Antimicrobial Drugs

Front 1

Ways to achieve selective toxicity

Back 1

1. Target a process vital and unique to the invading organism
2. Use a toxic drug that can only be activated by invading organism
3. Selective uptake of a toxic compound by the invading organism

Front 2

Mechanisms of action of antimicrobials

Back 2

1. Inhibition of cell wall synthesis (penicillins)
2. Inhibition of protein synthesis (tetracyclines)
3. Destruction of cell membrane function (azole anti-fungals)
4. Altered nucleic acid synthesis (fluoroquinolones)
5. Miscellaneous (metronidazole)

Front 3

Treatment goal

Back 3

Maintain circulating concentrations of the drug above minimum inhibitory concentration (MIC)

Front 4

Toxicity of antibiotics- most common adverse effect

Back 4

GI effects most common-
by disturbing the normal flora, antibiotics can cause overgrowth of non-suceptible organisms

Examples- candidiasis, antibiotic-associated colitis (overgrowth of clostridium difficile caused by clindamycin, amoxicillin, amplicillin)

Front 5

Pharmacokinetic definition

Back 5

Time course of antimicrobial concentration in the body

Front 6

Pharmacodynamics definition

Back 6

Relationship between drug concentration and antimicrobial effect(s)

Front 7

Time-Dependent Killing definition

Back 7

amount of time that serum concentration is above the MIC
T>MIC is best predictor of efficacy

Front 8

Concentration-Dependent Killing definition

Back 8

Killing increases as concentration increases above the MIC
AUC and Cmax/MIC are best predictors of efficacy

Front 9

Antiseptics and Germicides MOA

Back 9

For external use only

Front 10

Inhibitors of Bacterial Cell Wall Synthesis

Back 10

Beta-lactam antibiotics, vancomycin, bacitracin, fosfomycin

Front 11

Beta-Lactam Antibiotic Properties

Back 11

1. Most important class of cell wall synthesis inhibitors
2. Bind covalently to bacterial proteins called penicillin binding proteins (PBPs)
3. Major toxicity: allergic reactions
4. Beta-lactam ring has to remain intact to be effective

Front 12

Major Groups of Beta-Lactam Antibiotics

Back 12

Penicillins, cephalosporins, carbapenems, monobactams

Front 13

Mechanism of action of beta-lactam antibiotics

Back 13

Covalently bind to enzymes (PBPs) in the bacterial cell membrane that function in the building and remodeling of the bacterial cell wall, an especially important process during cell division

Front 14

Dosing requirements of beta-lactam antibiotics

Back 14

Bactericidal, time-dependent killing --> frequent dosing required

Front 15

Beta-lactam antibiotics bacterial targets (generally)

Back 15

Active against growing bacteria (bactericidal)

Beta-lactam ring must remain intact

Front 16

Mode of elimination of beta-lactam antibiotics

Back 16

Excreted unchanged in urine
Require dosage adjustments for renally impaired patients

Front 17

Problems associated with beta-lactam antibiotics

Back 17

1. Allergic reactions
2. Non-allergic toxicity - CNS problems (lethargy, confusion, seizures) associated with high blood and CSF levels

Front 18

Primary mechanism of resistance to beta-lactam antibiotics

Back 18

Beta-lactamases: microbial enzymes that hydrolyze the beta-lactam ring

Front 19

Penicillin Properties

Back 19

1. Beta-lactam antibiotic
2. 2 ring structure
3. Rapidly excreted in urine as unchanged drug (parenteral administration- potential sodium overload)
4. Agent of choice for gram positive bacteria

Front 20

Groups of Penicillins

Back 20

1. Pen G and V
2. Beta-lactamase-resistant penicillins
3. Extended spectrum penicillins
4. Extended spectrum penicillins with beta-lactamase inhibitors

Front 21

Penicillins G and V- properties

Back 21

Narrow spectrum, gram positive
Short half life (~30 min), problem of sodium or potassium overload

Front 22

Insoluble salts for Penicillin G administration (names and MOA)

Back 22

Procaine Penicillin G, Benzathine Penicillin G
Administer via I.M. injection, slowly dissolve
NEVER administer I.V.

