Pharmacology Flashcards
Identify non-opioid analgesics
and NSAIDs
non-opioid analgesics- Acetaminophen
NSAIDs non-selective COX inhibitors (aspirin, ibuprofen, naproxen) -inhibit both COX 1 and 2 equaly
Selective COX-2 inhibitors (celecoxib).
Explain the mechanism of action of non-steroidal anti-inflammatory (NSAIDs) medications
Arachidonic acid produces COX. NSAIDs inhibit COX metabolites- prostaglandins, thromboxane, and prostacyclin.
The downstream effects INCLUDE- alteration of vascular permeability, brochial constriction, increased secretion, brochospasm, INFLAMMATION.
Describe the difference between COX1 and COX 2 inhibition
COX-1
Expressed in most tissues
Regulates normal cellular processes: Gastric protection-mucosa Vascular homeostasis Platelet aggregation Kidney function
Generates- cytoprotective prostaglandins
Stimulated by hormones or growth factors
Inhibited by NSAIDs, aspirin
COX-2
Undetectable in most tissues
Expression increased during states of inflammation
Generates pro-inflammatory prostaglandins
Constitutively expressed in the brain, kidney, bone, and female reproductive system
Expression inhibited by glucocorticoids, NSAID, aspirin, Cox-2 inhibitors.
Recognize toxicities of NSAIDs
Side effects-
Hypertension/ dizziness/ HA
Myocardial infarction, congestive heart failure
Rash
Nausea, abdominal pain
Gastric erosion/ ulceration/ bleeding/ perforation
Inhibition of platelet activation, bleeding
Edema, sodium retention
Nephrotoxicity, urinary retention
Toxicity
GI- COX-1 especially, COX-2 easier on the GI
Cardiac COX-2 increased risk of MI
Describe cell damage associated with inflammation
Histamine Cytokines Lysosmal compounds from neutrophils Prostaglandins & leukotrienes Synthesized from arachidonic acid Eicosanoids Signaling molecules in inflammation
what are the physiologic effects of NSAID use?
Analgesia
Antipyretic-fever reduction
Anti-inflammatory
Anti-platelet
You can reach a ceiling with the analgesic effect so sever pain usually treated with opioids.
what are selective and non selective COX inhibitors? How are they used differently?
non-selective mild or moderate pain, decrease inflammation or fever.
selective-osteoarthritis, RA
What’s Reyes syndrome
acute non-inflammatory encephalophathy- increase risk is children with viral infections taking aspirin as treatment.
If you have a patient taking both aspirin and ibuprofen why would you suggest they take aspirin first and then ibuprofen later in the day?
Aspirin irreversibly binds platelets and ibuprofen does so reversibly and if given first would competitively bind the same platelets thus reducing aspirins effect.
How is arachidonic acid formed?
Directly from cell membrane phospholipids via phospholypase A2
Which enzyme is constitutivley active and which is induced by NSAIDs?
COX-1 constitutivley active
COX-2 is inducable
What is the function of transpeptidase? In MRSA what protects it from penicillin?
Transpeptidase provides bacterial cell wall rigidity by cross linking peptide chains together. Penicillin distrupts this process by binding to transpeptidase (PBP).
With MRSA the bacteria has a unique PBP so penicillins can’t bind to it.
a
the bacteria has beta-lactamases which target penicillin (beta lactam anti-biotic), preventing it from disrupting the stregth of the cell wall. This is why these drugs are delivered with a beta lactamase inhibitor so the penicillin can reach its target (PBP).
What are the 3 main types of beta lactamases bacteria produce to combate beta lactam antibiotics? What is their activity like?
ESBL (extended spectrum β-lactamases). Bind penicillins and 3rd gen cephalosporins
KPC (Klebsiella pneumoniae
NDM (New Delhi Metallo-β-lactamases)
last two are carbapenemases and degrade all beta lactams. More outbreak related.
What are the drugs of choice for group A strep?
Penicillin G
Penicillin V
Drugs of choice for MSSA? What about MRSA?
Beta-lactamase resistant b/c their structure is different. MSSA produces beta-lactamases but these drugs are not made with the classic ring structure.
Oxacillin
Nafcillin
Dicloxacillin
MRSA is resistant to penicillin because it has a different PBP (transpeptidase).
Aminopenicillins have what type of activity: name the two primary types
limited G- activity. Weak
ampicillin and amoxicillin, work better with a beta lactamase inhibitor, but still not as good as the extended spectrum penicillins.
Extended spectrum penicillins (ESP) only available with what? what are their names?
only available with beta lactamase inhibitors
Ticarcillin w/ clavulanic acid
Piperacillin with tazobactam
What’s key to remember with penicillin pharmakodynamics? Whats the most classic therapeutic drug interaction? What infections can penicillin treatment lead to?
Its a time dependent killer rather than concentration dependent. Just keep above the MIC for a long period of time.
Probenicid- gout drug extends its half life
C.diff
what are the top 3 G- isolates from infected patients?
E.coli
Klebsiella pneumoniae
Pseudomonas aeruginosa
Points of interest with Bacteroides fragilis
G- anaerobic, resistant to pen due to beta lactamase activity.
What’s the best treatment for P. aeruginosa?
Pip-tazo
What does Vancomycin like to kill? What’s its mechanism of binding, and how is resistance formed? How should it be administered? What’s the cool side effect from administering the drug to quickly?
MRSA
G+ aerobes and anaerobes
Binds ALA-ALA on peptide chain of cell wall and prevents PDG cross linking (stops transpeptidase from doing its job)
Resistant strains (vancomycin resistant enterococcus VRE) have D-lactate to replace ALA and prevent binding
Oral for C.diff
IV for MRSA
Why? It doesn’t absorb well so it work well in the intestines (C.diff), but not in the body where you would need it for MRSA.
Too fat=red neck syndrome
