Quizlets - Antimicrobia Flashcards
(167 cards)
1
Q
Antimicrobials by mechanism of action: Block cell wall synthesis by inhibition of peptidoglycan cross-linking
A
Drugs? Penicillin, ampicillin, ticarcillin, piperacillin, imipenem, aztreonam, cephalosporins [#1 below]
2
Q
Antimicrobials by mechanism of action: Block peptidoglycan synthesis Drugs?
A
Bacitracin, Vancomycin [#2 below]
3
Q
Antimicrobials by mechanism of action: Disrupt bacterial cell wall membranes Drugs?
A
Polymyxins [#3 below]
4
Q
Antimicrobials by mechanism of action: Block nucleotide synthesis Drugs?
A
Sulfonamides, Trimethoprim [#4 below]
5
Q
Antimicrobials by mechanism of action: Block DNA topoisomerases Drugs?
A
Quinolones [#5 below]
6
Q
Antimicrobials by mechanism of action: Block mRNA synthesis Drugs?
A
Rifampin [#6 below]
7
Q
Antimicrobials by mechanism of action: Block protein synthesis at 50S ribosomal subunit Drugs?
A
Chloramphenicol, macrolides, clindamycin, streptogramins (quinipristin, dalfopristin), linezolid [#7]
8
Q
Antimicrobials by mechanism of action: Block protein synthesis at the 30S ribosomal subunit Drugs?
A
Aminoglycosides, tetracyclines [#8 below]
9
Q
Bacterostatic antibiotics
A
E rythromycin C lindamycin S ulfamethoxazole T rimethoprim T etracylcines C hloramphenicol (We’re ECST aT iC about bacteriostatics )
10
Q
Bacteriocidal antibiotics
A
V ancomycin F luoroquinolones P enicillin A minoglycosides C ephalosporins M etronidazole V ery F inely P roficient A t C ell M urder
11
Q
Forms of Penicillin
A
Penicillin G (IV form), Penicillin V (oral form). Prototype Beta-lactam antibiotics.
12
Q
Mechanism of penicillin
A
1.) Bind penicillin-binding proteins 2.) Block transpeptidase cross-linking of cell wall 3.) Activate autolytic enzymes
13
Q
Mechanism of penicillinase-resistant penicillins: Methicillin, nafcillin, dicoxacillin
A
Same as penicillin*. Narrow speectrum; penicillinase resistant b/c of bulkier R group. * mechanism of PCN: 1.) Bind penicillin-binding proteins 2.) Block transpeptidase cross-linking of cell wall 3.) Activate autolytic enzymes
14
Q
Mechanism of aminopenicillins: Ampicillin, amoxicillin
A
Same as penicillin*. Wider spectrum; Penicillinase sensitive. Also combine w/ clavulanic acid (a penicillinase inhibitor) to enhance spectrum. AmO xicillin has greater O ral bioavailability than ampicillin. *Mechanism of PCN: 1.) Bind penicillin-binding proteins 2.) Block transpeptidase cross-linking of cell wall 3.) Activate autolytic enzymes
15
Q
Mechanism of antipseudomonals: Ticarcillin, carbenicillin, piperacillin
A
Same as penicillin*. Extended spectrum. *Mechanism of penicillin: 1.) Bind penicillin-binding proteins 2.) Block transpeptidase cross-linking of cell wall 3.) Activate autolytic enzymes
16
Q
Clinical use of penicillin
A
Bactericidal for Gram(+) cocci, Gram(+) rods, Gram(-) cocci, and spirochetes. Not penicillinase resistant.
17
Q
Toxicity of penicillin
A
Hypersensitivity rxtns. Methicillin: interstitial nephritis.
18
Q
Clinical use of aminopenicillins (ampicillin, amoxicillin)
A
Extended spectrum penicillin*: certain gram(+) bacteria and gram(-) rods: H aemophilus influenzae, E . coli, L isteria monocytogenes, P roteus mirabilis, S almonella, enterococci (Ampicillin/amoxicillin HELPS kill enterococci) *Think of amp icillin/amoxicillin as AMP ed up penicillin
19
Q
Toxicity of aminopenicillins (ampicillin, amoxicillin)
A
Hypersensitivity rxtns; Ampicillin rash; Pseudomembranous colitis.