Front 23

MOA of Penicillin V

Back 23

Acid stable --> given orally

Front 24

Clinical uses of IM Benzathine Penicillin G

Back 24

1. Single injection to treat beta-hemolytic streptococci pharyngitis
2. Single weekly injections for 1-3 wks to treat syphilis

Front 25

Clinical uses of Pen V

Back 25

1. Minor infections (usually use Amoxicillin instead)
2. Spirochete infections (Gram negative, exception to general rule that beta-lactam antibiotics combat Gram positive organisms)

Front 26

Beta-lactamase-resistant penicillins, also known as...

Back 26

Anti-staphylcoccal penicillins

Front 27

Spectrum of Penicillins G and V

Back 27

Narrow spectrum, Gram positive

Front 28

Spectrum of beta-lactamase-resistant penicillins

Back 28

Narrow spectrum, Gram positive

Front 29

Main drugs that are beta-lactamase-resistant penicillins

Back 29

Oxacillin, nafcillin, cloxacillin, dicloxacillin

Front 30

MOA of Oxacillin and Nafcillin

Back 30

Parenterally

Front 31

Clinical uses of beta-lactamase-resistant penicillins

Back 31

1. Beta-lactamase producing Staphylococci
2. Used in conjunction with gentamicin for acute bacterial endocarditis
3. Cellulitis

Front 32

MOA of Cloxacillin and Dicloxacillin

Back 32

Orally (PO)

Front 33

Notable points for beta-lactamase-resistant penicillins

Back 33

1. MRSA is resistant to these agents
2. Food interferes with the absorption of these drugs

Front 34

Bacterial target of Extended Spectrum Penicillins

Back 34

Gram positive and Gram negative

Front 35

Main drugs that are Extended Spectrum Penicillins

Back 35

Ampicillin and Amoxicillin

Front 36

MOA of Ampicillin

Back 36

Parenteral and oral (poor absorption)

Front 37

MOA of Amoxicillin

Back 37

Oral only (absorbed well even with food)

Front 38

Clinical uses of Ampicillin

Back 38

Prophylaxis against endocarditis

Front 39

Clinical uses of Amoxicillin

Back 39

1. Acute otitis media/sinusitis
2. Lower respiratory infections
3. Prophylaxis against endocarditis

Front 40

Main drugs classified as Anti-Pseudomonal Penicillin

Back 40

Ticarcillin, Piperacillin

Front 41

MOA of Ticarcillin

Back 41

Parenteral

Front 42

Side effects of Ticarcillin

Back 42

Sodium overload, increased bleeding times

Front 43

Properties of Piperacillin

Back 43

1. Broadest spectrum of the penicillins
2. Best activity against pseudomonas
3. Susceptible to beta-lactamase inactivation

Front 44

MOA of Piperacillin

Back 44

Parenteral only

Front 45

Penicillin Pharmacokinetics

Back 45

1. Absorption decreased by food (except Amoxicillin)
--> take 1 hr before or 2 hrs after a meal
2. Distribution:
* extracellular water only
* enter CSF if inflammation
* poor penetration into eye, prostate, and CNS

Front 46

Caution in using Penicillin

Back 46

Patients with renal insufficiency- high levels of penicillin can build up and cause seizures

Front 47

Penicillin drugs that do not require dosage adjustments in renally impaired patients

Back 47

1. Nafcillin (excretion is biliary)
2. Oxacillin, dicloxacillin, cloxacillin (excretion is via kidney and biliary)

Front 48

Most common type of penicillin allergy (category)

Back 48

Delayed- days to weeks past exposure get skin rashes, pruritis, urticaria

[Other 2 catagories are immediate and accelerated]

Front 49

Test for Penicillin allergy

Back 49

beta-lactam ring may hydrolize and form a hapten (major determinant)
PPL is used to test for penicillin allergy

