Antimircobials Flashcards
Folic acid synthesis (DNA methylation) inhibitors
Sulfonamides
Trimethoprim
DNA topoisomerase inhibitor
Fluoroquinolones
Damages DNA
Metronidazole
mRNA synthesis (RNA polymerase) inhibitor
Rifampin
Protein synthesis (50S subunit) inhibitors
Chloramphenicol, Clindamycin, Linezolid
Macrolides
Streptogramins
Protein synthesis (30S subunit) inhibitors
Aminoglycosides
Tetracyclines
Peptidoglycan cross-linking (of the cell wall) inhibitors
Penicillinase-sensitive penicillins Penicillinase-resistant penicillins Antipseduomonals Cephalosporins (I-V) Carbapenems Monobactams (Aztreonam)
Peptidoglycan synthesis (of the cell wall) inhibitors
Glycopeptides (bacitracin, vancomycin)
Penicillinase-sensitive penicillins
Amoxicillin
Ampicillin
Penicillin G, V
Pencillinase-resistant penicillins
Dicloxacillin
Nafcillin
Oxacillin
Antipseudomonals
Piperacillin
Ticarcillin
Cephalosporins (I-V)
1st-Cefazolin, Cephalexin (1 ZObra named LEXI) 2nd-Cefoxitin, Cefaclor, Cefuroxime (2 FOXes went into the FACtory and came out as FUR) 3rd-Ceftriaxone (3 taxidermists TRI to sell a DIMEsaur) 4th-Cefepime (I'm + 4 PIMEcones turned green/blue) 5th-Ceftaroline (5 TARred birds are MRSArible)
Carbapenems
Doripenem
Imipenem
Meropenem
Ertapenem
Aminoglycosides
Gentamicin Neomycin Amikacin Tobramycin Streptomycin Min (amino) GNATS caNNOT kill anerobes
Tetracyclines
Doxycline
Minocyline
Tetracycline
Macrolides
Azithromycin
Clarithromycin
Erthyromycin
Streptogramins
Dalfopristin
Quinupristin
Fluoroquinolones
Ciprofloxacin
Levofloxacin
Sulfonamides
Sulfadiazine
Sulfamethoxazole
Sulfisoxazole
Penicillin G, V
MOA: B-lactam antibiotics: bind penicillin-binding proteins (transpeptidases that build cell walls)
Use: Mostly used for Gram + (also N. meningitidis, T. pallidum)
Tox: Hypersensitivity reactions, hemolytic anemia
Penicillinase (a B-lactamase) sensitive
Amoxicillin, ampicillin
MOA: Broad spectrum B-lactam antibiotics
Oral bioavailability: AmOxicillin>ampicillin
Use: H. influenzae, H. pylori, E. Coli Listeria, Proteus, Salmonella, Shigella, Enterococci (HHELPSS kill enterococci)
Tox: Hypersensitivity reactions, rash, pseudomembranous colitis
Penicillinase sensitive: Combine w/ clavulanic acid to inhibit penicillinase
Dicloxacillin, oxacillin, nafcillin
“DON has a narrow mind and only Staphs certain people, even though he is not MRSAble”
MOA: Narrow spectrum B-lactam antibiotics
Use: S. aureus (except MRSA)
Tox: Hypersensitivity reactions, interstitial nephritis
Penicillinase resistant (bulky R-group blocks B-lactamase
Piperacillin, ticarcillin
“PIPER and TICA are on an EXTENDED jail sentence for using NEGATIVE language and hurting people with RODS
MOA: Antipseudomonals: Extended spectrum B-lactam antibiotics
Use: Pseudomonas and gram - rods
Tox: Hypersensitivity reactions
Penicillinase sensitive: Combine w/ clavulanic acid to inhibit penicillinase
B-lactamase inhibitors
Clavulanic acid, sulbactam, tazobactam (CAST)
Added to penicillin antibiotics to protect the antibiotic from destruction by B-lactamase (penicillinase)
Cephalosporin-1st generation
Cefazolin, cephaLEXIn (1 ZObra named LEXI)
MOA: B-lactams, peptidoglycan cross-linking inhibitors (bind PBP), less susceptible to penicillinases. Bactericidal.
