ID Beta-Lactams Flashcards
Penicillins MOA
Bind to PCN-binding proteins on bacterial cell wall/membrane; destroy cell wall by inhibiting transpeptidase (enzymes that cross-link peptidoglycan molecules to add strength) causing lysis (bacteriocidal)
Penicillins AE
Allergic reaction, n/v/d
Cephalosporins MOA
Bind to PCN-binding proteins on bacterial cell wall/membrane; destroy cell wall by inhibiting transpeptidase (enzymes that cross-link peptidoglycan molecules to add strength) causing lysis (bacteriocidal)
Cephalosporin AE
Cross-reactivity to penicillin; pseudomembranous colitits; bone marrow suppression; nephrotoxicity
Penicillins Prototype Drug
Penicillin G, Penicillin V
Cephalosporins Prototype Drug
First-generation: cephalexin; second-generation: cefaclor, cefuroxime; third-generation: ceftazidime; fourth-generation: cefepime
Carbapendems Prototype Drug
Imipenem (always combined with cilastatin to inhibit hydrolyzation by renal tubular dipeptidase)
Carbapendems MOA
Bind to PCN-binding proteins on bacterial cell wall/membrane; destroy cell wall by inhibiting transpeptidase (enzymes that cross-link peptidoglycan molecules to add strength) causing lysis (bacteriocidal)
Carbapendems AE
n/v, fever, imipenem may cause seizures
Glycopeptides Prototype Drug
Vancomycin
Glycopeptides MOA
Inhibit cell wall synthesis by attaching to the end of the peptidoglycan precursor units (D-alanyl-D-alanine terminus), thereby stopping peptidoglycan synthesis; bacteriocidal
Glycopeptides AE
Flushing (red man syndrome), neutropenia; in rare cases: ototoxicity when combined with another ototoxic agent & nephrotoxicity
Fluoroquinolones Prototype Drug
Ciprofloxacin
Fluoroquinolones MOA
Inhibit DNA gyrase (aka topoisomerase II) in gram-neg organisms and topoisomerase IV in gram-pos organims; bacteriocidal
Fluoroquinolones AE
Generally well-tolerated; n/v/d; tendon ruptures
Aminoglycosides Prototype Drug
Gentamicin
Aminoglycosides MOA
- Inhibit protein synthesis by irreversibly binding the 30S ribosomal subunit; at low concentrations, they cause misreading of the mRNA by ribosomes; at high concentrations, they halt protein synthesis, trapping ribosomes at the AUG start codon 2. create fissures and pores in the outer cell membrane, resulting in leakage of intracellular contents and increased antibiotic uptake
Aminoglycosides AE
Ototoxicity, nephrotoxicity (indicated by an increase in serum creatinine)
Lincosamides Prototype Drug
Clindamycin
Lincosamides MOA
Bind the 23S rRNA molecule of the 50S ribosome and inhibit peptidyl transferase, blocking the transfer of the new amino acid onto the growing chain; bacteriostatic; beneficial in toxin-producing infections
Lincosamides AE
Pseudomembranous colitis (extremely high incidence of C. diff)
Tetracyclines Prototype Drug
Tetracycline
Tetracycline MOA
First enter microorganism, then bind reversibly to 16S sununit of the 30S ribosome and inhibits translation; bacteriostatic; Demecloclycline inhibits the binding of ADH to its receptor
Tetracyclines AE
Significant n/v/d; mottling of teeth d/t Ca binding; photosensitivity; superinfection; diabetes insipidus; liver damage; kidney damage
Macrolides Prototype Drug
Erythromycin
Macrolides MOA
Bind to bacterial 50s ribosome and inhibit peptidyl transferase, blocking the transfer of the new amino acid onto the growing chain. Inhibition of protein synthesis does not typically kill bacteria cells, so these agents are generally bacteriostatic , but in high concentrations they can be bactericidal.
Macrolides AE
Significant GI upset due to increased gut motility; Acute cholestatic hepatitis . Are better tolerated but can also cause liver impairment
Oxazolidinones Prototype Drug
Linezolid
Oxazolidinones MOA
blocks the translocation step of protein synthesis by binding the 23S rRNA of the 50S RSU. Therefore bacteriostatic. Can also result in human mitochondrial suppression (mitochondrial inhibitor) causing rare but serous side effects.
