Pharm - Antibiotics, Antifungals, Antivirals Flashcards
(104 cards)
1
Q
Antimicrobial drugs do not readily enter
A
CNS, bone, prostate, eye
2
Q
Narrow spectrum penicillin exemplar
A
Penicillin V
3
Q
Penicillin V coverage
A
non-beta lactamase producing gram+ve cocci, treponema pallidum
4
Q
Extended spectrum penicillin exemplar
A
Amoxicillin
5
Q
Amoxicillin coverage
A
non-beta lactamase producing gram +ve cocci, gram -ve
Common bacterial infections - OM, strep, second line for UTI
6
Q
Amoxicillin resistance
A
- Escherichia d/t upregulation of beta-lactamases
- S pneumoniae - overcome by dose
- Moraxella, haemophilus - overcome by adding beta lactamase inhibitor
7
Q
Monobactam exemplar
A
Aztreonam
8
Q
Aztreonam coverage/ use
A
- Enhanced against gram -ve bacili, none against gram +ve
- For serious infections w/ resistant bacteria incld. pseudomonas (IV)
9
Q
Carbapenem exemplar
A
Meropenem
10
Q
Meropenem coverage/ use
A
- Similar to penicillins, larger spectrum of gram +ve and -ve
- resistance is growing
- systemic infections and multidrug resistant (IV)
11
Q
Cephalosporins coverage
A
1st gen primarily against gram +ve, later increased gram -ve and decreased gram +ve
12
Q
First gen cephalosporin exemplar
A
Cephalexin
13
Q
Cephalexin use
A
prior to surgery to eliminate skin flora
14
Q
Second gen cephalosporin exemplar
A
Cefuroxime
15
Q
Third gen cephalosporin exemplar
A
Ceftriaxone
16
Q
Ceftriaxone uses
A
- hospital acquired infections
- can enter CNS - meningitis
- gonorrhea
17
Q
Fourth gen cephalosporin exemplar
A
Cefepine
18
Q
Cefepime uses and drawbacks
A
- treatment of multi-drug resistant
- associated with higher all cause mortality d/t encephalopathy
19
Q
Beta lactam adverse effects
A
- common: N/V, diarrhea, rash, urticaria, superinfections (candida)
- less common: fever, vomiting, erythema, dermatitis, angioedema
- Pseudomembranous colitis d/t c difficile
- allergy/ anaphylaxis/ hypersensitivity
20
Q
Beta lactam classes
A
Pencillins, monobactam, carbapenems, cephalosporins
21
Q
Other cell wall inhibitor classes
A
UDP-MurNAc inhibitor, Glycopeptide, Beta lactamase inhibitor
22
Q
Fosfomycin mechanism
A
- interferes with synthesis of UDP-NAM near the beginning of the peptidoglycan synthesis pathway
- rapidly excreted which creates effectively high urinary levels
23
Q
Fosfomycin dosing
A
One large dose as resistance rapidly emerges
24
Q
Vancomycin mechanism
A
Binding to end of peptidoglycan and interfering with crosslinking
25
Vancomycin uses
- serious infections caused by gram +ve drug resistant (IV)
26
Vancomycin adverse effect
- can cause diffuse flushing and pruritis d/t histamine release (red man syndrome)
27
Beta lactamase inhibitors exemplar
Clavulanic acid aka clavulanate
28
Clavulanate mechanism
- inhibits class-A beta lactamases
- No intrinsic antimicrobial activity, but serves as surrogate beta-lactamase substrate when given with another beta lactam antibiotic and protects it from destruction
29
Common bacterial resistance mechanisms
- production of various classes of beta lactamases
- alteration of structure of penicillin-binding proteins
- changes to porins in outer membrane of gram -ve bacteria
30
Inhibitors of bacterial protein synthesis classes
- Affect 30s - aminoglycosides, tetracyclines
| - Affect 50S - macrolides, other
31
Aminoglycosides exemplar
Gentamicin
32
Aminoglycoside mechanism
Bind the 30S subunit and interfere with reading of mRNA code --> insertion of wrong amino acid in peptide chain
irreversible
33
Gentamicin usage
- active against wide range of grame -ve
- used in combination with penicillin to treat serious infection (bacterial endocarditis)
- IV or topical, measure plasma concentration
- has long post-antibiotic effect
34
Gentamicin adverse effects
- Nephrotoxicity, ototoxicity (more commonly vestibular)
- irreversible toxicity can occur even after drug is discontinued
- one of the most common causes of drug-indcued renal failure
35
Tetracyclines mechanism
Competitively blocks tRNA binding to the 30S subunit , preventing the addition of a new amino acid
Reversible (bacteriostatic)
36
Tetracycline dosing info
- oral
| - reduce bioavailability if taken w/ mineral supplements, antacids, bismuth salicylate products, dairy
37
Tetracycline coverage
- Broad spectrum bacteriostatic
