Block 3 ALL Flashcards
What are the penicillinase-sensitive penicillin’s?
What are they used to treat?
These include Amino-penicillin’s (Amoxicillin & Ampicillin
Treat: gram +ve & gram -ve infections:
- Acute otitis media
- Syphilis
- Rheumatic fever
- Strep pharyngitis
- Listeria
- H. pylori (Amoxicillin)
What are penicillin V & G
G penicillin (natural)
V penicillin (acid-resistant)
beta-lactam antibiotics
D-Ala-D-Ala structural analog bind & block PBP to inhibit cell wall synthesis
Treats:
1) Mainly gram-positive organisms (Streptococcus spp., Actinomyces)
2) Some gram-negative cocci (N. meningitidis) and spirochetes (T. pallidum)
Adverse Effects:
1) hypersensitivity reactions
2) Direct Coombs +ve hemolytic anemia
3) Interstitial nephritis
4) Pseudomembranous colitis
beta-lactam antibiotics
D-Ala-D-Ala structural analog bind & block PBP to inhibit cell wall synthesis
Treats:
1) Mainly gram-positive organisms (Streptococcus spp., Actinomyces)
2) Some gram-negative cocci (N. meningitidis) and spirochetes (T. pallidum)
Adverse Effects:
1) hypersensitivity reactions
2) Direct Coombs +ve hemolytic anemia
3) Interstitial nephritis
4) Pseudomembranous colitis
G penicillin (natural)
V penicillin (acid-resistant)
What are the Amino penicillin’s & what do they treat?
Adverse reaction?
gram +ve & gram -ve infections:
H. pylori (Amoxicillin)
H. influenzae
E. coli
Listeria monocytogenes
Proteus mirabilis
Salmonella
Shigella
Enterococci
Adverse Effects:
1) hypersensitivity reactions
2) Direct Coombs +ve hemolytic anemia
3) Interstitial nephritis
4) Pseudomembranous colitis
These include Amoxicillin (oral) & Ampicillin (IV)
HHEELPSSS
What are the penicillinase-Resistant penicillin’s?
What are they used to treat?
Adverse effects?
They have bulky R groups that block access to their beta-lactam rings making them resistant to cleavage by penicillinase enzymes.
They are a great narrow spectrum antibiotic for S. aureus infections (except MRSA) (gram +ve species)
Includes:
Methicillin
Cloxacillin
Dicloxacillin
Naficillin
Oxacillin
Adverse Effects:
1) hypersensitivity reactions
2) Direct Coombs +ve hemolytic anemia
3) Interstitial nephritis
4) Pseudomembranous colitis
They have bulky R groups that block access to their beta-lactam rings making them resistant to cleavage by penicillinase enzymes.
They are a great narrow spectrum antibiotic for S. aureus infections (except MRSA) (gram +ve species)
Includes:
Methicillin
Cloxacillin
Dicloxacillin
Naficillin
Oxacillin
Adverse Effects:
1) hypersensitivity reactions
2) Direct Coombs +ve hemolytic anemia
3) Interstitial nephritis
4) Pseudomembranous colitis
penicillinase-Resistant penicillin’s
What are two ways that bacteria can become resistant to penicillin?
1) by making penicillinases that cleave the beta-lactam rings of penicillin (use beta lactamase inhibitors to avoid this!)
2) by mutating the transpeptidases that penicillin’s target so the penicillin can no longer bind (PBP mutations)
Which drug should be added to a drug regime with a penicillinase-sensitive penicillin?
Give a beta-lactamase (penicillinase) inhibitor like clavulanic acid, sulbactam, & tazobactam)
Which beta lactamase inhibitor should you give with Amoxicillin?
Which beta lactamase inhibitor should you give with Ampicillin?
Which beta lactamase inhibitor should you give with Ticarcillin?
Which beta lactamase inhibitor should you give with Piperacillin?
Amoxicillin-Clavulanate (Augmentin)
Ampicillin-Sulbactam (Unasyn)
Ticarcillin-Clavulanate
Piperacillin-Tazobactam
clavulanic acid, sulbactam, & tazobactam are all examples of which type of drug?
beta-lactamase (penicillinase) inhibitor
How does S. aureus become resistant to penicillin?
Mutations in penicillin-binding proteins (PBPs) the beta-lactam cannot bind to PBPs
What is penicillin?
What is the MOA?
Adverse effects?
A beta-lactam antibiotic
(aka D-Ala D-Ala analogue) that inhibits cell wall synthesis by competing with bacterial D-Ala D-Ala for enzymes & binding PBP (transpeptidases) to block cell wall cross-linking via peptidoglycans & activating autolytic enzymes.
Adverse Effects:
1) hypersensitivity reactions
2) Direct Coombs +ve hemolytic anemia
3) Interstitial nephritis
4) Pseudomembranous colitis
A beta-lactam antibiotic
(aka D-Ala D-Ala analogue) that inhibits cell wall synthesis by competing with bacterial D-Ala D-Ala for enzymes & binding PBP (transpeptidases) to block cell wall cross-linking via peptidoglycans & activating autolytic enzymes.
Adverse Effects:
1) hypersensitivity reactions
2) Direct Coombs +ve hemolytic anemia
3) Interstitial nephritis
4) Pseudomembranous colitis
Penicillin
Which penicillin subtypes are involved in preventing cell wall synthesis (via B-lactams & PBPs)?
1) Penicillin-Sensitive Penicillin’s
2) Penicillin-Resistant Penicillin’s
3) Antipseudomonal penicillin’s
4) G & V penicillin’s
Which penicillin subtypes are involved in inhibiting peptidoglycan synthesis?
Vancomycin & Bacitracin
both are Beta lactam analogs that bind PBP to inhibit peptidoglycan formation & cross linking to inhibit cell wall building
which type of penicillin is most effective against Pseudomonas aeruginosa?
Antipseudomonal penicillin’s like
Piperacillin, Ticarcillin or Carbenicillin
What is vancomycin?
What is the MOA?
What is it used to treat?
Adverse effects?
Conferred resistance?
Glycopeptide antibiotic
MOA:
1) It inhibits cell wall peptidoglycan formation by binding D-Ala-D-Ala portion of cell wall precursors
Clinical use:
gram-positive bacteria only
**C.difficile
*MRSA
Others:
S. epidermidis &
Enterococci
Adverse effects:
1) Nephrotoxicity
2) Ototoxicity
3) Thrombophlebitis
4) Red Man Syndrome (Vancomycin infusion reaction)
6) DRESS syndrome
Organisms can modify the amino acids of D-Ala D-Ala to D- Ala D-Lac to confer resistance
(not susceptible to β-lactamases)
Glycopeptide antibiotic
MOA:
1) It inhibits cell wall peptidoglycan formation by binding D-Ala-D-Ala portion of cell wall precursors
2) It also indirectly prevents transpeptidation
Clinical use:
#1 Best for treating C. difficile given orally for pseudomembranous colitis
Other:
- MRSA
- S. epidermidis
- Enterococcus species
Adverse effects:
1) Nephrotoxicity
2) Ototoxicity
3) Thrombophlebitis
4) Red Man Syndrome (Vancomycin infusion reaction)
6) DRESS syndrome
Organisms can modify the amino acids of D-Ala D-Ala to D- Ala D-Lac to confer resistance
(not susceptible to β-lactamases)
Vancomycin
What is DRESS syndrome?
aka Drug reaction with eosinophilia and systemic symptoms
Manifestations include fever, lymphadenopathy, a diffuse rash, facial edema, and eosinophilia.
Patient presents with hot tub folliculitis, nosocomial pneumonia, nosocomial UTI
Microscopy shows motile gram-negative bacteria, catalase positive, oxidase positive.
What is the likely organism?
&
Which type of penicillin’s would you give?
Likely organism:
Pseudomonas aeruginosa infections
Treatment:
Give an Antipseudomonal Antibiotics like:
Penicillin’s
Carbenicillin, Piperacillin, or ticarcillin.
Patient presents with hot tub folliculitis, nosocomial pneumonia, nosocomial UTI
Microscopy shows motile gram-negative bacteria, catalase positive, oxidase positive.
What is the likely organism?
&
Which type of Carbapenems would you give?
Likely organism:
Pseudomonas aeruginosa infections
Treatment:
Give an Antipseudomonal Antibiotics like:
Carbapenems
Meropenem, Imipenem
Patient presents with hot tub folliculitis, nosocomial pneumonia, nosocomial UTI
Microscopy shows motile gram-negative bacteria, catalase positive, oxidase positive.
What is the likely organism?
&
Which type of Aminoglycosides would you give?
Aminoglycosides: Gentamicin, Amikacin, Tobramycin
Patient presents with hot tub folliculitis, nosocomial pneumonia, nosocomial UTI
Microscopy shows motile gram-negative bacteria, catalase positive, oxidase positive.
What is the likely organism?
&
Which type of Quinolones would you give?
Likely organism:
Pseudomonas aeruginosa infections
Treatment:
Give an Antipseudomonal Antibiotics like:
Quinolones
Ciprofloxacin, Levofloxacin
Patient presents with hot tub folliculitis, nosocomial pneumonia, nosocomial UTI
Microscopy shows motile gram-negative bacteria, catalase positive, oxidase positive.
What is the likely organism?
&
Which type of Polymyxins would you give?
Likely organism:
Pseudomonas aeruginosa infections
Treatment:
Give an Antipseudomonal Antibiotics like:
Polymyxins
Polymyxin B and Colistin
Patient presents with hot tub folliculitis, nosocomial pneumonia, nosocomial UTI
Microscopy shows motile gram-negative bacteria, catalase positive, oxidase positive.
What is the likely organism?
&
Which type of Monobactam would you give?
Likely organism:
Pseudomonas aeruginosa infections
Treatment:
Give an Antipseudomonal Antibiotics like:
Monobactam
Aztreonam
Patient presents with hot tub folliculitis, nosocomial pneumonia, nosocomial UTI
Microscopy shows motile gram-negative bacteria, catalase positive, oxidase positive.
What is the likely organism?
&
Which type of Cephalosporins would you give?
Likely organism:
Pseudomonas aeruginosa infections
Treatment:
Give an Antipseudomonal Antibiotics like:
Cephalosporins
3rd gen Ceftazidime &
Cefoperazone
4th gen Cefepime & Cefpirome
Microscopy shows motile gram-negative bacteria, catalase positive, oxidase positive.
What is the organism?
Pseudomonas aeruginosa
What are Carbapenems?
- 4 drugs
What is their MOA?
What are they used to treat?
Adverse effects?
Resistance?
Antipseudomonal Carbapenems
Imipenem
Meropenem
Ertapenem
Doripenem
MOA:
Beta-lactam antibiotics (DAlaDAla analogs) that bind & block PBP to prevent cross-linking of peptidoglycans thereby inhibiting cell wall synthesis
Clinical indications (broad spectrum β-lactamase resistant)
**Last-resort drugs
1. Pseudomonas aeruginosa infection
- Gram-positive cocci; except for MRSA
Adverse Effects:
1) GI distress
2) Rash
3) CNS toxicity (seizures) at high plasma levels
4) confusion
Mechanism of Resistance: They are inactivated by carbapenems (K. pneumonia, E. coli, E. aerogenes)
Imipenem
Meropenem
Ertapenem
Doripenem
MOA: These are broad spectrum β-lactamase resistant carbapenems
Clinical Indications:
Pseudomonas aeruginosa infection
Adverse Effects:
1) GI distress
2) Rash
3) CNS toxicity (seizures) at high plasma levels
4) confusion
Mechanism of Resistance: They are inactivated by carbapenems (K. pneumonia, E. coli, E. aerogenes)
Antipseudomonal Carbapenems
Why are carbapenems always given with cilastatin?
Cilastatin is a renal dehydroepeptidase inhibitor to reduce inactivation of the drug in renal tubules.
Which carbapenem has the lowest risk of seizures?
Meropenem
What are the antipseudomonal penicillin’s?
- 3 drugs
What is their MOA?
What are their adverse effects?
Antipseudomonal Penicillin’s are Carbenicillin, Piperacillin, & ticarcillin.
MOA:
They are D-Ala-D-Ala analogs (B-lactams) that block transpeptidase peptidoglycan cross-linking & they bind PBP (transpeptidases) to activate autolytic enzymes to trigger lysis
Adverse Effects:
1) hypersensitivity reactions
2) Direct Coombs +ve hemolytic anemia
3) Interstitial nephritis
4) Pseudomembranous colitis
What are cephalosporins?
What is their MOA?
Cephalosporins (beta-lactam antibiotics)
MOA:
β-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases & they bind PBP (transpeptidases) to activate autolytic enzymes to trigger lysis
Adverse Effects:
1) hypersensitivity reactions
2) autoimmune hemolytic anemia
3) disulfiram-like reaction
4) vitamin K deficiency
Mechanism of Resistance: inactivated by cephalosporinases (type of β-lactamase) –– structural change in PBPs
What is a concern when giving Cephalosporins with aminoglycosides?
There is a low rate of cross-reactivity even in penicillin-allergic patients resulting in an increase in nephrotoxicity
What is the MOA of Beta lactam antibiotics?
I.e All of these!
*Cephalosporins:
3rd gen:
Ceftriaxone
Cefotaxime
Cefpodoxime
Ceftazidime
4th gen:
Cefepime
*Antipseudomonal Penicillin’s are Carbenicillin, Piperacillin, & ticarcillin
*Penicillin
- Penicillin-sensitive penicillinase are Penicillin G & V, Ampicillin & Amoxicillin
- Penicillin-resistant penicillinase are Methicillin, Cloxacillin, & Dicloxacillin
*Antipseudomonal Carbapenems
Imipenem
Meropenem
Ertapenem
Doripenem
PBP/transpeptidase Inhibitor prevents cross linking of peptidoglycan to weaken the cell wall & trigger lysis
Which antipseudomonal penicillin’s are considered Ureidopenicillins?
Piperacillin & Mezlocillin
Which antipseudomonal penicillin’s are considered Carboxypenicillin?
Carbenicillin & Ticarcillin
What are cephalosporins?
What is their MOA?
What are they used to treat?
