Beta-Lactams and Aminoglycosides Flashcards
What is one of the most commonly used AMDs?
The penicillin’s
What are the two main beta-lactams we learnt about?
- Penicillin’s (Penicillin G and Amoxicillin)
- Cephalosporins
Why are the Beta-Lactams named that way/what is unique about them?
- they have a beta-lactam ring
- the ring can be destroyed by enzymes secreted by some bacteria
- temperature sensitive, the ring can be destroyed by warming or freezing
What is the mechanism of action of the penicillin’s?
- inhibit cell wall synthesis
- only affects growing bacteria because the beta-lactams bind to and inactivate the transpeptidase enzyme
- so when cell division occurs and new cell walls are made, the cell wall is defective and when they go to divide they lyse and die
Which type of bacteria do penicillin’s tend to work best against?
Gram-positive with a thick peptidoglycan layer
Why do penicillin’s have a tough time against gram negative bacteria?
- transpeptidases differ and may not bind well to the penicillin
- the external bilayer can be difficult to penetrate
- some bacteria secrete penicillinases into the periplasm
What are the main pharmokinetics of the penicillin’s?
- distribute well to extracellular fluids excep the CNS and prostate
- acid stability varies so some cannot be given orally
- short half lives (<2h)
- no metabolism so there is renal excretion of unaltered drug
What are the main adverse effects of penicillin?
- Hypersensitivity: as soon as you think of penicillin, think allergy
- Colitis in hindgut fermenters: if administered orally they can disturb gut flora so there is risk of serious GI disturbance
- Breakthrough seizures in epileptics: beta-lactams inhibit GABA receptors in the brain, allowing chlorine to freely flow in and cause action potentials
What are two instances we tend to see penicillin resistance?
- poor penetration of the outer bilayer in gram-negative bacteria
- acquired bacterial penicillinases that destroy the beta-lactam ring
What kind of spectrum does Penicillin G have and what does it affect most?
- narrow spectrum
- gram positive aerobes and anaerobes
How do we typically administer penicillin G?
Parenterally because it is not acid stable
What formulation do we typically use for Penicillin G and why?
- Depot formulation consists of penicillin bound to procaine or benzathine which allows for slower release of the drug = longer duration of action
- if you don’t use this formulation, you’ll have to administer frequently
What spectrum does Amoxicillin have and what is it typically effective against?
- extended spectrum penicillin
- gram positive aerobes, anaerobes and a variety of gram negative aerobes
Would you ever administer amoxicillin orally?
Yes, is has an oral bioavailability that exceeds 90%
What are potentiated penicillins?
Combination of broad-spectrum antibiotic with beta-lactamase inhibiting effect. Bacterial penicillinases can be inactivated with penicillinase inhibitors such as clavulanic acid.
What is the mechanism of action of cephalosporins?
Inhibit cell wall synthesis
What is the distribution, elimination and main adverse effects of cephalosporins?
Similar to penicillins!
- distributed well except CNS and prostate
- not metabolized so excreted whole in urine
- hypersensitivity, colic in hindgut fermenters, increase in seizure activity
What are the main differences of cephalosporins from penicillin’s?
- most are not acid stable so ineffective orally
- 3rd generation cephalosporins are effective against gram negative aerobes
- some 3rd generation cephalosporins enter the CNS
- there is a small link between those with a penicillin allergy and cephalosporin allergy so to be safe avoid both in those individuals
- cephalosporins are more resistant to beta-lactamases than the penicillin’s
What is the cephalosporin spectrum of activity?
1st Generation:
- similar to amoxicillin (GP aerobes, anaerobes and some GN aerobes)
- orally we use cephalexin in SA
- parenterally we use cefazolin or cephapirin
3rd Generation:
- mainly used against GN aerobes, some effectiveness against GP aerobes and anaerobes
- ceftiofur widely used
- Cefovecin (Convenia) has a very long half life with a 2-week formulation that almost guarantees inappropriate duration
What are the two main uses of aminoglycosides?
- systemic admin. for dangerous GN aerobic infections
- topical
What is the mechanism of action for aminoglycosides?
Inhibit protein synthesis
- some aminoglycosides will cause the wrong AA to be incorporated into growing protein forming a lethal porin (pore in membrane)
What are some key characteristics of aminoglycosides?
- highly ionized = limited ability to cross membranes (safe for use in eye)
- must be given parenterally for systemic treatment
- gentamicin is the most widely used drug in this group
What is the spectrum of activity of aminoglycosides?
- gram negative aerobes
- Some GP aerobes (Staph including MRSA and MRSP)
- Atypical bacteria like mycoplasma
What are two ways we typically see resistance in the aminoglycosides?
- constitutive: entry of drug into cell requires oxygen-dependent transport that anaerobes don’t have so AGs are completely ineffective against anaerobes
- plamsid-acquired: aminogycosidase (enzyme)