Front 50

Manifestations of Penicillin allergy

Back 50

1. Skin rashes
2. Angioedema
3. Anaphylaxis
4. Serum sickness
5. Hemolytic anemia
6. Neutropenia

Front 51

Non-allergic reactions to Penicillin

Back 51

1. CNS excitation
2. Reactions at injection site
3. Ampicillin rash (can also occur with amoxicillin) --> occurs in patients with infectious mononucleosis and lymphatic leukemia
4. Sodium overload with parental dosing
5. High dose oxacillin and nafcillin can cause hepatic abnormalities and impaired platelet function

Front 52

Drugs that are Beta-lactamase inhibitors

Back 52

Clavulanic Acid, Sulbactam, Tazobactam

Front 53

Properties of beta-lactamase inhibitors

Back 53

1. Poor antimicrobial effects
2. Irreversibly inhibit bacterial lactamases
3. Used only in combination with penicillins

Front 54

Augmentin- comination of drugs

Back 54

Clavulanic acid plus amoxicillin

Front 55

Notable use of beta-lactamase inhibitors

Back 55

Mixed aerobic and anaerobic infections such as intra-abdominal infections

Front 56

Properties of Cephalosporins

Back 56

1. Similar to penicillins chemically, MOA, toxicity profile
2. More stable than penicillins to many beta-lactamases
3. Broader spectrum of activity
4. Later generations have better Gram negative coverage and more resistance to beta-lactamases

Front 57

Reason why various cephalosporins have different pharmacokinetic properties and anti-bacterial activity

Back 57

3 R groups allows for numerous substitutions

Front 58

First generation cephalosporins- properties

Back 58

1. Extended spectrum
2. Effective against many Gram positive organisms
3. Effective against only a few Gram negative organisms
4. Primarily excreted in urine

Front 59

Notable clinical uses of Cephalosporins

Back 59

Cafazolin (parenteral) has good tissue penetration and often used for surgical prophylaxis (cardiac, thoracic, vascular, craniotomy, orthopedic, head and neck, C-section, etc.)

Front 60

Second generation of Cephalosporins- properties

Back 60

1. Extended spectrum
2. Same Gram positive coverage and better Gram negative coverage (notably Hemophilis influenzae and Neisseria gonorrhoea) compared to first generation
3. Some have activity against anaerobes --> Cefoxitin used for abdominal surgery prophylaxis

Front 61

Main surgical prophylaxis for anaerobe coverage

Back 61

Cefoxitin

Front 62

Notable uses of second generation Cephalosporins

Back 62

Surgical prophylaxis, sinusitis, otitis, lower respiratory tract infections

Front 63

Third generation Cephalosporins- properties

Back 63

1. Broad spectrum
2. Stable against most beta-lactamases
3. Tend to cross CSF better than other generations

Front 64

Notable clinical uses of third and fourth generation Cephalosporins

Back 64

Ceftriaxone and cefixime- treatment of gonorrhoeae
Ceftriaxone- treatment of meningitis from H. influenzae

Front 65

Cephalosporin toxicities

Back 65

1. DO NOT give cephalosporins to patients who have anaphylactic shock from penicillin
Cross reactivity of most 2nd, 3rd, 4th generation cephalosporins with penicillin is low
2. CNS excitation from high doses
3. Bleeding abnormalites and alcohol intolerance especially associated with NMTT side chain --> inhibits clotting factors

Front 66

Contraindications of cephalosporin use (cross drug reaction)

Back 66

Ceftriaxone (3rd generation cephalosporin used for gonorrheae and meningitis) should NOT be mixed with IV solutions containing calcium
- Fatalities in neonates
- Contraindicated for all ages
- Do not co-administer in same or different infusion lines or sites within 48 hrs of each other

Front 67

Main drug classified as a Carbapenem

Back 67

Imipenem

Front 68

Imipenem metabolized by...

Back 68

Dehydropeptidase in kidney

Front 69

What is coadministered with Imipenem and why

Back 69

Cilistatin is co-administered to block metabolism and nephrotoxicity

Front 70

Clinical uses of Carbapenems

Back 70

Drug of choice for enterobacter infections (nosocomial pathogens responsible for range of infections: lower respiratory tract, skin, soft tissue, UTI, opthalmic, etc.)