Use: Gram + cocci, Proteus, E. coli, Klebsiella, Pre-surgery prophylaxis to prevent S. aureus wound infections
Tox: Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency, exhibit cross-reactivity with penicilllins,
increases nephrotoxicity of aminoglycosides
Cephalosporin-2nd generation
Cefoxitin, cefaclor, cefuroxime (2 FOXes go to the FACtory and come out as FUR)
MOA: B-lactams, peptidoglycan cross-linking inhibitors (bind PBP), less susceptible to penicillinases. Bactericidal.
Use: Gram + cocci, H. influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. Coli, Klebsiella, Serratia marcescens
Tox: Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency, exhibit cross-reactivity with penicilllins,
increases nephrotoxicity of aminoglycosides
Cephalosporin-3rd generation
Cefotaxime, Ceftriaxone, , cefazidime (3 TAXidermists TRI to sell a DIMEsaur)
MOA: B-lactams, peptidoglycan cross-linking inhibitors (bind PBP), less susceptible to penicillinases. Bactericidal.
Use: Serious gram - infections resistant to other B-lactams
Ceftriazone-meningitis, gonorrhea, disseminated lyme dz
Ceftazidime-Pseudomonas
Tox: Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency, exhibit cross-reactivity with penicilllins,
increases nephrotoxicity of aminoglycosides
Cephalosporin-4th generation
CefePIME (I’m +/- (unsure) if 4 PIMEcones turned green/blue)
MOA: B-lactams, peptidoglycan cross-linking inhibitors (bind PBP), less susceptible to penicillinases. Bactericidal.
Use: gram - org., esp Pseudomonas, gram + org.
Tox: Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency, exhibit cross-reactivity with penicilllins,
increases nephrotoxicity of aminoglycosides
Cephalosporin-5th generation
CefTARoline (5 TARred birds are MRSArible)
MOA: B-lactams, peptidoglycan cross-linking inhibitors (bind PBP), less susceptible to penicillinases. Bactericidal.
Use: Broad gram + and gram - org., including MRSA
Tox: Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency, exhibit cross-reactivity with penicilllins,
increases nephrotoxicity of aminoglycosides
Mechanism of resistance to cephalosporins
Structural change in penicillin-binding proteins (transpeptidases)
CarbaPENEMs
Imipenem, meropenem, ertapenem, doripenem
MOA: B-lactams, peptidoglycan cross-linking inhibitors (bind PBP)
Use: Gram + cocci, gram - rods, anaerobes
Wide spectrum, but side effects that limit use to last resort
Tox: GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels
Meropenem
Carbapenem: has a decrease risk of seizures and stable to dehydopeptidase I
Imipenem
Carbapenem: broad spectrum, B-lactamase resistant.
Take with cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules.
Monobactams
Aztreonam
MOA: B-lactam, peptidoglycan cross-linking inhibitors (bind PBP3).
Less susceptible to B-lactamases & synergistic with aminoglycosides.
