Pharmacology - Antibiotics Flashcards
Bacteriostatic or bactericidal: beta-lactams
bactericidal
Mechanism of action: beta-lactams
bind and inhibit penicillin binding proteins which are needed to catalyze the cross-linking (transpeptidation) of the peptidoglycan layer of bacterial cell walls; When PBPs are inactivated by β-lactam antibiotics, bacterial enzymes that hydrolyze the peptidoglycan cross-links during cell wall remodeling continue to function, which breaks down the cell wall further. The accumulation of peptidoglycan precursors also triggers activation of cell wall hydrolases, with further digestion of intact peptidoglycan. The end result is bac- terial rupture.
Why do different beta-lactam antibiotics have different spectrums of activities?
bacteria possess multiple penicillin binding proteins, which vary in their affinities for different beta-lactams; inhibition of PBP1a and PBP1b leads to cell lysis, whereas inhibition of PBP2 results in rounded cells called spheroblasts. Drugs that produce rapid lysis (e.g., carbapenems) are the most bactericidal and have highest affinity for PBP1.
Mechanisms of resistance to beta-lactams?
Beta-lactamase production, altered penicillin binding proteins (e.g. PBP2a), exclusion of drugs that normally diffuse through porins to their site of action
Time or concentration-dependent: beta-lactams
time-dependent
T/F: Beta-lactamase inhibitors possess weak intrinsic antibacterial activity.
TRUE
Method of excretion: penicillins
rapid renal elimination - active drug is concentrated in the urine
MIC for gram-negative vs gram-positive bacteria: penicillins
Penicillin MICs are generally higher for gram- negative bacteria than gram-positive bacteria; therefore, higher penicillin dosages may also be needed for gram-negative bacte- rial infections.
What are cephalosporins derived from?
Acremonium
Spectrum of activity: Cephalosporins
As the generation increases, there is an increase in gram-negative spectrum, and fourth-generation drugs have truly broad-spectrum activity
T/F: Cephalosporins are resistant to extended-spectrum beta-lactamase.
False: extended-spectrum β-lactamase (ESBL) enzymes can hydrolyze even third-generation cephalosporins and present an important therapeutic challenge
Method of excretion: 1st generation cephalosporins
excreted unchanged in the urine
What third generation cephalosporins are approved for use in small animals?
ceftiofur, cefpodoxime proxetil, and cefovecin
Adverse effects: cephalosporins
GI signs, hypersensitivity reactions; false-positive results on test strips that use copper reduction for urine glucose detec- tion. Certain cephalosporins, such as cefotetan and ceftriaxone, may exacerbate bleeding tendencies due to vitamin K antago- nism.8 Reversible bone marrow suppression has been reported in dogs given high doses of ceftiofur, cefonicid, and cefazedone long-term
What is ceftiofur approved for in small animals?
urinary tract infections in DOGS
Mechanism of action: carbapenem
They penetrate the outer membrane of gram- negative bacteria more effectively than many other β-lactam antibiotics and bind to a variety of PBPs, which leads to rapid lysis of a broad spectrum of bacteria
Adverse effects: imipenem
Imipenem is degraded by dehydropeptidase-1, a brush border enzyme in the proximal renal tubules, which results in produc- tion of an inactive metabolite that is nephrotoxic. In order to prevent nephrotoxicity and maximize imipenem’s antibacterial activity, imipenem is administered with cilastatin, which inhib- its the dehydropeptidase-1 enzyme
Adverse effects: carbapenems
vomiting, nausea, and pain on injection. Neurologic signs, including tremors, nystagmus, and seizures, can occur following rapid infusion of imipenem-cilastatin or in animals with renal insufficiency. Imipenem must be administered slowly in intravenous fluids. Slow administration is not required for meropenem
Mechanism of action: glycopeptides
cyclic glycosylated peptide antimicrobials that inhibit the synthesis of peptidoglycan by binding to amino acids (d-alanyl-d-alanine) in the cell wall, preventing the addi- tion of new units
Antibiotic class: Vancomycin?
glycopeptide
Bacteriostatic or bactericidal: glycopeptides
Bactericidal (vancomycin)
Mechanism of resistance to vancomycin?
Resistance to vancomycin results from bacterial alteration of the terminal amino acid to which vancomycin binds.
Adverse effects: vancomycin
histamine release after rapid infusion
Mechanism of action: fluoroquinolones
bind to DNA gyrase (AKA topoisomerase II) and topoisomerase IV – enzymes that cleave DNA during DNA replication. The result is disruption of bacterial DNA and protein synthesis