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IC4 Flashcards

1
Q

Common clinical indications for macrolides

A

atypical microbes

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1
Q

Common clinical indications for macrolides

A

atypical microbes, respiratory tract infections (CAP), Chlamydial infections, Diphtheria, H.pylori (Clarithromycin/Azithromycin + omeprazole +amoxicillin), Mycobacterial infections

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2
Q

Which macrolides is usually destroyed by gastric acid and thus administered in either enteric-coated tablets or esterified forms?

A

Erythromycin

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3
Q

ROA for macrolides

A

IV and Oral except clarithromycin (Oral only)

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4
Q

Adverse effects of macrolides

A
  • Gastric distress and motility (Less with clarithromycin and azithromycin than erythromycin (motilin agonist))
  • Hepatotoxicity: Cholestatic jaundice
  • Ototoxicity
  • may prolong the QT interval and should be used with caution in those patients with pro-arrhythmic conditions
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5
Q

which other drug can antagonise action of clindamycin?

A

Although clindamycin and erythromycin are not structurally related, they act at sites of proximity, and can antagonise each others action.

Cross resistance with macrolides due to (erm) methylases can also occur

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6
Q

what is clindamycin useful against?

A

anaerobic infection

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7
Q

dosage form for clindamycin

A

Oral and IV; topical solution, gel, or lotion and vaginal cream

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8
Q

Contraindication for clindamycin

A

CDAD, pseudomembranous colitis / ulcerative colitis

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9
Q

MOA of Resistance in clindamycin

A
  1. Alteration of the 50S ribosomal subunit by aa substitution
  2. Alteration in the 23S ribosomal RNA subunit by methylation and nucleotidylation of the hydroxyl group of clindamycin.
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10
Q

Activity of linezolid

A

Gram positive only (incl MRSA, VRE, VRSA)

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11
Q

MOA of linezolid

A

Binds the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex, which is an essential component of the bacterial translation process.

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12
Q

Dosage form for linezolid

A

Oral and IV

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12
Q

MOA of Resistance to linezolid

A
  1. Mutations in the 23S ribosomal RNA is the major cause of linezolid resistance in VRE and MRSA.
  2. Resistance can also be conferred by the cfr rRNA methyltransferase against lincosamides and oxazolidinones
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13
Q

Adverse effects of linezolid

A
  1. GI effects
  2. Bone Marrow Suppression: Thrombocytopenia has been reported in patients taking the drug for >10 days. (Need to monitor blood counts)
  3. may lead to serotonin syndrome if given concomitantly with selective serotonin reuptake inhibitors, or MAO inhibitors (reversible)
  4. Irreversible peripheral neuropathies and optic neuritis (causing blindness) have been associated with > 28 days of use
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14
Q

Contraindication for linezolid

A
  1. Treatment of catheter-related bloodstream infections or catheter-site infections
  2. Do not use within two weeks of MAO inhibitors, e.g., phenelzine
  3. Tyramine-containing foods and serotonergic drugs, as these may precipitate a hypertensive crisis.

Examples of tyramine-containing foods include aged cheese, cured or smoked meats, draft beer, fava beans, and soy products.

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15
Q

MOA for fluoroquinolones

A
  1. targets DNA gyrase, primarily in Gram-negative bacteria
  2. targets topoisomerase IV in Gram-positive bacteria

to inhibit DNA replication

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16
Q

Clearance method for various fluoroquinolones

A

Levofloxacin/ Ciprofloxain: Renal CL
Moxifloxacin: Hepatic CL

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17
Q

Generation for various fluoroquinolones

A

2nd: Ciprofloxacin
3rd: Levofloxacin, Moxifloxacin

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18
Q

3rd gen fluoroquinolones vs 2nd gen advantage

A
  • Better coverage against Gram positive organisms, especially S. pneumoniae
  • Increased coverage against atypical pathogens such as Mycoplasma pneumoniae and Chlamydia pneumoniae

Hence 3rd gen known as respiratory quinolones

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19
Q

Adverse effects of fluoroquinolones

A
  1. GI related (most common) - nausea, vomiting, and diarrhoea
  2. Risk of dysglycaemia especially in diabetic patients
  3. Aortic dissections or ruptures of an aortic aneurysm - rare
  4. Increased risk of C. diff colitis as they clear the bowel flora, esp with
    ciprofloxacin
  5. Headache and dizziness or light headedness may occur. Thus, patients with CNS disorders, such as epilepsy, should be treated cautiously with these drugs.
  6. phototoxicity
  7. An increased risk of tendinitis or tendon rupture may occur with systemic fluoroquinolone use.
  8. may prolong the QTc interval (more common with third gen)
  9. Peripheral Neuropathy with systemic use
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20
Q

Contraindication for fluoroquinolones

A
  1. Not recommended for infants or children < 18 years of age as they have been shown to cause joint problems (arthropathy) in young animals.
  2. Ciprofloxacin in lactation
  3. Patients with myasthenia gravis because it may exacerbate muscle weaknesses.
  4. G6PD deficiency

Quinolones may also raise the serum levels of warfarin, and cyclosporine.

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21
Q

Contraindication for sulfonamide

A

Due to the danger of kernicterus, sulfa drugs should be avoided in < 2 months of age, and in pregnant women at term.

