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MN Pharmacology > Antibiotics > Flashcards

Antibiotics Flashcards

1
Q

What are antibiotics?

A

Antibiotics are substances derived from microorganisms or synthesized chemically that inhibit the growth of bacteria or kill them outright.

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2
Q

What is the primary mode of action of antibiotics?

A

The primary mode of action of antibiotics is to inhibit bacterial cell wall synthesis, protein synthesis, nucleic acid synthesis, or disrupt bacterial cell membranes.

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3
Q

What is the difference between bactericidal and bacteriostatic antibiotics?

A

Bactericidal antibiotics kill bacteria directly, while bacteriostatic antibiotics inhibit bacterial growth without killing them.

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4
Q

Name the four main targets of antibiotics.

A

The four main targets of antibiotics are cell wall synthesis, protein synthesis, nucleic acid synthesis, and cell membrane integrity.

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5
Q

What is the difference between narrow-spectrum and broad-spectrum antibiotics?

A

Narrow-spectrum antibiotics target specific types of bacteria, while broad-spectrum antibiotics are effective against a wide range of bacteria, including both gram-positive and gram-negative bacteria.

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6
Q

What are the differences between gram-positive and gram-negative bacteria in terms of their cell wall structure?

A

Gram-positive bacteria have a thick layer of peptidoglycan in their cell wall, while gram-negative bacteria have a thin layer of peptidoglycan surrounded by an outer membrane containing lipopolysaccharides.

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7
Q

What is the mechanism of action of beta-lactam antibiotics?

A

Beta-lactam antibiotics inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), preventing the cross-linking of peptidoglycan strands. (Inhibit transpeptidation)

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8
Q

Name a beta-lactam antibiotic.

A

Penicillin, Carbapenem, cephalosporins and monobactams

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9
Q

What is the role of the enzyme beta-lactamase in antibiotic resistance?

A

Beta-lactamase breaks down beta-lactam antibiotics, rendering them ineffective against bacteria that produce this enzyme.

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10
Q

Which class of antibiotics inhibits protein synthesis by binding to the 30S ribosomal subunit?

A

Aminoglycosides, such as gentamicin and streptomycin, bind to the 30S ribosomal subunit to inhibit protein synthesis. Tetracylines as well.

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11
Q

How do tetracyclines inhibit bacterial protein synthesis?

A

Tetracyclines inhibit protein synthesis by binding to the 30S ribosomal subunit and blocking the attachment of aminoacyl-tRNA to the mRNA-ribosome complex.

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12
Q

Name an antibiotic that targets the 50S ribosomal subunit.

A

Macrolides like: Erythromycin
Lincosamides: clindamycin ( also 23 ribosomal subunit)

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13
Q

How does erythromycin inhibit bacterial protein synthesis?

A

Erythromycin binds to the 50S ribosomal subunit and prevents the translocation of the growing peptide chain, inhibiting protein synthesis.

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14
Q

What is the mechanism of action of fluoroquinolone antibiotics?

A

Fluoroquinolones inhibit bacterial DNA synthesis by targeting DNA gyrase and topoisomerase IV, enzymes involved in DNA replication and repair.

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15
Q

Name a fluoroquinolone antibiotic.

A

Ciprofloxacin is a fluoroquinolone antibiotic.

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16
Q

How do sulfonamides inhibit bacterial growth?

A

Sulfonamides inhibit bacterial folate synthesis by competing with para-aminobenzoic acid (PABA) for the active site of dihydropteroate synthase, an enzyme involved in folate synthesis.

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17
Q

What is the mechanism of action of trimethoprim?

A

Trimethoprim inhibits bacterial folate synthesis by blocking dihydrofolate reductase, an enzyme involved in the conversion of dihydrofolate to tetrahydrofolate.

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18
Q

Name an antibiotic that disrupts bacterial cell membrane integrity.

A

Polymyxin B is an antibiotic that disrupts bacterial cell membrane integrity. (detergent like) & daptomycin

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19
Q

How does polymyxin B exert its antibacterial effect?

A

Polymyxin B binds to the lipid component of bacterial cell membranes, disrupting membrane integrity and causing leakage of intracellular contents.