Cephalosporins:
1st: Cefazolin
2nd: Cefotetan
3rd gen: ceftriaxone, cefotaxime, cefpodoxime, & ceftazidime
4th gen: cefepime & Cefpirome
5th: Ceftaroline & Ceftobiprole
MOA:
β-lactam antibiotic (transpeptidase/PBP inhibitor) that inhibits cell wall synthesis but that is less susceptible to penicillinases
AE:
1) Hypersensitivity (allergy) most common with cefazolin
2) Autoimmune hemolytic anemia (+ve Coombs test)
3) Disulfiram-like reaction to alcohol
4) Vitamin K deficiency
5) Increases nephrotoxicity of aminoglycosides
1st: Cefazolin
2nd: Cefotetan
3rd gen: ceftriaxone, cefotaxime, cefpodoxime, & ceftazidime
4th gen: cefepime & Cefpirome
5th: Ceftaroline & Ceftobiprole
MOA:
β-lactam antibiotic (transpeptidase/PBP inhibitor) that inhibits cell wall synthesis but that is less susceptible to penicillinases
AE:
1) Hypersensitivity (allergy) most common with cefazolin
2) Autoimmune hemolytic anemia (+ve Coombs test)
3) Disulfiram-like reaction to alcohol
4) Vitamin K deficiency
5) Increases nephrotoxicity of aminoglycosides
Cephalosporins
How do bacteria develop resistance against Cephalosporin drugs? (2 ways)
Cephalosporins get inactivated by cephalosporinases (type of β-lactamase) or structural change in PBPs
What are the most important 5th generation cephalosporins used to treat MRSA & VRSA infections?
5th: Ceftaroline & Ceftobiprole
4th generation cephalosporin drugs useful for treating life-threatning pseudomonas infection
Cefepime
A 1st gen cephalosporin good for pre op prep in surgery because it’s targeted at gram +ve bacteria.
Cefazolin
What are the most important 2nd & third generation cephalosporins that are effective in treating gram -ve bacteria?
2nd: Cefotetan
3rd gen: ceftriaxone, cefotaxime, cefpodoxime, & ceftazidime
What is Aztreonam?
What are the adverse effects?
Monobactam (Beta-lactam antibiotic)
MOA:
It is less susceptible to β-lactamases & it prevents peptidoglycan cross-linking by binding to penicillin-binding protein 3 (PBP3) it treats gram -ve infections (E.coli & pseudomonas)
Its Synergistic with aminoglycosides
Adverse Effects:
1) Gi upset
2) Phlebitis
3) Skin rash
4) Occasional liver dysfunction
only good for gram -ve bacteria (E.coli & pseudomonas) & it has no cross reactivity! (good for penicillin allergies)
Monobactam (Beta-lactam antibiotic)
MOA:
It is less susceptible to β-lactamases & it prevents peptidoglycan cross-linking by binding to penicillin-binding protein 3 (PBP3) it treats gram -ve infections (E.coli & pseudomonas)
Its Synergistic with aminoglycosides
Adverse Effects:
1) Gi upset
2) Phlebitis
3) Skin rash
4) Occasional liver dysfunction
only good for gram -ve bacteria (E.coli & pseudomonas) & it has no cross reactivity! (good for penicillin allergies)
Aztreonam
What are Polymyxins (Colistin [polymyxin E], polymyxin B)? What are their adverse effects?
MOA:
Cation polypeptides that bind to phospholipids on cell membrane of gram-negative bacteria to disrupt the cell membranes integrity leading to leakage of cellular components and subsequent cell death
Adverse Effects:
1) nephrotoxicity
2) neurotoxicity (slurred speech, weakness, paresthesia)
3) respiratory failure
MOA:
Cation polypeptides that bind to phospholipids on cell membrane of gram-negative bacteria to disrupt the cell membranes integrity leading to leakage of cellular components and subsequent cell death
Adverse Effects:
1) nephrotoxicity
2) neurotoxicity (slurred speech, weakness, paresthesia)
3) respiratory failure
Polymyxins (Colistin [polymyxin E], polymyxin B)
Imipenem, Meropenem, Doripenem, & Ertapenem are all considered which class of drug?
Carbapenems, they are synthetic beta-lactam antibiotics
Carbapenems, they are synthetic beta-lactam antibiotics include with 4 drugs?
Imipenem, Meropenem, Doripenem, & Ertapenem
Which carbapenem can cause nephrotoxicity & why?
Imipenem because it is metabolized in the kidney into an inactive form which can be toxic
Which drug do you co-administer with imipenem to avoid nephrotoxicity?
Cilastatin
Cefazolin
1st gen cephalosporin
Cefotetan & cefotaxime
2nd gen cephalosporins
ceftriaxone, cefotaxime, cefpodoxime, & ceftazidime
3rd gen cephalosporins
cefepime & Cefpirome
4th gen cephalosporins
Ceftaroline & Ceftobiprole
5th gen cephalosporin
What are Beta-lactam inhibitors?
They bind Beta-lactam enzymes & prevent them from inactivating antibiotics these include Clavulanic acid, Sulbactam & Tazobactam
Clavulanic acid, Sulbactam & Tazobactam are examples of which type of drug?
Beta-lactam inhibitors that bind Beta-lactam enzymes & prevent them from inactivating antibiotics
What are TCA’s?
What do they treat & was are the adverse side effects?
MOA:
They bind to 30S subunit of bacterial ribosomes to prevent the attachment of aminoacyl-tRNA & block bacterial protein synthesis.
Treat infections like cholera, Rocky Mountain Spotted Fever, Chlamydia, & Lyme disease
Adverse effects:
1) Gastric discomfort
2) Esophagitis
3) Hepatotoxicity at high doses (minocycline)
MOA:
They bind to 30S subunit of bacterial ribosomes to prevent the attachment of aminoacyl-tRNA & block bacterial protein synthesis.
Treat infections like cholera, Rocky Mountain Spotted Fever, Chlamydia, & Lyme disease
Adverse effects:
1) Gastric discomfort
2) Esophagitis
3) Hepatotoxicity at high doses (minocycline)
TCAs
Tetracycline, Doxycycline, & Minocycline are all examples of which type of drug?
TCAs (30s inhibitors)
Aminoglycosides
Gentamycin
Neomycin
Amkimycin
Tobramycin
Streptomycin
Bactericidal drugs that inhibit the 30S subunit to inhibit the formation of the initiation complex, translocation, & causing misreading mRNA &
preventing bacterial protein synthesis.
It is used for treating serious gram -ve bacilli infections (pseudomonas)
Adverse effects:
1) Ototoxicity (avoid with loop diuretics)
2) Nephrotoxicity (ATN)
3) Neuromuscular paralysis (avoid in myasthenia gravis!)
4) Dermatitis (topical neomycin)
5) Teratogenic
Bactericidal drugs that inhibit the 30S subunit to inhibit the formation of the initiation complex, translocation, & causing misreading mRNA &
preventing bacterial protein synthesis.
It is used for treating serious gram -ve bacilli infections (pseudomonas)
Adverse effects:
1) Ototoxicity (avoid with loop diuretics)
2) Nephrotoxicity (ATN)
3) Neuromuscular paralysis (avoid in myasthenia gravis!)
4) Dermatitis (topical neomycin)
5) Teratogenic
Aminoglycosides
Gentamycin
Neomycin
Amkimycin
Tobramycin
Streptomycin
Which TCA is safe to use in patients with renal failure & why?
Doxycycline because it is excreted in the poop
What do you want to avoid when taking TCAs?
Avoid milk, antacids, or iron-containing preparations because things like Calcium, magnesium, and iron ions (divalent ions) bind to drug, inhibiting drug’s absorption in gut
Which organisms are TCAs effective against?
Rickettsia (Rocky Mountain Spotted Fever)
Borrelia burgdorferi
Chlamydia spp.
M. pneumoniae
Acne
Community-acquired MRSA
How can organisms develop resistance against TCAs?
1) Plasmid-encoded active transport pumps will reduce the uptake or increased the efflux out of bacterial cells
&
2) By making a protein that enables translation despite TCA presence
Because aminoglycans requires O2 for uptake it can only treat which type of organisms?
Treats aerobic organisms only & especially Severe gram-negative rod infections (pseudomonas)
Which Aminoglycoside is used for Bowel surgery infection prophylaxis?
Neomycin
Which aminoglycoside is used as a second line Mycobacterium tuberculosis treatment?
Streptomycin
What is a potential complication of nephrotoxicity as a side effect of aminoglycosides?
Acute tubular necrosis
What is a potential complication of ototoxicity as a side effect of aminoglycosides?
Presents with hearing loss and tinnitus
Risk compounded with loop diuretics (also cause ototoxicity)
Damage to CN VIII can also lead to vestibular ataxia and vertigo
How do organisms confer resistance to aminoglycosides?
Through enzyme modification of the drug, bacterial transferases inactivate the drug via acetylation, phosphorylation, & adenylation.
Seen with Enterococcus
Which drug do you give penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides
Aztreonam
How do organisms develop resistance to aztreonam?
They develop resistant against beta-lactamases (penicillinase)
Red Man syndrome is a side effect of vancomycin, what is it?
Its a condition that is mediated by histamine (pseudo-allergic reaction) from mast cells, & it is not dependent on IgE signaling
Preventable with pre-treatment with antihistamines
They are beta lactam antibiotics
They are effective against gram-positive cocci like staph and strep bacteria so their used for preoperative antibiotic prophylaxis, to prevent wound infections caused by skin bacteria
What are first generation cephalosporins?
cefaZOLIN
cephaLEXIN
What are second generation cephalosporins?
cefoxitin, cefaclor, cefuroxime, and cefotetan
They are beta lactam antibiotics
highly effective against gram-positive cocci like staph and strep bacteria so they are used for preoperative antibiotic prophylaxis, to prevent wound infections caused by skin bacteria
Also good against some gram -ve:
H. influenzae
Enterobacter aerogenes
Neisseria
Serratia marcescens
Proteus mirabilis
E. Coli
Klebsiella pneumoniae
They are beta lactam antibiotics
highly effective against gram-positive cocci like staph and strep bacteria so they are used for preoperative antibiotic prophylaxis, to prevent wound infections caused by skin bacteria
Also good against some gram -ve:
H. influenzae
Enterobacter aerogenes
Neisseria
Serratia marcescens
Proteus mirabilis
E. Coli
Klebsiella pneumoniae
What are second generation cephalosporins?
cefoxitin, cefaclor, cefuroxime, and cefotetan
What are 3rd generation cephalosporins?
cefTRIAXONE
cefTAZIDIME
CefoTAXIME
CefPODOXIME
ceFIXime
They are beta-lactam antibiotics that are widely used in the hospital setting.
They have broad coverage, as they are effective against both gram +ve and gram -ve bacteria.
Ceftriaxone is used to treat bacterial meningitis, Lyme disease, and gonorrhea. Ceftazidime can treat pseudomonas infections.
They are beta-lactam antibiotics that are widely used in the hospital setting.
They have broad coverage, as they are effective against both gram +ve and gram -ve bacteria.
Ceftriaxone is used to treat bacterial meningitis, Lyme disease, and gonorrhea. Ceftazidime can treat pseudomonas infections.
What are 3rd generation cephalosporins?
cefTRIAXONE
cefTAZIDIME
CefoTAXIME
CefPODOXIME
ceFIXime
Ceftriaxone
a 3rd gen cephalosporin used to treat:
1) Meningitis: Crosses blood-brain-barrier (BBB)
2) Neisseria gonorrhoeae
3) Lyme
Ceftazidime
a 3rd gen cephalosporin used to treat:
Pseudomonas aeruginosa
a 3rd gen cephalosporin used to treat:
1) Meningitis: Crosses blood-brain-barrier (BBB)
2) Neisseria gonorrhoeae
3) Lyme
Ceftriaxone
a 3rd gen cephalosporin used to treat:
Pseudomonas aeruginosa
Ceftazidime
What are 4th generation cephalosporins?
Cefepime
beta-lactam antibiotics that are relatively newer cephalosporin drugs.
Broad gram positive and negative coverage
& especially used to treat Pseudomonas aeruginosa
Broad gram positive and negative coverage
Pseudomonas aeruginosa
What are 4th generation cephalosporins?
Cefepime
What are 5th generation cephalosporins?
ceftaroline
A broad spectrum coverage against gram +ve and gram -ve bacteria,
Reserved as one of the only effective treatments against MRSA, or methicillin-resistant staph aureus.\
Does NOT cover Pseudomonas aeruginosa
A broad spectrum coverage against gram +ve and gram -ve bacteria,
Reserved as one of the only effective treatments against MRSA, or methicillin-resistant staph aureus.
Does NOT cover Pseudomonas aeruginosa
What are 5th generation cephalosporins?
ceftaroline
What is Tigecycline?
Glycycline
a broad-spectrum antibiotic (TCA derivative) that binds & inhibits 30S to block bacterial protein synthesis.
It is used as a last resort treatment for multi-drug resistant organisms (MRSA & VRE)
Adverse effects:
Severe bleeding
Nausea/vomiting
Higher mortality rate
Glycycline
a broad-spectrum antibiotic (TCA derivative) that binds & inhibits 30S to block bacterial protein synthesis.
It is used as a last resort treatment for multi-drug resistant organisms (MRSA & VRE)
Adverse effects:
Severe bleeding
Nausea/vomiting
Higher mortality rate
Tigecycline
What are the macrolides? & What are they used for treating?
Suffix “-thromycin”
Azithromycin
Clarithromycin
Erythromycin.
MOA: Bacteriostatic
(Bind to the 23S rRNA of the 50S ribosomal subunit to block translocation to inhibit bacterial protein synthesis
Used for treating:
1) Atypical pneumonias (Legionella or Mycoplasma)
2) STI (chlamydia and gonorrhea)
3) Bordetella pertussis
4) Gram-positive cocci (streptococcal) in patients allergic to penicillin
Adverse:
Motility issues
Arrythmias (prolonged QT)
acute Cholestatic hepatitis (in patients with liver dysfunction)
Rash
eOsinophilia
“MACRO”
Complication:
Torsades de Pointes
Resistance:
Methylation of 23S rRNA-binding site prevents binding of drug
MOA: Bacteriostatic
(Bind to the 23S rRNA of the 50S ribosomal subunit to block translocation to inhibit bacterial protein synthesis
Used for treating:
1) Atypical pneumonias (Legionella or Mycoplasma)
2) STI (chlamydia and gonorrhea)
3) Bordetella pertussis
4) Gram-positive cocci (streptococcal) in patients allergic to penicillin
Adverse:
Motility issues
Arrythmias (prolonged QT)
acute Cholestatic hepatitis (in patients with liver dysfunction)
Rash
eOsinophilia
“MACRO”
Complication:
Torsades de Pointes
Resistance:
Methylation of 23S rRNA-binding site prevents binding of drug
adverse effects of macrolides
(Bind to the 23S rRNA of the 50S ribosomal subunit to block translocation to inhibit bacterial protein synthesis)
Macrolides
Azithromycin
Clarithromycin
Erythromycin
Which macrolide accumulates into the macrophages, neutrophils, & fibroblasts
Azithromycin
What is chloramphenicol?