Front 71

Main drug classified as a Monobactam

Back 71

Aztreonam

Front 72

Notable feature of Aztreonam structure and its benefits

Back 72

Beta-lactam ring is not fused to the second ring --> low degree of cross allergenicity with other beta-lactam antibiotics

Front 73

Targets of Aztreonam

Back 73

Gram negative bacilli only (e.g. Pseudomonas Aeruginosa)

Front 74

Summary points of beta-lactams

Back 74

1. High degree of selective toxicity
2. Most bacteria respond to beta-lactams (resistance due to inactivation by beta-lactamases)
3. High incidence of allergic reactions (cross-allergic reactions can occur 5%)
4. Primarily renal excretion
5. CNS symptoms occur at high levels (Carbapenems most problematic)

Front 75

Benefit of other inhibitors of cell wall synthesis

Back 75

Do not contain beta-lactam rings and therefore are useful against beta-lactamase-producing bacteria

Front 76

Drugs with no beta-lactam ring that are cell wall synthesis inhibitors

Back 76

Vancomycin, Bacitracin, Fosfomycin

Front 77

MOA of Vancomycin

Back 77

Prevents cross-linking of peptidoglycan chains in cell wall

Front 78

Bacterial targets of Vancomycin

Back 78

Gram positive bacteria, particularly staphylococcus (*MRSA*) and flavobacterium

Front 79

Adverse side effects of Vancomycin

Back 79

1. Causes tissue necrosis if given IM
2. Must be given by slow IV infusion (too fast and get red man syndrome)
3. Nephrotoxic

Front 80

Notable clinical uses of Vancomycin

Back 80

MRSA, spesis, endocarditis, severe skin and soft tissue infection caused by MRSA, taken orally for antibiotic-resistant colitis (if resistant to metronidazole)

Front 81

Optimal dose of Vancomycin

Back 81

At least 10 mg/L serum concentration

Front 82

Uses of Bacitracin

Back 82

Used topically for surface lesions of skin, in wounds, and on mucous membranes

Front 83

Uses of Fosfomycin

Back 83

Urinary tract infections, single dose; safe for pregnant women

Front 84

Bacterial protein synthesis inhibitors- MOA

Back 84

Bacteriostatic (*except Aminoglycosides*)

Front 85

Main groups of Bacterial Protein Synthesis Inhibitors that bind 50S ribosome

Back 85

Macrolides, Lincosamides, Pleuromutilins, Streptogramins, Oxazolidinones

Front 86

General properties of Macrolides

Back 86

Bind 50 S Ribosome, extended spectrum

Front 87

Macrolide pharmacokinetics

Back 87

Hepatic elimination (can have drug interactions from altered CYP metabolism), varible half life, well distributed throughout body but do not enter CSF

Front 88

Major drugs classified as Macrolides (Bacterial Protein Synthesis Inhibitors which bind 50S ribosome)

Back 88

Erythromycin, Clarithromycin, Azithromycin

Front 89

Properties of Erythromycin

Back 89

1. Similar spectrum of activity to Penicillin G and often used in patients with penicillin allergy
2. Cross resistance complete between erythromycin and other macrolides

Front 90

Pharmacokinetics of Erythromycin

Back 90

1. Estolate salt is the best absorbed oral form
2. Ethylsuccinate commonly used for pediatric patients
3. Can displace other drugs from P450 enzyme

Front 91

Adverse side effects of erythromycin

Back 91

Acute cholestatic hepatitis (fever, jaundice, impaired liver function) --> allergic reaction

Front 92

Notable clinical uses of Erythromycin

Back 92

Penicillin allergic patients with staph, strep, or pneumococci infection are treated with erythromycin

Front 93

Organisms targeted by Clarithromycin

Back 93

Intracellular organisms (legionella, M. leprae, Toxoplasma gondii)

Front 94

Advantages of Clarithromycin over Erythromycin

Back 94

1. Relatively more potent
2. Acid stable
3. Better absorbed, less GI upset
4. Longer half life (BID dosing vs. QID for erythromycin)

Front 95

Advantages of Azithromycin

Back 95

1. Long half life (~3 days)- QD dosing
2. Not metabolized (doesn't affect metabolism of other drugs in liver)
3. Tissue:blood ratios (very low plasma levels)--> good distribution

