequently), methemoglobinemia, sulfone syndrome- exacerbation of lepromatous leprosy
41
Agents that block attachment and penetration
Gamma globulin
42
amantadine
blocks viral penetration and uncoating
only specific for influenza A
43
Sulfasalazine
- not well absorbed form GI
- Used in ulcerative colitis and IBD, b/c converted to 5- ASA and sulfapyridine to have an anti inflammatory effect and immune modulating properties
- sulfapyridine IS absorbed and causes hemolysis in G6-PD
44
Amphotericin B
antifungal therapy for sub Q and systemic mycosis
-creates pores in membranes causeing leaking and death of fungus
-SE-nephrotoxicity( increased w/ conccurrent treatment of aminos or cyclosporons), anemia due to decreased production of EPO
- systemic fungal infections iv or intrathecal, superficial from candidia
- protozoa infections
45
Ketoconazole
imidazole
antifungal therapy for sub Q and systemic mycosis
- inhibit 14 a demethylase-> buildup of 14 a methyl sterols(lanosterol)->impairing membrane bound enzymes systems, and permeability of fungal membrane
- fungistatic at low [ ] and tidal at higher [ ]
- endocrinological abnormalities- inhibition of steroid synthesis, inhibit of P450 enzymes
46
Miconazole
imidazole
antifungal therapy for sub Q and systemic mycosis
--inhibit 14 a demethylase-> buildup of 14 a methyl sterols(lanosterol)->impairing membrane bound enzymes systems, and permeability of fungal membrane
-low tox w/ oral iv or intrathecal arm
47
Fluconazole
triazole
antifungal therapy for sub Q and systemic mycosis
--inhibit 14 a demethylase-> buildup of 14 a methyl sterols(lanosterol)->impairing membrane bound enzymes systems, and permeability of fungal membrane
- 25-30 hr halflife-> once daily dosing ,increses concentration of drugs met by P450 enzymes
- low tox, no effect on pts plasma level of test or response to ACTH
48
Itraconazole
triazole
-antifungal therapy for sub Q and systemic mycosis
--inhibit 14 a demethylase-> buildup of 14 a methyl sterols(lanosterol)->impairing membrane bound enzymes systems, and permeability of fungal membrane
- 30 hr t1/2, increses concentration of drugs met by P450 enzymes
- low tox, nausea, heart burn , headache
49
drugs to treat systemic mycosis
```
Amphotericin B
Ketoconazole
Miconazole
Fluconazole
Itraconazole
```
50
Griseofulvin
MOA- disrupts the cells mitotic spindle structure , arresting cell in metaphase
-SE- CNS headache
GI- epigastric pain, NVD
Hypersensitivity- rare
precaution:periodic assessment of renal hepatic and hematopoietic function should be performed
-used in treatment of dermatophytes , not for tinea versicolor or candidia
51
Nystatin
- binds to sterols in fungal cell membranes-> resulting in membrane not acting as a selective barrier-> loss of K and other cell contents
- SE_ very rare w topical use, hypersensitivity rare
- too toxic for parenteral use
- used mainly for cutaneous, mucocutaneous, and oral cavity candidal infections
52
Tolnaftate
inihibts squalene monooxygesase ->build up of squalene and changes in membrane properties
_low tox
- main use is dermatophytes
53
Terbinafine HCl
inihibts squalene monooxygesase ->build up of squalene and changes in membrane properties
- low tox
- main use is dermatophytes
54
Caspofungin
- echinocandins antifungal
- MOA- inhibits the synthesis of B 1-3 D-glucan( essential component of fungal walls
SE-rach fever, phlebitis at injection site, NV fluching
-use in treating invasive aspergillosis and esophageal candidiasis in PTS REFRACTORY TO OTHER ANTIFUNGAL MEDICATIONS
