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Chemotherapeutic drugs, Beta-lactams and more - Coggle Diagram
Chemotherapeutic drugs
Agents to treat HSV and VZV
Acyclovir
Activity against, HSV-1, -2 and VZV
But higher doses required for VZV
Guanosine derivative
short half-life meaning multiple daily doses
Renal excretion
Valacyclovir
Treats zoster-associated pain better
Nausea, headache, rash, CNS effects
AIDS patients who received valacyclovir reported GI intolerance, TTP, HUS
Famciclovir
after oral administration
deacylated and oxidized by first-pass metabolism to drug
Penciclovir
Penciclovir doesn't cause chain termination
Has lower affinity for viral DNA polymerase
Achieves higher intracellular concentrations
Available for topical use
Active against, HSV-1, -2, VZV, EBV and HBV
One-day usage accelerates healing of genital herpes and herpes labialis
Useful for treatment of zoster associated pain
Diarrhea and headache may occur
Docosanol
Inhibits fusion between plasma membrane and HSV envelope
Thereby inhibiting viral entry
Needs to be applied within 12 hours of onset of prodromal symptoms
Trifluridine
Fluorinated pyrimidine nucleoside
Active against HSV-1, -2, CMV
Effective for keratoconjuctivitis and recurrent epithelial keratitis
Can be used with Interferon alpha for acyclovir resistant HSV infections
Ganciclovir
Also has activity against HHV-6, -8
clearance related to creatinine clearance
Readily cleared by hemodialysis
Oral form carries reduced risk of myelosuppression and catheter-related complications
Entry inhibitors
Enfuvirtide
Elimination through proteolytic hydrolysis
Binds GP41
Resistance acquired through mutations in gp41
Erythematous nodules at injection sites
Hypersensitivity, CNS symptoms
Eosinophilia can occur
Possible increased rate of bacterial pneumonia
By subcutaneous injection
Maraviroc
binds CCR&
Do tropism testing to see which co-receptor it binds
Most of it excreted in feces and some in urine, (80%-20%)
Contra-indicated
with end-stage renal impairment
With CYP3A inducers or inhibitors
with HBV or HCV and preexisting hepatic impairment
Good penetration into cervicovaginal fluid
Substrate for P-glycoprotein, which limits intracellular concentrations of the drug
Cough, upper respiratory tract infections, postural hypotension, muscle joint and abdominal pain, diarrhea and sleep disturbance
Increased cardiovascular risk
Raltegravir
Pyrimidine analog
Usually for strains of HIV-1. resistant to multiple other agents
Metabolized by glucuronidation but does not interfere with P450 system
Bioavailability is food-dependent
Dose should be increased in combination with rifampin, inducer of UDP-glucuronosyl transferase 1A1
Taken with caution with antacids as polyvalent cations can interfere with intergrase inhibitors
Should be used in combination
Potential myopathy or rhabdomyolysis
Interferon alpha
Alfa interfereons are filtered at glomerulus and undergo rapid proteolytic degradation during tubular reabsorption
Pegylated one
Results in slower clearance, longer half-lives, meaning less frequent dosing for HCV
Renal elimination accounts for 30% so must be adjusted for impaired renal function
Transient hepatic enzyme increase
Contra-indications
Hepatic decompensation, autoimmune disease. history of cardiac arrhythmia
SHOULD NOT BE GIVEN DURING PREGNANCY
Drug-interactions, include theophylline and methadone, didanosine, zidovudine
Anti-influenza agents
Oseltamivir and Zanamivir
neuraminidase inhibitor
sialic acid
Once-daily prophylaxis
Oseltamivir
Activated by hepatic esterases
75 mg twice daily for 5 days
Dosage must be modified in patients with renal insufficiency
Excretion is by glomerular filtration and tubular secretion through urine
Probenecid reduces renal clearance
Gi symptoms occur
CNS symptoms
Zanamivir
Delivered directly to respiratory tract via inhalation
Concentration is 1000 times the IC50 for neuraminidase
Amantadine + rimantadine
Block the M2 proton ion channel of virus particle
Inhibits uncoating of viral RNA within infected host cells
Rimantadine 4-10 times more active
nasal mucous concentrations of rimantidine are 50%
Amantidine excreted unchanged in urine
Rimantadine undergoes extensive metabolism
Excretion tied to creatinine clearance so dose reductions required for patients with renal insufficiency
CNS side effects less common with rimantadine
Teratogenic
NNRTIs
Delavirdine
Metabolized by CYP enzymes
Levels decreased by antacids
Increased levels by azoles and macrolides
Teratogen
Can cause skin rash
Efavirenz
Long half life
Fatty foods may enhance bioavailability
Metabolized by CYT enzymes
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TMP/SMX
Beta-lactams and more
Cephalosporins
Broader spectrum of activity
Activity against gram positive cocci
E coli, K pneumoniae, Proteus mirabilis sensitive, Elektra, Kitty pride and Punisher are good for spiderman
P auerginosa, indole-positive proteus species, Enterobacter sp, S marcescens, Citrobacter sp, and Acinobacter sp is poor, (The prowler, Iguana, Electro, Sandman, Chameleon and Arcade are all bad for spiderman)
Penicillin
Active against gram+, gram - cocci, and non-B-lactamase producing anaerobes, however no activity against G- rods
Antistaphylococcal penicillins
Resistant to staph B-lactamases
Active against staph, strep
Not active against enterococci, anaerobic bacteria and G- cocci and rods
Nafcillin
Resistance
Inactivation by B-lactamase
Modification of target PBPs
Efflux
Impaired penetration of drug to target PBps
Differences between G- and G+
Outer membrane is present in G-
Membrane is thicker in G+
Monobactams
Effective
Pseudomonas
Not effective
AMP C beta lactamases
E. coli
K. pneumoniae
Extended-spectrum beta lactamases
Extended-spectrum penicillins
Amoxicillin
Better absorbed orally