No cross-allergenicity with penicillins
Use: Gram - rods ONLY. For penicillin-allergic patients and those with renal insufficiency who can’t use aminoglycosides
Tox: Occasional GI upset
Vancomycin
MOA: Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors. Bactericidal. B-lactamase resistant
Use: Gram + ONLY. Serious, multidrug resistant organisms, including MRSA, S. epidermis, sensitive Enterococcus spp, and C. Diff. (oral dose for pseudomembranous colitis)
Tox: Well tolerated except NOT. Nephrotoxicity, Ototoxicity, Thrombophlebitis. Red man syndrome (prevent with H1 antagonist and slow infusion)
Resistance: bacterial aa modification, D-ala D ala-> D-ala D-lac
Aminoglycosides: names
Gentamicin, neomycin, amikacin, tobramycin, streptomycin
Aminoglycosides: MOA
Bactericidal. Irreversible inhibition of initiation complex through binding of the 30s subunit. Misreading of mRNA. Ineffective against anaerobes (needs 02)
Aminoglycosides: Use
Severe gram - rod infections. Synergistic with B-lactam antibiotics. Neomycin for bowel surgery
Aminoglycosides: Toxicity and resistance
Tox: Nephrotoxicity, neuromuscular blockade, ototoxicity, (esp. with loop diuretic), teratogen.
Resistance: Bacterial transferase enzymes inactivate the drug by acteylation, phosphorylation, adenylation
Tertracycline: names
Tetracyline, doxycline, minocycline
Tertracycline: MOA
Bacteriostatic: binds to 30S and presents tRNA binding.
CNS penetration.
Can’t take with milk (ca2+), anatacids (Ca2+/Mg2+) or iron containing preparations. All inhibit absorption.
Tertracycline: Clinical use
Borrelia burgdorferi. M. pneumoniae. Rickettsia. Chlamydia. Acne.
BM CAR makes your teeth YELLOW
Tertracycline: toxicity
GI distress, discoloration of teeth, inhibition of bone growth in children, photosensitivity, contraindicated in pregnancy..
Doxycycline is fecally eliminated so can give with renal failure.
Tertracycline: Mechanism of resistance
Decrease uptake or ^ efflux out of bacterial cells by plasmid-encoded transport pumps
Chloramphenicol: MOA
Blocks peptidyltransferase at 50S ribosomal subunit.
Bacteriostatic
Chloramphenicol: Clinical use
Meningitis (H. influ, N. meningitidis, S. pneumo)
Rocky mountain spotted fever (Rickettsia rickettsii)
Chloramphenicol: toxicity
Anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome (premature infants lack UDP-glucuronyl transferase)
Chloramphenicol: Mechanism of resistance
Plasmid-encoded acteryltransferase that inactivates the drug
Clindamycin: MOA
Blocks peptide transfer at 50S ribosomal subunit.
Bacteriostatic
Clindamycin: Clinical use
“Clinda the good witch kills the anaemy (anaerobic) above the diaphragm”
Anaerobic infections (Bacteriodes, C. perfringens) due to aspiration pneumonia, lung abscess, and oral infection.
Also effective against group A strep
*Treats anaerobic infections above the diaphragm. Metronidazole treats anaerobic infections below the diaphragm
Clindamycin: toxicity
Pseduomembranous colitis (C. diff overgrowth), fever, diarrhea
Linezolid: MOA
Inhibits protein synthesis by binding to 50S subunit and preventing formation of the initiation complex
Linezolid: Clinical use
Gram+ species including MRSA and VRE
Linezolid: toxicity
Bone marrow suppression (thrombocytopenia)
Peripheral neuropathy
Serotonin syndrome
Linezolid: Mechanism of resistance
Point mutation of ribosomal RNA
Macrolides: names
Azithromycin, Clarithromycin, Erythromycin
Macrolides: MOA
Inhibit protein synthesis by blocking translocation (macroslides). Bind to 23S rRNA of the 50S ribosomal subunit
Macrolides: Clinical use
Atypical pneumonias (Mycoplasma, chlamydia, legionella)
Macrolides: toxicity
MACRO: Motility issues in GI, Arrhythmia (prolonged QT interval), acute Cholestatic hepatitis, Rash, eOsinophilia
Increases serum theophyllines, oral anticoagulants.
Clarithro and Erythro inhibit p450
Macrolides: mechanism of resistance
Methylation of 23S rRNA binding site prevents binding of drug
Trimethoprim: MOA
Inhibits bacterial dihydrofolate reductase.