Oxazolidinones AE
Rare but serious. Serotonin Syndrome, Hyperlactatemia and Metabolic Acidosis, Nerve Damage (neuropathies), and Hematologic (bone marrow suppression and low blood count)
Sulfonamides Prototype Drug
Sulfamethoxazole
Sulfonamides MOA
inhibitors of folate sythesis (bacteriostatic)
Sulfonamides AE
Crystalluria, hematuria, nausea, vomiting, diarrhea, photosensitivity, hypersensitivity. Rare and Serious: Stevens-Johnson Syndrone (SJS), Blood Cell Problems (hemolytic Anemia, Aplastic Anemia, Thrombocytopenia), Kernicterus (jaundice in newborns)
Metronidazole Prototype Drug
Metronidazole
Metronidazole MOA
Prodrug: ferredoxin reduces nitrogen side chain from drug which results in production of toxic products that damage DNA. Effective for anaerobic bacteria
Metronidazole AE
Nausea, Metallic Taste, CNS toxicity (ataxia, encephalopathy, siezure), RARE: neutropenia, pacreatitis, peripheral neuropathy, hepatitis
Ethambutol Prototype Drug
Ethambutol (EMB or E)
Ethambutol MOA
Disrupts formation of the tuberculous cell wall by blocking arabinosyl transferases. bacteriostatic , suppress the growth of TB but does not kill it
Ethambutol AE
Neurologic, ( Optic neuritis, perminant blindness, red-green color blindness, peripheral neuropathy)Rash, and Fever
Isoniazid Prototype Drug
Isoniazid (INH or H)
Isoniazid MOA
Inhibits mycobacterial cell wall synthesis
Isoniazid AE
Hepatitis, Peripheral Neuropathy, mild CNS effects, and Rash
Pyrazinamide Prototype Drug
Pyrazinamide (PZA or Z)
Pyrazinamide MOA
Prodrug: first needs to be converted to pyrazinoic acid by a mycobacterial enzyme called pyrazinamidase. This inhibits cell wall synthesis by inhibiting enzyme called fatty acid sythase I .Drug is active only if the bacterium is in an acidic environment
Pyrazinamide AE
Serous: Hepatic Injury (drug induced hepatitis) More Common: Arthalgia (joint pain), Increased uric acid, Anorexia, Nausea and Vomiting
Rifamycins Prototype Drug
Rifampin (rifampicin)
Rifamycins MOA
Inhibit bacterial RNA sythesis by binding prokaryotic (bacterial) RNA polymerase. bactericidal for extracellular and intracellular bacteria. is highly lipophilic
Rifamycins AE
Common: Discoloration of secretions (tears, urine, sweat, stool, saliva), Cholestatic Jaundice and Hepatitis, Rash Rare but Serous: Acute interstitial nephritis (AIN) and Thrombocytopenia
CCR5 Antagonists Prototype Drug
Maraviroc
CCR5 Antagonists MOA
Block interaction of gp120 (HIV envelope glycoprotein on cell surface-eventually binds w/ CCR5 to initiate conformational change) w/ CCR5 (chemokine coreceptor), preventing viral entry into human cells; Patients w/ HIV may express CXCR4 or CCR5 or a combo of both (“dual-mixed”); CCR% antagonists typically used for those w/ CCR5; use of CCR5 antagonists in patients who are dual-mixed leads to selection of CCRX4 & resistance
CCR5 Antagonists AE
Antiretrovirals typically administered in combo regimens therefore tough to decipher side effects; However, postural hypotension & syncope is common; Hepatotoxicity (rare); Cardiovascular events such as MI
Fusion Inhibitors Prototype Drug
Enfuvirtide
Fusion Inhibitors MOA
Mimics the HIV machinery required to fuse to the CD4 cell; Competes with the HIV proteins & prevents entry of the virus into the CD4 cell; gp120 binds HIV & activates gp41–>gp41 changes conformation & creates pore into cell–>enfuvirtide binds gp41 & prevents conformational change
Fusion Inhibitors AE
Injection site irritation; Peripheral neuropathy
Integrase Inhibitors Prototype Drug
Raltegravir
Integrase Inhibitors MOA
Responsible for incorporating viral DNA into the host genome; Prevent the formation of covalent bonds w/ host DNA therefore preventing incorporation of HIV into host genome
Integrase Inhibitors AE
Well-tolerated
Nucleoside Reverse Transcriptase Inhibitors Prototype Drug
Zidovudine
Nucleoside Reverse Transcriptase Inhibitors MOA