MOA: Bacteriostatic
It binds the 50S subunit of bacterial ribosomes to prevent bacterial protein synthesis
It is used as a second- or third-line therapy for
1) Bacterial Meningitis (H.influenzae, N. meningitis, S.pneumoniae)
2) Rickettsial diseases
MOA: Bacteriostatic
It binds the 50S subunit of bacterial ribosomes to prevent bacterial protein synthesis
It is used as a second- or third-line therapy for
1) Bacterial Meningitis (H.influenzae, N. meningitis, S.pneumoniae)
2) Rickettsial diseases
Adverse Effects:
1) Anemia (dose dependent)
2) Leukopenia
3) Thrombocytopenia
(Reversible by stopping medication)
4) Aplastic anemia (dose independent)
5) Gray-baby syndrome
Premature infants lack liver UDP-glucuronosyltransferase and cannot metabolize the drug, leading to toxic accumulation
Resistance:
acetyltransferase to inactivate the drug
chloramphenicol
Presents in babies as gray skin, vomiting, lethargy, and cardiorespiratory suppression
Gray baby syndrome, an adverse effect of Chloramphenicol
Chloramphenicol
MOA: Bacteriostatic
It binds the 50S subunit of bacterial ribosomes to prevent bacterial protein synthesis
It is used as a second- or third-line therapy for
1) Bacterial Meningitis (H.influenzae, N. meningitis, S.pneumoniae)
2) Rickettsial diseases
Adverse Effects:
1) Anemia (dose dependent)
2) Leukopenia
3) Thrombocytopenia
(Reversible by stopping medication)
4) Aplastic anemia (dose independent)
5) Gray-baby syndrome
Premature infants lack liver UDP-glucuronosyltransferase and cannot metabolize the drug, leading to toxic accumulation
Resistance:
acetyltransferase to inactivate the drug
What is clindamycin?
MOA:
It targets the 50S subunit of bacterial ribosomes by blocking bacterial protein synthesis and stopping bacterial growth.
Treats:
1) anaerobic bacterial infections that arise above the diaphragm
e.g. Bacteroides spp., Clostridium perfringens
2) Aspiration pneumonia
3) lung abscesses
4) bacterial vaginosis
5) oral infections
6) Invasive group A streptococcal (S. pyogenes) infection
Adverse effects:
Pseudomembranous colitis
MOA:
It targets the 50S subunit of bacterial ribosomes by blocking bacterial protein synthesis and stopping bacterial growth.
Treats:
1) anaerobic bacterial infections that arise above the diaphragm
e.g. Bacteroides spp., Clostridium perfringens
2) Aspiration pneumonia
3) lung abscesses
4) bacterial vaginosis
5) oral infections
6) Invasive group A streptococcal (S. pyogenes) infection
Adverse effects:
Pseudomembranous colitis
clindamycin
What is a Linezolid? What does it treat?
MOA:
It binds the 50S subunit of bacterial ribosomes & blocks the formation of initiation complex to inhibit bacterial protein synthesis
Treats:
1) Gram-positive species including MRSA and VRE
(Usually as a last-resort for multi-drug resistant infections)
Adverse effects:
1) Bone marrow suppression
(Anemia, leukopenia, and thrombocytopenia)
2) Neuropathy
optic neuritis and peripheral neuropathy)
3) Serotonin syndrome
(Due to partial monoamine oxidase (MAO) inhibition
A higher risk with the use of other serotonergic drugs (e.g. MAOIs, SSRIs)
Resistance:
A Point mutation of ribosomal RNA that changes the 50S binding site
MOA:
It binds the 50S subunit of bacterial ribosomes & blocks the formation of initiation complex to inhibit bacterial protein synthesis
Treats:
1) Gram-positive species including MRSA and VRE
(Usually as a last-resort for multi-drug resistant infections)
Adverse effects:
1) Bone marrow suppression
(Anemia, leukopenia, and thrombocytopenia)
2) Neuropathy
optic neuritis and peripheral neuropathy)
3) Serotonin syndrome
(Due to partial monoamine oxidase (MAO) inhibition
A higher risk with the use of other serotonergic drugs (e.g. MAOIs, SSRIs)
Resistance:
A Point mutation of ribosomal RNA that changes the 50S binding site
Linezolid
What are Polymyxins?
Colistin (polymyxin E)
Polymyxin B
MOA:
Cation polypeptides that disrupts cell membrane causing leakage of cellular components and cell death
Treat:
colistin and other polymyxins last-resort therapy for multidrug-resistant gram-negative bacteria
e.g. P. aeruginosa, E. coli, K. pneumoniae
Adverse effects:
1) Nephrotoxicity
2) Neurotoxicity (slurred speech, weakness, paresthesia’s)
3) Respiratory failure
MOA:
Cation polypeptides that disrupts cell membrane causing leakage of cellular components and cell death
Treat:
colistin and other polymyxins last-resort therapy for multidrug-resistant gram-negative bacteria
e.g. P. aeruginosa, E. coli, K. pneumoniae
Adverse effects:
1) Nephrotoxicity
2) Neurotoxicity (slurred speech, weakness, paresthesia’s)
3) Respiratory failure
Polymyxins
Colistin (polymyxin E)
Polymyxin B
What are streptogramins?
Quinupristin & Dalfopristin
MOA:
50S inhibitors to prevent bacterial protein synthesis
What are fluoroquinolones? What are they used to treat?
suffix “-floxacin”
Ciprofloxacin, Moxifloxacin, or Levofloxacin
MOA:
Inhibit topoisomerase II (DNA gyrase) and topoisomerase IV
to impair bacterial DNA synthesis by preventing inhibiting DNA winding and unwinding, which causes the strand breaks
avoid antacids
(they reduce oral absorption of drug, reducing its efficacy)
Treat:
1) Gram -ve rods in urinary and GI tracts (e.g. Pseudomonas)
2) Some gram-positive organisms
3) Otitis externa
Adverse effects:
1) Tendonitis/Tendon rupture (Achilles tendon rupture)
2) Possible cartilage damage (Avoid in children)
3) Prolonged QT interval (Torsades de Pointes risk)
4) Superinfections
Resistance:
1) Mutated DNA gyrase/topoisomerase genes
2) Efflux pumps
MOA:
Inhibit topoisomerase II (DNA gyrase) and topoisomerase IV
to impair bacterial DNA synthesis by preventing inhibiting DNA winding and unwinding, which causes the strand breaks
avoid antacids
(they reduce oral absorption of drug, reducing its efficacy)
Treat:
1) Gram -ve rods in urinary and GI tracts (e.g. Pseudomonas)
2) Some gram-positive organisms
3) Otitis externa
Adverse effects:
1) Tendonitis/Tendon rupture (Achilles tendon rupture)
2) Possible cartilage damage (Avoid in children)
3) Prolonged QT interval (Torsades de Pointes risk)
4) Superinfections
Resistance:
1) Mutated DNA gyrase/topoisomerase genes
2) Efflux pumps
fluoroquinolones
suffix “-floxacin”
Ciprofloxacin, Moxifloxacin, or Levofloxacin
Which fluoroquinolone inhibits CYP450 enzyme?
& What is a potential complication of this?
Ciprofloxacin
Can lead to drug interactions (e.g. warfarin, theophylline)
Bacteriostatic describes drugs that
Inhibit bacterial protein synthesis
30S inhibitors
50S inhibitors
Folate antagonists
Bactericidal antibiotics are drugs that
that inhibit cell wall synthesis
Peptidoglycan synthesis inhibitors:
1) Glycopeptides
Peptidoglycan cross-linking:
1) Penicillinase-Sensitive penicillin’s
2) Penicillinase-resistant penicillin’s
3) Antipseudomonal
4) Cephalosporins
5) Carbapenems
6) Monobactams
What are the quinolones?
Nalidixic acids
Inhibit topoisomerase II (DNA gyrase) and topoisomerase IV
to impair bacterial DNA synthesis by preventing inhibiting DNA winding and unwinding, which causes the strand breaks
Inhibit topoisomerase II (DNA gyrase) and topoisomerase IV
to impair bacterial DNA synthesis by preventing inhibiting DNA winding and unwinding, which causes the strand breaks
Nalidixic acids
What are Sulfonamides?
Sulfamethoxazole (SMX)
Sulfisoxazole
Sulfadiazine
MOA: Folate antagonists (Impairs folate synthesis in bacteria)
The drugs have chemical analogs of para-aminobenzoic acid (PABA), a folic acid precursor for bacteria which binds to and inhibits dihydropteroate synthase, preventing bacterial conversion of PABA to folic acid
Clinical use (with trimethoprim):
1) Synergistic block of bacterial folate synthesis
2) Gram-positive organisms (e.g. Nocardia)
3) Gram-negative organisms
Adverse effects:
1) Hypersensitivity reactions (sulfa allergy)
2)Hemolysis with G6PD deficiency
3) Nephrotoxicity (tubulointerstitial nephritis)
4) Photosensitive rash (Can develop into Stevens-Johnson syndrome)
5) Infantile kernicterus
6) Causes drug interactions (e.g. raises warfarin levels)
Resistance:
1) Mutations in enzyme (bacterial dihydropteroate synthase)
2) Decreased uptake
3) Increased PABA synthesis
If sulfonamides are given with ________ it causes it to be a bactericidal drug (i.e inhibits cell wall synthesis)
trimethoprim
MOA: Folate antagonists (Impairs folate synthesis in bacteria)
The drugs have chemical analogs of para-aminobenzoic acid (PABA), a folic acid precursor for bacteria which binds to and inhibits dihydropteroate synthase, preventing bacterial conversion of PABA to folic acid
Clinical use (with trimethoprim):
1) Synergistic block of bacterial folate synthesis
2) Gram-positive organisms (e.g. Nocardia)
3) Gram-negative organisms
Adverse effects:
1) Hypersensitivity reactions (sulfa allergy)
2)Hemolysis with G6PD deficiency
3) Nephrotoxicity (tubulointerstitial nephritis)
4) Photosensitive rash (Can develop into Stevens-Johnson syndrome)
5) Infantile kernicterus
6) Causes drug interactions (e.g. raises warfarin levels)
Resistance:
1) Mutations in enzyme (bacterial dihydropteroate synthase)
2) Decreased uptake
3) Increased PABA synthesis
sulfonamides
What is trimethoprim? What does it treat?
MOA:
Folate antagonist (it inhibits bacterial folate synthesis) by blocking bacterial dihydrofolate reductase (DHFR)
Broad-spectrum when used in with sulfonamides:
1) Urinary tract infections (UTIs)
2) Shigella
3) Salmonella
4) Pneumocystis jirovecii pneumonia
5) Toxoplasmosis prophylaxis
6) Community-acquired MRSA
Adverse effects:
1) Hyperkalemia (high doses)
2) drug interactions (e.g. raises warfarin levels) by inhibiting CYP Enzymes
3) Displace warfarin from albumin, increasing effective dosing
4) Folate deficiency
5) Teratogenic (neural tube defects)
MOA:
Folate antagonist (it inhibits bacterial folate synthesis) by blocking bacterial dihydrofolate reductase (DHFR)
Broad-spectrum when used in with sulfonamides:
1) Urinary tract infections (UTIs)
2) Shigella
3) Salmonella
4) Pneumocystis jirovecii pneumonia
5) Toxoplasmosis prophylaxis
6) Community-acquired MRSA
Adverse effects:
1) Hyperkalemia (high doses)
2) drug interactions (e.g. raises warfarin levels) by inhibiting CYP Enzymes
3) Displace warfarin from albumin, increasing effective dosing
4) Folate deficiency
5) Teratogenic (neural tube defects)
trimethoprim
megaloblastic anemia, leukopenia, granulocytopenia; Bone marrow contains rapidly-dividing hematopoietic cells that are more affected by relative folate deprivation NO NEURO SYMPTOMS
Folate deficiency
What are the Rifampins?
Rifampin
Rifabutin
MOA:
Inhibits DNA-dependent RNA polymerase to reduce mRNA synthesis
Used to treat:
1) Mycobacteria (M. tuberculosis (TB)) (RIPE regimen)
2) M. leprae (Delays resistance to dapsone when used for leprosy)
3) M. avium complex
4) N. meningitidis (Used for prophylaxis of close contacts)
5) H. influenzae type b (Used for prophylaxis of close contacts)
Adverse effects:
1) orange body fluids
2) Induces CYP450 enzymes
3) Hepatotoxicity (Elevations of AST and ALT levels)
4) Nephrotoxicity (May cause acute interstitial nephritis)
Resistance:
1) Mutations in RNA polymerase reduce drug binding
2) Monotherapy in TB rapidly leads to resistance
MOA:
Inhibits DNA-dependent RNA polymerase to reduce mRNA synthesis
Used to treat:
1) Mycobacteria (M. tuberculosis (TB)) (RIPE regimen)
2) M. leprae (Delays resistance to dapsone when used for leprosy)
3) M. avium complex
4) N. meningitidis (Used for prophylaxis of close contacts)
5) H. influenzae type b (Used for prophylaxis of close contacts)
Adverse effects:
1) orange body fluids
2) Induces CYP450 enzymes
3) Hepatotoxicity (Elevations of AST and ALT levels)
4) Nephrotoxicity (May cause acute interstitial nephritis)
Resistance:
1) Mutations in RNA polymerase reduce drug binding
2) Monotherapy in TB rapidly leads to resistance
Rifampins
Rifampin
Rifabutin
Rifampin, rifabutin, & rifapentine are all examples of which type of drug?
Rifampin’s
Which Rifampin is favored & why?
Rifabutin is favored in patients with an HIV infection because of less CYP450 induction
What is Metronidazole? What does it treat?
MOA:
It forms toxic free radicals in the bacterial cell wall that damage DNA
Bactericidal, antiprotozoal
Used to treat:
1) Giardia
2) Entamoeba histolytica
3) Trichomonas vaginalis
4) Gardnerella vaginalis
5) Anaerobes (Bacteroides, C. difficile)
6) Used to treat anaerobic infections below the diaphragm (clindamycin used above)
7) H. pylori (in patients with penicillin allergies)
Adverse effects:
1) Disulfiram-like reaction with alcohol (Inhibition of acetaldehyde dehydrogenase, a toxic buildup of acetaldehyde occurs)
2) GI upset (nausea, vomiting, abdominal pain)
3) Neuropathy (paresthesia’s, dizziness)
4) Headache
MOA:
It forms toxic free radicals in the bacterial cell wall that damage DNA
Bactericidal, antiprotozoal
Used to treat:
1) Giardia
2) Entamoeba histolytica
3) Trichomonas vaginalis
4) Gardnerella vaginalis
5) Anaerobes (Bacteroides, C. difficile)
6) Used to treat anaerobic infections below the diaphragm (clindamycin used above)
7) H. pylori (in patients with penicillin allergies)
Adverse effects:
1) Disulfiram-like reaction with alcohol (Inhibition of acetaldehyde dehydrogenase, a toxic buildup of acetaldehyde occurs)
2) GI upset (nausea, vomiting, abdominal pain)
3) Neuropathy (paresthesia’s, dizziness)
4) Headache
Metronidazole
Presents with severe flushing, tachycardia, hypotension
Metallic taste in mouth
Disulfiram-like reaction with alcohol (Inhibition of acetaldehyde dehydrogenase, a toxic buildup of acetaldehyde occurs)
What is Daptomycin?