Front 96

Notable clinical uses of Azithromycin

Back 96

Mild/moderate skin infections, lower respiratory infections, chlamydial infection of urethra and cervix, community acquired pneumonia, acute bacterial sinusitis, bacterial conjunctivitis

Front 97

Telithromycin

Back 97

Another macrolide, increased activity against bacteria that have become resistant to to other macrolides

Front 98

Caution about Telithromycin

Back 98

Serious hepatotoxicity

Front 99

Notable clinical uses of Telithromycin

Back 99

Respiratory tract infection (pneumonia, bronchitis, pharyngitis, sinusitis)

Front 100

Major drug classified as a Lincosamide

Back 100

Clindamycin

Front 101

Properties of Clindamycin

Back 101

1. Highly effective against anaerobic pathogens, including Bacteroides Fragilis
2. Excellent penetration into bone
3. Antibiotic-associated colitis is a concern --> caused by overgrowth of C. difficile

Front 102

Treatment of C. Difficile

Back 102

Metronidazole or Vancomycin

Front 103

Notable clinical use of clindamycin

Back 103

Treat severe anaerobic infections (bacteroides)

Front 104

Major drug classified as a Pleuromutilin

Back 104

Retapamulin

Front 105

MOA of Retapamulin

Back 105

Binds to 50S ribosome and inhibits protein synthesis

Front 106

Clinical use of Retapamulin

Back 106

Active against MRSA

Front 107

Clinical use of Chloramphenicol

Back 107

Salmonella
Effective against anaerobes

Rickettsial infections
Meningococcal meningitis

Front 108

Unique property of chloramphenicol and clinical implication

Back 108

Highly lipophilic, excellent penetration into CSF, ocular, and joint fluids

Front 109

Toxicity of chloramphenicol

Back 109

Aplastic anemia due to stem cell damage (low RBC, WBC, PLT)
Grey Baby Syndrome

Front 110

Main drugs classified as Streptogramins

Back 110

Quinupristin, Dalfopristin

Front 111

Combination of Quinupristin and Dalfopristin

Back 111

Synergistic--> bactericidal (drug named Synercid)

Front 112

Primary use of Quinupristin and Dalfopristin combo (Synercid)--->Streptogramins

Back 112

Used for bacteria resistance to older drugs (MRSA, vancomycin-resistant E. faecium)

Front 113

Indications for Streptogramins use

Back 113

Infections from vancomycin-resistant strains of E. faecium

Front 114

Major drug classified as Oxazolidinones

Back 114

Linezolid

Front 115

Unique property of Linezolid

Back 115

Unique ribosome binding sites

Front 116

Indication for Linezolid use

Back 116

Indicated for bacteria resistant to other protein synthesis inhibitors

Front 117

Clinical use of Oxazolidinones

Back 117

Reserved for treatment of infection caused by multiple drug resistant gram positive bacteria

Front 118

Properties of 50S Ribosomal Inhibitors

Back 118

Bacteriostatic, gram positive spectrum significant, non-renal elimination

Front 119

Antibiotics that bind 30S bacterial ribosome

Back 119

Tetracyclines, Aminoglycosides, Spectinomycin

Front 120

Tetracycline properties

Back 120

Broad spectrum, bacteriostatic, absorption decreased by food (drug interactions with antacids, calcium, iron)

Front 121

Main resistance mechanism for tetracyclines

Back 121

Drug export

Front 122

Major drugs classified as Tetracyclines

Back 122

Tetracycline (short-acting), Doxycline (long-acting)

Front 123

Caution when using tetracyclines

Back 123

Tetracyclines form insoluble complexes with cations found in antacids, multivitamins, dairy products

Front 124

Advantage of doxycline and minocycline

Back 124

Well absorbed with food

Front 125

Disadvantage of tetracyclines

Back 125

Do not go into CSF well

Front 126

Advantage of tetracyclines

Back 126

High concentrations in skin, saliva--> dermatological and dental uses

Front 127

Which tetracycline is drug of choice for renally impaired patients and why

Back 127

Doxycycline is used in renally impaired patients because excreted in feces

Front 128

Adverse effects of tetracyclines

Back 128

Suprainfections (overgrowth in gut), damage to developing teeth and bone, phototoxicity, renal toxicity