Bacteriostatic
Trimethoprim: Clinical use
Use with sulfonamides (TMP-SMX)–>sequential block of folate synthesis.
UTIs, shigella, Salmonella, P. Jirovecii
Prophylaxis for P. Jirovecii and toxoplasmosis
Trimethoprim: toxicity
Megaloblastic anemia, leukopenia, granulocytopenia
TriMethoPrim: Treats Marrow Poorly
Sulfonamides: names
Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine
Sulfonamides: MOA
Inhibits folate synthesis by inhibiting dihydropteroate synthase (PABA–>dihydropteroic acid)
Bacteriostatic alone. Bacteriocidal with TMP.
Dapsone for leprosy works in a similar way
Sulfonamides: clinical use
Gram positives, gram negatives, Nocardia, Chlamydia
Triple sulfas or SMX for simple UTI
Sulfonamides: toxicity
Hypersensitivity reactions, hemolysis if G6PD deficient.
Nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus (bilirubin in the brain) in infants, displace other drugs from albumin (warfarin)
Sulfonamides: Mechanism of resistance
Altered enzyme (bacterial dihydropteroate synthase), decrease uptake, ^PABA synthesis
Fluoroquinolones: names
Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, moxifloxacin, gemifloxacin, enoxacin
Fluoroquinolones: clinical use
Gram negative rods or urinary and GI tracts including pseudomonas, Neisseria, some gram +
Fluoroquinolones: toxicity
GI upset, superinfections, skin rashes, HA, dizziness.
Less common: leg cramps, myalgias
Contraindicated: pregnancy, nursing, children under 18.
May cause tendonitis or tendon rupture in people >60 and those taking prednisone
Fluoroquinolones: mechanism of resistance
CHromosome-endcoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps
Daptomycin: clinical use
S. aureus skin infections, esp. MRSA, bacteremia, endocarditis, and VRE
Daptomycin: MOA
Lipopeptide that disrupts cell membrane of gram + cocci
Fluoroquinolones: MOA
Inhibit prokaryotic enzymes topoisomerase II (DNA gyrase) and topo. IV.
Bactericidal. Don’t take with antacids!
Daptomycin: Toxicity
myopathy, rhabdomyolysis
Metronidazole: MOA
Forms toxic free radical metabolites in the bacterial cell that damage DNA.
Bactericidal and antiprotozoal.
Metronidazole: Clinical use
GET on the metro: Giardia, Entamoeba, Trichomonas
Mind the GAP: Gardnerella vaginalis, Anaerobes (bacteriodes/C. Diff. , h. Pylori
Metronidazole: toxicity
Disulfiram-like reaction with alcohol.
HA
Metallic taste
Treats anerobic infections below the diaphragm (vs. clindamycin)
M. Tuberculosis prophylaxis
Isoniazid
M. Tuberculosis treatment
RIPE:
Rifampin, isoniazid, pyrazinamide, ethambutal
M. avium prophylaxis
Azithromycin, rifabutin
M. avium treatment
Most drug resistant that TB.
Azithromycin or clarithromycin + ethambutol
Can add rifabutin or ciprofloxacin
M. leprae treatment
Dapsone+ rifampin=tuberculoid form
Dapsone+rifampin+clofazimine=lepromatous form
Mycobacterial drugs that target the cell wall
Isoniazid-Mycolic acid synthesis
Ethambutol-Arabinogalactan synthessi
Mycobacterial drugs that target mRNA synthesis
Rifabutin
Rifampin
Rifamycins (Rifabutin/Rifampin): MOA
Inhibit DNA-dependent RNA polymerase (mRNA synthesis)
Rifamycins (Rifabutin/Rifampin): clinical use
Mycobacterium tuberculosis
Delay resistance to dapsone when used for leprosy
Meningococcal prophylaxis and chemoprophylaxis in contacts with children with HIB
4 R’s of rifampin
RNA polymerase inhibitor Ramps up microsomal cytochrome p450 Red/orange body fluids Rapid resistance if used alone (rifabutin does not ramp up p450
Rifamycins (Rifabutin/Rifampin): toxicity
Minor hepatotoxicity and drug interactions (^cytochrome p450)
Orange body fluids
Rifabutin flavored over rifampin in HIV patients due to less p450 stimulation
Rifamycins (Rifabutin/Rifampin): Mechanism of resistance
Mutations reduce drug binding to RNA polymerase.