MOA:
Disrupts cell membranes by creating transmembrane channels
Causes intracellular leakage and membrane depolarization
Ultimately inhibits DNA, RNA, and protein synthesis, leading to bacterial death
Used to treat (Gram +ve bacterial infections):
1) Gram-positive cocci
2) S. aureus skin infections (esp. MRSA)
3) bacteremia
4) endocarditis
5) VRE
Adverse effects:
1) Myopathy
2) Rhabdomyolysis
3) Creatinine kinase (CK) levels may rise due to release from skeletal muscle
MOA:
Disrupts cell membranes by creating transmembrane channels
Causes intracellular leakage and membrane depolarization
Ultimately inhibits DNA, RNA, and protein synthesis, leading to bacterial death
Used to treat (Gram +ve bacterial infections):
1) Gram-positive cocci
2) S. aureus skin infections (esp. MRSA)
3) bacteremia
4) endocarditis
5) VRE
Adverse effects:
1) Myopathy
2) Rhabdomyolysis
3) Creatinine kinase (CK) levels may rise due to release from skeletal muscle
Daptomycin
What can Daptomycin NOT be used to treat & why?
Not used for pneumonia
Avidly binds to and is inactivated by alveolar surfactant
Colistin (polymyxin E) & Polymyxin B
MOA:
Makes cation glycoproteins against cell membranes
A last-resort therapy for multidrug-resistant gram-negative bacteria
(P. aeruginosa, E. coli, K. pneumoniae)
Adverse effects:
1) Nephrotoxicity
2) Neurotoxicity (slurred speech, weakness, paresthesia’s)
3) Respiratory failure
MOA:
Makes cation glycoproteins against cell membranes
A last-resort therapy for multidrug-resistant gram-negative bacteria
(P. aeruginosa, E. coli, K. pneumoniae)
Adverse effects:
1) Nephrotoxicity
2) Neurotoxicity (slurred speech, weakness, paresthesia’s)
3) Respiratory failure
Colistin (polymyxin E) & Polymyxin B
What are Caspofungin, Micafungin, & Anidulafungin?
Clinical use
Adverse effect
Echinocandins:
MOA:
They inhibit cell wall synthesis by inhibiting the synthesis of B-glucan
Used to treat:
1) Invasive aspergillus
2) Candida infection
Adverse Effects:
1) Hepatotoxicity (Elevated AST and ALT)
2) GI upset (mild)
3) Infusion-associated hypersensitivity
(Rash, hypotension, bronchospasm, and angioedema rarely occur due to local histamine release)
Echinocandins:
MOA:
They inhibit the synthesis of beta-glucan to block fungal cell wall synthesis (very good for Aspergillus and Candida)
Note: targets fungal wall, not fungal membrane
Adverse Effects:
1) Hepatotoxicity (Elevated AST and ALT)
2) GI upset (mild)
3) Infusion-associated hypersensitivity
(Rash, hypotension, bronchospasm, and angioedema rarely occur due to local histamine release)
adverse effects of Caspofungin, Micafungin, & Anidulafungin (Echinocandins)
What are NRTI’s (Nucleoside Reverse Transcriptase Inhibitors)?
Abacavir (ABC)
Zidovudine (ZDV)
Emtricitabine (FTC)
Lamivudine (3TC)
Didanosine (ddI)
Stavudine (d4T)
Tenofovir (TDF)
Clinical use?
Adverse effect
MOA:
Nucleoside analogs inhibit reverse transcriptase by competing with nucleosides, leading to DNA chain termination. They lack a 3’OH group, preventing synthesis of DNA from viral RNA. Activation through phosphorylation is necessary, except for tenofovir.
Clinical use:
1) HIV (HIV 1 & 2)
2) ZDV (general prophylaxis and during pregnancy to reduce risk of fetal transmission)
Adverse effect:
1) Hypersensitivity (Abacavir)
2) Bone marrow suppression
3) Anemia (zidovudine)
4) Pancreatitis (didanosine)
5) Lipoatrophy
6) hepatic steatosis
7) Wasting of subcutaneous fat
8) Peripheral neuropathy
9) Lactic acidosis
What is the association with the hypersensitivity reaction side effect of Abacavir?
Hypersensitivity (Abacavir) it is seen in patients with HLA B*57:01 allele. It is caused by Type 4 HSR with fever, nausea, vomiting, rash
How can bone marrow suppression (Myelosuppression) as side effect of NRTI’s be reversed?
They can be reversed with granulocyte colony-stimulating factor (G-CSF) and erythropoietin
MOA:
Nucleoside analogs inhibit reverse transcriptase by competing with nucleosides, leading to DNA chain termination. They lack a 3’OH group, preventing synthesis of DNA from viral RNA. Activation through phosphorylation is necessary, except for tenofovir.
Clinical use:
1) HIV (HIV 1 & 2)
2) ZDV (general prophylaxis and during pregnancy to reduce risk of fetal transmission)
Adverse effect:
1) Hypersensitivity (Abacavir)
2) Bone marrow suppression
3) Anemia (zidovudine)
4) Pancreatitis (didanosine)
5) Lipoatrophy
6) hepatic steatosis
7) Wasting of subcutaneous fat
8) Peripheral neuropathy
9) Lactic acidosis
NRTI’s
What is an adverse effect of Abacavir
Hypersensitivity
Which NRTI is a nucleotide?
Tenofovir (the rest are nucleosides)
What is Zidovudine?
Adverse Effects: bone marrow suppression (reversed with G-CSF and erythropoietin), peripheral neuropathy, lactic acidosis, anemia
Clinical uses
Adverse effect
Classification: NRTI
MOA:
Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3’OH group). It needs to be phosphorylated to be activated.
Clinical uses:
1) HIV therapy
2) General prophylaxis and during pregnancy to decrease risk of fetal transmission (ZDV)
Adverse effect:
1) bone marrow suppression (reversed with G-CSF and erythropoietin)
2) peripheral neuropathy
3) lactic acidosis
4) anemia
Classification: NRTI
MOA:
Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3’OH group). It needs to be phosphorylated to be activated.
Clinical uses:
1) HIV therapy
2) General prophylaxis and during pregnancy to decrease risk of fetal transmission (ZDV)
Adverse effect:
1) bone marrow suppression (reversed with G-CSF and erythropoietin)
2) peripheral neuropathy
3) lactic acidosis
4) anemia
Zidovudine
What are the antivirals Acyclovir (famciclovir, valacyclovir)?
Clinical uses?
MOA:
They are Guanosine analog inhibits viral DNA polymerase. They causes DNA chain termination, to prevent viral DNA replication
NEED phosphorylation by HSV/VZV thymidine kinase to be activated
Clinical use:
1) HSV (used for mucocutaneous and genital lesions, meningoencephalitis but they can’t eliminate latent forms)
2) VZV (they can’t eliminate latent forms)
MOA:
They are Guanosine analog inhibits viral DNA polymerase. They causes DNA chain termination, to prevent viral DNA replication
NEED phosphorylation by HSV/VZV thymidine kinase to be activated
Clinical use:
1) HSV (used for mucocutaneous and genital lesions, meningoencephalitis but they can’t eliminate latent forms)
2) VZV (they can’t eliminate latent forms)
Acyclovir, Valaciclovir, & Famciclovir
What are the antivirals (acyclovir, valaciclovir, & famciclovir) are not very good at treating
They are negligible activity against EBV and CMV
(EBV and CMV produce different thymidine kinases with lower affinity for acyclovir, reducing phosphorylation and activation
What are Fluroquinolones
Adverse effects
Resistance
MOA:
A bactericidal that inhibits prokaryotic enzymes topoisomerase II (DNA gyrase) and topoisomerase IV
Avoid with antacids
Adverse effects:
superinfections
Tendonitis/rupture
Resistance: chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps
MOA:
A bactericidal that inhibits prokaryotic enzymes topoisomerase II (DNA gyrase) and topoisomerase IV
Avoid with antacids
Adverse effects:
GI upset
superinfections
Tendonitis/rupture
skin rashes
headaches
dizziness
leg cramps and myalgias
Resistance: chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps
fluroquinolones
What are Rifampins?
Clinical uses?
Adverse effects?
Classification: rifamycin
MOA:
It inhibits DNA-dependant RNA polymerase
Used for treating:
1) Mycobacterium tuberculosis (delay resistance to Dapsone when used for leprosy)
2) meningococcal prophylaxis
3) chemoprophylaxis in contacts of children with H. influenza type b
Adverse Effects:
1) minor hepatotoxicity
2) drug interactions (increases cytochrome P450)
3) orange body fluids
Resistance:
mutations reduce drug binding to RNA polymerase –– monotherapy rapidly leads to resistance
MOA:
It inhibits DNA-dependant RNA polymerase
Used for treating:
1) Mycobacterium tuberculosis (delay resistance to Dapsone when used for leprosy)
2) meningococcal prophylaxis
3) chemoprophylaxis in contacts of children with H. influenza type b
Adverse Effects:
1) minor hepatotoxicity
2) drug interactions (increases cytochrome P450)
3) orange body fluids
Resistance:
mutations reduce drug binding to RNA polymerase –– monotherapy rapidly leads to resistance
Rifampins
What are Macrolides? What do they treat?
Adverse effects?
MOA: bacteriostatic
Inhibit protein synthesis by blocking translocation by binding to the 23S rRNA of the 50S ribosomal subunit
Clinical Indications:
1) atypical pneumonias (Mycoplasma, Chlamydia, Legionella)
2) STIs (Chlamydia)
3) gram positive cocci (streptococcal infections in patients allergic to penicillin)
4) B. pertussis
Adverse effects:
MACRO:
gastrointestinal Motility issues (stimulate motilin)
Arrhythmia (prolonged QT interval)
acute Cholestatic hepatitis
Rash
eOsinophilia
MOA: bacteriostatic
Inhibit protein synthesis by blocking translocation by binding to the 23S rRNA of the 50S ribosomal subunit
Clinical Indications:
1) atypical pneumonias (Mycoplasma, Chlamydia, Legionella)
2) STIs (Chlamydia)
3) gram positive cocci (streptococcal infections in patients allergic to penicillin)
4) B. pertussis
Adverse effects:
MACRO:
gastrointestinal Motility issues (stimulate motilin)
Arrhythmia (prolonged QT interval)
acute Cholestatic hepatitis
Rash
eOsinophilia
Macrolides
aminoglycosides?
Gentamycin
amikin
Neomycin
Streptomycin
Tobramycin
Clinical uses?
Adverse effects?
Classification: aminoglycosides
MOA: bactericidal
It irreversibly inhibits the initiation of the complex through binding of the 30S subunit which can cause misreading of mRNA & also block translocation.
They require O2 for uptake; therefore, ineffective against anaerobes.
Clinical Indications:
1) severe gram-negative rod infections (synergistic with β-lactam antibiotics)
Adverse Effects:
1) nephrotoxicity (proteinuria, hypokalemia, acidosis, acute tubular necrosis)
2) neuromuscular blockage (decrease release of Ach [absolute contraindication with MG])
3) ototoxicity (especially with loop diuretics)
4) teratogenicity
Resistance:
bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation MOA
MOA: bactericidal
It irreversibly inhibits the initiation of the complex through binding of the 30S subunit which can cause misreading of mRNA & also block translocation.
They require O2 for uptake; therefore, ineffective against anaerobes.
Clinical Indications:
1) severe gram-negative rod infections (synergistic with β-lactam antibiotics)
Adverse Effects:
1) nephrotoxicity (proteinuria, hypokalemia, acidosis, acute tubular necrosis)
2) neuromuscular blockage (decrease release of Ach [absolute contraindication with MG])
3) ototoxicity (especially with loop diuretics)
4) teratogenicity
Resistance:
bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation MOA
Aminoglycosides
Adverse Effects:
1) nephrotoxicity (proteinuria, hypokalemia, acidosis, acute tubular necrosis)
2) neuromuscular blockage (decrease release of Ach [absolute contraindication with MG])
3) ototoxicity (especially with loop diuretics)
4) teratogenicity
aminoglycosides
How do organisms develop resistance against aminoglycosides?
bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation
What is Chloramphenicol? What does it treat?
Clinical uses
Adverse effects?
Classification: bacteriostatic antibiotic
MOA:
It blocks peptidyl transferase at 50S ribosomal subunit ––
Clinical Indications:
1) meningitis (H. influenzae, N. meningitidis, S. pneumoniae)
2) rickettsial diseases (Rocky Mountain Spotted Fever)
Adverse Effects:
1) bone marrow suppression (dose dependant)
2) anemia (dose independent)
3) aplastic anemia (dose dependant)
4) gray baby syndrome (premature infants because they lack UDP-glucuronosyltransferase)
Resistance:
plasmid-encoded acetyltransferase inactivates the druga
Classification: bacteriostatic antibiotic
MOA:
It blocks peptidyl transferase at 50S ribosomal subunit ––
Clinical Indications:
1) meningitis (H. influenzae, N. meningitidis, S. pneumoniae)
2) rickettsial diseases (Rocky Mountain Spotted Fever)
Adverse Effects:
1) bone marrow suppression (dose dependant)
2) anemia (dose independent)
3) aplastic anemia (dose dependant)
4) gray baby syndrome (premature infants because they lack UDP-glucuronosyltransferase)
Resistance:
plasmid-encoded acetyltransferase inactivates the druga
Chloramphenicol
What is Ganciclovir?
Clinical uses
Adverse effects?
