Deck 1 Flashcards
1
Q
Name 3 fluroquinolones
A
Ciprofloxacin
Levofloxacin
Moxifloxacin
2
Q
Name 3 folic acid inhibitors
A
Sulfonamides
Trimethoprim
Cotrimoxazole
3
Q
Name a Urinary Antiseptic
A
Nitrofurantoin
4
Q
Name 2 Polymyxins
A
Polymyxin B
Colistin
5
Q
Describe MOA of fluroquinolones
A
Target DNA gyrase, primarily in G(-) bacteria & topoisomerase IV in G(+) bacteria to inhibit DNA replication
- DNA gyrase: Introduces negative supercoils into DNA to prevent excessive positive supercoiling
- Topoisomerase IV: Promotes separation of chromosomal DNA into daughter cells (more common with G(+) bacteria e.g. Streptococci)
6
Q
Describe MOA of sulfonamides
A
- Competitive inhibitors of dihydropteroate synthase, the bacterial enzyme responsible for incorporation of para-aminobenzoic acid into dihydropteroic acid, the immediate precursor of folic acid
- Sensitive microorganisms are those that must synthesize their own folic acid; bacteria that can use preformed folate are not affected
- Bacteriostasis induced by sulfonamides is counteracted by PABA competitively
- Mammalian cells require preformed folic acid, cannot synthesize it, are insensitive to drugs acting by this mechanism
7
Q
Describe MOA of trimethoprim
A
- Inhibits reduction of dihydrofolic acid by dihydrofolate reductase to its active form
- Leads to decreased availability of tetrahydrofolate cofactors required for purine, pyrimidine, aa synthesis
8
Q
Describe MOA of Cotrimoxazole
A
- Synergistic antimicrobial activity of cotrimoxazole results from inhibition of two sequential steps in synthesis of tetrahydrofolic acid
- Sulfamethoxazole inhibits incorporation of PABA into dihydrofolic acid precursors; Trimethoprim prevents reduction of dihydrofolate to tetrahydrofolate
9
Q
Describe MOA of urinary antiseptics (Nitrofuratonin)
A
- Sensitive bacteria reduce the drug to a highly active intermediate that inhibits various enzymes & disrupt the synthesis of proteins, DNA, RNA & metabolic processes
10
Q
Describe MOA of Polymyxins
A
- Bactericidal, cationic, surface-active agents that disrupt the structure of cell membrane phospholipids & increase cell permeability by a detergent like action
- G(-) much more sensitive than G(+) because they contain more phospholipid in their cytoplasm & outer membranes
11
Q
Describe MOA of Fosfomycin
A
- Bactericidal
- Interferes with cell wall synthesis in both G(+) & G(-) by inhibiting initial step involving phosphoenolpyruvate synthetase
- Enters cells of Fosfomycin-susceptible bacteria by means of two different transport uptake systems & inhibits synthesis of peptidoglycan by blocking formation of N-acetylmuramic acid from N-acetylglucosamine and phosphoenolpyruvate
12
Q
ROA of Fluroquinolones
A
- Oral
- IV
- Ophthalmic
13
Q
ROA of sulfonamides
A
Oral
14
Q
ROA of trimethoprim
A
Oral
15
Q
ROA of cotrimoxazole
A
- Oral (common; full cup water)
- IV (severe pneumonia, UTI caused by susceptible organism where pt unable to take orally)
16
Q
ROA of Nitrofurantonin
A
Oral
17
Q
ROA of Polymyxin B
A
IV
18
Q
Prodrug of Colistin
A
CMS (Colistimethate)
19
Q
ROA of Colistin
A
- Inhalation
- IV
20
Q
ROA of Fosfomycin
A
Oral
21
Q
List drug(s)/ drug class(es) best taken on empty stomach
A
Fluroquinolones
Fosfomycin
22
Q
Fluroquinolones should not be taken with
A
with Ca or other divalent cations e.g. Al/Mg containing antacids, or dietary supplements containing Fe/Zn
23
Q
Name the drug which has the following property: Not absorbed orally or suppository, thus reserved for tx of chronic inflammatory bowel disease (e.g. ulcerative colitis)