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20
Q

What are the major adverse effects associated with aminoglycoside antibiotics?

A

Major adverse effects of aminoglycoside antibiotics include nephrotoxicity and ototoxicity.

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21
Q

Which antibiotic class is contraindicated during pregnancy due to the risk of tooth discoloration and inhibition of bone growth in the fetus?

A

Tetracyclines are contraindicated during pregnancy due to the risk of tooth discoloration and inhibition of bone growth in the fetus.

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22
Q

Which antibiotics are commonly used to treat urinary tract infections?

A

Fluoroquinolones, such as ciprofloxacin and levofloxacin, and sulfonamides, such as trimethoprim-sulfamethoxazole (TMP-SMX), are commonly used to treat urinary tract infections.Fosfomycin, Nitrofurantoin

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23
Q

What is the mechanism of action of macrolide antibiotics?

A

Macrolide antibiotics inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and preventing the translocation of the growing peptide chain.

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24
Q

Which antibiotics are considered first-line treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections?

A

Vancomycin and daptomycin are considered first-line treatment for MRSA infections.

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25
Q

What is the mechanism of action of vancomycin?

A

Vancomycin inhibits bacterial cell wall synthesis by binding to the D-alanine-D-alanine terminus of peptidoglycan precursors, preventing their incorporation into the cell wall.

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26
Q

How does bacterial resistance to vancomycin develop?

A

Bacterial resistance to vancomycin can develop through the acquisition of the VanA gene, which modifies the D-alanine-D-alanine terminus of peptidoglycan precursors, reducing vancomycin binding affinity.

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27
Q

What is the primary mechanism of resistance to fluoroquinolone antibiotics?

A

Resistance to fluoroquinolone antibiotics primarily occurs through mutations in DNA gyrase and topoisomerase IV, reducing drug binding affinity.

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28
Q

What is the role of efflux pumps in antibiotic resistance?

A

Efflux pumps actively extrude antibiotics from bacterial cells, reducing intracellular drug concentrations and conferring resistance.

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29
Q

How does antibiotic stewardship contribute to combating antibiotic resistance?

A

Antibiotic stewardship promotes the appropriate use of antibiotics, minimizing unnecessary antibiotic prescriptions and reducing the emergence of antibiotic-resistant bacteria.

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30
Q

Which antibiotic class is commonly associated with pseudomembranous colitis?

A

Clindamycin is commonly associated with pseudomembranous colitis caused by Clostridium difficile overgrowth

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31
Q

Which antibiotics are commonly used to treat anaerobic bacterial infections?

A

Metronidazole, clindamycin carbapenems (imipenem, meropenem and ertapenem) and chloramphenicol,are commonly used to treat anaerobic bacterial infections.

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32
Q

What is the mechanism of action of metronidazole?

A

Metronidazole is a prodrug that undergoes intracellular reduction to produce reactive intermediates, which damage bacterial DNA and inhibit nucleic acid synthesis.

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33
Q

What precautionary advice should you give to a patient that is taking metronidazole?

A

Not to take alcohol for the next 48hours. Increase alcohol effects.

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34
Q

Which antibiotic class is commonly used to treat atypical bacterial infections such as Mycoplasma pneumoniae and Legionella pneumophila?

A

Macrolide antibiotics, such as azithromycin and clarithromycin, are commonly used to treat atypical bacterial infections.
And fluroquinolones.

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35
Q

What is the mechanism of action of azithromycin?

A

Azithromycin inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit and preventing the translocation of the growing peptide chain.

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36
Q

Which antibiotic is commonly used as prophylaxis against bacterial endocarditis in individuals undergoing dental procedures?

A

Clindamycin/ Amoxicillin is commonly used as prophylaxis against bacterial endocarditis in individuals undergoing dental procedures.

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37
Q

What is the mechanism of action of amoxicillin?

A

Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), preventing the cross-linking of peptidoglycan strands.

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38
Q

Which antibiotic class is commonly used to treat Clostridium difficile infections?

A

Metronidazole and vancomycin are commonly used to treat Clostridium difficile infections.

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39
Q

What is the mechanism of action of daptomycin?

A

Daptomycin disrupts bacterial cell membrane integrity by inserting into the bacterial membrane and causing depolarization and cell death.

