Pharm Roop Part 2 Flashcards
A 56 year old man presents to the ED with a productive cough. Temp. = 103F. Chest x-ray shows pneumonia on left lower lobe. Sputum and blood cultures taken. Pt receives IM injection of PCN G. The following day the symptoms have not improved. Result of cultures = S. pneumoniae not sensitive to PCN. What type of bacterium is S. pneumoniae?
-Streptococcus pneumoniae are lancet-shaped, gram-positive, facultative anaerobic bacteria
»Usually find them in pairs
»Facultative anaerobic- if oxygen is present, it will make ATP with oxygen but it oxygen is low it will use anaerobic methods to make ATP
What is the MOA of PCN to sensitive bacteria?
-kills susceptible bacteria by specifically inhibiting the transpeptidase that catalyzes the final step in cell wall biosynthesis, the cross-linking of peptidoglycan
-First gen penicillin → G and V do this
Biochemically, what are B-lactam antibiotics? Which antibiotics fall into this class?
-Has beta lactam ring → 3 carbons, 1 nitrogen
-B-lactams bind to transpeptidase active site on the bacteria
antibiotics that make up b-lactam class:
-Penicillin
-cephalosporin (gen1-5)
-monobactams
-carbapenems
-beta lactamase inhibitors
The target for the B-lactams are known collectively as penicillin binding proteins (PBPs)
What are β-lactamases?
-enzymes produced by the bacteria that inactivate the antibiotics by hydrolyzing the peptide bond of the lactam ring
-Beta lactam ring = active part of penicillin
-4 classes of b-lactamases
»class A → extended spectrum beta lactamases (ESBLs)
-“Chasing the bacteria”
-Some class A and D enzymes are inhibited by β-lactamase inhibitors, e.gs. clavulanate and tazobactam.
There also other methods by which the bacteria can become resistant to antibiotics
A 68 year old woman has contracted an S. epidermidis infection that is not methicillin resistant. An infectious disease specialist recommends a penicillinase-resistant PCN. What does penicillinase resistant mean? Name the drugs in this class that are available in the U.S
-penicillinase-resistant [also referred to as second generation penicillins] are semisynthetic modifications of natural penicillins that are resistant to bacterial enzyme B-lactamase and are used to treat staphylococcal and streptococcal bacterial infections
Drugs in the class
-Methicillin (not available in the US)
-nafcillin (highly resistant to penicillinase)
-oxacillin
-cloxacillin (not in US)
-dicloxacillin
-MRSA → stopped using methicillin because it caused high incidence of nephritis, lots of side effects
MRSA are resistant to all the penicillinase- resistent PCNs, and the cephalosporins
»»Now use vancomycin for MRSA
-Anything ending with “cillin” is likely a 2nd gen penicillin
A 7 year old girl has had otitis media for the past three days. She is given a prescription for amoxicillin. After the first dose her mother notices the child’s lips are swollen and she is having slight difficulty in breathing. She is taken to the ED where she is diagnosed with a PCN allergy and the medication is discontinued. This is a hypersensitivity reaction. What is a hypersensitivity reaction?
-Exaggerated immune response to something innocuous
»Allergens or haptens
»Mild things like dander, body sees it as foreign when it binds to our proteins
Type 4 = delayed
Type 1-3 = immediate
This child has type 1 hypersensitivity
What is otitis media?
middle ear infection
A 7 year old girl has had otitis media for the past three days. She is given a prescription for amoxicillin. After the first dose her mother notices the child’s lips are swollen and she is having slight difficulty in breathing. She is taken to the ED where she is diagnosed with a PCN allergy and the medication is discontinued. This is a hypersensitivity reaction. This means that PCN and their breakdown products combine with body proteins and act as haptens or allergens. What is the most abundant breakdown product of PCN that accounts for 75% of all hypersensitivity reactions?
-Penicilloyl → major allergenic determinant)
»When you break the beta lactam ring
Allergy to penicillin → do you have a higher chance of being allergic to those in the group?
-Anaphylaxis = major reaction you can get with allergy to PCN
-If MILD → you should monitor them if you’re giving them another beta lactam antibiotic (ie. keflex)
What are the differences among the now, five generations of cephalosporins?
Cephalosporins are antimicrobials grouped into five generations based on their spectrum of coverage against gram-positive and gram-negative bacteria and their discovery
1st generation has mainly gram-positive activity
2nd and 3rd generation has more gram-negative activity with decreased activity against gram-positive bacteria
3rd generation:
-When given IV can penetrate the BBB
-Ceftriaxone (Rocephin) has a half-life of approx. 8 hours and so can be given in one dose.
-Effective against gonorrhea and disseminated Lyme disease
4th generation
-broad spectrum of activity
-Cefepime can penetrate the CSF
5th generation
-Ceftaroline has activity against Gram-positive bacteria, including MRSA
A 43-year-old man has a gram-negative bacterial infection and is being treated with aztreonam. To what subclass of beta-lactam antibiotics does aztreonam belong? What is unique about it?
-First member of monobactams
-Active against gram negative aerobic bacteria and inactive against gram positive bacteria
-The only monobactam currently approved by the FDA against gram negative bacteria
A 64-year-old woman develops a severe sore throat after caring for her three-year-old grandson who has similar symptoms. Pt has type 2 diabetes. She is given amoxicillin and clavulanic acid (Augmentin). Clavulanic acid is a β-lactamase inhibitor. What does this mean, and what are the other drugs in this class?
Amoxicillin = 3rd gen penicillin
Clavulanic acid = Beta-lactamase inhibitor
»Inhibits the bacteria producing beta lactamase
»First generation
Other 1st gen b-lactamase inhibitors=
-sulbactam and tazobactam
Carbapenems have broad antibacterial spectrum and include imipenem (most commonly used), meropenem, doripenem and ertapenem. Imipenem is marketed primarily in combination with cilastatin. It is not absorbed well from the GI tract, and so it is given _____ and _____. It is metabolized by renal dehydropeptidase. Cilastatin inhibits renal dehydropeptidase thereby…..
IM and IV
prolonging the action of the antibiotic
The MOA of penicillin is….
the disruption of the synthesis of peptidoglycan
All of the following are beta-lactamase inhibitors except:
A) aztreonam
B) sulbactam
C) culvanic acid
D) tazobactam
A) aztreonam (its a 1st gen monobactem)
Which of the following is not a type of beta lactam antibiotics?
A) penicillins
B) carbapenems
C) cephalosporins
D) aminoglycosides
D) aminoglycosides