Monotherapy rapidly leads to resistance
Isoniazid: mechanism of action
Decrease synthesis of mycolic acids.
Bacterial catalase peroxidase (encoded by KatG) needed to convert INH to active metabolite
Isoniazid: clinical use
Mycobacterium tuberculosis
Only prophylaxis against TB
Isoniazid: toxicity
Neurotoxicity, hepatotoxicity.
Pyridoxine (B6) can prevent neurotoxicity
Isoniazid: mechanism of resistance
Mutations leading to underexpression of KatG (lack of activation)
Pyrazinamide: MOA
Uncertain
Pyrazinamide: Clinical use
Mycobacterium tuberculosis
Pyrazinamide: toxicity
Hyperuricemia, hepatotoxicity
Ethambutol: MOA
Decreases carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase
Ethambutol: clinical use
Mycobacterium tuberculosis
Ethambutol: toxicity
Optic neuropathy (colorblindness) "EYEthembutol"
Clinical scenario prophylaxis:
High risk for endocarditis and undergoing surgical/dental procedures
Amoxicillin
Clinical scenario prophylaxis:
Exposure to gonorrhea
Ceftriaxone
Clinical scenario prophylaxis:
History of recurrent UTIs
TMP-SMX
Clinical scenario prophylaxis:
Exposure to meningococcal infection
Ceftriaxone, ciprofloxacin, or rifampin
Clinical scenario prophylaxis:
Pregnant women carrying group B strep
Penicillin G
Clinical scenario prophylaxis:
Prevention of gonococcal conjunctivitis in newborn
Erythromycin ointment
Clinical scenario prophylaxis:
Prevention of post-surgical infection due to S. aureus
Cefazolin
Clinical scenario prophylaxis:
Prophylaxis of strep pharyngitis in child with prior rheumatic fever
Benzathine penicillin G or oral peniCillin V
Clinical scenario prophylaxis:
Exposure to syphilis
Benzathine penicillin G
How do you treat MRSA?
Vancomycin, daptomycin, linezolid, tigecycline, ceftaroline
How do you treat VRE?
Linezolid and streptogramins (50S inhibitors)
Amphotericin B: MOA
Binds ergosterol (component of fungal cell membrane) Forms membrane pores that allow leakage of electrolytes
Amphotericin B: clinical use
Serious, systemic mycoses:
Cryptococcus (with flucytosine for cryptococcal meningitis)
Blastomyces, Coccidioides, Histoplasma, Candida
INtrathecally for funal meningitis. Supplement K+ and Mg2+ because of altered renal tubule permeability.
Amphotericin B: toxicity
Fever/chills “shake and bake”
Hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis.
Hydration decreases nephrotoxicity
Liposomal amp decreases toxicity
Nystatin: MOA
Binds erogsterol and forms membrane pores that allow leakage of electrolytes
Nystatin: clinical use
Oral candidiasis (thrush), topical for diaper rash or vaginal candidiasis
Flucytosine: MOA
Inhibits fungal DNA and RNA biosynthesis by conversion of 5-fluorouracil by cytosine deaminase
Flucytosine: clinical use
Systemic fungal infections (esp. meningitis caused by cryptococcus) in combination with amp B
Flucytosine: toxicity
Bone marrow suppression
-m/nazole: MOA
Inhibit fungal ergosterl synthessi by inhibiting the p450 enzyme that converts lanosterol to ergosterol
-m/nazole: clinical use
Local and less serious systemic mycoses.