A
Sulfasalazine
24
Q
Distribution of fluroquinolones
A
- High levels in bone, urine (except moxi), kidney, prostatic tissue
- Concentrations in lungs exceed serum
25
Distribution of sulfonamides
- Bound to serum albumin
- Distribute throughout bodily fluids & penetrate well into CSF fluid (even in absence of inflammation)
- Pass placental barrier & enter fetal tissues
26
Name the drug(s)/ drug class(es) which penetrate well into CSF fluid
Folic acid inhibitors (sulfonamide, trimethoprim, cotrimoxazole)
Fosfomycin
Anti-Protozoal Agent (Metronidazole)
27
Name the drug class(es) & drug(s) which satisfy the following:
- Achieves very high urinary conc while limiting systemic exposure (due to rapid clearance), ideal targeted medication for UTI
Urinary antiseptics (Nitrofuratoin)
28
Distribution of trimethoprim
- Weak base, so higher conc of trimethoprim achieved in relatively acidic prostatic & vaginal fluids
- Widely distributed into body tissues & fluids, incl penetration into CSF
29
List the drugs which are excreted renally
```
Fluroquinolones (cipro, levo, NOT moxi)
Folic Acid Inhibitors (all three)
Urinary antiseptics (Nitrofuratonin)
Polymyxins (ONLY CMS, NOT Colistin & Polymycin B)
Fosfomycin
Anti-Protozoal Agent (Metronidazole)
```
30
Name the drug(s) metabolized by liver
Moxifloxacin
Sulfonamides
Metronidazole
31
Drug(s) which causes crystalluria & potential damage to kidney
Sulfonamides
32
Describe MOA of Metronidazole
- Amoebas possess electron transport proteins that participate in metabolic electron removal reactions
- Metronidazole is a nitroimidazole
- Nitro group of metronidazole is able to serve as an electron acceptor, forming cytotoxic free radicals that results in protein & DNA damage, and death of the E. histolytica trophozoites
- Reduction in metronidazole requires strong reducing conditions & anaerobic organisms have more reducing potential than aerobic organisms
33
ROA of Metronidazole
Oral
34
Describe absorption of metronidazole
Completely & rapidly absorbed after oral administration
35
Drug(s) that crosses placenta
Sulfonamides
| Fosfomycin
36
Drug(s) that are found in breast milk
Fosfomycin
| Metronidazole
37
Drug(s)/ Drug Class(es) which require dose adjustment in renal failure
Fluroquinolones (cipro, levo)
| Folic acid inhibitors (Sulfonamides, Trimethoprim)
38
Drug which turns urine brown
Nitrofurantoin
39
Name an inactive prodrug
CMS (Colistimethate)
40
Describe the indications & spectrum of activity of ciprofloxacin
1) Active agst G(-) strains & enteric coliform incl penicillin, cephalosporin, aminoglycoside-resistant strains
2) Highly active agst P. aeruginosa
- Commonly used in cystic fibrosis pts for this indication
3) Skin, bone & joint infections
4) Traveler’s diarrhea caused by e. coli, food poisoning caused by all Enterobacteriaceae (E. Coli, Salmonella, Shigella), and Campylobacter jejuni
5) Typhoid fever caused by Salmonella typhi
6) UTI (not first line for simple UTI due to increasing resistance & adverse effects)
7) Used agst anthrax caused by Bacillus anthracis
8) Prostatitis
AVOIDED in MRSA due to resistance
INEFFECTIVE agst anaerobes
NOT VERY EFFECTIVE agst streptococci & enterococci
41
Can ciprofloxacin be used against MRSA? Why?
Avoided in MRSA infections
- Associated with high incidence of staphylococcal resistance
- Ineffective against anaerobes
- Not very effective against streptococci & enterococci
42
Name 2 3rd generation furoquinolones
Levofloxacin
| Moxifloxacin
43
Which drug(s) are known as respiratory fluroquinolones?