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40
Q

Which antibiotic class is associated with the adverse effect of photosensitivity?

A

Tetracyclines are associated with the adverse effect of photosensitivity.
Anti-folate agents: sulphonamides and trimethoprim

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41
Q

What is the mechanism of action of linezolid?

A

Linezolid inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit and preventing the formation of the initiation complex.

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42
Q

Which antibiotic class is commonly used to treat Helicobacter pylori infections?

A

Proton pump inhibitors (PPIs), clarithromycin, and amoxicillin or metronidazole are commonly used to treat Helicobacter pylori infections.

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43
Q

What is the mechanism of action of nitrofurantoin?

A

Nitrofurantoin damages bacterial DNA and inhibits nucleic acid synthesis by forming reactive intermediates in the bacterial cell.

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44
Q

What antibiotics causes the urine to turn brown?

A

Nitrofurantoin

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45
Q

Which antibiotic class is commonly used to treat community-acquired pneumonia caused by Streptococcus pneumoniae?

A

Macrolide antibiotics, such as azithromycin and clarithromycin, are commonly used to treat community-acquired pneumonia caused by Streptococcus pneumoniae.

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46
Q

What is the mechanism of action of clindamycin?

A

Clindamycin inhibits bacterial protein synthesis by binding to the 50S and 23S ribosomal subunit and preventing peptide bond formation.

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47
Q

Which antibiotic class is commonly associated with the adverse effect of tendon rupture?

A

Fluoroquinolone antibiotics are commonly associated with the adverse effect of tendon rupture.

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48
Q

What is the mechanism of action of fosfomycin?

A

Fosfomycin inhibits bacterial cell wall synthesis by blocking the formation of peptidoglycan precursors.

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49
Q

Which antibiotic class is commonly used to treat infections caused by Pseudomonas aeruginosa?

A

Aminoglycosides, such as gentamicin and tobramycin, and antipseudomonal penicillins, such as piperacillin-tazobactam, are commonly used to treat infections caused by Pseudomonas aeruginosa.

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50
Q

What is the mechanism of action of colistin?

A

Colistin disrupts bacterial cell membrane integrity by binding to lipopolysaccharides in the outer membrane of gram-negative bacteria. (Polymyxin family)

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51
Q

Which antibiotic class is commonly used to treat skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA)?

A

Clindamycin and trimethoprim-sulfamethoxazole (TMP-SMX) are commonly used to treat skin and soft tissue infections caused by MRSA.

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52
Q

What is the mechanism of action of tigecycline?

A

Tigecycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit and preventing the attachment of aminoacyl-tRNA to the mRNA-ribosome complex.

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53
Q

Which antibiotic class is commonly used to treat infections caused by Enterococcus faecalis?

A

Ampicillin and vancomycin are commonly used to treat infections caused by Enterococcus faecalis.

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54
Q

What abx is contraindicated in CAP?

A

Daptomycin is contraindicated in CAP as it interacts with the pulmonary surfactant in the lungs.

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55
Q

What is the mechanism of action of chloramphenicol?

A

Chloramphenicol inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit and preventing the peptidyl transferase activity.

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56
Q

What classes of antibiotics are contraindicated in pregnancy?

A

Metronidazole, Chloramphenicol, Aminoglycosides, Tetracycline, Fluoroquinolones, Sulfonamides and Nitrofurantoin.

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57
Q

What is the mechanism of action of sulfamethoxazole?

A

Sulfamethoxazole inhibits bacterial folate synthesis by competing with para-aminobenzoic acid (PABA) for the active site of dihydropteroate synthase.

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58
Q

Which antibiotic class is commonly used to treat infections caused by Haemophilus influenzae?

A

β-lactam antibiotics, such as amoxicillin and ceftriaxone, are commonly used to treat infections caused by Haemophilus influenzae.

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59
Q

What is the mechanism of action of gentamicin?

A

Answer: Gentamicin inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit and causing misreading of the mRNA codon. (Aminoglycosides)

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60
Q

What is the mechanism of action of aztreonam?

A

Aztreonam inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), preventing the cross-linking of peptidoglycan strands.