Classification: viral DNA/RNA polymerase inhibitor
MOA:
A Guanosine analog that inhibits viral DNA polymerase causing DNA chain termination & preventing viral DNA replication. It needs CMV kinase to phosphorylate it to its active triphosphate form
Clinical Indications:
1) CMV (especially in immunocompromised patients)
Adverse Effects:
1) hepatic and neurologic dysfunction
2) bone marrow suppression (leukopenia, neutropenia, thrombocytopenia)
3) renal toxicity
4) seizures (overdose)
Resistance:
through mutated viral kinase
Classification: viral DNA/RNA polymerase inhibitor
MOA:
A Guanosine analog that inhibits viral DNA polymerase causing DNA chain termination & preventing viral DNA replication. It needs CMV kinase to phosphorylate it to its active triphosphate form
Clinical Indications:
1) CMV (especially in immunocompromised patients)
Adverse Effects:
1) hepatic and neurologic dysfunction
2) bone marrow suppression (leukopenia, neutropenia, thrombocytopenia)
3) renal toxicity
4) seizures (overdose)
Resistance:
through mutated viral kinase
Ganciclovir
What is Valganciclovir?
a prodrug of ganciclovir that has better oral bioavailability
acyclovir?
Clinical use
Adverse effects
Resistance
Classification: guanine analog
MOA:
monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells therefore few adverse effects. The triphosphate is formed by cellular enzymes & preferentially inhibits viral DNA polymerase by chain termination
Clinical Indications:
1) HSV and VZV
weak activity against EBV used for HSV-induced mucocutaneous and genital lesions as well as for encephalitis
2) prophylaxis in immunocompromised patients
Adverse Effects:
1) nausea, diarrhea and headache (oral dosing)
2) obstructive crystalline nephropathy and acute kidney injury if not adequately hydrated
Resistance:
mutated viral thymidine kinase
Classification: guanine analog
MOA:
monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells therefore few adverse effects. The triphosphate is formed by cellular enzymes & preferentially inhibits viral DNA polymerase by chain termination
Clinical Indications:
1) HSV and VZV
weak activity against EBV used for HSV-induced mucocutaneous and genital lesions as well as for encephalitis
2) prophylaxis in immunocompromised patients
Adverse Effects:
1) nausea, diarrhea and headache (oral dosing)
2) obstructive crystalline nephropathy and acute kidney injury if not adequately hydrated
Resistance:
mutated viral thymidine kinase
acyclovir
What is Zidovudine?
Clinical uses?
Adverse effects?
Classification: NRTI
MOA:
It competitively inhibits nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3’OH group). It needs to be phosphorylated to be activated.
Clinical Indications:
1) HIV therapy
2) general prophylaxis and during pregnancy to decrease risk of fetal transmission
Adverse Effects:
bone marrow suppression (reversed with G-CSF and erythropoietin), peripheral neuropathy
lactic acidosis
anemia
Classification: NRTI
MOA:
It competitively inhibits nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3’OH group). It needs to be phosphorylated to be activated.
Clinical Indications:
1) HIV therapy
2) general prophylaxis and during pregnancy to decrease risk of fetal transmission
Adverse Effects:
bone marrow suppression (reversed with G-CSF and erythropoietin), peripheral neuropathy
lactic acidosis
anemia
Zidovudine
What is Raltegravir? What is it used to treat?
Adverse effects?
Classification: integrase inhibitor
MOA:
It inhibits the HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase (HIV-1 and HIV-2). There are no CYP interactions making it relatively safe.
It is used to treat:
1) HIV
Adverse Effects:
1) toxicity leads to increased creatine kinase
Classification: integrase inhibitor
MOA:
It inhibits the HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase (HIV-1 and HIV-2). There are no CYP interactions making it relatively safe.
It is used to treat:
1) HIV
Adverse Effects:
1) toxicity leads to increased creatine kinase
Raltegravir
What is Foscarnet?
Clinical uses?
Adverse effects?
Resistance?
Classification: viral DNA/RNA polymerase inhibitor and HIV reverse transcriptase inhibitor
MOA: It binds to the pyrophosphate-binding site of enzyme & it does not require any kinase activation.
Clinical Indications:
1) CMV retinitis in immunocompromised patients when ganciclovir fails 2) acyclovir-resistant HSV
Adverse Effects:
1) nephrotoxicity
2) electrolyte abnormalities (hyper/hypocalcemia, hyper/hypophosphatemia, hypokalemia, hypomagnesemia) can lead to seizures
Resistance:
mutated DNA polymerase
Classification: viral DNA/RNA polymerase inhibitor and HIV reverse transcriptase inhibitor
MOA: It binds to the pyrophosphate-binding site of enzyme & it does not require any kinase activation.
Clinical Indications:
1) CMV retinitis in immunocompromised patients when ganciclovir fails 2) acyclovir-resistant HSV
Adverse Effects:
1) nephrotoxicity
2) electrolyte abnormalities (hyper/hypocalcemia, hyper/hypophosphatemia, hypokalemia, hypomagnesemia) can lead to seizures
Resistance:
mutated DNA polymerase
Foscarnet
What are Integrase Inhibitors? What do they treat?
Drug Names (-tegravir ending)
Raltegravir
Dolutegravir
Bictegravir
Elvitegravir
Adverse effects?
They Inhibit retroviral integrase & blocks integration of HIV viral DNA (made by reverse transcriptase) into host cell chromosome to prevent viral replication
Used to treat:
1) HIV
They are effective againstHIV-1 and HIV-2
(they are apart of the highly-active antiretroviral therapy (HAART)
Usually 3 drugs: 2 NRTIs and integrase or protease inhibitor)
Myositis (myopathy)
Increase creatine kinase levels
They Inhibit retroviral integrase & blocks integration of HIV viral DNA (made by reverse transcriptase) into host cell chromosome to prevent viral replication
Used to treat:
1) HIV
They are effective againstHIV-1 and HIV-2
(they are apart of the highly-active antiretroviral therapy (HAART)
Usually 3 drugs: 2 NRTIs and integrase or protease inhibitor)
Myositis (myopathy)
Increase creatine kinase levels
Integrase Inhibitors
Drug Names (-tegravir ending)
Raltegravir
Dolutegravir
Bictegravir
Elvitegravir
What is Amantadine? What are the adverse effects?
Adverse effects?
Classification: NMDA receptor antagonist (antiviral)
MOA:
It blocks muscarinic receptors to increase DA release and decrease DA reuptake
Adverse Effects:
1) insomnia
2) dizziness
3) confusion
4) ankle edema
5) atropine-like
6) livedo reticularis
Classification: NMDA receptor antagonist (antiviral)
MOA:
It blocks muscarinic receptors to increase DA release and decrease DA reuptake
Adverse Effects:
1) insomnia
2) dizziness
3) confusion
4) ankle edema
5) atropine-like
6) livedo reticularis
Amantadine
What is the trade name of Oseltamivir?
Tamiflu
What do Oseltamivir and zanamivir treat?
Adverse effects?
Classification: Sialic acid analogs
MOA:
That bind & inhibit neuraminidase which prevents cleavage of viral progeny off of the cell surface & blocking the new viral particles to exit the cell. They may also slow the viral penetration into the airway epithelium
They treat:
1) Influenza virus (flu) both influenza A and B infections
Beginning within 48 hours of symptom onset can shorten course of illness
Adverse effects:
1) Gastrointestinal upset
2) Zanamivir may exacerbate COPD and asthma
(because it is an inhaled dry powder)
Classification: Sialic acid analogs
MOA:
That bind & inhibit neuraminidase which prevents cleavage of viral progeny off of the cell surface & blocking the new viral particles to exit the cell. They may also slow the viral penetration into the airway epithelium
They treat:
1) Influenza virus (flu) both influenza A and B infections
Beginning within 48 hours of symptom onset can shorten course of illness
Adverse effects:
1) Gastrointestinal upset
2) Zanamivir may exacerbate COPD and asthma
(because it is an inhaled dry powder)
Oseltamivir and zanamivir
What is Raltegravir? what does it treat?
Adverse effects?
Classification: integrase inhibitor
MOA:
It inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase (HIV-1 and HIV-2). It doesn’t have any CYP interactions
Clinical Indications: HIV therapy
Adverse Effects: toxicity leads to increased creatine kinase
Classification: integrase inhibitor
MOA:
It inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase (HIV-1 and HIV-2). It doesn’t have any CYP interactions
Clinical Indications: HIV therapy
Adverse Effects: toxicity leads to increased creatine kinase
Raltegravir
What is Ribavirin? What does it treat?
Adverse effects?
MOA:
It inhibits synthesis of guanine nucleotide by competitively inhibiting IMP dehydrogenase
Clinical Indications:
1)Hepatitis C
2)RSV
Adverse Effects:
1) Hemolytic anemia
2) severe teratogen
MOA:
It inhibits synthesis of guanine nucleotide by competitively inhibiting IMP dehydrogenase
Clinical Indications:
1)Hepatitis C
2)RSV
Adverse Effects:
1) Hemolytic anemia
2) severe teratogen
Ribavirin
What is Amphotericin B?
Clinical uses?
Adverse effects?
Classification: cell membrane integrity inhibitor (polyene)
MOA:
It binds ergosterol to form membrane pores that allow leakage of electrolytes
Clinical Indications:
1) serious, systemic mycoses
2) Cryptococcus
3) Blastomyces
4) Coccidiosis
5) Histoplasmosis
6) Candida
7) Mucor
Adverse Effects:
1) fever/chills
2) hypotension
3) nephrotoxicity
4) arrythmias
5) anemia
6)IV phlebitis
hydration helps decrease nephrotoxicity
Classification: cell membrane integrity inhibitor (polyene)
MOA:
It binds ergosterol to form membrane pores that allow leakage of electrolytes
Clinical Indications:
1) serious, systemic mycoses
2) Cryptococcus
3) Blastomyces
4) Coccidiosis
5) Histoplasmosis
6) Candida
7) Mucor
Adverse Effects:
1) fever/chills
2) hypotension
3) nephrotoxicity
4) arrythmias
5) anemia
6)IV phlebitis
hydration helps decrease nephrotoxicity
Amphotericin B
Amphotericin B is given with or without __________ when treating cryptococcal meningitis?
+/– flucytosine
What should you give a patient experiencing the adverse effects of nephrotoxicity (Hypokalemia & Hypomagnesemia) when given Amphotericin B?
Supplement K+
and Mg2+ because of altered
renal tubule permeability
What can decrease nephrotoxicity in patients being treated with amphotericin B?
Hydration reduces nephrotoxicity
What is Caspofungin? What does it treat?
Adverse effects?
Classification: echinocandins (cell wall synthesis inhibitor)
MOA:
It inhibits cell wall synthesis by inhibiting synthesis of β-glucan
Clinical Indications:
1) invasive aspergillosis
2) Candida
Adverse Effects:
1) GI upset
2) flushing (r/t histamine release)
Classification: echinocandins (cell wall synthesis inhibitor)
MOA:
It inhibits cell wall synthesis by inhibiting synthesis of β-glucan
Clinical Indications:
1) invasive aspergillosis
2) Candida
Adverse Effects:
1) GI upset
2) flushing (r/t histamine release)
Caspofungin
What is Ketoconazole (azole)?
Clinical use?
Adverse effects?
Classification: ergosterol synthesis inhibitor (azoles)
MOA:
It inhibits fungal sterol (ergosterol) synthesis by inhibiting the cytochrome P-450 enzyme (14-α-demethylase) that converts lanosterol to ergosterol
Clinical Indications:
1) alternative drugs in candidemia and infections caused by Aspergillus, Blastomyces, Cryptococcus, and Histoplasma
Note ketoconazole is rarely used in systemic fungal infections
Adverse Effects:
1) testosterone synthesis inhibition (gynecomastia, decreased libido)
2) liver dysfunction (increased LFTs, hepatoxicity [inhibits cytochrome P-450])
Classification: ergosterol synthesis inhibitor (azoles)
MOA:
It inhibits fungal sterol (ergosterol) synthesis by inhibiting the cytochrome P-450 enzyme (14-α-demethylase) that converts lanosterol to ergosterol
Clinical Indications:
1) alternative drugs in candidemia and infections caused by Aspergillus, Blastomyces, Cryptococcus, and Histoplasma
Note ketoconazole is rarely used in systemic fungal infections
Adverse Effects:
1) testosterone synthesis inhibition (gynecomastia, decreased libido)
2) liver dysfunction (increased LFTs, hepatoxicity [inhibits cytochrome P-450])
Ketoconazole
Which drug interactions cause Hemolysis in G6PD
deficiency as a side effect?
Isoniazid, sulfonamides, dapsone, primaquine,
aspirin, ibuprofen, nitrofurantoin
“hemolysis is D PAIN”
Isoniazid, sulfonamides, dapsone, primaquine,
aspirin, ibuprofen, nitrofurantoin
Drug interactions all result in what complication?
Hemolysis in G6PD
deficiency
Which drug interactions cause Gray baby syndrome as a side effect?
Chloramphenicol
Chloramphenicol
Drug interaction results in what complication?
Gray baby syndrome
Which drug interactions cause Agranulocytosis as a side effect?
Dapsone, clozapine, carbamazepine,
propylthiouracil, methimazole, colchicine,
ticlopidine, ganciclovir
“Drugs Can Cause Pretty Major Collapse To
Granulocytes”
Dapsone, clozapine, carbamazepine,
propylthiouracil, methimazole, colchicine,
ticlopidine, ganciclovir
Drug interactions all result in what complication?
Agranulocytosis
Which drug interactions cause Aplastic anemia as a side effect?
Carbamazepine, methimazole, NSAIDs,
benzene, chloramphenicol, propylthiouracil
“Can’t Make New Blood Cells Properly”
Carbamazepine, methimazole, NSAIDs,
benzene, chloramphenicol, propylthiouracil
Drug interactions all result in what complication?
Aplastic anemia
Which drug interactions cause Direct Coombs ⊕
hemolytic anemia as a side effect?
Penicillin, methylDopa, Cephalosporins
“P Diddy Coombs”
Penicillin, methylDopa, Cephalosporins
Drug interactions all result in what complication?
Direct Coombs ⊕
hemolytic anemia
Which drug interactions cause Drug reaction with
eosinophilia and systemic symptoms as a side effect?
Allopurinol, antiBiotics, antiConvulsants, sulfa
drugs
“ABCs”
Allopurinol, antiBiotics, antiConvulsants, sulfa
drugs
Drug interactions all result in what complication?
Drug reaction with
eosinophilia and systemic symptoms
Which drug interactions cause Thrombocytopenia as a side effect?
Indinavir, heparin, quinidine, ganciclovir,
vancomycin, linezolid, abciximab
“I Have Quickly Gotten Very Low Amounts”
Indinavir, heparin, quinidine, ganciclovir,
vancomycin, linezolid, abciximab
Drug interactions all result in what complication?
Thrombocytopenia
Which drug interactions cause Rash (Stevens-Johnson
syndrome) as a side effect?
