Flashcards in Exam 7: Penicillins Deck (45):
Name 4 natural penicillins
Penicillin G Procaine
Penicillin G Benzathine
Name 3 Penicillinase Resistant Penicillins. What are they used for?
* Anti staphylococcal penicillins!!
Penicillinase is Beta lactamase
2 Extended Spectrum Penicillins
* Extended coverage includes gram negatives that penicillin G doesnt have goo coverage against
Name 2 anti-pseudomonal penicillins
Ticarcillin + Clavulanate potassium
Piperacillin + Tazobactam
* If the question has a patient infected with pseudomonas, pick one of these.
* one ring structure, as opposed to the rest of the beta lactase, which are 2 ringed.
Imipenem + Cilustatin
* These have the broadest spectrum of the penicillin family members on our drug list
2 Beta lactamase inhibitors
* Dont have antibacterial activity on their own. They are used to prevent beta lactamase from breaking down other penicillin antibiotics (overcome resistance)
Name 3 combinations containing beta lactam antibiotics.
Augmentin (Amoxicillin + Clavulanic acid)
Timentin (Ticarcillin + Clavulanic acid)
Zosyvn (Piperacillin + Tazobactam)
* they'll give us both the brand name and the generics
Describe the structure of penicillin family members
6-aminopenicillanic acid is the core structure (except for Azetreonam)
Intact ring structure is required for antibacterial activity
R groups differ between family members and result in different properties.
Beta Lactam Mechanism
BACTERICIDAL (kill, don't just inhibit growth)
Inhibit bacterial cell wall synthesis by inhibiting Transpeptidase (aka Penicillin Binding Protein PBP)
Transpeptidase normally crosslinks cell wall precursors
This leads to lysis and killing of the bacteria
Penicillin resembles (mimics) the normal substrate of Transpeptidase
Good selective toxicity because human cells don't have cell walls.
4 Mechanisms of resistance to Penicillins
1. Enzymatic destruction of penicillin by cleaving open the beta lactam ring (most important). There are many different types of Beta Lactamases (penicillinases). Their production can be induced by penicillin drugs. We can use Beta lactamase inhibitors to combat this (Clavulanic acid)
2. Production of high molecular weight PBPs that have low affinity for penicillin family members. MRSA and many Strep pneumo types use this. Can sometimes be over come with high doses of penicillin.
3. Gram negative bacteria have outer membranes that can prevent penicillin from penetrating and reaching their site of action. They can have porins that can allow penicillin in, but some don't (Pseudomonas), and the porins can become down regulated.
4. Efflux pumps can spit the drug out of the bacteria once it gets in. Especially seen in gram negatives.
Pharmacokinetics of Penicillins
Variable oral absorption, usually given 1-2 hrs after meal. Except Amoxicillin, which can be given with food.
Mostly moderately protein bound except for the antistaphylococcals.
Tissue concentrations usually equal plasma concentrations.
Dont cross BBB, reach prostate, or reach eye very well.
** During meningitis, the BBB is compromised, which can allow Penicillins into the CSF.
Rapidly excreted by the kidneys (mostly by tubular secretion). Probenecid can block this tubular secretion and therefore increase plasma levels of penicillins.
Must adjust dose in patients with compromised renal function (i.e. premature infants)
Which Penicillins are highly protein bound?
** Anti staphylococcals
More binding leaves less free to fight infection. This can result in clinical failure.
How can penicillins treat meningitis if they don't cross the BBB?
They can cross the BBB during meningitis because the BBB becomes leaky due to the disease.
Which penicillins are mostly excreted via the bile?
They don't need adjusted doses with renal compromise, but might need adjustment in with liver failure.
**** This will be a test question
Adverse effects of penicillins
1. Hypersensitivity reactions can happen in response to the intact drugs or to their degradation products. Even people who've never received a penicillin can have anti-penicillin antibodies. This happens more commonly with IV and Topical administration than with oral administration. if you're allergic to one, you're probably allergic to the rest.
2. Hyperkalemia, hypernatremia because theyre given as salts (large doses)
3. Can cause seizures (don't inject directly into CSF). Antagonize GABA. high blood levels can cause this (seen in renal failure, drugs that compete for organic acid secretion)
What is the major antigenic determinant for Penicillins?
This is a degradation product the binds to tissue proteins and causes production of anti penicillin antibodies.
What type of hypersensitivity reaction is a penicillin allergy?
Type 1 (1-72 hours)
Mediated by IgE Abs which trigger the release of histamine from mast cells.
How can penicillin allergies present?
Skin reactions (rash, hives, angioedema)
Respiratory tract- dyspnea, wheezing
CV- Hypotension, tachycardia, arrhythmia
Fatality is rare, but possible.
How do we test for penicillin allergy?
Skin testing (Pre-Pen only contains Major Antigenic determinant, Benzyl penicilloyl)
This only tests for Type I Hypersensitivities. It does not predict the likelihood of Types II, III, IV reactions.
What can you do if a patient really needs a Penicillin, but is allergic?