An enzyme that transcribes viral RNA into viral DNA; Upon entry into the cell are converted to nucleotides by host cell kinases; The nucleotides then compete w/ endogenous nucleosides for incorporation into viral DNA; act as competitive inhibitors of reverse transcriptase; Once incorporated into DNA, cause termination of DNA chain (halts viral replication); also inhibit host cell DNA polymerase; not specific for HIV-1 however nonnucleoside may act directly against HIV-1
Nucleoside Reverse Transcriptase Inhibitors AE
Myalgia; Headache; Diarrhea; Lactic acidosis; Lipodystrophy; Peripheral neuropathy; Pancreatitis; Hepatotoxicity; Bone marrow suppression; Hypersensitivity; Acute renal failure; Stomatitis & oral ulcers
Nonnucleoside Reverse Transcriptase Inhibitors Prototype Drug
Nevirapine
Nonnucleoside Reverse Transcriptase Inhibitors MOA
bind to a site distant from the active site of the reverse transcriptase and induce a conformational change in the enzyme; NO ACTIVITY against DNA polymerase; Binding is very specific to reverse transcriptase
Nonnucleoside Reverse Transcriptase Inhibitor AE
Rash (macular or papular- pruritic); Rash may progress to Stevens-Johnson syndrome; Hepaptitis (more common in females during pregnancy, result of hypersensitivy reaction);
Protease Inhibitors Prototype Drug
Saquinavir
Protease Inhibitors MOA
Disrupts viral maturation; Bind to proteases and prevent viral maturation which produces immature, noninfectious virus particles
Protease Inhibitors AE
GI (n/v/d); Hyperlipidemia; Lipodystrophy (fat redistribution); Hyperglycemia/insulin resistance (inhibit activity of glucose transporter GLUT-4); Crystalluria/nephrolithiasis; Hyperbilirubinemia
Uncoating Inhibitors Prototype Drug
Amantadine
Uncoating Inhibitors MOA
Prevents the virus from uncoating not allowing the viral DNA to be translated into mRNA; Uncoating is mediated by a M2 protein which serves as a proton channel facilitating the dissociation of the RNA-protein complex; This dissociation is pH-dependent so when drug prevents the influx of protons through M2, prevent dissociation from occuring; may also inhibit a late step of viral assembly
Uncoating Inhibitors AE
CNS-Amantadine (nervousness, lightheadedness, difficulty concentrating, insomnia); Loss of appetite, Nausea
Neuroaminidase Inhibitors Prototype Drug
Zanamivir
Neuraminidase Inhibitors MOA
Influenza viruses possess 2 surface glycoproteins. Changes in these result in new diseases year after year; cleave the sialic acid residues that are bound to viral hemagglutinin & result in the release of new virus from cells; block the cleavage of sialic acid residues & prevent the release of new virus from early infected cells (earlier administration of drug is more successful)
Neuraminidase Inhibitors AE
Bronchospasms may occur/worsening of respiratory symptoms; GI symptoms (n/v/abd cramping)
Nucleoside Analogues Prototype Drug
Acyclovir
Nucleoside Analogues MOA
Act as DNA polymerase inhibitors; Reduces DNA synthesis & viral replication; Serve as guanosine analogs; Important step in viral life cycle = synthesis of viral DNA; Viral & host cell kinases convert the nucleoside analogues to active nucleoside triphosphates; Nucleoside triphosphates compete w/ viral DNA polymerase for part of the primer strand of viral DNA; Some nucleoside analogues (acyclovir & valacyclovir) cause chain termination when incorporated into DNA strand; Penciclovir inhibits DNA elongation; Selective toxicity based upon (1) affinity for HSV thymidine kinase 200x greater for viral enzyme than human enzyme & (2) greater affinity for viral vs. human DNA polymerase
Nucleoside Analogues AE
Nausea & diarrhea, Rash, Headache, CNS (confusion, hallucinations, tremor) - Acyclovir & valacyclovir - Esp. renal patients; Nephrotoxicity - Acyclovir & valacyclovir; UNIQUE Hematologic (leukopenia, thrombocytopenia); Reproductive (aspermatogenesis)