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61
Q

What are some antibiotics contraindicated in G6PD patients?

A

Nitrofurantoin & Sulfonamides

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62
Q

What is the mechanism of action of ceftriaxone?

A

Ceftriaxone inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), preventing the cross-linking of peptidoglycan strands.

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63
Q

Which antibiotic class is commonly used to treat infections caused by methicillin-sensitive Staphylococcus aureus (MSSA)?

A

Penicillin and nafcillin are commonly used to treat infections caused by methicillin-sensitive Staphylococcus aureus (MSSA).

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64
Q

What is the primary use of ampicillin?

A

Ampicillin is primarily used to treat bacterial infections caused by susceptible organisms, including respiratory tract infections and urinary tract infections.

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65
Q

What is the mechanism of action of ampicillin?

A

Ampicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs).

66
Q

What is the mechanism of action of minocycline?

A

Minocycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit.

67
Q

What is the primary use of levofloxacin?

A

Levofloxacin is primarily used to treat respiratory tract infections, urinary tract infections, and skin infections.

68
Q

Name a common side effect of levofloxacin.

A

Nausea is a common side effect of levofloxacin.

69
Q

What is the mechanism of action of levofloxacin?

A

Levofloxacin inhibits bacterial DNA gyrase and topoisomerase IV, preventing DNA replication and repair.

70
Q

Which antibiotic class is often used to treat bacterial meningitis caused by Neisseria meningitidis?

A

Third-generation cephalosporins, such as ceftriaxone and cefotaxime, are often used to treat bacterial meningitis caused by Neisseria meningitidis.

71
Q

What is the primary use of ertapenem?

A

Ertapenem is primarily used to treat intra-abdominal infections and complicated urinary tract infections.

72
Q

What is the mechanism of action of ertapenem?

A

Ertapenem inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs).

73
Q

What is the mechanism of action of amoxicillin/clavulanate?

A

Amoxicillin/clavulanate inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs) and inactivating beta-lactamases.

74
Q

Name a common side effect of amoxicillin/clavulanate.

A

Diarrhea is a common side effect of amoxicillin/clavulanate.

75
Q

What is the primary use of ceftazidime?

A

Ceftazidime is primarily used to treat serious infections caused by Gram-negative bacteria.

76
Q

Which antibiotic class is often used to treat infections caused by Pseudomonas aeruginosa?

A

Aminoglycoside antibiotics, such as gentamicin and tobramycin, are often used to treat infections caused by Pseudomonas aeruginosa.

77
Q

Name a common side effect of daptomycin.

A

Muscle pain and weakness are common side effects of daptomycin.

78
Q

What are concentration dependent antibiotics?

A

Aminoglycosides, Fluoroquinolones, Lipopeptides and Lipoglycopeptides

79
Q

Drugs that increases warfarin effects

A

Cephalosporins, cotrimoxazoles, sulphonamides, fluoroquinolones and metronidazole

80
Q

Antibiotics contraindicated in elderly

A

Nitrofluorantonin & fluoroquinolones

81
Q

Nephrotoxic abx

A

aminoglycosides, polymyxins, anti-folate and glycopeptides

82
Q

Ototoxicity abx

A

Aminoglycosides, vancomycin

83
Q

Abx that can cross CSF

A

Cephalosporins ( Gen 3 and above), Carbapenems(meropenem imipenem.

84
Q

Drug drug interaction of daptomycin with statin, what do u need to monitor?

A

Monitoring of weekly creatinine phosphokinase level

85
Q

What is the MOA of polymyxins

A

They interact strongly with phospholipids and disrupts the structure membranes.

86
Q

Which drug would cause a DDI with polymyxin?

A

Neuromuscular blockers, they would result in muscle weakness and apnea

87
Q

Distinguish the differences in MOA between beta lactams and glycoproteins

A

Beta lactams inhibit transpeptidation reaction in the cell wall halting
peptidoglycan
synthesis, while glycoproteins inhibits transglycosylase preventing polymerization
and further elongation of
peptidoglycan and crosslinking.