Anti-epileptic drugs (especially lamotrigine),
allopurinol, sulfa drugs, penicillin
“Steven Johnson has Epileptic Allergy to Sulfa
drugs and Penicillin”
Anti-epileptic drugs (especially lamotrigine),
allopurinol, sulfa drugs, penicillin
Drug interactions all result in what complication?
Rash (Stevens-Johnson
syndrom
Which drug interactions cause Tendon/cartilage
damage as a side effect?
Fluoroquinolones
Fluoroquinolones
Drug interaction results in what complication?
Tendon/cartilage
damage
Which drug interactions cause Myopathy as a side effect?
Statins, fibrates, niacin, colchicine, daptomycin,
hydroxychloroquine, interferon-α,
penicillamine, glucocorticoids
Statins, fibrates, niacin, colchicine, daptomycin,
hydroxychloroquine, interferon-α,
penicillamine, glucocorticoids
Drug interactions all result in what complication?
Myopathy
Where does enfuvirtide act & what does it do?
A → fusion inhibitor
Where do NRTIs and NNRTIS act?
B → NRTIs and NNRTIS
Where does oseltamivir act & what does it do?
C → It inhibits virion release because it’s a neuraminidase inhibitor
Where does a de-Integrase inhibitor act?
D → Integrase inhibitor
Where does Amantadine act, What does it do, & what does it specifically treat?
E → It inhibits uncoating of the influenza A virus only
Fill in the boxes
What is Amantadine?
Clinical use?
Adverse effect?
Classification: NMDA receptor antagonist (antiviral)
MOA:
It blocks the muscarinic receptors to increase DA release and decrease DA reuptake
Clinical use: HIV
Adverse Effects:
1) insomnia
2) dizziness/confusion
3) ankle edema
4) atropine-like, livedo reticularis
What are the azole antifungals?
Fluconazole
Itraconazole
Ketoconazole
Voriconazole
Isavuconazole
Clotrimazole
Miconazole
Clinical uses?
Adverse effects?
MOA:
They Inhibit fungal ergosterol synthesis by inhibiting the 14-alpha-demethylase (a cytochrome P450 enzyme), thereby blocking ergosterol synthesis Inhibits formation of fungal cell membrane (note: no effect on fungal cell wall)
Clinical uses:
1) Local and less serious mycoses
2) Cryptococcal meningitis in AIDS (fluconazole)
3) Candida (fluconazole)
4) Blastomyces
5) Coccidiodes
6) Histoplasma
7) Sporothrix schenckii (itraconazole)
8) Topical fungal infections (clotrimazole, miconazole)
9) Aspergillus (voriconazole, isavuconazole)
Adverse effects:
1) GI upset
2) Antiandrogen (Inhibits testosterone synthesis ie. gynecomastia)
3) Inhibits CYP450 Enzymes which can lead to drug interactions (e.g. with warfarin, theophylline)
4) Hepatotoxicity
(Mild hepatitis and liver dysfunction)
MOA:
They Inhibit fungal ergosterol synthesis by inhibiting the 14-alpha-demethylase (a cytochrome P450 enzyme), thereby blocking ergosterol synthesis Inhibits formation of fungal cell membrane (note: no effect on fungal cell wall)
Clinical uses:
1) Local and less serious mycoses
2) Cryptococcal meningitis in AIDS (fluconazole)
3) Candida (fluconazole)
4) Blastomyces
5) Coccidiodes
6) Histoplasma
7) Sporothrix schenckii (itraconazole)
8) Topical fungal infections (clotrimazole, miconazole)
9) Aspergillus (voriconazole, isavuconazole)
Adverse effects:
1) GI upset
2) Antiandrogen (Inhibits testosterone synthesis ie. gynecomastia)
3) Inhibits CYP450 Enzymes which can lead to drug interactions (e.g. with warfarin, theophylline)
4) Hepatotoxicity
(Mild hepatitis and liver dysfunction)
azole antifungals
Fluconazole
Itraconazole
Ketoconazole
Voriconazole
Isavuconazole
Clotrimazole
Miconazole
What is Nyastatin?
Clinical use?
Adverse effect?
MOA:
It binds to ergosterol to form holes in fungal membranes (unique to fungal membranes) causing membrane holes/pores, allowing electrolytes that cause fungal cell lysis to leak out
Clinical use:
1) Candidiasis (Swish and swallow for oral thrush)
2) Topical for diaper rash/vaginal candidiasis
Adverse effect:
Skin irritation or hypersensitivity
MOA:
It binds to ergosterol to form holes in fungal membranes (unique to fungal membranes) causing membrane holes/pores, allowing electrolytes that cause fungal cell lysis to leak out
Clinical use:
1) Candidiasis (Swish and swallow for oral thrush)
2) Topical for diaper rash/vaginal candidiasis
Adverse effect:
Skin irritation or hypersensitivity
Nystatin
What is Flucytosine?
Clinical use?
Adverse effects?
Antimetabolite:
A fungal DNA polymerase and RNA polymerase inhibitor
MOA:
Flucytosine is converted into 5-fluorouracil (5-FU) by cytosine deaminase a Fluorinated analog of cytosine which inhibits fungal DNA and RNA polymerase thereby blocking DNA replication and fungal protein synthesis
Clinical use:
Used in combination with amphotericin B to treat
1) Cryptococcal meningitis
Adverse effects:
1) Bone marrow suppression (anemia, thrombocytopenia, or leukopenia)
2) Nephrotoxicity
3) Hepatotoxicity
4) Nausea/vomiting
How is Flucytosine cleared?
It is cleared renally so avoid in patients with renal failure
Antimetabolite:
A fungal DNA polymerase and RNA polymerase inhibitor
MOA:
Flucytosine is converted into 5-fluorouracil (5-FU) by cytosine deaminase a Fluorinated analog of cytosine which inhibits fungal DNA and RNA polymerase thereby blocking DNA replication and fungal protein synthesis
Clinical use:
Used in combination with amphotericin B to treat
1) Cryptococcal meningitis
Adverse effects:
1) Bone marrow suppression (anemia, thrombocytopenia, or leukopenia)
2) Nephrotoxicity
3) Hepatotoxicity
4) Nausea/vomiting
Flucytosine
What is Terbinafine?
Clinical use?
Adverse effects?
A squalene oxidase inhibitor (fungal enzyme)
MOA:
It inhibits the synthesis of lanosterol, a precursor to ergosterol, which forms fungal cell membrane
(Cleared via liver metabolism)
Clinical use:
1) Dermatophytosis (tinea) Especially onychomycosis - fungal infections of nails
2) Paracoccidioidomycosis
3) Seborrheic dermatitis
Adverse effects:
1) Headache
2) Loss of taste (dysgeusia) can lead to weight loss,
3) depression/anxiety
4) Hepatotoxicity
5) GI upset
A squalene oxidase inhibitor (fungal enzyme)
MOA:
It inhibits the synthesis of lanosterol, a precursor to ergosterol, which forms fungal cell membrane
(Cleared via liver metabolism)
Clinical use:
1) Dermatophytosis (tinea) Especially onychomycosis - fungal infections of nails
2) Paracoccidioidomycosis
3) Seborrheic dermatitis
Adverse effects:
1) Headache
2) Loss of taste (dysgeusia) can lead to weight loss,
3) depression/anxiety
4) Hepatotoxicity
5) GI upset
Terbinafine?
What are the first line drugs used in the treatment of TB?
“RIPES”
First line drugs -RIPES
1) ISONIAZID (H)
2) RIFAMPICIN (R)
3) PYRAZINAMIDE (Z)
4) ETHAMBUTOL (E)
5) STREPTOMYCIN (S)
First line drugs -RIPES
1) ISONIAZID (H)
2) RIFAMPICIN (R)
3) PYRAZINAMIDE (Z)
4) ETHAMBUTOL (E)
5) STREPTOMYCIN (S)
TB
What is Isoniazid (INH)?
Clinical use?
Adverse effects?
MOA:
It impairs the synthesis of mycolic acid (a key component of mycobacterial cell wall) that must be activated by bacterial catalase-peroxidase (encoded by KatG). It is an inactive pro-drug that must be converted into its active drug by an mycobacterial enzyme
Clinical use:
1) Mycobacteria (especially M. tuberculosis, RIPE therapy for active TB & a Monotherapy for latent TB, TB prophylaxis
Adverse effects:
1) Vitamin B6 (pyridoxine) deficiency
(Isoniazid inhibits pyridoxine phosphokinase, which normally activates vitamin B6 into its active form (PLP))
2) Inhibits CYP450 Enzymes it can lead to drug interactions (e.g. warfarin, theophylline)
3) Drug-induced lupus-like reaction
4) Hepatotoxicity
5) Anion gap metabolic acidosis
MOA:
It impairs the synthesis of mycolic acid (a key component of mycobacterial cell wall) that must be activated by bacterial catalase-peroxidase (encoded by KatG). It is an inactive pro-drug that must be converted into its active drug by an mycobacterial enzyme
Clinical use:
1) Mycobacteria (especially M. tuberculosis, RIPE therapy for active TB & a Monotherapy for latent TB, TB prophylaxis
Adverse effects:
1) Vitamin B6 (pyridoxine) deficiency
(Isoniazid inhibits pyridoxine phosphokinase, which normally activates vitamin B6 into its active form (PLP))
2) Inhibits CYP450 Enzymes it can lead to drug interactions (e.g. warfarin, theophylline)
3) Drug-induced lupus-like reaction
4) Hepatotoxicity
5) Anion gap metabolic acidosis
Isoniazid (INH)
What is Pyrazinamide (PZA)?
Clinical use?
Adverse effects?
an antibiotic used to treat active tuberculosis
MOA:
Exact mechanism is unknown but it is activated by the conversion to pyrazinoic acid by the mycobacterial enzyme pyrazinamidase
(more active at acidic pH (e.g. in macrophage phagolysosomes))
Clinical use:
Active Mycobacterium tuberculosis
(Part of RIPE regimen of rifamycin, isoniazid, pyrazinamide, and ethambutol)
Adverse effects:
1) Hepatotoxicity (Dose-dependent that is synergistic with rifampin’s hepatotoxic effect (also in RIPE treatment for TB))
2) Hyperuricemia/Gout
(Pyrazinamide competes with uric acid for secretion by the kidneys, resulting in increased uric acid levels)
3) Arthralgias8
an antibiotic used to treat active tuberculosis
MOA:
Exact mechanism is unknown but it is activated by the conversion to pyrazinoic acid by the mycobacterial enzyme pyrazinamidase
(more active at acidic pH (e.g. in macrophage phagolysosomes))
Clinical use:
Active Mycobacterium tuberculosis
(Part of RIPE regimen of rifamycin, isoniazid, pyrazinamide, and ethambutol)
Adverse effects:
1) Hepatotoxicity (Dose-dependent that is synergistic with rifampin’s hepatotoxic effect (also in RIPE treatment for TB))
2) Hyperuricemia/Gout
(Pyrazinamide competes with uric acid for secretion by the kidneys, resulting in increased uric acid levels)
3) Arthralgias8
Pyrazinamide (PZA)
What is Chloroquine?
clinical uses?
adverse effects?
develop resistance?
MOA:
It blocks the breakdown of heme to hemozoin by inhibiting heme polymerase it can also cause Heme accumulation is toxic to plasmodia
Treats:
1) Plasmodium spp. (Malaria)
Adverse effects:
1) Retinopathy (Rare chronic use)
2) Myopathy
3) Pruritus (Occurs more commonly in dark-skinned individuals)
4) GI upset
5) Headaches/dizziness
Resistance:
Membrane efflux pump
MOA:
It blocks the breakdown of heme to hemozoin by inhibiting heme polymerase it can also cause Heme accumulation is toxic to plasmodia
Treats:
1) Plasmodium spp. (Malaria)
Adverse effects:
1) Retinopathy (Rare chronic use)
2) Myopathy
3) Pruritus (Occurs more commonly in dark-skinned individuals)
4) GI upset
5) Headaches/dizziness
Resistance:
Membrane efflux pump
Chloroquine
Chloroquine-resistant P. falciparum is treated with which drugs?
artemisinins
atovaquone-proguanil
mefloquine (quinidine analog)
What is Ethambutol?
What is the clinical use?
adverse effects?
MOA:
It inhibits arabinosyltransferase which prevents the production of arabinogalactan, a key component of mycobacterial cell wall
Clinical uses:
1) Mycobacterium tuberculosis
(Part of RIPE regimen of rifamycin, isoniazid, pyrazinamide, and ethambutol)
2) mycobacterium avium complex (MAC)
Adverse effects:
1) Optic neuropathy
Clinically manifests as red-green color blindness, decreased visual acuity, and central scotoma
Reversible with discontinuation of the drug
MOA:
It inhibits arabinosyltransferase which prevents the production of arabinogalactan, a key component of mycobacterial cell wall
Clinical uses:
1) Mycobacterium tuberculosis
2) mycobacterium avium complex (MAC)
Adverse effects:
1) Optic neuropathy
Clinically manifests as red-green color blindness, decreased visual acuity, and central scotoma
Reversible with discontinuation of the drug
Ethambutol
Antimycobacterial cyclic peptide that binds to the 30s ribosomal subunit
Treats:
M. TB, M. kansasi, & MYCOBACTERIUM AVIUM CELLULAR
Adverse effects:
Ototoxicity
Nephrotoxicity
Capreomycin?
MOA:
Inhibits inhA gene & blocks mycolic acid synthesis
Treats: TB & Multidrug resistant TB
Adverse effects:
1) Postural hypotension
2) Depression
3) Drowsiness/anesthenia
4) Neurological toxicity
Recommended to be given with pyridoxine
Ethionamide
MOA:
They bind to 30S ribosomal subunit
Treat:
TB
Mycobacterium Avium Cellular
DIC
the 2ns choice after streptomycin & Capreomycin to treat TB
Adverse effects:
1) Ototoxicity
2) Nephrotoxicity
Kanamycin
Amikacin
MOA:
It inhibits DNA gyrase & topoisomerase
Treats:
TB
used in combination with other drugs to treat multi-drug resistant Mycobacterium Avium cellular in patients with AIDS
Fluoroquinolone
Ciprofloxacin
MOA:
Binds to 30S ribosomal unit prevent formation of ‘initiation complex’ of peptide synthesis
Treats:
bactericidal mainly for extracellular bacilli
Adverse effects:
Ototoxicity
Nephrotoxicity
Hypersensitivity reactions
Anaphylaxis
Rash
Fever
Streptomycin
IM, IV
MOA:
Cycloserine inhibits reactions in which D-alanine is involved in cell wall synthesis
Treats:
TB
Adverse effects:
Peripheral neuropathy
Dizziness tremors
Psychotic changes
Cycloserine
MOA:
A less potent inducer of cyt p450.