Fluconazole for chronic suppression of cryptococcal meningitis in AIDS patients and candidal infections of all types.
Itraconazole for Blastomyces, Coccidiodes, Histoplasma.
Clotrimazole and miconazole for topical fungal infections
-m/nazole: toxicity
Testosterone synthesis inhibition (gynecomastia, esp with ketoconazole), liver dysfunction-inhibits p450
Terbinafine: MOA
Inhibits the fungal enzyme squalene epoxidase to prevent lanosterol synthesis (precursor of ergosterol)
Terbinafine: clinical use
Dermatophytoses (esp onychomycosis)
Terbinafine: toxicity
GI upset, hepatotoxicity, taste disturbance
Echinocandins: names
Anidulafungin, capofungin, micafungin
Echinocandins: MOA
Inhibit cell wall synthesis by inhibiting synthesis of B-glucan
*MAC won’t let people discriminate and put up WALLS to ruin the FUNgin
Echinocandins: clinical use
Invasive aspergillosis, candida
Echinocandins: toxicity
GI upset, flushing (by histamine release)
Griseofulvin: MOA
Interferes with microtubule function; disrupts mitosis.
Deposits in keratin-containing tissues (ie nails)
Griseofulvin: clinical use
Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm)
Griseofulvin: toxicity
Teratogenic, carcinogenic, confusion, HA, ^ p450 and warfarin metabolism
Antiprotozoan therpy
Pyrimethamine (toxoplasmosis), suramin and melarsoprol (Trypanosoma brucei), nifurtimox (t. cruzi), sodium stibogluconate (leishmaniasis)
Anti-mite/louse therapy
Permethrin (blocks Na+ channels->neurotoxicity)
Malathion (acetylcholinesterase inhibitor)
Lindane (blocks GABA channels->neurotoxicity)
Used to treat scabies (Sarcoptes scabiei) and lice (pediculus and pthirus)
Chloroquine: MOA
Blocks detoxification of heme into hemozosin. Heme accumulates and is toxic to plasmodia
Chloroquine: clinical use
Treatment of plasmodial species other than P. falciparum (frequency of resistance in P. falciparum is too high)
Antihelminthic therapy
Mebendazole, pyrantel pamoate, ivermectin, diethylcarbamazine, praziquantel
Cholorquine: toxicity
Retinopathy, pruritus
If you’re in the chlorine pool too long your eyes get blurry and your body gets itchy
Oseltamivir, zanamivir: MOA
Inhibit influenza neuraminidase–> decreased release of progeny virus
Gpa Ose and gma Zana and can’t get the flu out of them every winter
Oseltamivir, zanamivir: clinical use
Treatment and prevent of Influenza A and B
famiciclovir, acyclovir, valacyclovir: MOA
My FAV animal is an iGUANA
Guanosine analogs. Monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells–>few adverse effects.
Triphosphate formed by cellular enzymes.
Preferentially inhibit viral DNA polymerase by chain termination
Acyclovir, famiciclovir, valacyclovir: Clinical use
HSV (mucocutaneous and genital lesions as well as for encephalitis) and VZV. Prophylaxis in immunocompromised
Weak activity against EBV.
No activity against CMV.
Prophylaxis in immunocompromised patients.
No effects on latent forms of HSV and VZV.
Valacyclovir: prodrug of acyclovir, better oral bioavailability.
Herpes zoster: famciclovir
Ganciclovir: MOA
Guanosine analog. 5-monophosphate formed by a CMV viral kinase. Triphosphate formed by cellular kinases. Preferentially inhibits viral DNA polymerase by chain termination.
Ganiciclovir: clinical use
CMV, esp. in immunocompromised.
Valganciclovir, a prodrug of ganciclovir with ^ bioavailability
Ganiciclovir: Toxicity
Leukopenia, neutropenia, thrombocytopenia, rental toxicity.
More toxic to host enzymes than acyclovir.