Front 129

Patients who cannot take tetracycline

Back 129

Pregnant women and children under 8 yrs old

Front 130

Instance when tetracycline causes renal toxicity

Back 130

Taking expired tetracycline, patients advised to discard outdated tetracycline

Front 131

Clinical uses of tetracyclines

Back 131

Lyme disease, STDs (gonorrhea, syphillis, chlamydia)

Acne, entamoeba histolytica, rickettsial infection,

Front 132

Drug of choice among tetracyclines

Back 132

Doxycycline

Front 133

New tetracycline drug and its advantages

Back 133

Tigecycline used for complicated skin and intra-abdominal infections, CANNOT be given to pregnant women or children under 8 yrs old

Front 134

Major drugs classified as Aminoglycosides

Back 134

Amikacin, Tobramycin, Streptomycin, Gentamicin

Front 135

Unique MOA of aminoglycosides as compared to other protein synthesis inhibitors

Back 135

Bactericidal- bind 30S ribosome and compromise integrity of membrane

Front 136

Properties of aminoglycosides

Back 136

Extended spectrum, anti-mycobacterial activity, only useful for aerobic organisms,has post-antibiotic effects, eliminated via kidney

Front 137

Bacteria targeted by aminoglycosides

Back 137

Gram negative bacteremia/sepsis and for pseudomonas aeruginosa infections

Front 138

Resistance mechanism against aminoglycosides

Back 138

Modification of aminoglycosides by bacterial enzymes

Front 139

Toxicity of aminoglycosides

Back 139

Concentration and time dependent, nephrotoxic, ototoxic (vestibular > auditory)

Front 140

Patients who shouldn't be given aminoglycoside

Back 140

Patients with neuromuscular disease

Front 141

Dosing of aminoglycoside

Back 141

Every 8 hours, alternative single dosing

Front 142

Combination therapy seen in aminoglycosides

Back 142

Aminoglycosides work synergistically with beta-lactam antibiotics to treat severe infections

Front 143

Caution when using aminoglycoside + beta-lactam antibiotic combination

Back 143

Do not mix aminoglycoside and beta-lactam antibiotic in the same injection solution, they will chemically inactivate one another

Front 144

Drugs classified as aminoglycosides

Back 144

Gentamicin, Tobramycin, Neomycin, Kanamycin

Front 145

Clinical use of gentamicin

Back 145

Gentamicin- Aminoglycoside (30S subunit protein synthesis inhibitor)

Gram negative infections, used synergistically with beta-lactams to treat severe infections (sepsis and pneumonia) that resist other antibiotics [seen in immunocompromised patients]

Front 146

Clinical use of tobramycin

Back 146

Active against pseudomonas aeruginosa

Front 147

Clinical use of neomycin and kanamycin

Back 147

Topically on surface wounds

Front 148

Drugs classified as nucleic acid inhibitors

Back 148

Fluoroquinolones, rifamycins, metronidazole, sulfonamides and trimethoprim

Front 149

Quinolones properties- mechanism of action and bacteria targeted

Back 149

Bactericidal- inhibit DNA gyrase (Inhibitor of Nucleic Acid Synthesis), highly effective against Gram negative bacteria

Front 150

Classic generation 2 quinolone (fluoroquinolone) drug

Back 150

Ciprofloxacin- treat meningitis caused by p. aeruginosa

Front 151

Subdivisions of fluoroquinolones and their properties

Back 151

Generation 1- some Gram negative coverage
Generation 2- excellent Gram negative activity
Generation 3- adds Gram positive bacteria, excellent for strep pneumoniae
Generation 4- effective against anaerobes

Front 152

Classic generation 3 quinolone (fluoroquinolone) drug

Back 152

Levofloxacin- treat strep. pneumoniae

Front 153

Classic generation 4 quinolone (fluoroquinolone) drug

Back 153

Moxifloxacin- effective against anaerobes

Front 154

Absorption, distribution and excretion of fluoroquinolones

Back 154

Orally effective but drug interactions with cations, penetrate well into prostate and bone, excreted renally (longer acting ones excreted by liver)

