Flashcards in Pharmacology 3.13 Deck (36):
How does inflammation affect drugs' ability to penetrate the blood brain barrier?
increase permeability by opening up junctions between the endothelial cells
Which type of antimicrobials are optimal to treat meningitis?
bactericidal agents in high doses; less phagocytic cells present
What is the relationship between ionization and solubility in terms of how effective drugs are in crossing the blood brain barrier?
-high lipid solubility
Why is so much penicillin/ceftriaxone needed to treat S. pneumoniae infections in the CNS?
resistant isolates have penicillin-binding proteins (PBPs) with decreased affinity for penicillin
Why is the MIC breakpoint different for CNS and Non-CNS S. pneumoniae infections?
breakpoint based on ability to achieve therapeutic blood levels at the site of infection
Why is vancomycin often added to ceftriaxone when treating meningitis caused by S. pneumoniae?
-S. pneumoniae is only 89% susceptible to ceftriaxone
-100% susceptible to vancomycin
What is the primary regimen for treating meningitis in an adult?
-ceftriaxone (S. pneumoniae)
-vancomycin (drug-resistant S. pneumoniae)
-dexamethasone (inflammation; reduce TNF-alpha production)
+ ampicillin (if Listeria is suspected etiology/OLD AGE)
What is de-escalation for treating meningitis?
-initially give entire drug cocktail
-once etiology is known, only give antimicrobial which matches infection source
When is antibiotic prophylaxis indicated for meningitis?
NOT: S. pneumoniae
**only for close contacts
What is the most common etiology of encephalitis?
Herpes simplex virus
What is the suggested treatment for suspected encephalitis?
1) acyclovir (all viral)
2) doxycycline (tick-bourne infections)
What is the MOA of acyclovir?
inhibit nucleic acid synthesis within the nucleus of the infected cell
What is required for acyclovir activation and how is its activation initiated?
-requires 3 phosphorylation steps
-initiated by viral kinase [allows drug to only be active in infected cells]
Against which viruses is acyclovir active?
HSV I and II
What is the MOA of flucytosine?
-inhibits DNA and RNA synthesis within the nucleus of the fungal cell
-5-FU allows for selective cytotoxicity
What is the MOA of amphotericin B?
-leads to pore in the cell membrane
-causes cell to leak electrolytes and die
What is the MOA of echinocandins?
-inhibits beta-glucan synthase
-disrupts cell wall synthesis
What is the black box warning of flucytosine?
-extreme caution in patients with impaired renal function
-metabolism in GI leads to conversion into fluorouracil causing bone marrow and GI toxicity
What are the echinocandins used in practice?
What is the spectrum of echinocandins?
-inhibits ergosterol synthesis
What is the most important thing to consider when administering an azole antifungal?
-potential for causing drug-drug interactions via:
-CYP 3A4 inhibition
What is the de-escalation for fluconazole?
high bioavailablility allows for quick de-escalation from IV to oral
What are the side effects of Amphotericin B Deoxycholate?
-fever and chills from infusion
-phlebitis (vein inflammation)
-renal loss of K+ and Mg++
What was done to combat some of the side effects of amphotericin B?
(but more expensive)
-lack of efficacy data
-medication errors from product confusion due to dosage differences
Which specific infection is amphotericin B preferred over fluconazole?
Which specific infection is fluconazole preferred over other anti-fungals?
What is the MOA of tetracycline?
-inhibition of protein metabolism at 30S ribosomal subunit
What is parrot fever?
-pneumonia caused by Chlamydia psittaci; found in birds
-treat with doxycycline (tetracycline)
What is Rocky Mountain Spotted Fever treated with?
**doxycycline and tigecycline
Which drug typically causes discoloration of teeth in kids under the ago of 8?
What is the etiology and clinical presentation of drug-induced photosensitivity?
-large amount of sun exposure causes exaggerated sunburn
-small aount of sun exposure causes antibody formation and presents as dermatitis
What are the drug interactions with tetracyclines?
GI absorption decreased when taken with:
-calcium (and dailry products)
What are the methods of tetracycline resistance?
-ribosomal protection proteins
**tigecycline created to overcome these bacterial resistance mechanisms**
Which antimicrobials can be used to treat Gr- organisms producing a carbapenemase (KPC, NDM)?