22
Q

Drug potentiation for sulfonamide

A

Transient potentiation of the anticoagulant effect of warfarin

23
Adverse effects of sulfonamide
1. Crystalluria 2. Hypersensitivity 3. Hematopoietic disturbances - haemolytic anaemia, G6PD deficiency 4. Kernicterus
24
How to prevent crystalluria in sulfonamide use?
Hydration and alkalinisation of urine can prevent the problem by reducing the concentration of drug and promoting its ionization.
25
MOA for trimethorpim
Trimethoprim inhibits the reduction of dihydrofolic acid by dihydrofolate reductase to its active form. This leads to a decreased availability of the tetrahydrofolate cofactors required for purine, pyrimidine, and amino acid synthesis.
26
MOA for sulfonamide
Sulfonamides are competitive inhibitors of dihydropteroate synthase, the bacterial enzyme responsible for the incorporation of para- aminobenzoic acid (PABA) into dihydropteroic acid, the immediate precursor of folic acid
27
Sensitive microorganisms for sulfonamide
those that must synthesize their own folic acid; bacteria that can use preformed folate are not affected
28
Activity of trimethoprim and sulfonamide
Enterobacter spp, E.coli, Klebsiella pneumoniae
29
Clearance method for sulfonamide/ trimethoprim
Renal CL
30
Which grps of patient have incr risk of folic acid deficiency?
Pregnant women, those having very poor diets
31
Management of folic acid deficiency
Folinic acid (readily converted to tetrahydrofolic acid)
32
Composition for Cotrimoxazole
1 Trimethoprim: 5 sulfamethoxazole
33
Trade names for cotrimoxazole
Bactrim; Septra
34
Which grp of patients experience more adverse reactions to cotrimoxazole such as fever, rashes, hyperkalaemia, hyponatremia and diarrhea?
Immunocompromised patients, such as those with HIV/AIDS
35
Activity of cotrimoxazole
1. UTIs, E.coli. Low dose TMP-SMX can also be given to women for recurrent UTI as prophylaxis. 2. Respiratory tract infections caused by Haemophilus sp, Moraxella catarrhalis and Klebsiella pneumonia 3. MRSA and community-acquired skin and soft tissue infections caused by this organism. 4. Pneumocystis pneumonia caused by Pneumocystis jiroveci
36
Adverse effects of cotrimoxazole
1. Skin reactions like rash are common. 2. Photosensitivity 3. Nausea and vomiting are the most common gastrointestinal adverse effects. 4. Glossitis and stomatitis can occur. 5. Hemolytic anemia may occur in patients with G6PD deficiency due to the sulfamethoxazole component. 6. Megaloblastic anemia, leukopenia, and thrombocytopenia may occur and can be fatal. 7. Use with caution in pregnancy as it can cause folate deficiency
37
DDI with cotrimoxazole
Can increase the half life of phenytoin, enhance the effect of warfarin.
38
MOA for nitrofurantoin
Reduced in bacteria to a highly active intermediate that inhibits various enzymes and disrupt the synthesis of proteins, DNA, RNA, and metabolic processes.
39
Activity of nitrofurantoin
E. coli and enterococcus
40
Which bacteria is nitrofurantoin NOT active against?
Proteus and Pseudomonas and many species of Enterobacter and Klebsiella are resistant
41
dosage form for nitrofurantoin
oral
42
indication for nitrofurantoin
prevention and treatment of lower UTIs (acute lower UTI, prophylaxis of lower UTI)
43
Low / high pH enhances activity of nitrofurantoin
Low; Acidic urine (pH < 5.5) greatly enhances drug activity
44
Adverse effects of nitrofurantoin
1. Nausea, vomiting, and diarrhea are common. Macrocrystalline preparation is better tolerated. 2. Hypersensitivity reactions occasionally occur e.g. chills and fever, 3. Leukopenia, hemolytic anemia (a/w G6PD deficiency), 4. Cholestatic jaundice, and hepatocellular damage. (Its nitro-reductive metabolism produces injurious oxidative free radicals which can damage hepatocytes) (rare) 5. Elderly patients are especially susceptible to the pulmonary toxicity of nitrofurantoin. 6. Peripheral neuropathies are most likely to occur in patients with impaired renal function and in persons on long-continued treatment. (rare) 7. Often there is a prolonged incubation period to onset of liver injury due to nitrofurantoin, and this frequently leads to mistaken or delayed diagnosis. 8. colours the urine brown
45
contraindication for nitrofurantoin
1. Individuals with impaired renal function (creatinine clearance <40 mL/minute) 2. Pregnant women (38 to 42 weeks gestation), during labor and delivery, or when the start of labor is imminent 3. Infants <1 month of age should not receive nitrofurantoin
46
structure of anti-protozoal agent
unicellular eukaryotes
47
what is amebiasis caused by?
Entamoeba histolytica
48
what kind of agent does metronidazole belong to?
anti-protozoal agent
49
MOA of metronidazole
Nitro group of metronidazole serves as an electron acceptor, forming cytotoxic free radicals that results in protein and DNA damage, and death of the E. histolytica trophozoites
50
Activity of metronidazole
Amebic infections, anaerobes, H. pylori, surgical prophylaxis
51
Clearance method for metronidazole
Hepatic
52
DDI with metronidazole
warfarin
53
contraindication for metronidazole
avoid in pregnancy (1st trimester) & alcohol
54
adverse effects of metronidazole
1. GI: nausea, vomiting, epigastric distress, and abdominal cramps. 2. An unpleasant, metallic taste is commonly experienced. 3. Oral moniliasis (yeast infection of the mouth) 4. Central and Peripheral Nervous System Effects: Convulsive seizures, optic and peripheral neuropathy. Rare but discontinue the drug if it happens.

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