Less interactions with PI/NNRTI
Treats:
Better activity
against MAC.
M.leprae/M.fortitum
Adverse effects:
Skin rash
GI intolerance
Hepatitis
Red orange discoloration of urine
Rifabutin
Aminosalicylic acid (PAS)
MOA:
Inhibits folic acid synthesis of bacteria
Treats:
Bacteriostatic
Highly specific to M. TB
Adverse effects:
GI intolerance
HS reactions
Hematological
Abnormalities
What is Bedaquiline?
diarylquinoline
MOA:
It targets C subunit of mycobacterial ATP synthase to Inhibit of proton pump activity.
It is good for shortening the duration of treatment without any increased risk of relapse
Used to treat:
MDR-TB
Adverse effects:
1) AST and/or ALT elevations
2) Amylase and/or lipase elevation
3) Musculoskeletal system abnormalities- myalgia
4) Cardiac rhythm disturbances (prolonged QT interval)
5) Gi issues
diarylquinoline
MOA:
It targets C subunit of mycobacterial ATP synthase to Inhibit of proton pump activity.
It is good for shortening the duration of treatment without any increased risk of relapse
Used to treat:
MDR-TB
Adverse effects:
1) AST and/or ALT elevations
2) Amylase and/or lipase elevation
3) Musculoskeletal system abnormalities- myalgia
4) Cardiac rhythm disturbances (prolonged QT interval)
5) Gi issues
Bedaquiline
What does Pretomanid treat?
Treatment:
XDR-TB or MDR-TB who are treatment-intolerant or non-responsive (collectively “highly drug-resistant TB”)
What are Ifosfamide, Cyclophosphamide
Clinical uses
Classification: alkylating agents
MOA:
They cross-link DNA at guanine (N7) & they need require bioactivation by liver to be activated
Clinical Indications: 1
1) solid tumors
2) leukemia
3) lymphomas
4) rheumatic disease (SLE, granulomatosis with polyangiitis [Wegner’s])
Adverse Effects:
1) alopecia
2) myelosuppression
3) SIADH
4) Fanconi syndrome (ifosfamide)
5) hemorrhagic cystitis and bladder cancer
Classification: alkylating agents
MOA:
They cross-link DNA at guanine (N7) & they need require bioactivation by liver to be activated
Clinical Indications: 1
1) solid tumors
2) leukemia
3) lymphomas
4) rheumatic disease (SLE, granulomatosis with polyangiitis [Wegner’s])
Adverse Effects:
1) alopecia
2) myelosuppression
3) SIADH
4) Fanconi syndrome (ifosfamide)
5) hemorrhagic cystitis and bladder cancer
Ifosfamide & Cyclophosphamide
What is Vincristine?
Clinical use
Adverse effect
An [M-phase specific] microtubule inhibitor
MOA:
It is a vinca alkaloid that binds 𝛃-tubulin and inhibits its polymerization into microtubules which prevents the mitotic spindle formation (M-phase arrest) Overall it decreases microtubule polymerization
Clinical Indications:
1) solid tumors
2) leukemias
3) Hodgkin and non-Hodgkin lymphomas
4) Wilms
Adverse Effects:
1) alopecia
2) SIADH
3) neurotoxicity (areflexia, peripheral neuritis)
4) constipation (paralytic ileus)
no myelosuppression
An [M-phase specific] microtubule inhibitor
MOA:
It is a vinca alkaloid that binds 𝛃-tubulin and inhibits its polymerization into microtubules which prevents the mitotic spindle formation (M-phase arrest) Overall it decreases microtubule polymerization
Clinical Indications:
1) solid tumors
2) leukemias
3) Hodgkin and non-Hodgkin lymphomas
4) Wilms
Adverse Effects:
1) alopecia
2) SIADH
3) neurotoxicity (areflexia, peripheral neuritis)
4) constipation (paralytic ileus)
no myelosuppression
Vincristine
What is Doxorubicin?
Clinical use
Adverse effect
Classification: anthracyclines
MOA:
They generate free radicals which intercalates in the DNA leading to breaks in DNA resulting in decreased replication. It interferes with topoisomerase II enzyme
Clinical Indications:
1) solid tumors
2) leukemias
3) lymphomas
Adverse Effects:
1) cardiotoxicity (dilated cardiomyopathy)
2) myelosuppression, alopecia
Classification: anthracyclines
MOA:
They generate free radicals which intercalates in the DNA leading to breaks in DNA resulting in decreased replication. It interferes with topoisomerase II enzyme
Clinical Indications:
1) solid tumors
2) leukemias
3) lymphomas
Adverse Effects:
1) cardiotoxicity (dilated cardiomyopathy)
2) myelosuppression, alopecia
Doxorubicin
What should you use to prevent cardiotoxicity when giving Doxorubicin?
Use dexrazoxane (iron chelating agent) used to prevent cardiotoxicity
What is Cyclosporine?
Clinical use
Adverse effect
Classification: calcineurin inhibitor
MOA:
It binds cyclophilin that blocks T-cell activation by preventing IL-2 transcription
Clinical Indications:
1) psoriasis
2) rheumatoid arthritis
Adverse Effects:
1) nephrotoxic
2) hypertension
3) hyperlipidemia
4) neurotoxicity
5) gingival hyperplasia
6) hirsutism
What is Ifosfamide & Cyclophosphamide?
clinical use
adverse effects
Classification: alkylating agent (nitrogen mustards)
MOA:
They cross-link DNA at guanine (N7) & they need bioactivation by liver
Clinical Indications:
1) solid tumors
2) leukemia
3) lymphomas
4) rheumatic disease (SLE, granulomatosis with polyangiitis [Wegner’s])
Adverse Effects:
1) alopecia
2) myelosuppression
3) SIADH, Fanconi syndrome (ifosfamide)
4) hemorrhagic cystitis and bladder cancer
(prevented with mesna [sulfhydryl group of mesna binds toxic metabolites] and adequate hydration [cyclophosphamide])
Classification: alkylating agent (nitrogen mustards)
MOA:
They cross-link DNA at guanine (N7) & they need bioactivation by liver
Clinical Indications:
1) solid tumors
2) leukemia
3) lymphomas
4) rheumatic disease (SLE, granulomatosis with polyangiitis [Wegner’s])
Adverse Effects:
1) alopecia
2) myelosuppression
3) SIADH, Fanconi syndrome
4) hemorrhagic cystitis and bladder cancer
(prevented with mesna [sulfhydryl group of mesna binds toxic metabolites] and adequate hydration
cyclophosphamide & ifosfamide
Classification: alkylating agent (nitrogen mustards)
MOA:
They cross-link DNA at guanine (N7) & they need bioactivation by liver
Clinical Indications:
1) solid tumors
2) leukemia
3) lymphomas
4) rheumatic disease (SLE, granulomatosis with polyangiitis [Wegner’s])
Adverse Effects:
1) alopecia
2) myelosuppression
3) SIADH, Fanconi syndrome (ifosfamide)
4) hemorrhagic cystitis and bladder cancer
(prevented with mesna [sulfhydryl group of mesna binds toxic metabolites] and adequate hydration [cyclophosphamide])
Ifosfamide & Cyclophosphamide
What is Doxorubicin?
CLinical uses
Adverse effects
Classification: anthracyclines
MOA:
It generates free radicals through intercalate in DNA causing breaks in DNA resulting in decreased replication which interferes with topoisomerase II enzyme
Clinical Indications:
1) solid tumors
2) leukemias
3) lymphomas
Adverse Effects:
1) cardiotoxicity (dilated cardiomyopathy) (use dexrazoxane (iron chelating agent) used to prevent cardiotoxicity
2) myelosuppression
3) alopecia
Classification: anthracyclines
MOA:
It generates free radicals through intercalate in DNA causing breaks in DNA resulting in decreased replication which interferes with topoisomerase II enzyme
Clinical Indications:
1) solid tumors
2) leukemias
3) lymphomas
Adverse Effects:
1) cardiotoxicity (dilated cardiomyopathy) (use dexrazoxane (iron chelating agent) used to prevent cardiotoxicity
2) myelosuppression
3) alopecia
Doxorubicin
What is Methotrexate?
Clinical uses
Adverse effects
Classification: antimetabolite
MOA:
It is a folic acid analog that competitively inhibits DHF reductase leading to decrease in dTMP resulting in decreased DNA synthesis
Clinical Indications:
1) cancers (leukemia [ALL], lymphoma, & choriocarcinoma sarcoma)
2) non-neoplastic (ectopic pregnancy & medical abortion)
3) rheumatoid arthritis
4) psoriasis
5) IBD
6) vasculitis
Adverse Effects:
1) myelosuppression (reversible with leucovorin [folinic acid] rescue)
2) hepatotoxicity
3) mucositis (mouth ulcers)
4) pulmonary fibrosis
5) folate deficiency
6) nephrotoxicity
Classification: antimetabolite
MOA:
It is a folic acid analog that competitively inhibits DHF reductase leading to decrease in dTMP resulting in decreased DNA synthesis
Clinical Indications:
1) cancers (leukemia [ALL], lymphoma, & choriocarcinoma sarcoma)
2) non-neoplastic (ectopic pregnancy & medical abortion)
3) rheumatoid arthritis
4) psoriasis
5) IBD
6) vasculitis
Adverse Effects:
1) myelosuppression (reversible with leucovorin [folinic acid] rescue)
2) hepatotoxicity
3) mucositis (mouth ulcers)
4) pulmonary fibrosis
5) folate deficiency
6) nephrotoxicity
methotrexate
What are the Tyrosine Kinase inhibitors? (-tinib)?
Imatinib
Gefitinib
Erlotinib
Dasatinib
Sunitinib
Adavosertib
Clinical uses
Adverse effects
MOA:
They are tyrosine kinase inhibitors of BCR-ABL (encoded by Philadelphia chromosome [t(9;22)] fusion gene in CML) and c-kit (common in GIST)
Clinical uses:
1) CML
2) GIST
Adverse E8ffects: fluid retention
MOA:
They are tyrosine kinase inhibitors of BCR-ABL (encoded by Philadelphia chromosome [t(9;22)] fusion gene in CML) and c-kit (common in GIST)
Clinical uses:
1) CML
2) GIST
Adverse E8ffects: fluid retention
What are the adverse effects of Tyrosine Kinase inhibitors? (-tinib)
Imatinib
Gefitinib
Erlotinib
Dasatinib
Sunitinib
Adavosertib
What is Vincristine?
Clinical uses
Adverse effect
Classification: microtubule inhibitors
MOA:
They are vinca alkaloids that bind β-tubulin and inhibit its polymerization into microtubules which prevents mitotic spindle formation (M-phase arrest) to decrease microtubular polymerization
Clinical Indications:
1) solid tumors
2) leukemias
3) Hodgkin and non-Hodgkin lymphomas
4) Wilms
Adverse Effects:
1) alopecia
2) SIADH
3) neurotoxicity (areflexia, peripheral neuritis)
4) constipation (paralytic ileus)
no myelosuppression
Classification: microtubule inhibitors
MOA:
They are vinca alkaloids that bind β-tubulin and inhibit its polymerization into microtubules which prevents mitotic spindle formation (M-phase arrest) to decrease microtubular polymerization
Clinical Indications:
1) solid tumors
2) leukemias
3) Hodgkin and non-Hodgkin lymphomas
4) Wilms
Adverse Effects:
1) alopecia
2) SIADH
3) neurotoxicity (areflexia, peripheral neuritis)
4) constipation (paralytic ileus)
no myelosuppression
Vincristine
What is 6-Mercaptopurine?
Clinical use
Adverse effect
Classification: antimetabolite
MOA:
A purine (thiol) analog that results in decreasing de novo purine synthesis that is activated by HGPRT
Clinical Indications:
1) preventing organ rejection
2) rheumatoid arthritis
3) IBD
4) SLE
Adverse Effects:
1) immunosuppression
2) myelosuppression
3) GI and liver toxicity
(metabolized by xanthine oxidase, therefore, increase risk of toxicity with allopurinol or febuxostat)
Which medication is used to wean patients off steroids in chronic disease and to treat steroid-refractory chronic disease
6-Mercaptopurine
Classification: antimetabolite
MOA:
A purine (thiol) analog that results in decreasing de novo purine synthesis that is activated by HGPRT
Clinical Indications:
1) preventing organ rejection
2) rheumatoid arthritis
3) IBD
4) SLE
Adverse Effects:
1) immunosuppression
2) myelosuppression
3) GI and liver toxicity
(metabolized by xanthine oxidase, therefore, increase risk of toxicity with allopurinol or febuxostat)
adverse effects of 6-Mercaptopurine
List the following adverse effects for:
Cisplatin & Carboplatin
Vincristine
Bleomycin & Busulfan
Doxorubicin
Trastuzumab
Cyclophosphamide
Cisplatin & Carboplatin:
Ototoxicity & nephrotoxicity
Vincristine: Peripheral neuropathy
Bleomycin & Busulfan: Pulmonary fibrosis
Doxorubicin: Cardiotoxicity
Trastuzumab: Cardiotoxicity
Cyclophosphamide: Hemorrhagic cystitis
Topoisomerase inhibitors inhibit which parts of the cell cycle?
Etoposide
Teniposide
Irinotecan
Topotecan
S phase (DNA synthesis)
G2 (Double check repair)
An anticancer drug that inhibits
S phase (DNA synthesis)
G2 (Double check repair)
Topoisomerase inhibitors:
Etoposide
Teniposide
Irinotecan
Topotecan
“Topoisomerase Inhibitors Are Tough Enough”
Antimetabolites inhibit which part of the cell cycle?
Azathioprine
Cladribine
Cytarabine
5-Fluorouracil
Hydroxyurea
Methotrexate
6-Mercaptopurine
An anticancer drug that inhibits
S phase (DNA synthesis)
An anticancer drug that inhibits only
S phase (DNA synthesis)
Antimetabolites:
Azathioprine
Cladribine
Cytarabine
5-Fluorouracil
Hydroxyurea
Methotrexate
6-Mercaptopurine
Bleomycin inhibits which part of the cell cycle?
G2 phase (Double check repair)
An anticancer drug that inhibits only
G2 phase (DNA synthesis)
Bleomycin
Microtubule inhibitors inhibit which part of the cell cycle?
Paclitaxel
Vinblastine
Vincristine
M phase (Inhibits Mitosis)
Which anticancer drug inhibits the M phase (mitosis)?