- includes rickettsia, spirochetes, mycoplasma, chlamydia
- many common pathogens have developed resistance
38
Tetracycline adverse effects
- CI in pregnancy, children <8 d/t it concentrating in growing bones and teeth
- permanent tooth discoloration and hypoplasia of enamel
- nephrotoxicity rare - increased risk close to expiration date, w/ other nephrotoxic drugs
- hepatoxicity, esp in pregnancy
- photosensitivity
39
Macrolides exemplar
Azithromycin
40
Macrolides mechanism
- Affect 50S subunit
- inhibit peptidyl transferase which links amino acids in growing peptide chain
- interferes with translocation
41
Macrolides usage
- covers many of the bacteria that cause respiratory tract infections and CAP
- pts with penicillin allergy
- pneumonia in pregnancy
- pts taking other CYP3A4 drugs
42
Azithromycin use
- reserved for pts w/ penicillin allergies d/t rising resistance and treatment failure
- pneumoniae in pregnancy
- may be preferred for pts taking other CYP3A4 drugs (little effect on this system)
43
Azithromycin adverse effects
- Common: stomatitis, heartburn, nausea, anorexia, abdominal pain, diarrhea
- Less affinity for motilin receptor and less GI side effects
- Potential cardiac conduction issuse
44
"Other" 50S affecting exemplar
Clindamycin
45
Clindamycin mechanism
Interferes with translocation
46
Clindamycin usage
- Resistant infections like MRSA
| - Skin infections in pencillin allergic pts
47
Clindamycin adverse effects
- Higher rates of GI superinfections than other antibiotics
48
Antifolate drugs exemplar
Trimethoprim-Sulfamethoxazole
49
TMP-SMX mechanism
- Synergistic effect by sequential blockade of folate synthesis
- [SMX] 20: [TMP] 1
50
TMP-SMX usages
- Bacterial prostatitis, vaginitis
| - UTI
51
TMP-SMX adverse effects
- N/V, diarrhea, rash, renal impairment, thrombocytopenia, anemia, agranulocytosis
- May cause false elevation in creatine, hypoglycemia w/ sulfonylureas
- Hypersensitivity reaction, CI in pts with sulfa allergy
- Megaloblastic anemia if dietary folate is low
52
Fluoroquinolone exemplar
Ciprofloxacin
53
Fluoroquinolone mechanism
Inhibit the A subunit of DNA gyrase --> inhibits genetic replication d/t accumulation of double stranded breaks
54
Ciprofloxacin usage
- Second line for UTI, prostatitis, PID
- Should be reserved for serious UTI, when others are not effective
- Resistance increasing through efflux pumps and change to porins
55
Ciprofloxacin dosing
Absorption decreased if taken w/ mineral supplements, antacids, bismuth salicylate products
56
Ciprofloxacin adverse effects
- Tendonitis, tendon rupture (high risk in pts >60, concomitant steroid use, transplant pts)
- May cause permanent peripheral neuropathy, alterations in blood glucose
- Seizures, phototoxicity, prolonged QT interval
- Restlessness/ anxiety/ insomnia/ confusion
57
"Other" Nucleic acid disruptor exemplar
Nitrofurantoin
58
Nitrofurantoin mechanism
Reduced by bacterial flavoproteins to reactive intermediates which inactivate or alter bacterial ribosomal proteins and other macromolecules
59
Nitrofurantoin usages
UTI, not pyelonephritis
| D/t very short elimination half life, does not persist long enough to be systemically used
60
Nitrofurantoin adverse effects
- HA, GI (reduced when used in monohydrate/ macrocrystal formulation)
- Long term may cause hepatic toxicity, rarely pulmonary
61
Clostridium difficile risk
Highest - fluoroquinolones, cephalosporins, aztreonam, carbapenems
Moderate - macrolides, TMP-SMX, Penicillins
62
Antifungal classes
Polyene, Azole derivatives, allylamines, echinocandins. other
63
Polyene exemplar
Nystatin
64
Nystatin uses
- Often used in suspension ("swish and swallow"), available in various
- prophylactic prevention of oral candidiasis in immunocompromise
- Topical not routinely recommended
65
Polyene mechanism
Selectively binds to ergosterol in membrane, is incorporated, and forms micropores
66
Azole derivates mechanism
- Inhibit ergosterol biosynthesis via 14 alpha-demethylase --> disrupted membrane structure and function
67
Azole derivates exemplar
Fluconazole
68
Fluconazole usage
- Drug of choice for prophylaxis and treatment of common fungal infections, oral and vulvovaginal candidiasis
- only azole derivative that concentrates in CSF - meningitis
69
Fluconazole adverse effects
- Less affinity for CYP450s, so fewer drug interactions