Levofloxacin
| Moxifloxacin
44
Describe spectrum of activity of 3rd generation fluroquinolones as compared to ciprofloxacin
- Better coverage agst G(+), esp S. pneumoniae
- Increased coverage agst atypical pathogens e.g. Mycoplasma pneumoniae & chlamydia pneumoniae (vs cipro)
- Useful agst respi infections due to a/m organisms & Mycobacterium tuberculosis
45
What drugs can sulfonamides be combined with, what are they used for in their respective combinations?
- Combi with trimethoprim (co-trimoxazole): for Pneumocystis carinii (now known as P. jirovecii)
- Combi with pyrimethamine: for drug-resistant malaria & for toxoplasmosis
46
Name an intermediate acting sulfonamide drug
Sulfamethoxazole
47
Describe the indications of sulfonamides
- Inflammatory bowel disease: sulfasalazine (sulfapyridine-aminosalicylate combination)
- Infected burns: silver sulfadiazine; topically
- Some STIs: e.g. trachoma, chalmydia, chancroid
- Respi infections: use confined to a few special problems e.g. infection with Nocardia
- Acute UTI: now seldom used
48
What strains are now resistant to sulfonamides?
Many strains of formerly susceptible species incl meningococci, pneumococci, streptococci, staphylococci, gonococci are now resistant
49
What drug has a similar spectrum of activity to sulfamethoxazole? List 3 species that are sensitive to both drugs.
Drug: Trimethoprim
Species: Enterobacter spp, E. coli, Klebsiella pneumoniae
50
Describe the uses of Trimethoprim
May be used alone in tx of UTIs & in tx of bacterial prostatitis (although fluroquinolones are preferred)
51
Is the spectrum of Cotrimoxazole broader, narrower, or the same as compared to sulfa drugs?
Broader
52
What is Cotrimoxazole effective in treating? (5 points)
1) UTIs, E. coli
- Low dose can be given to women for recurrent UTI as prophylaxis or those with penicillin allergies
2) RTI caused by Haemophilus sp, Moraxella catarrhalis & Klebsiella pneumonia
3) Toxoplasmosis
4) MRSA & community-acquired skin & sort tissue infections caused by this organism
5) Pneumocystis pneumonia cause by Pneumocystis jiroveci
- (more common in immunocompromised patients, e.g. those with HIV/AIDS)
- (These pts also present with more adverse reactions e.g. fever, rashes, hyperkalemia, hyponatremia & diarrhea)
53
Indication of Nitrofurantonin
Used in prevention & tx of lower UTIs (acute lower UTI, prophylaxis of lower UTI)
54
Nitrofurantonin is effective against strains of (name 2)
- E. coli
| - Enterococci
55
What species are resistant to nitrofurantonin?
most species of Proteus & Pseudomonas & many species of Enterobacter & Klebsiella
56
Antibacterial activity of nitrofurantoin is ___ in acidic urine
higher
57
Poymyxins have a ___ antibacterial spectrum, mainly Gram ___
Narrow; Negative
58
Describe uses & spectrum of activity of polymyxins
Used for serious infections with multidrug-resistant G(-) bacteria
- Especially those caused by Enterobacteriaceae family, including E. coli, Enterobacter spp, Klebsiella spp., Salmonella spp., Shingella spp.
- Also have significant activity against Acinetobacter baumannii & P. aeruginosa
59
What is polymyxins not active against?