Microtubule inhibitors
Paclitaxel
Vinblastine
Vincristine
What is Albendazole?
CLinical use?
Adverse effects?
Classification: anthelmintic
MOA:
It decreases the glucose uptake and decrease microtubular structure
Clinical Indications: most intestinal nematodes
Adverse Effects:
1) leukopenia
2) alopecia
3) elevation of LFTs
Classification: anthelmintic
MOA:
It decreases the glucose uptake and decrease microtubular structure
Clinical Indications: most intestinal nematodes
Adverse Effects:
1) leukopenia
2) alopecia
3) elevation of LFTs
Albendazole
What is Bleomycin?
MOA:
An antitumor antibiotic that binds to DNA in the G2 phase of the cell cycle and induces free radical formation to induce DNA breaks
What are Dactinomycin & Actinomycin D?
Clinical uses?
Adverse effects
Dactinomycin and actinomycin D are two interchangeable names for the same intercalating agent.
MOA:
They intercalate into the DNA their molecules insert between two strands of DNA blocking RNA polymerases from accessing DNA strands preventing RNA synthesis in rapidly dividing cells.
Used for childhood tumors:
1) Wilms tumor
2) Ewing sarcoma
3) rhabdomyosarcoma
Adverse effects:
1) Myelosuppression (obvious)
Dactinomycin and actinomycin D are two interchangeable names for the same intercalating agent.
MOA:
They intercalate into the DNA their molecules insert between two strands of DNA blocking RNA polymerases from accessing DNA strands preventing RNA synthesis in rapidly dividing cells.
Used for childhood tumors:
1) Wilms tumor
2) Ewing sarcoma
3) rhabdomyosarcoma
Adverse effects:
1) Myelosuppression (obvious)
Dactinomycin & Actinomycin D
What are Doxorubicin and daunorubicin? (3 ways)
Adverse effects?
Doxorubicin and daunorubicin are chemotherapeutics
MOA:
1) They cause DNA strand breaks by inducing free radical formation
2) They can insert themselves or intercalate into DNA
3) These drugs inhibit topoisomerase II (prevents the enzyme from unwinding or fixing knots in DNA)
Adverse effects:
1) myelosuppression
2) alopecia
3) cardiotoxicity
Doxorubicin and daunorubicin are chemotherapeutics
MOA:
1) They cause DNA strand breaks by inducing free radical formation
2) They can insert themselves or intercalate into DNA
3) These drugs inhibit topoisomerase II (prevents the enzyme from unwinding or fixing knots in DNA)
Adverse effects:
1) myelosuppression
2) alopecia
3) cardiotoxicity
Doxorubicin and daunorubicin
What is Ivermectin?
clinical uses
Adverse effects?
Classification: anthelmintic
MOA:
It intensifies GABA-mediated neurotransmission in nematodes and causes immobilization of parasites, facilitating the removal by the reticuloendothelial system (does not cross BBB)
Clinical Indications:
1) onchocerciasis
2) cutaneous larva migrans
3) strongyloidiasis
4) filariasis
Adverse Effects:
1) fever/headache/
2) dizziness
3) rash/pruritus
4) tachycardia
5) hypotension
6) pain in joints, muscles and lymph glands
contraindicated in pregnancy
Classification: anthelmintic
MOA:
It intensifies GABA-mediated neurotransmission in nematodes and causes immobilization of parasites, facilitating the removal by the reticuloendothelial system (does not cross BBB)
Clinical Indications:
1) onchocerciasis
2) cutaneous larva migrans
3) strongyloidiasis
4) filariasis
Adverse Effects:
1) fever/headache/
2) dizziness
3) rash/pruritus
4) tachycardia
5) hypotension
6) pain in joints, muscles and lymph glands
contraindicated in pregnancy
Ivermectin
Metronidazole
Clinical use
Adverse effects?
Classification: nitroimidazoles (bactericidal & antiprotozoal)
MOA:
It forms toxic free radical metabolites in bacterial cell that damage DNA
Clinical Indications:
1) Giardia
2) Entamoebae
3) Trichomonas
4) Gardnerella vaginalis
5) Anaerobes (Bacteroides, C. difficile) –– can be used in place of amoxicillin in H. pylori ‘triple therapy’ in case of penicillin allergy
Adverse Effects:
1) disulfiram-like reaction (sever flushing, tachycardia, hypotension) with alcohol
2) headache
3) metallic taste
Classification: nitroimidazoles (bactericidal & antiprotozoal)
MOA:
It forms toxic free radical metabolites in bacterial cell that damage DNA
Clinical Indications:
1) Giardia
2) Entamoebae
3) Trichomonas
4) Gardnerella vaginalis
5) Anaerobes (Bacteroides, C. difficile) –– can be used in place of amoxicillin in H. pylori ‘triple therapy’ in case of penicillin allergy
Adverse Effects:
1) disulfiram-like reaction (sever flushing, tachycardia, hypotension) with alcohol
2) headache
3) metallic taste
Metronidazole
What is Isoniazid?
Clinical use
adverse effects
Classification: antituberculosis
MOA:
It decreases the synthesis of mycolic acid. It needs bacterial catalase peroxidase (encoded by KatG) in order to convert INH to active metabolite
Clinical Indications:
1) mycobacterium tuberculosis (only agent used as solo prophylaxis against TB and monotherapy for latent TB)
Adverse Effects:
1) hepatoxicity
2) hemolysis in G6PD deficiency
3) cytochrome P-450 inhibition
4) drug-induced SLE
5) anion gap metabolic acidosis
6) vitamin B6 deficiency (peripheral neuropathy, sideroblastic anemia)
7) seizures (high doses –– refractory to benzodiazepines) –– administer with pyridoxine
Classification: antituberculosis
MOA:
It decreases the synthesis of mycolic acid. It needs bacterial catalase peroxidase (encoded by KatG) in order to convert INH to active metabolite
Clinical Indications:
1) mycobacterium tuberculosis (only agent used as solo prophylaxis against TB and monotherapy for latent TB)
Adverse Effects:
1) hepatoxicity
2) hemolysis in G6PD deficiency
3) cytochrome P-450 inhibition
4) drug-induced SLE
5) anion gap metabolic acidosis
6) vitamin B6 deficiency (peripheral neuropathy, sideroblastic anemia)
7) seizures (high doses –– refractory to benzodiazepines) –– administer with pyridoxine
Isoniazid
How do organisms develop resistance to Isoniazid?
Mechanism of Resistance:
mutations leading to under expression of KatG
What is a Sulfonamide?
Sulfamethoxazole (SMX)
Sulfisoxazole
Sulfadiazine
Clinical use
Adverse effects?
Classification: folic acid synthesis inhibitor
MOA:
They inhibit dihydropteroate synthase, thus inhibiting folate synthesis it is a bacteriostatic (bactericidal when
combined with trimethoprim)
Clinical Indications:
1) Gram-positive organisms (e.g. Nocardia)
2) gram negative
Adverse Effects:
1) hypersensitivity reactions
2) hemolysis if G6PD deficient
3) nephrotoxicity (tubulointerstitial nephritis)
4) photosensitivity
5) SJS
6) kernicterus in infants
7) displace other drugs from albumin
Classification: folic acid synthesis inhibitor
MOA:
They inhibit dihydropteroate synthase, thus inhibiting folate synthesis it is a bacteriostatic (bactericidal when
combined with trimethoprim)
Clinical Indications:
1) Gram-positive organisms (e.g. Nocardia)
2) gram negative
Adverse Effects:
1) hypersensitivity reactions
2) hemolysis if G6PD deficient
3) nephrotoxicity (tubulointerstitial nephritis)
4) photosensitivity
5) SJS
6) kernicterus in infants
7) displace other drugs from albumin
Sulfonamides
Sulfamethoxazole (SMX)
Sulfisoxazole
Sulfadiazine
How do organisms develop resistance to Sulfonamides?
Through altered enzyme (bacterial dihydropteroate synthase), decrease uptake or increase PABA synthesis
What is Dapsone?
Classification: sulfones
MOA:
inhibit dihydropteroate synthase, to inhibit folate synthesis it is a bacteriostatic (bactericidal when combined with trimethoprim)
Clinical Indications:
1) leprosy
2) PJP prophylaxis or treatment when combined with TMP
Adverse Effects:
1) hemolysis if G6PD deficient
2) methemoglobinemia
3) agranulocytosis
Classification: sulfones
MOA:
similar to sulfonamides, but structurally distinct
They inhibit dihydropteroate synthase, thus inhibiting folate synthesis it is a bacteriostatic (bactericidal when combined with trimethoprim)
Clinical Indications:
1) leprosy
2) PJP prophylaxis or treatment when combined with TMP
Adverse Effects:
1) hemolysis if G6PD deficient
2) methemoglobinemia
3) agranulocytosis
Dapsone
What is 6-Mercaptopurine?
Clinical use
Adverse effect
Classification: antimetabolite
MOA:
A purine (thiol) analog leading to decrease de novo purine synthesis that is activated by HGPRT
Clinical Indications:
1) preventing organ rejection
2) rheumatoid arthritis
3) IBD
4) SLE –– used to wean patients off steroids in chronic disease and to treat steroid-refractory chronic disease
Adverse Effects:
1) immunosuppression
2) myelosuppression
3) GI and liver toxicity (metabolized by xanthine oxidase, therefore, increase risk of toxicity with allopurinol or febuxostat)
Classification: antimetabolite
MOA:
A purine (thiol) analog leading to decrease de novo purine synthesis that is activated by HGPRT
Clinical Indications:
1) preventing organ rejection
2) rheumatoid arthritis
3) IBD
4) SLE –– used to wean patients off steroids in chronic disease and to treat steroid-refractory chronic disease
Adverse Effects:
1) immunosuppression
2) myelosuppression
3) GI and liver toxicity (metabolized by xanthine oxidase, therefore, increase risk of toxicity with allopurinol or febuxostat)
6-Mercaptopurine
What is Primaquine? & what does it treat?
Adverse effects?
Classification: antiprotozoal
Mechanism of Action: unknown?
Clinical Indications:
1) P. vivax
2) P. ovale
3) PJP
Adverse Effects:
1) GI distress
2) pruritus
3) headache
4) methemoglobinemia
5) blood cytopenia’s
6) hemolysis in G6PD deficiency
Contraindicated in pregnancy
Classification: antiprotozoal
Mechanism of Action: unknown?
Clinical Indications:
1) P. vivax
2) P. ovale
3) PJP
Adverse Effects:
1) GI distress
2) pruritus
3) headache
4) methemoglobinemia
5) blood cytopenia’s
6) hemolysis in G6PD deficiency
Contraindicated in pregnancy
Primaquine
What are Tyrosine Kinase Inhibitors (-tinib)?
What do they treat?
What are the adverse effects?
MOA:
They are tyrosine kinase inhibitors of BCR-ABL (encoded by Philadelphia chromosome [t(9;22)] fusion gene in CML) and c-kit (common in GIST)
Clinical Indications:
1) CML
2) GIST
Adverse Effects: fluid retention
MOA:
They are tyrosine kinase inhibitors of BCR-ABL (encoded by Philadelphia chromosome [t(9;22)] fusion gene in CML) and c-kit (common in GIST)
Clinical Indications:
1) CML
2) GIST
Adverse Effects: fluid retention
Tyrosine Kinase Inhibitors (-tinib)
What is aspirin?
clinical use
Adverse effect
Classification: NSAID
MOA:
An NSAID that irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) by covalent acetylation leading to decrease synthesis of TXA2 and prostaglandins. It increases bleeding time but doesn’t effect PT & PTT
Clinical Indications:
1) decrease platelet aggregation (low dose)
2) antipyretic and analgesic (intermediate dose)
3) anti-inflammatory (high dose)
Adverse Effects:
1) gastric ulceration
2) tinnitus (CN VIII)
3) allergic reactions (patients with asthma or nasal polyps)
4) acute kidney injury (chronic)
5) interstitial nephritis
6) GI bleeding
7) Risk of Reye syndrome in children treated with aspirin for viral infection
Classification: NSAID
MOA:
An NSAID that irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) by covalent acetylation leading to decrease synthesis of TXA2 and prostaglandins. It increases bleeding time but doesn’t effect PT & PTT
Clinical Indications:
1) decrease platelet aggregation (low dose)
2) antipyretic and analgesic (intermediate dose)
3) anti-inflammatory (high dose)
Adverse Effects:
1) gastric ulceration
2) tinnitus (CN VIII)
3) allergic reactions (patients with asthma or nasal polyps)
4) acute kidney injury (chronic)
5) interstitial nephritis
6) GI bleeding
7) Risk of Reye syndrome in children treated with aspirin for viral infection
Aspirin
Respiratory alkalosis early, but transitions to mixed metabolic acidosis-respiratory. Describes which toxicity?
treatment of overdose: NaHCO3-.
What is Ibuprofen?
clinical use
adverse effect
Classification: NSAID
MOA:
It reversibly inhibit cyclooxygenase (1 & 2) to block prostaglandin synthesis
Clinical Indications:
1) antipyretic
2) analgesic
3) anti-inflammatory
Adverse Effects:
1) interstitial nephritis
2) gastric ulcer (prostaglandins protect gastric mucosa)
3) renal ischemia (prostaglandins vasodilate afferent arteriole)
4) aplastic anemia
Classification: NSAID
MOA:
It reversibly inhibit cyclooxygenase (1 &2 ) to block prostaglandin synthesis
Clinical Indications:
1) antipyretic
2) analgesic
3) anti-inflammatory
Adverse Effects:
1) interstitial nephritis
2) gastric ulcer (prostaglandins protect gastric mucosa)
3) renal ischemia (prostaglandins vasodilate afferent arteriole)
4) aplastic anemia
Ibuprofen
What is Nitrofurantoin?
What is it’s clinical use?
What are the adverse effects?
Classification: anthelmintic
MOA: Bactericidal and bacteriostatic
Clinical Indications:
1) UTI (not Proteus or Pseudomonas)
Adverse Effects:
1) GI distress
2) rash
3) pulmonary infiltrates
4) phototoxicity
5) neuropathies
6) hemolysis in G6PD deficiency
Classification: anthelmintic
MOA:
bactericidal and bacteriostatic
Clinical Indications:
1) UTI (not Proteus or Pseudomonas)
Adverse Effects:
1) GI distress
2) rash
3) pulmonary infiltrates
4) phototoxicity
5) neuropathies
6) hemolysis in G6PD deficiency
Nitrofurantoin
What can Augmentin (Amoxicillin-Clavulanate) & Unasyn (Amoxicillin-Sulbactam) treat?
Acute sinusitis
Animal bites
Aspiration pneumonia