88
Q

Some clinical application for penicillins

A

Streptococcal infections, meningococcal infections,
neurosyphilis

89
Q

Some clinical applications for cephalosporins

A

Skin and soft tissue infections, urinary tract infections,
surgical prophylaxis

90
Q

Some clinical application for carbapenems

A

Serious infections such as pneumonia and sepsis. UTI,
lower respiratory infections; intra-abdominal and
gynecological infections; and skin, soft tissue, bone,
and joint infections.

91
Q

Which drug has DDI with penicillins?

A

Oral contraceptives- decrease the effectiveness of oral contraceptives
Probenecid- will cause accumulation of beta lactam

92
Q

What do u need to look out for when reconstituting ceftriaxone ?

A

Not to reconstitute with any calcium diluents(Ringers’ solution)

93
Q

What antibiotics should be contraindicated when taking valproate?

A

Carbapenems- it will reduce effects on the seizure control

94
Q

Which abx causes increases nephrotoxicity and ototoxicity when used with vancomycin?

A

Aminoglycosides

95
Q

What is a side effect when vancomycin is transfused too quickly?

A

Red man syndrome- due to a release of histamine.

96
Q

What are the components in co-trimoxazole?

A

Sulphonamides and trimethoprim (5:1)

97
Q

MOA of Sulphamethoxazole

A

It inhibit dihydropteroate synthase and folate
production.

98
Q

MOA of trimethoprim

A

It is a dihydrofolate reductase inhibitor.

99
Q

Clinical applications for sulphonamides

A

Lower urinary tract infections

Sulphadiazine+ pyrimethamine:
* 1st line for toxoplasmosis
* 2nd line for malaria.

100
Q

Why is sulfonylurea hypoglycemic agents contraindicated in patients taking sulphonamides abx?

A

It can potentiate the hypoglycemic effect of the sulfonylurea drugs

101
Q

Which drugs would have a DDI interactions with co-trimoxazole

A

Warfarin, Methotrexate, phenytoin, ace inhibitors.

102
Q

Sulphonamides when taken by pregnant woman will cause….

A

Kernicterus- hypoalbuminemia, also goes into breast milk.

103
Q

What abx causes QT prolongation

A

fluoroquinolones- Moxi> Cipro> levo
And macrolides

104
Q

What abx is a also used as a prophylaxis of lower UTI

A

Nitrofurantoin

105
Q

Antacids will have a decrease effect when used with this antibiotic…

A

Nitrofurantoin,tetracycline fluoroquinolones

106
Q

What antibiotics causes a metallic bitter taste after taking?

A

Metronidazole

107
Q

contraindication of aminoglycosides use

A

Myasthenia gravis patients, hypocalcemia and hypomagnesemia

108
Q

Differences between tetracycline and tigecycline, in their absorption and their half life

A

Tetracycline- absorbed well orally, but tigecycline, is poor absorbed via oral.
Tetracycline and doxycline half life is 6-12 hours, 12-24hrs, but tigacycline half life is 24 to 42 hours.

109
Q

Tetracyclines interact with _____________, which reduces the oral absorption of oral tetracyclines

A

Cations: Calcium (milk), iron and antacids

110
Q

Aminoglycosides can interact with_________- to cause neuromuscular blockade.

A

Calcium channel blockers

111
Q

Which hepatic enzyme inducers affects tetracycline metabolism?

A

Phenytoin, carbamazepine and phenobarbitone

112
Q

Which drugs causes inhibition of CYP450 in the liver, and causes a drug drug interaction?

A

amiodarone, amitriptyline, aprepitant, carvedilol, chloramphenicol, cimetidine, ciprofloxacin, clarithromycin, codeine, donepezil, fluvoxamine, haloperidol, imatinib, ketoconazole, metoprolol, paroxetine, risperidone, ritonavir, tramadol, verapamil.

113
Q

Lincosamide are well absorbed orally, give 1 example of the abx under lincosamide

A

Clindamycin

114
Q

Lincosamide DDI with _______

A

Neuromuscular blocking agents - clindamycin inhibit neuromuscular transmission

115
Q

Adverse effect of linezolid

A

GI intolerance, myelosuppression, Mao Inhibition, peripheral and optic neuropathy and lactic acidosis

116
Q

What kind of monitoring is needed for linezolid?