20
Q
Clinical use of: Ticarcillin, carbenicillin, piperacillin
A
(antipseudomonals – TCP : T ake C are of P seudomonas) Used for Pseudomonas spp. and gram(-) rods; susceptible to penicillinase; Use w/ clavulinic acid (Beta-lactamase inhibitor).
21
Q
Toxicity of antipseudomonals (Ticarcillin, carbenicillin, piperacillin)
A
Hypersensitivity rxtns.
22
Q
Mechanism of cephalosporins
A
Beta-lactam drugs that inhibit cell wall synthesis, but are less susceptible to penicillinases. Bactericidal.
23
Q
Clinical use of 1st generation cephalosporins (Cefazolin, cephalexin)
A
Gram(+) cocci, P roteus mirabilis, E . c oli, K lebsiella pneumoniae (1st gen = PEcK )
24
Q
Clinical use of 2nd generation cephalosporins (cefoxitin, cefaclor, cefuroxime)
A
Gram(+) cocci, H aemophilus influenzae, E nterobacter aerogenes, N eisseria spp. P roteus mirabilis, E. c oli, K lebsiella pneumoniae, S erratia marcescens (2nd Gen = HEN PEcKS )
25
Clinical use of 3rd generation cephalosporins (ceftriaxone, cefotaxime, ceftazidime)
Serious gram(-) infxns resistant to other beta-lactams; meningitis (most penetrate the BBB). Examples: Ceftazidime for Pseudomonas Ceftriaxone for gonorrhea
26
Clinical use of 4th generation cephalosporins (Cefepime)
Increased activity against Pseudomonas and gram(+) organisms.
27
Toxicity of cephalosporins
Hypersensitivity rxtn. Cross-hypersensitivvity w/ penicillins occurs in 5-10% of pts. Increased nephrotoxicity of aminoglycosides; disulfiram-like rxtn w/ ethanol (in cephalosporins w/ methylthitetrazole group, e.g., cefamandole)
28
Mechanism of aztreonam
A monobactam resistant to beta-lactamases. Inhibits cell wall synthesis (binds to PBP3). Synergistic w/ aminoglycosides. No cross-allergenicity w/ penicillins.
29
Clinical use of aztreonam
Gram(-) rods - Klebsiella spp., Pseudomonas spp., Serratia spp. No activity against gram(+)'s or anaerobes. For penicillin-allergic pts and those w/ renal insufficiency who cannot tolerate aminoglycosides.
30
Toxcity of Aztreonam
Usually nontoxic; occasional GI upset. No cross-sensitivity w/ penicillins or cephalosporins.
31
Mechanism of Imipenem/cilastatin, meropenem
Imipenem is a broad-spectrum, beta-lactamase-resistant carbapenem. Always administer w/ cilastatin (inhibitor of renal dihydropeptidase I) to decrease inactivation in renal tubules. (With imipenem, the kill is LASTIN' with ciLASTATIN )
32
Clinical use of imipenem/cilastatin, meropenem
Gram(+) cocci, gram(-) rods, and anaerobes. DOC for Enterobacter. The significant side effects limit use to life-threatening infxns, or after other drugs have failed. Meropenem, howevver, has a reduced risk of seizures and is stable to dihydropeptidase I.
33
Toxicity of Imipenem/cilastatin, meropenem
GI distress, skin rash, and CNS toxicity (seizures) @ high plasma levels
34
Mechanism of vancomycin
Inhibits cell wall mucopeptide formation by binding D-ala D-ala portion of cell wall precursors. Bactericidal. Resistance occurs w/ AA change of D-ala D-ala to D-ala D-lac
35
Clinical use of vancomycin
Used for serious, gram(+) multidrug-resistant organisms, including S. aureus and Clostridium difficile (pseudomembranous colitis)
36
Toxicity of vancomycin
N ephrotoxicity, O totoxicity, T hromophlebitis, diffuse flushing - red man syndrome (can largely prevent by pretreatment w/ antihistamines and slow infusion rate) Well toleraterd in general -- does NOT have many problems.