- Proteus spp. Legionella, Campylobacter, Vibrio cholera, G(-) cocci (Neisseria spp.), G(+) & anaerobic bacteria
60
Describe uses of Inhaled CMS
- Pseudomonas is a major cause of lung infections in people with cystic fibrosis (less so in Singapore)
- Useful in respi infections & severe pneumonia due to MDR G(-) microbes
61
Describe uses of Polymyxin B
- Acute infections due to MDR G(-) microbes with no alternatives (E. coli, UTI, Klebsiella pneumoniae bacteremia)
- UTI & bloodstream infections due to P. aeruginosa
62
Fosfomycin has a ___ spectrum of activity against a ___ range of Gram ___ bacteria
broad; wide; positive & negative
63
Name 2 Gram positive & 2 gram negative pathogens fosfomycin is active against
S. aureus & enterococcus
| P. aeruginosa & Klebsiella pneumoniae
64
Describe the uses of fosfomycin
- Mainly in tx of UTIs, particularly caused by E. coli & Enterococcus faecalis
- In combi with other abx in tx of nosocomial infections due to resistant G(+) & G(-) bacteria
- Can have synergistic effects with beta lactam abx
- Not suitable for pyelonephritis or severe urinary sepsis due to poor systemic absorption
65
Describe the uses & spectrum of metronidazole (describe 4)
1) Amebic infections caused by Protozoa including:
- Entamoeba histolytica, Trichomonas vaginalis (vaginitis), Giardia lamblia (Giardiasis)
2) Anaerobes such as:
- Bacteroides species & Clostridium difficile
3) Helicobacter pylori (part of triple therapy for H. pylori infection)
4) Surgical prophylaxis (30-60 mins before incision)
66
State & describe use of fluroquinolones in pregnancy
Cat C
- Arthropathy observed in immature animals
- Cipro detected in breast milk; Not recommended during breastfeeding
67
State & describe use of sulfonamides in pregnancy
Avoid in pregnant women at term
68
State the pregnancy classification of trimethoprim
Cat C
69
State & describe use of cotrimoxazole in pregnancy
Use with caution
| - Can cause folate deficiency
70
State & describe use of nitrofurantoin in pregnancy
```
Contraindicated:
(38-42 wks gestation)
- During labor or delivery
- When start of labor is imminent
- Reason: Possibility of hemolytic anemia
```
71
State pregnancy category of fosfomycin
B
72
State & describe pregnancy category of metronidazole
Cat B
- But avoid use in first trimester
- Only use if clearly needed (carcinogen in rodents)
73
8 adverse events of fluroquinolones
1) N/V/D (most common)
2) C. diff colitis (especially cipro)
3) HA/dizziness/light HA
- Caution in pts with CNS disorders e.g. epilepsy
4) Phototoxicity
- Use sunscreen, avoid excess exposure to light
5) Tendinitis or tendon rupture
- Increased risk with systemic use
6) Joint problems (arthropathy)
- In young animals
- Not recommended in infants/children < 18yo
7) Prolong QTc interval (more common with 3rd gen)
- Should not be used in pts who are predisposed to arrhythmias or those who are taking other medications that cause QT prolongation
8) Peripheral Neuropathy
- With systemic use
- May occur any time during tx, may persist for months to years (even permanent) after drug stopped
74
5 Adverse events of sulfonamides
1) Crystalluria
- Can result in development of nephrotoxicity
- Prevention by hydration & alkalization of urine; reduces concentration of drug & promotes its ionization
2) Hypersensitivity
- E.g. rashes, angioedema, SJS
- Previous sulfa allergies (note description)
3) Hematopoietic disturbances
- Hemolytic anemia encountered in patients with G6PD deficiency (lower ability to counter oxidative stress)
- Can also cause thrombocytopenia
4) Kernicterus
- May occur in newborns if taken by mums in late pregnancy
- Sulfa drugs displace bilirubin from binding sites on serum albumin
- Bilirubin is then free to pass into CNS, as BBB not fully developed
5) Drug potentiation
- Transient potentiation of anticoagulant effect of warfarin results from displacement from binding sites on serum albumin
- Reported in pts receiving both sulfamethoxazole & warfarin; increased monitoring recommended
75
Name an adverse effect of trimethoprim & its effects
Effects of folic acid deficiency:
- Megaloblastic anemia, leukopenia, granulocytopenia
- Especially in pregnant pts & those having very poor diets
76