A

Weekly FBC,esp platelets , blood pressure and visual changes

117
Q

What is the MOA of Choramphenicol?

A

It binds to 50s portion and inhibit formation of peptide bond

118
Q

Grey baby syndrome is caused by which antibiotics?

A

Chloramphenicol

119
Q

antibiotics safe for pregnant patient with uti

A

fosfomycin

120
Q

Macrolides side effect

A

1) GIT disturbance
2) thrombophlebitis
3) ototoxicity
4) hepatotoxicity (c&a better tolerated)
5) QT prolongation

Allergic can cause fever rash eosinophilia

121
Q

Beta lactam side effect

A

1) hypersensitivity
2) bone marrow suppression (reversible)
3) seizure
4) hepatotoxicity
5) GI disturbance

All reversible

122
Q

Penicillin 2 DDI

A

W oral contraceptives (decrease contractive level)

bacteria cannot hydrolyse conjugated hormones
W probenecid
( accumulate BL; block secretion at renal tubular cells)

123
Q

Cephalosporin SE

A
  1. Hypersensitivity: rash, pruritus, fever
    2 .Anorexia, nausea, flatulence
  2. Supra infection: ceftriaxone, cefoperazone and cefotetan may cause bleeding tendencies
  3. Taking cefotetan and alcohol may cause serious disulfiram like reaction
124
Q

Cephalosporins DDI

A

Cephalosporins + warfarin can increase warfarin effects
l reduce the absorption of vitamin K in the body.
l Long-term use (more than 10 days) of antibiotics may result in vitamin K deficiency because these drugs kill not only harmful bacteria but also beneficial, vitamin K- activating bacteria

Increase the anticoagulant effect of warfarin

125
Q

Carbapenem DDI

A

Valproate + Meropenem can decrease valproate levels (may apply to all carbapenems); AVOID CONCOMITANT USE

  1. Decreased absorption of VPA secondary to inhibition of intestinal transporters by carbapenems;
  2. Decreased enterohepatic recirculation of VPA due to decreased gut bacterial beta-glucuronidase, which may be disrupted due the broad-spectrum activity of carbapenems;
  3. Increased distribution of VPA into erythrocytes; and
    Disruption of the normal metabolism of VPA
126
Q

Glycopeptide SE

A

A
1. Dermatological rash; haemotologic (neutropenia and thrombocytopenia with prolonged therapy (reversible)
2. Thrombophlebitis, fever, chills (10%)
3. “Red-neck” or “Red man syndrome”
(rash above the nipple line due to histamine release when vancomycin is infused too rapidly). Give antihistamine or prolong infusion time.
4. Increased nephrotoxicity and ototoxicity when vancomycin is used with aminoglycoside

127
Q

Glycopeptide DDI

A

Aminoglycoside

Polymyxin

128
Q

Daptomycin SE

A

Myopathy (muscle weakness due to dysfunction of muscle fibre)
Monitoring of weekly creatinine phosphokinase levels recommended

129
Q

Polymyxin SE

A

Adverse effects of Polymyxins
1. Polymyxin B applied to intact or denuded skin or mucous membranes produces no systemic reactions and almost complete lack of absorption.
2. Nephrotoxic: avoid aminoglycosides or other nephrotoxins.
3. Interfere with neurotransmission at the neuromuscular
junction, resulting in muscle weakness and apnea.
4. Other neurological reactions include paresthesias, vertigo, and slurred speech.

130
Q

Polymyxin DDI

A

Avoid aminoglycoside
Vancomycin

Not w neuromuscular blocker

131
Q

Aminoglycoside SE

A

1) ototoxicity
Associated with excessively high peak concentration on in conventional onal dosing
* Auditory and vestibular damage – Auditory- High frequency hearing loss
first
– Vestibular – affect balance, nausea, vomiting ng, ver=go
* May be reversible/ irreversible

Nephrotoxicity
* Reported up to 20%
* Due to uptake into proximal renal tubular epithelial cells * A saturable process
Risk factors:
Trough conc >2-3 mg/L for gentamicin, tobramycin, netilmicin and >10mg/L for amikacin
– Prolonged duration on of therapy (>10-14 days) – Advance age
– Concomitant nephrotoxins (vancomycin) – Sepsis
– Gentamicin/ Amikacin > tobramycin * Reversible
3) neuromuscular blockage
Reversible with calcium gluconate