- systemic administration can cause skin rash, hepatic injury, hematopoietic toxicity, GI distress
- Birth defects with chronic use in doses >400 mg during first trimester
70
Allylamine mechanism
- Similarly to azole derivatives
| - inhibits squalene epoxidase --> disrupts biosynthesis of ergosterol, results in accumulation of toxic squalene
71
Allylamine exemplar
Terbinafine
72
Terbinafine usage
Oral drug of choice for fungal nail infections (preferred d/t higher tolerability, efficacy, lower drug interactions)
73
Terbinafine adverse effects
- GI upset, HA, rash, sensory loss
| - rarely severe hepatotoxicity
74
Other antifungal exemplar
Flucytosine
75
Flucytosine mechanism
- Pyrimidine analog accumulated by fungal cells --> acts as false nucleotide
- mammalian cells unable to activate drug
- always given with amphotericin B d/t rapid development of resistance
76
Flucytosine usage
-Cryptococcus neoformans meningitis in advanced HIV/ AIDS
77
HIV treatment classes
NRTI, NNRTI, Protease inhibitor, fusion/ entry inhibitor, integrase strand transfer inhibitor
78
Attachment/ entry inhibitor exemplar
Maraviroc
79
Maraviroc mechanism
Targets host chemokine receptor CCR5
80
Maraviroc usages
- treatment of HIV when other drugs are ineffective or resistance is high to other drugs
- only effective if pt is infected with HIV that only uses CCR5
- metabolized by CYP3A4 so combination therapy used
81
NRTI exemplar
Emtricitabine/ Tenofovir
82
Emtricitabine/ Tenofovir usages
- Treatment of established HIB, pre-exposure prophylaxis
- One of the preferred combinations during pregnancy
- Common backbone to all three common HIV treatment regimes
83
NRTI mechanism
- Converted to nucleotides by host cell
| - Compete with endogenous nucleotides for incorporation into viral DNA, causing chain termination
84
Emtricitabine/ Tenofovir adverse effects
- Renal, liver toxicity
- Lactic acidosis
- Decreased bone density and risk of fracture
- Lipodystrophy
- HA, nausea, diarrhea, fatigue, depression, insomnia
85
NNRTI mechanism
- Do not require metabolic activation and directly inhibit reverse transcription
- act synergistically with NRTs and are never used alone
86
NNRTI exemplar
Efavirenz
87
Efavirenz usages
- Addition to NRTIs is 1 common regime
| - NNRTI of choice when viral load is <100,000
88
Efavirenz adverse effects
- CNS toxicity - sleep disturbances, abnormal dreams, depression
- Avoid in pts with history of anxiety, depression, psychosis
- Rash
- CI in 1st trimester of pregnancy
- many serious interactions with NNRTIs
89
HIV Protease inhibitors mechanism
- Inhibits protease activity --> production of immature, non-infectious viral particles
- Synergistic with NRTIs
90
HIV Protease inhibitor exemplar
Atazanavir
91
Atazanavir usage
- Combination with NRTIs one of the common regimes
| - Given alongside other drugs (boosted therapy) Ritonavir or Cobicistat
92
Protease inhibitor adverse effects
-Lipodystrophy, hyperlipidemia, insulin resistance and diabetes, liver damage, prolongation of PR interval
93
HIV integrase inhibitor mechanism
Inhibits integrase, which incorporates viral DNA into DNA of CD4+ cells
94
HIV integrase inhibitor exemplar
Raltegravir
95
Raltegravir usage
- Combination with NRTIs one of common regimes
96
Raltegravir adverse effects
- Cause far fewer as a class
- HA, diarrhea, nausea
- less commonly, neuropsych
- Rarely life threatening skin and hypersensitivity reactions
97
Herpes DNA polymerase inhibitor mechanism
- Similar to NRTIs
| - viral and host kinases must activate
98
Herpes DNA polymerase inhibitor exemplar
Acyclovir
99
Acyclovir usage
- Treatment of HSV 1 or 2
- Must be started w/ in 1 hr for orolabial and 7 days for genital
- IV for serious infection
- Suppressive for people who experience 4+ recurrences per year
100
Acyclovir adverse effects
- Not many - GI, HA, rash most common
101
Influenza neuraminidase inhibitor exemplar
Oseltamivir
102
Neuraminidase inhibitor mechanism
- Neuraminidase cannot cleave sialic acid from membrane glycoproteins --> virus remains tethered
103
Oseltamivir useage
- Chemoprophylaxis and treatment of flu A and B during outbreaks
- dosing dependent on renal function
- Treatment best initiated w/in 48 hours of sx onset
- reduces complications influenza
104
Oseltamivir adverse effects
N/V, HA
