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Chemotherapeutic drugs pt.2 - Coggle Diagram
Chemotherapeutic drugs pt.2
Macrolides
Good oral bioavailability
Azithromycin
Impeded by food
Unique in that it achieves higher levels in tissues and phagocytes than that in plasma
Slow half life and not extensively metabolized
Excreted mostly unchanged in bile and urine
Similar to erythromycin but is active also against H influenza. M. catarrhalis and Neisseria
Erithromycin
Metabolized primarily by CP450 system and excreted in bile
Very rapid half-life and excretion
Deployed with enteric coating to prevent destroying by stomach acid
Clarithromycin
Metabolized by liver by CYP3A4 and excreted in urine and feces
Resistance
Caused by efflux pump mechanisms
production of a methylase
Adds methyl group to ribosomal binding sites
There is cross-resistance to other macrolides
Is active
Gram-positive cocci
beta-lactamase producing staphylococci
Fidaxomicin
Inhibits protein synthesis by inhibiting RNA polymerase
Selective against G+ aerobes and anaerobes
Effective for treatment for C. difficile with lower relapse rate than vancomycin
Tetracyclines
Resistance
Modification of ribosomal binding site
Cross-reistance between macrolides and streptograms
Enzymatic inactivation by esterases
Dose adjustment in renal failure required, except for doxycycline
high concentration in bile, tears and saliva, low penetration to CNS
Damage to bones and teeth while growing, teratogen
No longer used that much due to resistance
Used for rickettsiae
Anthrax, protozoal infections (doxycicline) and for SIADH (demeclocycline)
Tigecycline
Skin and soft tissue infections
Complicated intra-abdominal infections
Community-acquired pneumonia
Clindamycin
Resistance
Methylation of binding sites of 50s ribosome
G- aerobes intrinsically resistance because of poor penetration of clindamycin through outer membrane
Cross-resistance between macrolides is common
Eliminated by biliary and renal excretion
Uses
Backup drug against g+cocci
prophylaxis for endocarditis in patients allergic to penicillin
Pneumocystis jirovecii
Used in combination with pyrimethamine for AIDS-related toxoplasmosis
Aminoglycoside
Cause concentration-dependent killing
As in that they kill more bacteria as time goes on
Capable of exerting a post-antibiotic effect where they kill even after plasma levels have diminished
Better as a single large dose
Polar compounds, not absorbed after oral administration
Plasma levels are greatly affected by changes in renal function
Toxicity
Ototoxicity proportional to plasma levels
risk may be increased in a patient with renal dysfunction
ototoxicity reported after fetal exposure, contraindicated with pregnancy
Streptomycin + penicillins more effective in enterococcal carditis
no activity against anaerobes, S. pneumoniae
Resistance
Enzymatic inactivation
Impaired renal entry into the cell
Modification of ribosomal binding site
Clinical uses, Ps
Pus (sepsis, fever and infection), pump (heart, endocarditis), pneumonia, pelvic infections, pyelonephritis, post-traumatic and -operative meningitis and osteomyelitis, potbelly (intraabdominal infections), peek (ototoxicity
Risk factors
Old age, dehydration and kidney problems
Spectinomycin
Intramuscular infections, used to treat gonorrhea
reaction can occur at infusion sites
can be used for patients allergic to penicillin
can be used for drug-resistant gonorrhea
Fluoroquinolones
Good oral bioavailability
Except norflaxin which does not reach adequate plasma levels
Elimination through kidneys via tubular secretion
Most need monitoring of kidney function except moxifloxacin
Resistance
Efflux and changes in porin structure
Emerged in case of campylobacter, gonococci, G+ cocci, Pseudomonas and Serratia
Third generation of fluoroquinolones also called respiratory quinolones
Azole
Fluconazole, posaconazole and voraconazole (triazoles) all have good oral bioavailability
Fluconazole
excreted mostly unchanged in the kidney
Single dose, absorbed well orally
Least effect of all azoles on drug metabolism
Itraconazole
Inducers of drug metabolizing enzymes like rifampin decrease bioavailability
for Blastomyces and sporothryx, as well as subcutaneous chromoblastomycosis
Ketoconazole
Causes more adverse effects
rarely used and not available parenterally
Used for mucocutaneous candidiasis and dermatophytes
Inhibitor of hepatic cyt P450 isoenzymes
Posaconazole
Broadest spectrum
Has activity against most species of candida, aspergillus and only azole active against Rhizopus
Used for mucormycosis
Given in salvage therapy in invasive aspergillosis
NRTI
Ketolides
Telithromycin
Less susceptible to methylase resistance
Like azithromycin with concentration levels
Visual side effects with slowed accomodation
Oxazolidinones
Linezolid
No cross-resistance
Unique oxidative metabolism, no interaction with CYP enzymes
Interaction with adrenergic and serotonergic agents due to inhibition of MAO
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Nitrofurans
Gram positive and negative except pseudomonas, proteus and anaerobic bacteria
Resistance rare
Protozoa
Urine alkalization reduces activity
UTIs
Adverse effects
GI
hypersensitivity
Hemolytic anemia
pulmonary sideeffects