37
Protein synthesis inhibitors: 30S inhibitors
A = A minoglycosides (streptomycin, gentamycin, tobramycin, amikacin) [bacteriostatic] T = T etracyclines [bacteriostatic] (But AT 30 , CCELL (sell) at 50) [*note different specific sites of action of Aminoglycosides and TCNs below]
38
Protein Synthesis Inhibitors: 50S inhibitors
C = C hloramphenicol, C lindamycin [bacteriostatic] E = E rythromycin [bacteriostatic] L = L incomycin [bacteriostatic] L = L inezolid [variable] (But AT 30, CCELL (sell) at 50 ) [note different specific sites of action below]
39
Aminoglycosides (list)
G entamycin N eomycin A mikacin T obramycin S treptomycin (Mean GNATS [mean = amin oglycosides)
40
Mechanism of aminoglycosides (gentamycin, neomycin, amikacin, tobramycin, streptomycin)
Bactericidal; inhibit formation of initiation complex and cause misreading of mRNA. Require O2 for uptake; therefore ineffective against anaerobes. (Mean GNATS canNOT kill anaerobes)
41
Clinical use of aminogyclosides (gentamycin, neomycin, amikacin, tobramycin, streptomycin)
Severe gram (-) rod infxns. Synergistic w/ beta-lactam ABX. Neomycin for bowel surgery.
42
Toxicity of aminoglycosides (gentamycin, neomycin, amikacin, tobramycin, streptomycin)
N ephrotoxicity (especially when used w/ cephalosporins) O totoxicity (especially when used w/ loop diuretics) T eratogen. (Mean GNATS canNOT kill anaerobes)
43
Tetracyclines (list)
Tetracylcine Doxycycline Demeclocycline Minocycline
44
Mechanism of tetracyclines (tetracycline, doxycycline, demeclocyclline, minocycline)
Bacteriostatic; bind to 30S and prevent attachment of aminoacyl-tRNA. Limited CNS penetration. Doxycyline is fecally eliminated and can be used in pts w/ renal failure. Must NOT take w/ milk, antacids, or iron-containing preparations b/c divalent cations inhibit absorption in gut. D emeclocycline is an ADH antagonist (acts as a D iuretic in SIADH)
45
Clinical use of tetracyclines (tetracycline, doxycycline, demeclocyclline, minocycline)
V ibrio cholerae A cne C hlamydia U reaplasma U realyticum M ycoplasma pneumoniae T ularemia H . pylori B orrelia burgdorferi (Lyme dz) R ickettsia (VACUUM TH e B edR oom)
46
Toxicity of tetracyclines (tetracycline, doxycycline, demeclocyclline, minocycline)
GI distress Discoloration of teeth and inhibition of bone growth in children Photosensitivity Contraindicated in pregnancy.
47
Macrolides (list)
Erythromycin, azithromycin, clarithromycin
48
Mechanism of macrolides (Erythromycin, azithromycin, clarithromycin)
Inhibit protein synthesis by blocking translocation; bind to the 23S rRNA of the 50S ribosomal subunit. Bacteriostatic.
49
Clinical use of macrolides (Erythromycin, azithromycin, clarithromycin)
URIs, pneumonias STDs -- gram(+) cocci (streptococcal infxns in pts allergic to penicillin) Mycoplasma Legionella Chlamydia Neisseria
50
Toxicity of macrolides (Erythromycin, azithromycin, clarithromycin)
GI discomfort (most common cause of noncompliance) Acute cholestatic hepatitis Eosinophilia Skin rashes Increases serum concentration of theophyllines, oral anticoagulants.
51
Mechanism of chloramphenicol
Inhibits 50S peptidyltransferase activity. Bacteriostatic.
52
Clinical use of chloramphenicol
Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae) Conservative use, owing to toxicities.
53
Toxicity of chloramphenicol
Anemia (dose dependent) Aplastic anemia (dose independent) Gray baby syndrome (in premature infants b/c they lack liver UDP-glucuronyl transferase)
54
Mechanism of clindamycin
Blocks peptide bond formation at 50S ribosomal subunit. Bacteriostatic.
55
Clinical use of clindamycin
Tx anaerobic infxns (e.g., Bacteroides fragilis, Clostridium perfringens) (Treats anaerobes above the diaphragm)
56
Toxicity of clindamycin
Pseudomembranous colitis (C. difficile overgrowth) Fever Diarrhea
57
Sulfonamides (list)
Sulfamethoxazole (SMX) Sulfisoxazole Sulfadiazine
58
Mechanism of sulfonamides (sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine)
PABA antimetabolites inhibit dihydropteroate synthetase [see below]. Bacteriostatic.
59
Clinical use of of sulfonamides (sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine)
Gram(+), gram(-), Nocardia, Chlamydia. Triple sulfas or SMX for simple UTI.