Front 155

Adverse effects of fluoroquinolones

Back 155

Fluoroquinolones:

1. Effects on cartilage development (permanent in animals)
Contraindicated for pregnancy and for children <18 yrs old
2. Prolonged QT interval (with sparfloxacin)
3. Crystalluria --> especially with norfloxacin
Have to drink copious amounts of water

Front 156

Notable clinical uses of fluorquinolones

Back 156

Fluorquinolones:

1. Most Gram negative organisms
2. Excellent pseudomonas activity
3. Prostatitis
4. Soft tissue, bone, joint, intra-abdominal and respiratory infections (except norfloxacin b/c of poor gut absorption)

Front 157

Drugs classfied as Rifamycins

Back 157

Rifampin, Rifabutin, Rifapentin, Rifaxamin

Front 158

MOA of Rifamycins

Back 158

Inhibit bacterial RNA polymerase

Front 159

Rifamycin- common use

Back 159

Not used alone, most commonly used in treatment of mycobacterial diseases (especially TB)

Front 160

Weird side effect of Metronidazole

Back 160

Black furry tongue

Front 161

Weird side effect of Riframycins

Back 161

Red coloration of skin, eyes, urine

Front 162

Metronidazole bacterial target

Back 162

Anaerobic bacteria (Bacteriodes and Clostridium)
and E. histolytica

Front 163

Side effect of Metronidazole

Back 163

Disulfiram-like effect (NMTT side chain, alcohol --> projectile vomit

Front 164

Clinical uses of Metronidazole

Back 164

Antibiotic-associated enterocolitis

Front 165

Drawback of inhibitors of cell membrane function

Back 165

Too toxic for routine use

Front 166

Drugs classified as inhibitors of cell membrane function

Back 166

Polymixin B, Colistin (Polymixin E), Daptomycin

Front 167

Advantage of Polymixin B

Back 167

Excellent for pseudomonas

Front 168

Uses of Daptomycin

Back 168

Indicated for Gram positive organisms that are resistant to other drugs (MRSA), used for skin and soft tissue infections

Front 169

Drugs classified as inhibitors of intermediary metabolism

Back 169

Sulfonamides, Trimethoprim

Front 170

MOA of sulfa drugs

Back 170

Compete with para-aminobenzoic acid (PABA) for enzyme dihydropteroate synthase
Bacteriostatic

Front 171

Antimicrobial activity (generally) of sulfonamides

Back 171

Broad spectrum

Front 172

Distribution of Sulfonamide

Back 172

Lipophillic drug --> highly protein bound in serum, can displace other protein-bound drugs and proteins and limits renal elimination of sulfonamides

Front 173

Sulfonamide toxicity

Back 173

Crystalluria, Kernicterus in neonates, Stevens-Johnson Syndrome

Front 174

Prevention of crystalluria in sulfa drugs

Back 174

1. High fluid intake
2. Alkalinization of urine
3. Use mix of sulfa drugs so each drug dose is lower than would be taken individually

Front 175

Description of Steven Johnson Syndrome

Back 175

Skin and membrane eruption, detachment of epidermis, potentially fatal

Front 176

Notable clinical uses of sulfanomides

Back 176

UTIs, topical treatment of burns, bacterial conjunctivitis

Front 177

MOA of Trimethoprim

Back 177

Inhibits dihydrofolate reductase

Front 178

Combination of Trimethoprim and sulfamethoxazole

Back 178

Synergistic effect (Bactrim is the name of the combo)

Front 179

Patients who should not receive Bactrim

Back 179

AIDS patients with PCP

Front 180

Most common cause of UTIs

Back 180

E. Coli (~80% of cases)- a Gram negative bacteria

Front 181

Drugs classified as urinary antiseptics

Back 181

Methenamine and Nitrofurantoin

Front 182

MOA of Methenamine

Back 182

Releases formaldehyde into acidic environment (urine)