Starting with a low dose and slowly increasing dosing into therapeutic range
This causes a slow release of histamine from mast cells so that when you give the big doses, they don't have a massive reaction.
Make sure to have antihistamine, epinephrine, and maybe corticosteroids ready in case they have a reaction.
Additional adverse effect of Methicillin
Type IV Hypersensitivity mediated by T Cells
This is why we don't use Methicillin anymore in the US
What is a strange side effect that can be seen with Ampicillin and Amoxicillin?
Non-allergic reactions 1-28 days after treatment
More likely to happen if the person has a viral infection (EBV)
What causes NVD with Penicillin usage?
Killing off of gut NF.
Also predisposes patient to superinfections (pseudomembranous colitis, fungal infections)
What are the major causative organisms of Acute Otitis Media?
Strep pneumo (GPC)
H. influenzae (nontypable) (GNR)
Moraxella catarrhalis (GNC)
Can also be viral.
We definitely want to target Strep pneumo, because it is the least likely to resolve on its own.
Penicillin G vs Penicillin V
Both Natural Penicillins
Penicillin V is more acid stable, therefore is better absorbed orally.
Penicillin G is given IV, V is given Orally
Penicillin G tends to be used for more serious infections
Pen G and V
Resistance is a big problem, especially with Staph aureus
Pneumococcal meningitis is usually sensitive, treat empirically until you prove it is sensitive
Good at treating Strep pharyngitis
Treats enterococcal endocarditis in combination with an aminoglycoside
Treats Neisseria g./m. and Clostridium sp.
resistance is a problem.
Penicillin G is Highly active against Treponema Pallidum (Syphilis)
Also treats Actinomyces israeleii
What form of Penicillin G is given IM?
Penicillin G + Procaine or Benzathine
The added drugs act like a local anesthetic, and make it much less painful.
Results in slow release into the blood and long duration of action. Better compliance.
Don't inject them into a nerve...
May be more likely to cause development of penicillin G
Use of Penicillin G IM (w/ benzathine)
Often used for Strep pharyngitis (Strep pyogenes)
Rheumatic fever prophylaxis
What is special about Methicillin, Nafcillin, Oxacillin?
They have a bulky R group that resists breakdown by Staphylococcal beta-lactamases (Nafcillin is most resistant).
Good for treating Staph infections.
Their dose DOES NOT need to be adjusted with renal impairment because they're secreted in the bile.
** Might need to adjust dose for patients with decreased liver function
Methicillin, Nafcillin, Oxacillin Uses
Cant use them if it's MRSA
NOT EFFECTIVE against gram negative.
What drugs are used to treat MRSA?
a bunch of other stuff...
Extended spectrum penicillins
Better than Penicillin G with gram negatives because they're better at penetrating the outer membrane
Susceptible to breakdown by beta lactamases. Often combined with beta lactamase inhibitors (clavulanic acid)
Spectrum of Amoxicillin, Ampicillin
H influenzae (URI)
E coli (UTI)
Listeria (meningitis in babies, immunocompromised)
Moraxella catarrhalis (very resistant, use combo with beta lactamase inhibitor)
Enterococcus faecalis (Gram + cocci)
Ampicillin, Amoxicillin drug interaction
Decrease effectiveness of oral contraceptives.
What drug shouldn't we mix with Penicillin in the same IV solution? Why not?
Penicillins are negatively charged, aminoglycosides are positive. They will react and deactivate each other.
Good against gram negative bacilli (Pseudomonas, Klebsiella)
Synergistic with aminoglycosides
Used to treat Community acquired pneumonia
Used to treat nocosomial pneumonia, in combo with aminoglycosides
Also used in serious gram negative infections
Less sodium (better for CHF patients) than Ticarcillin.
Less bleeding that Ticarcillin.
Highly resistant to Beta Lactamase enzymes produced by gram negatives.
Active against MDR-Pseudomonas a.
*** Does NOT cause allergic reactions in patients allergic to other Penicilins!!!
Carbapenem (Widest spectrum of the penicillins)
Is broken down quickly by a dipeptidase in the proximal tubule. We give it with Cilastatin because it inhibits this enzyme and prevents Imipenem's breakdown (other Carbapenems don't need this protection)
Very resistant to most Beta Lactamases
High affinity for PBPs
Eliminated by the kidneys (adjust dosage in renal failure)
Useful against more than 90% of clinically important bugs (some MRSA, C diff, and Enterococcus are resistant)
Reserved for serious infections in hospitalized patients.
Carbapenems Adverse effects
Induce beta lactamase production (can cause resistance to other antibiotics)
Seizures (w/ renal failure especially)
What types of Beta lactamases are best inhibited by beta lactamase inhibitors?
Those encoded in plasmids
When do we use Augmentin?
UTIs caused by resistant bacteria
Human and animal bite wounds (good activity against Staph aureus and anaerobes)
What do you do if you're treating AOM with Amoxicillin, but it isn't working?
The bug is resistant. Try Augmentin because it could be a beta lactamase producing bug.
You could also try Ceftriaxone or Clindamycin