60
Toxicity of sulfonamides (sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine)
Hypersensitivity rxtns Hemolysis if G6PD deficient Nephrotoxicity (tubulointerstitial nephritis) Photosensitivity Kernicterus in infants Displace other drugs from albumin (e.g., warfarin)
61
Mechanism of trimethoprim (TMP)
Inhibits bacterial dihydrofolate reductase. Bacteriostatic.
62
Clinical use of trimethoprim (TMP)
Used in combination w/ sulfonamides (trimethoprim-sulfamethoxazole [TMP-SMX]), causing sequential block of folate synthesis. Combination used for recurrent UTIs, Shigella, Salmonella, Pneumocystis jiroveci pneumonia.
63
Toxicity of trimethoprim (TMP)
Megaloblastic anemia Leukopenia Granulocytopenia (may alleviate w/ supplemental folinic acid) (Trimethoprim = TMP : T reats M arrow P oorly)
64
Sulfa drug allergies -- what do you need to avoid?
Pts who do not tolerate sulfa drugs should not be given sulfonamides or other sulf drugs such as: Sulfasalazine Sulfonylureas Thiazide diuretics Acetazolamide Furosemide
65
Fluoroquinolones (list)
Ciprofloxacin Norfloxacin Ofloxacin Sparfloxacin Moxifloxacin Gatifloxacin Enoxacin [above are fluoroquinolones] Nalidixic acid [a quinolone]
66
Mechanism of fluoroquinolones
Inhibit DNA gyrase (topoisomerase II). Bactericidal. Must not be taken w/ antacids.
67
Clinical use of fluoroquinolones
Gram(-) rods of urinary and GI tracts (including Pseudomonas), Neisseria, some gram(+) organisms
68
Toxicity of fluoroquinolones
GI upset, superinfections, skin rashes, HA, dizziness. Contraindicated in pregnant women and in children b/c animal studies show damage to cartilage. Tendonitis and tendon rupture in adults; leg cramps and myalgias in kids. (FlouroquinoLONES hur the attachments to your BONES )
69
Mechanism of metronidazole
Forms toxic metabolites in the bacterial cell that damage DNA. Bactericidal, antiprotozoal.
70
Clinical use of metronidazole
Treats: G iardia E ntamoeba T richomonas G ardnerella vaginalis A naerobes (Bacteroides, Clostridium) Used w/ bismuth and amoxicillin (or TCN) for triple therapy against H. P ylori (GET GAP on the METRO !) Treats anaerobic infxns below the diaphragm.
71
Toxicity of metronidazole
Disulfiram-like rxtn w/ alcohol Headache Metallic taste
72
Polymyxins (list)
Polymyxin B Polymyxin E
73
Mechanism of polymyxins
Bind to cell membranes of baccteria and disrupt their osmotic properties. Polymyxins are cationic, basic proteins that act like detergents. (MYXins MIX up membranes)
74
Clinical use of polymyxins
resistant gram(-) infxns
75
Toxicity of polymyxins
Neurotoxicity, acute renal tubular necrosis
76
Antimycobacterial drugs: for M. tuberculosis
Prophylaxis: Isoniazid Tx: R ifampin I soniazid P yrazinamide E thambutol (RIPE for treatment)
77
Antimycobacterial drugs: for M. avium-intracellulare
Prophylaxis: Azithromycin Tx: Azithromycin Rifampin Ethambutol Streptomycin
78
Antimycobacterial drugs for M. leprae
Tx: Dapsone Rifampin Clofazimine
79
Anti-TB drugs
S treptomycin, P yrazinamide, I soniazid (INH ), R ifampin, E thambutol (INH-SPIRE [inspire]) Cycloserine (2nd-line therapy)
80
Side effects of anti-TB drugs
Important SE of ethambutol: optic neuropathy (red-green color blindness) For other drugs: hepatotoxicity.
81
Mechanism of isoniazid (INH)
Decreases synthesis of mycolic acids. *note that there are different INH half-lives in fast vs. slow acetylators.
82
Clinical use of isoniazid (INH)
Mycobacterium tuberculosis. The only agent used as solo prophylaxis against TB.
83
Toxicity of isoniazid (INH)
Neurotoxicity, hepatotoxicity. Pyridoxine (Vitamin B6) can prevent neurotoxicity. (INH I njures N eurons and H epatocytes)
84
Mechanism of rifampin
Inhibits DNA-dependent RNA polymerase
85
Clinical use of rifampin
Mycobacterium tuberculosis. Delays resistance to dapsone when used for leprosy. Used for meningococcal prophylaxis and chemoprophylaxis in contacts of children w/ Haemophilus influenzae type B.
