Exam 7: Penicillins Flashcards
Name 4 natural penicillins
Penicillin G
Penicillin B
Penicillin G Procaine
Penicillin G Benzathine
Name 3 Penicillinase Resistant Penicillins. What are they used for?
Methicillin Nafcillin Oxacillin * Anti staphylococcal penicillins!! Penicillinase is Beta lactamase
2 Extended Spectrum Penicillins
Ampicillin
Amoxicillin
* 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.
1 Monobactam
Aztreonam
* one ring structure, as opposed to the rest of the beta lactase, which are 2 ringed.
1 Carbapenem
Imipenem + Cilustatin
* These have the broadest spectrum of the penicillin family members on our drug list
2 Beta lactamase inhibitors
Clavulanic acid
Tazobactam
* 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
- 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)
- 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.
- 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.
- 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?
Nafcillin (90%) Oxacillin (94%) Dicloxaclillin (98%) ** 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?
Nafcillin
Oxacillin
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
- 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.
- Hyperkalemia, hypernatremia because theyre given as salts (large doses)
- 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?
Benzyl penicilloyl
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)
Immediate hypersensitivity
Mediated by IgE Abs which trigger the release of histamine from mast cells.