In management of folic acid deficiency with trimethoprim, ___ administration of ___ is given
Simultaneous; folinic acid
77
___ is a 5-formyl derivative of ___ which is readily converted to ___, which is then utilized for important cellular metabolic functions
Folinic acid; tetrahydrofolic acid; tetrahydrofolic acid
78
List & describe 6 adverse events involving cotrimoxazole
1) Skin reactions e.g. rash (common)
2) Photosensitivity
3) GI effects e.g. N/V (most common)
4) Glossitis & stomatitis
5) Hemolytic anemia
- In pts with G6PD deficiency due to sulfamethoxazole component
6) Megaloblastic anemia, leukopenia, thrombocytopenia
- Can be fatal
- Hematologic effects reversed by concurrent administration of folinic acid, which protect pt & does not enter microorganism
79
List & describe 7 common adverse effects of nitrofurantoin
1) N/V/D (common)
- Macrocrystalline preparation better tolerated
2) Hypersensitivity reactions (occasionally)
- Chills, fever
3) Leukopenia, hemolytic anemia (associated with G6PD deficiency)
4) Cholestatic jaundice & hepatocellular damage (rare)
- Nitro-reductive metabolism produces injurious oxidative free radicals which can damage hepatocytes
5) Pulmonary toxicity
- Elderly patients especially susceptible
6) Peripheral neuropathies (rare)
- Most likely to occur in pts with impaired renal function & persons on long-continued tx
7) Prolonged incubation period to onset of liver injury due to nitrofurantoin
- Frequently leads to mistaken or delayed dx
80
List & describe 3 adverse events related to polymyxins
1) Nephrotoxicity (toxic to renal tubule cells)
- Avoid use with other nephrotoxic agents
2) Neurotoxicity (visual disturbances, vertigo, confusion, hallucinations, seizures)
- Usually associated with high serum levels in patients with renal impairment or nephrotoxicity
- DO NOT use in neuromuscular blockade agents & in pt with myasthenia gravis
3) Adverse events related to aerosolized CMS:
- Sore throat, cough, bronchoconstriction, chest tightness
- Bronchoconstriction can occur due to direct chemical stimulation, liberation of histamine, allergy in airway, irritation from chemicals
- Bronchoconstriction usually requires discontinuation of medication, administration of bronchodilators & supplemental oxygen
81
List 3 adverse events of foscfomycin
1) GI disturbances (e.g. N/D)
2) HA
3) Vaginitis
82
List 4 adverse events of metronidazole
1) GI
- N/V, epigastric distress, abdominal cramps
2) Unpleasant, metallic taste (common)
3) Oral moniliasis (yeast infection of mouth)
4) CNT & PNS Effects
- Convulsive seizures, optic & peripheral neuropathy
- Rare, but discontinue drug if happens
Avoid alcohol
83
Contraindication of fluroquinolones
Avoid in pts with myasthenia gravis
| - May exacerbate muscle weakness
84
List 2 contraindication of sulfonamides
- Newborns & infants < 2/12 age
| - Pregnant women at term
85
List 3 contraindications of urinary antiseptics
1) Impaired renal function (CrCl < 40 mL/min)
2) Pregnant women (38-42 wks gestation)
- During labor or delivery
- When start of labor is imminent
- Reason: Possibility of hemolytic anemia
3) Infants < 1 month of age
- Reason: Possibility of hemolytic anemia
86
Quinolones may ___ serum levels of ___ & ___
raise; warfarin; cyclosporine
87
Ciprofloxacin can ___ serum levels of ___ by ___
increase; theophylline; inhibiting its metabolism
88
Cotrimoxazole can:
1) ___ half-life of ___
2) ___ effect of ___
increase; phenytoin;
| enhance; warfarin
89
metronidazole may ___ effects of ___
potentiate; warfarin
90
Describe two mechanisms of resistance against trimethoprim
Resistance in G(-) bacteria due to:
- Presence of altered dihydrofolate reductase that has lower affinity for trimethoprim
- Efflux pumps & decreased permeability to the drug
91
Describe resistance of bacterial against nitrofurantoin
- Approved only for tx of UTI caused by microorganisms known to be susceptible to drug
- Bacterial resistance to nitrofurantoin more frequent than resistance to fluroquinolones or trimethoprim-sulfamethoxazole
92
Resistance to metronidazole ___(is/is not)___ a therapeutic problem for ___, although strains of ___ resistant to drug ___(have/have not)___ been reported
is not; amebiasis; trichomonads; have