86
Toxicity of rifampin
Minor hepatotoxicity and drug interactions (induces P-450) Orange body fluids (nonhazardous side effect)
87
Rifampin's 4 R's
R NA polymerase inhibitor R evs up microsomal P-450 R ed/orange body fluids R apid resistance if used alone
88
Most common resistance mechanism for: Penicillins/cephalosporins
Beta-lactamase cleavage of beta-lactam ring, or altered PBP in cases of MRSA or penicillin-resistant S. pneumoniae.
89
The following is the most common mechanism of resistance for what drug? Beta-lactamase cleavage of beta-lactam ring, or altered PBP in cases of MRSA or penicillin-resistant S. pneumoniae.
Penicillins/cephalosporins
90
Most common resistance mechanism for: Aminoglycosides
Modification via acetylation, adenylation, or phosphorylation.
91
The following is the most common mechanism of resistance for what drug? Modification via acetylation, adenylation, or phosphorylation.
Aminoglycosides
92
Most common resistance mechanism for: Vancomycin
Terminal D-ala of cell wall component replaced with D-lac, decreased affinity.
93
The following is the most common mechanism of resistance for what drug? Terminal D-ala of cell wall component replaced with D-lac, decreased affinity.
Vancomycin
94
Most common resistance mechanism for: Chloramphenicol
Modification via acetylation
95
The following is the most common mechanism of resistance for what drug? Modification via acetylation
Chloramphenicol
96
Most common resistance mechanism for: Macrolides
methylation of rRNA near erythromycin's ribosome-binding site
97
The following is the most common mechanism of resistance for what drug? methylation of rRNA near erythromycin's ribosome-binding site
Macrolides
98
Most common resistance mechanism for: Tetracycline
Decreased uptake or increased transport out of cell.
99
The following is the most common mechanism of resistance for what drug? Decreased uptake or increased transport out of cell.
Tetracycline
100
Most common resistance mechanism for: Sulfonamides
Altered enzyme (bacterial dihydropteroate synthetase), decreased uptake, or increased PABA synthesis.
101
The following is the most common mechanism of resistance for what drug? Altered enzyme (bacterial dihydropteroate synthetase), decreased uptake, or increased PABA synthesis.
Sulfonamides
102
Most common resistance mechanism for: Quinolones
Altered gyrase or reduced uptake.
103
The following is the most common mechanism of resistance for what drug? Altered gyrase or reduced uptake.
Quinolones
104
Nonsurgical antimicrobial prophylaxis of: meningococcal infxn
Rifampin (DOC), minocycline
105
Nonsurgical antimicrobial prophylaxis of: gonorrhea
Ceftriaxone
106
Nonsurgical antimicrobial prophylaxis of: syphilis
Benzathine penicillin G
107
Nonsurgical antimicrobial prophylaxis of: Hx of recurrent UTIs
TMP-SMX
108
Nonsurgical antimicrobial prophylaxis of: Pneumocystis jiroveci pneumonia
TMP-SMX (DOC), aerosolized pentamidine.
109
Nonsurgical antimicrobial prophylaxis of: endocarditis w/ surgical or dental procedures
Penicillins.
110
Tx of highly resistant bacteria
MRSA: vancomycin VRE: linezolid and streptogramins (quinupristin/dalfopristin)
111
Mechanism of Amphotericin B
Binds ergosterol (unique to fungi); Forms membrane pores that allow leakage of electrolytes. (Amphotear acin 'tears' holes in fungal membranes by forming pores) [on left, below]
112
Clinical use of Amphotericin B
Use for wide spectrum of systemic mycoses. Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, Mucor (systemic mycoses). Intrathecally for fungal meningitis; does not cross BBB.
113
Toxicity of Amphotericin B
Fever/chills (shake and bake), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis (amphotericin = amphoterrible). Hydration reduces nephrotoxicity. Liposomal amphotericin reduces toxicity.
114
Mechanism of Nystatin
Binds to ergosterol, disrupting fungal membranes. Too toxic for systemic use. [on left w/ amphotericin, below]
115
Clinical use of nystatin
Swish and swallow for oral candidiasis (thrush); topical for diaper rash or vaginal candidiasis.