4) risk factor
Myasthenia gravis
HypoCa
HypoMg

132
Q

Aminoglycoside DDI

A

Avoid polymyxin
Vancomycin
Not w CCB

133
Q

Tetracycline SE

A

GI disturbance
Liver failure
Vertigo
Desorption in bone and teeth
Photo toxicity
Avoid pregnancy

134
Q

Drug to Avoid in pregnancy

A

Quinolones
Sulfonamides
Nitrofurantoin
Metronidazole
Chloramphenicol
Aminoglycoside
Tetracycline

135
Q

Aminoglycoside DDI

A
  1. amphotericin B,
  2. Vancomycin
  3. NSAIDs- Nephrotoxic
    reduce renal blood flow by inhibiting prostaglandin production
136
Q

Tetracycline DDI

A
  1. Phenytoin
  2. Carbamazepine
  3. Phenobarbitone
  4. Antacids

Hepatic enzyme inducers -shorten the plasma
half-life of doxycycline by 50%

Antacid Reduce absorption
Cations: Ca++, Fe++ and Al+++
- reduce the absorption of oral
tetracycline

137
Q

Tigecycline SE

A

Side effects of Tigecycline
1. Nausea, vomiting (20-30%)
2. Photosensitivity (uncommon)
3. Superinfection
4. Increase risk of mortality and treatment failure

138
Q

Macrolide DDI

A

Simvastatin
Carbamazepine
Cyclosporine
Inhibition of CYP450 3A4
Lead to increase level of these drugs
*azithromycin: doesn’t inhibit CYP 450
Digoxin

By inactivating gastrointestinal bacteria thought to metabolize digoxin in the gut?
Increase digoxin conc by 2-4x can suffer digoxin-induced toxicity, including arrhythmias, anorexia, altered color vision, and mental change

138
Q

Tigecycline DDI

A

Warfarin increase R warfarin AUC 40% but don’t affect INR

139
Q

Clindamycin SE

A

Hypersensitivity
Gastrointestinal (most common)
* Diarrhea and nausea
* C difficile Pseudomembranous colitis
Hepatotoxicity (rare)Are Adverse effects of Clindamycin

140
Q

Lincosamide DDI

A

Neuromuscular blocking agents

Clindamycin can inhibit neuromuscular transmission; therefore potentiate effects

141
Q

Linezolid SE

A
  1. GI intolerance (nausea, vomiting ng, diarrhoea)
  2. Myelosuppression (thrombocytopenia, anemia) Most oien with treatment duration of >2 weeks
    Increase risk in patients with renal failure, pre-existing myelosuppression, on drugs that can cause myelosuppression
    Reversible upon discontinuation
  3. Monoamine oxidase inhibition (Serotonin Syndrome ) Additive with other agents (MAOI, SSRI, etc)
  4. Peripheral and optic neuropathy
  5. Lactic acidosis
142
Q

Clinical implication linezolid

A

Weekly FBC, especially platelets

  • BP
  • Visual changes
143
Q

Linezolid DDI

A

monoamine oxidase inhibitors
1. SSRI
2. tyramine rich
food
3. adrenergic
agents

Reason: Monoamine oxidase inhibition (Serotonin Syndrome )

Rifampicin
Rifampicin induce CYP450 enzymes
decrease linezolid AUC by 32%

144
Q

Macrolide clinical application

A

1 Community-acquired pneumonia pertussis

  1. Corynebacterial
  2. chlamydial infection
145
Q

Lincosamide clinical applications

A
  1. Skin and soft tissue infections; anaerobic infections
    2.Prophylaxis against endocarditis prior to dental procedures in patients with valvular heart disease.
  2. Treat Pneumocystis jaroveci infection in HIV patients
146
Q

Oxazolidinone clinical application

A

Treatment of severe infections caused by Gram-positive bacteria that are resistant to other antibiotics.
Agst MRSA, VRE (equivalent to vancomycin but can be taken orally!)