Front 183

Clinical use of Nitrofurantoin

Back 183

Used in patients with recurrent UTIs

Front 184

Patients who should not take Nitrofurantoin and toxic result

Back 184

Patients with glucose-6-phosphate dehydrogenase deficiency, get hemolytic anemia and peripheral neuropathy

Front 185

MOA of Fosfomycin

Back 185

Inhibits pyruvyl transferase (cell wall synthesis enzyme)
Single dose (3 g) cure uncomplicated UTI
Safe for pregnant patients

Front 186

General treatment strategy for mycobacterial disease

Back 186

Long-term treatment with combinations of drugs

Front 187

Challenges of treating mycobacterial infections

Back 187

1. Mycobacteria grow slowly
2. Lipid rich cell wall- keeps out drugs
3. Intracellular pathogens
4. Quick to develop resistance

Front 188

Primary antitubercular drugs

Back 188

Isoniazid (INH), Rifampin, Pyrazinamide, Ethambutol

Front 189

Drug of choice for prophylaxis and therapy of TB

Back 189

Isoniazid

Front 190

MOA of Isoniazid

Back 190

Inhibits mycolic acid biosynthesis (cell wall)

Front 191

Adverse effects of isoniazid

Back 191

Hepatotoxic, given with pyridoxine (vitamin B6) to prevent peripheral neuropathy (adults) and convulsions (kids), dose adjustment for slow/fast acetylators

Front 192

Most frequent major toxicity of isoniazid

Back 192

Hepatitis (1% of patients), can be fatal and must discontinue therapy immediately if occurs

Front 193

Most common drug used in combination with isoniazid to combat TB

Back 193

Rifampin

Front 194

Adverse effects of Rifampin

Back 194

1. Induces liver P450 enzymes (oral contraceptives don't work)
2. Red-orange color of urine, tears, body fluids
3. Hepatotoxic (cholestatic jaundice and hepatitis)

Front 195

Replacement drug for Rifampin in AIDS patients

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Rifabutin recommended in place of Rifampin for AIDS patients taking protease inhibitors or NNRTIs

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MOA of ethambutol

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Inhibits mycobacterial cell wall synthesis by blocking arabinosyl transferase

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Adverse side effect of ethambutol

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Retrobulbar neuritis- loss of visual acuity, red-green color blindness, vision checks recommended regularly

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Use of pyrazinamide

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Highly effective as combo therapy with INH and rifampin for short term (6 mo.) anti-TB regimens

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Adverse effect of pyrazinamide

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Liver toxicity (1-5% of patients)

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Standard 4 drug regimen for TB

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Isoniazid, rifampin, pyrazinamide, ethambutol

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Second-line TB drug

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Streptomycin sulfate, used when an injectable drug is needed

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Drug of choice for leprosy

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Dapsone

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Administration of dapsone

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Once a week dosing (similar to sulfonamides)

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Other treatment option for leprosy besides Dapsone

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Rifampin

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Most important use of antimicrobial prophylaxis

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Bacterial endocarditis

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Patients who should receive prophylactic antibiotics in dentistry to prevent bacterial endocarditis

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Only those at highest risk (prosthetic heart valve, positive history for bacterial endocarditis, congenital heart disease, etc.)

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Drugs to treat mycobacteria

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Anti-TB
Rifamycin, Combo Therapy: Isoniazid, Rifampin,Ethambutol, Pyrazinamide, Streptomycin Sulfate (second line therapy)
Anti-Leprosy
Dapson, Rifampin

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Drugs to treat anaerobic bacteria

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Second generation Cephalosporin (Cefoxitin), Beta-lactamase inhibitors, Clindamycin (Lincosamide that combats Bacteroides Fragilis), Macrolide (Chloramphenicol), Metronidazole (combats Bacteroides, Clostridium, E. Histolytica)

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Drugs to treat pseudomonas

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Piperacillin, Aztreonam, Aminoglycosides (Tobramycin), Fluoroquinolones (Ciprofloxacin),

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Drugs to treat MRSA

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Vancomycin, Linezolid, Daptomycin (except if pneumonia)

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Drugs to treat meningitis

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Ceftriaxone (for meningitis caused by H.Influenzae)