116
Azoles (list)
Fluconazole Ketoconazole, Clotrimazole, miconazole, itraconazole, voriconazole
117
Mechanism of azoles
Inhibit fungal sterol (ergosterol) synthesis [below, top/middle]
118
Clinical use of azoles
Systemic mycoses. Fluconazole for cyptococcal meningitis in AIDS pts (b/c it can cross the BBB) and candidal infxns of all types (i.e., yeast infxns). Ketoconazole for Balstomyces, Coccidioides, Histoplasma, Candida albicans, hypercortisolism. Clotrimazole and miconazole for topical fungal infxns.
119
Toxicity of azoles
Hormone synthesis inhibition (gynecomastia), liver dysfunction (inhibits cytochrome P-450), fever, chills
120
Flucytosine mechanism
Inhibits DNA synthesis by conversion to 5-fluorouracil [below, middle]
121
Clinical use of flucytosine
Used in systemic fungal infxns (e.g., Candida, Cryptococcus) in combination w/ amphotericin B
122
Toxicity of flucytosine
Nausea, vomiting, diarrhea, bone marrow suppression
123
Mechanism of Caspofungin
Inhibits cell wall synthesis by inhibiting synthesis of beta-glucan. [not included in image of anti-fungal mechanisms]
124
Clinical use of caspofungin
Invasive aspergillosis
125
Toxicity of caspofungin
GI upset, flushing.
126
Mechanism of terbinafine
Inhibits the fungal enzyme squalene epoxidase. [below, top/right]
127
Clinical use of terbinafine
Used to Tx dermatophytoses (especially onychomycosis)
128
Mechanism of griseofulvin
Interferes w/ microtubule fxn; disrupts mitosis. Deposits keratin-containing tissues (e.g., nails). [below, bottom/right]
129
Clinical use of griseofulvin
Oral Tx of superficial infxns; inhibits growth of dermatophytes (tinea, ringworm)
130
Toxicity of griseofulvin
Teratogenic, ccarcinogenic, confusion, HA, induces P-450 (increasing warfarin metabolism).
131
Mechanism of amantadine
Blocks viral penetration/uncoating (M2 protein); may buffer pH of endosome. (A man to dine [amantadine] takes of his coat .) Also causes the release of dopamine from intact nerve terminals. [below, top/right]
132
Clinical use of amantadine
Prophylaxis and Tx for influenza A; Parkinson's Dz. (A mantadine blocks influenza A and rubellA , and causes problems w/ the cerebellA )
133
Toxicity of amantadine
Ataxia, dizziness, slurred speech. (A mantadine blocks influenza A and rubellA , and causes problems w/ the cerebellA ) Rimantidine is a derivative w/ fewer CNS side effects (does not cross BBB)
134
Mechanism of resistance to amantadine
Mutated M2 protein. 90% of all influenza A strains are resistant to amantadine, so not used.
135
Mechanism of: Zanamivir, oseltamivir
Inhibit influenza neuraminidase, decreasing the release of progeny virus. [below, bottom/left: Neuraminidase inhibitors]
136
Clinical use of Zanamivir, oseltamivir
Both influenza A and B
137
Mechanism of ribavirin
Inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenase. [not included in figure, but acts at point of NA synthesis, bottom/right]
138
Clinical use of ribavirin
RSV Chronic hepatitis C
139
Toxicity of ribavirin
Hemolytic anemia. Severe teratogen.
140
Mechanism of acyclovir
Monophosphorylated by HSV/VZV thymidine kinase. Guanosine analog. Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA polymerase by chain termination. [fits w/ NA analogs below, bottom/right]
141
Clnicial use of acyclovir
HSV, VZV, EBV. Used for HSV-induced mucocutaneous and genital lesions as well as for encephalitis. Prophylaxis in immunocompromised pts. For herpes zoster, use a related agent (famciclovir). No effect on latent forms of HSV and VZV.
142
Toxicity of acyclovir
Generally well-tolerated.
143
Mechanism of resistance to acyclovir
Lack of thymidine kinase
144
Mechanism of ganciclovir
5'-monophosphate formed by a CMV viral kinase or HSV/VZV thymidine kinase. Guanosine analog. Triphosphate formed by cellular kinases. Preferentially inhibits viral DNA polymerase. [fits in w/ NA analogs below, bottom/right]
145
Clinical use of ganciclovir
CMV, especially in immunocompromised pts
146
Toxicity of ganciclovir
Leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to host enzymes than acyclovir.