147
Q

Anti folate SE

A
  1. Gastrointestinal disturbances (common) - Nausea, vomiting, and diarrhea
  2. Hypersensitivity/ allergic reactions - due to the products of sulpha
  3. Photosensitivity
  4. Renal
    – False increase in creatinine (ave 18%) (common) – .Nephrotoxicity, allergic nephritis
    – Crystalluria
  5. Hyperkalemia (with higher doses +/‐ renal impairment)
  6. Bone marrow suppression
    Megaloblastic anemia (Give folinic acid supplementation in special cases- pregnant, malnourished)
    May cause hemolytic reactions in G6PD patients Thrombocytopenia in high doses
148
Q

Sulphonamide clinical application

A

Lower urinary tract infections
Sulphadiazine+pyrimethamine: -1st line for toxoplasmosis
-2nd line for malaria.

149
Q

Trimethoprim clinical application

A
  1. Urinary tract infections
  2. P jaroveci pneumonia
  3. Toxoplasmosis
  4. Nocardiosis
150
Q

Cotrimoxazole DDI

A

Oral anticoagulants: Warfarin
Poss mechanisms: disrupts vitamin K synthesis; Enhance the antithrombotic effect

Methotrexate
Increase levels of methotrexate (by displacing warfarin/methotrexate from protein binding, decreased renal tubular elimination).

Hydantoin anticonvulsants: Phenytoin
Increase the half-life of phenytoin (by inhibiting its metabolism)

Sulfonylurea hypoglycemic agents
increase risk of hypoglycemia – monitor
– Poss mechanisms: protein binding displacement

2-4. Inhibit metabolism of drugs and displace bilirubin from albumin

151
Q

Fluroquinolone SE

A
  1. Gastrointestinal disturbances (common)
    - Nausea, vomiting, diarrhea and dyspepsia
  2. Central Nervous systems
    - Headache, agitation, insomnia, dizziness, rarely, hallucinations and seizures (elderly)
  3. Hypersensitivity
  4. Cardiac
    QT interval prolongaJon; Moxi> cipro, levo
  5. Articular Damage
    Arthopathy including arJcular carJlage damage, arthralgias, and joint swelling
  6. Tendinitis and tendon rupture (black box warning)
  7. Alterations in blood glucose
152
Q

Nitrofurantoin SE

A
  1. GIT disturbances - the principal adverse effects
  2. Hypersensitivity reactions (occasional and reversible): skin rash, pneumonitis, chills and fever
  3. Pulmonary interstitial fibrosis with chronic use, especially in the elderly
  4. Blood dyscrasias – neutropenia; hemolysis in infants and G6PD-deficient subjects
  5. Brown Urine
    **Best to avoid use in pregnancy and the elderly
153
Q

Fluroquinolone DDI

A

Divalent/trivalent cations (eg in antacid, enteral feeds, iron)
- Co‐administration reduce fluoroquinolone absorption
- Reduce fluoroquinolone conc > treatment failure
- Separate by at least 2‐4 hours

Warfarin:
increase anticoagulation effect

Drugs that can cause QTc prolongation (eg quinidine, procainamide, amiodarone
— increase QT risk

154
Q

Nitrofurantoin DDI

A

Antacid—–Reduce nitrofurantoin conc.

155
Q

Fluroquinolone Clinical application

A

1.Urinary tract infections
2.Gastroenteritis
3.Osteomyelitis
4.Anthrax
5. TB (2nd line)

156
Q

Nitrofurantoin uses

A
  1. Acute UTI
  2. Prophylaxis of lower UTI
157
Q

Fosfomycin Clinical application

A

Uncomplicated lower UTI (safe for pregnancy)

158
Q

Metronidazole DDI

A

Warfarin
Potentiate anticoagulant effect

Ethanol
Disulfiram like reaction

Lithium
Reduced Li renal elimination –> concentration

159
Q

Metronidazole clinical uses

A

Effective against amoebiasis, giardasis, anaerobic peritoneal infections (CDAD) and bacteremia, Helicobacter
pylori

160
Q

Polymyxin causes _______

A

Muscles weakness
Nephrotoxic

161
Q

Monobactam Side effect

A

Well tolerated has minimal side effects, occasionally some GI effects

MN Pharmacology (11 decks)

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