Resistance: mutated viral kinase
Foscarnet: MOA
Viral DNA/RNA polymerase inhibitor and HIV reverse transcriptase inhibitor. Binds pyrophosphate binding site of enzyme. No activation required.
“binds to PyroFOSphate binding site of polymerase analog”
Foscarnet: clinical use
CMV retinitis in immunocompromised when ganciclovir fails.
Acyclovir resistant HSV.
Foscarnet: toxicity
Nephrotoxicity, electrolyte abnormalities can lead to seizures
Mech. of resistance: mutated DNA polymerase
Cidofovir: MOA
Inhibits viral DNA polymerase. Does not require activation by viral kinase.
Cidofovir: clinical use
CMV retinitis in immunocompromised patients.
Acyclovir-resistant HSV.
Cidofovir: toxicity
Nephrotoxicity (give with probenecid and IV saline to decrease toxicity)
What drugs do you give for acyclovir-resistant HSV?
Foscarnet or cidofovir
HIV therapy
HAART: Highly active antiretroviral therapy initiated at the time of HIV diagnosis.
Strongest indication for patients present with AIDS defining illness, low CD4 cell counts or high viral load.
2 NRTIs +
1 NNRTI OR protease inhibitor OR integrase inhibitor
Protease inhibitor: MOA
-navir
Prevents maturation of new viruses by cleaving HIV1 protease, preventing required mRNA cleaving.
Protease inhibitor: toxicity
Hyperglycemia, GI intolerance, lipodystrophy Nephropathy, hematuria Rifampin contraindicated (decreased protease inhibitor concentration)
NTRIs: MOA
Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain.
Tenofavir is the nucleoTide and does not need to be virally activated like the others.
“Have you dined (vudine) with my nuclear(side) family?
NTRI: toxicity
Bone marrow suppression-reverse with G-CSF and EPO.
Peripheral neuropathy, lactic acidosis, anemia (ZDV), and pancreatitis
NNRTIs: names
Delavirdine, Efavirenz, Nevirapine
“Okay, DEN, we gotta get rid of this HIV with one of DEmN NNRTI’s
NNRTIs: MOA
Bind reverse transcriptase at site different from NRTIs. No activation needed.
NNRTIs: toxicity
Rash and hepatotoxicity.
Efavirenz: vivid dreams, CNS symptoms
NOT with pregnancy: delavirdine and efavirenz
Integrase inhibitor: MOA and toxicity
Raltegravir
Inhibits HIV genome intergration into host cell Cr by reversibly inhibiting HIV integrase
^creatine kinase
Enfuvirtide: MOA and toxicity
Fusion inhibitor
Binds p41: inhibits viral fusion (skin reaction at injection site)
Maraviroc: MOA and toxicity
Binds CCR-5 on surface T cells/monocytes and inhibits interaction with gp120
Interferons: MOA
Glycoproteins normally synthesized by virus-infected cells, exhibiting a wide range of antiviral and antitumoral properties
Interferons: clinical use
IFN-a: chronic hepatitis B/C, kaposi sarcoma, hairy cell uekemia, condyloma acuminatum, RCC, malignant melanoma
IFN-B: Multiple sclerosis
IFN-g: CGD
Interferons: toxicity
Neutropenia and myopathy
Hepatitis C therapy
Ribavirin
Simeprevir
Sofosbuvir
Antibiotics to avoid in pregnancy
SAFe Children Take Really Good Care Sulfonamides- Kernicterus Aminoglycosides- Otoxicity Fluoroquinolones- Cartilage damane Clarithromycin-Embryotoxic Tetracyclines- Discolored teeth, inhibition of bone growth Ribarvirin (antiviral)- teratogenic Griseofulvin (antifungal)- teratogenic Chloamphenicol- grey baby syndrome
What viral drugs do not need to be activated?
Foscarnet, cidofovir, Tenofovir (NRTI)