147
Mechanism of resistance to ganciclovir
Mutated CMV DNA polymerase or lack of viral kinse.
148
Mechanism of foscarnet
Viral DNA polymerase inhibitor that binds to the pyrophosphate-binding site of the enzyme. Does not require activation by viral kinase. (FOS carnet = pyroFOS phate analog) [would fit into DNA synthesis on bottom/right]
149
Clinical use of foscarnet
CMV retinitis in immunocompromised pts when ganciclovir fails; acyclovir-resistant HSV.
150
Toxicity of foscarnet
Nephrotoxicity.
151
Mechanism of resistance to foscarnet
Mutated DNA polymerase.
152
HIV therapy: Protease inhibitors (list)
Saquinavir Ritonavir Indinavir Nelfinavir Amprenavir [all protease inhibitors end in -avir ] (NAVIR (never) TEASE a proTEASE )
153
HIV therapy: Mechanism of protease inhibitors
Inhibit maturation of new virus by blocking protease in progeny of virus.
154
HIV therapy: Toxicity of protease inhibitors
GI intolerance (nausea, diarrhea) Hyperglycemia Lipodystrophy Thrombocytopenia (indinavir)
155
HIV therapy: Reverse transcriptase inhibitors --> nucleosides (list)
Zidovudine (ZDV, formerly AZT) Didanosine (ddI) Zalcitabine (ddC) Stavudine (d4T) Lamivudine (3TC) Abacavir (Have you dined (vudine ) with my nuclear (nucleosides ) family?)
156
HIV therapy: Reverse transcriptase inhibitors --> non-nucleosides (list)
N evirapine, E favirenz, D elaviridine (N ever E ver D eliver nucleosides.)
157
HIV therapy: Mechanism of reverse transcriptase inhibitors
Preferentially inhibit reverse transcriptase of HIV; prevent incorporation of DNA copy of viral genome into host DNA. [below, bottom/right]
158
HIV therapy: Toxicity of reverse transcriptase inhibitors
Bone marrow suppression* (neutropenia, anemia) Peripheral neuropathy Lactic acidosis (nucleosides) Rash (non-nucleosides) Megaloblastic anemia (ZDV) *GM-CSF and erythropoietin can be used to reduce BM suppression.
159
HIV therapy: Clinical use of reverse transcriptase inhibitors
Highly active antiretroviral therapy (HAART) generally entails combination Tx w/ protease inhibitors and reverse transcriptase inhibitors. Initiated when pts have low CD4 counts (<500 cells/mm^3) or high viral load. ZDV is used for general prophylaxis and during pregnancy to reduce risk of fetal transmission.
160
HIV therapy: Fusion inhibitor (there's one -- what is it?)
Enfuvirtide
161
HIV therapy: Mechanism of fusion inhibitors (enfuvirtide)
Bind viral gp41 subunit; inhibit conformational change required for fusion w/ CD4 cells. Therefore block entry and susequent replication.
162
HIV therapy: Toxicity of fusion inhibitors (enfuvirtide)
Hypersensitivity rxtns Rxtns at subcutaneous injection site Increased risk of bacterial pneumonia
163
HIV therapy: Clinical use of fusion inhibitors (enfuvirtide)
In pts w/ persistent viral replication in spite of antiretroviral Tx. Used in combination w/ other drugs.
164
Mechanism of interferons (as antimicrobials)
Glycoproteins from human leukocytes that block various stages of viral RNA and DNA synthesis. Induce ribonuclease that degrades viral mRNA.
165
Clinical use of interferons
IFN-alpha: chronic hepatitis B and C, Kaposi's sarcoma IFN-beta: MS IFN-gamma: NADPH oxidase deficiency
166
Toxicity of interferons
Neutropenia
167
Antibiotics to avoid in pregnancy (list -- what are they, and why for each one?)
(SAFE M oms T ake R eally G ood C are.) S ulfonamides -- kernicterus A minoglycosides -- ototoxicity F luoroquinolones -- cartilage damage E rythromycin -- acute cholestatic hepatitis in mom (and clarythromycin -- embryotoxic) M etronidazole -- mutagenesis T etracyclines -- discolored teeth, inhibition of bone growth R ibavirin (antiviral) -- teratogenic Griseofulvin (antifungal) -- teratogenic Chloramphenicol -- gray baby
