Pharmacology Session 8

So this maybe the longest post to date and there are a lot of very complex topics discussed. We go over antibiotics, antivirals, and anti-fungals. There is a very strong correlation to each class and their prefix or suffix, so pay close attention to the minor differences between them. Within each class there is very little deviation from the prototype drug discussed so as long as the class can be identified then the other traits should be easy to understand. Happy studying!

-Peter

Session 8

Pharmacology

  1. how are people exposed to antibiotics in their environment?
    1. in  the drinking water and in the food we eat.
  1. why do some people not finish their antibiotics?
    1. feel better, the dosing schedule, and can give you are yeast infection
  1. the most important action to prevent the spread of infection is to
    1. wash hands
  2. John is an alcoholic and develops cellulitis. whis is the factors that increase johns susceptibility to infection?
    1. poor nutritional status (could be poor circulation if the cellulitis is in the periphery)
  3. Monitoring you pt given a penicillin type drug, what should be especially assessed.
    1. allergic reaction
  4. why use Augmentin vs, amoxicillin alone for otitis media
    1. bacterial susceptibility is increased because augmentin can stop beta lactamase
  5. vancomycin pt should be monitored for what?
    1. ototoxicity
  6. what is a common side effect of Clindamycin
    1. frequent, bloody, watery stool
  7. fluoroquinolones are classified as_____ and are especially effective against _____
    1. antibacterial, P. aeruginosa
  8. life threatening systemic fungal infections may be treated with
    1. amphotericin B
  9. Most common bacteria that cause UTI?
    1. E. coli
      1. outpatient: Klebsiella, Proteus, Pseudomonas, Enterobacter
      2. In patient: Staph, Enterococci, 80% E. coli.

Basic principles of antimicrobial therapy

Antibiotic – kill (bactericidal) or weaken (bacteriostatic)

Selective toxicity – the trait of an antibiotic that can harm/kill a bacteria while leaving the host (patient) unharmed.

  • This is the basis for their therapeutic use.

Classify the antibiotic to choose more effective medication

  • susceptibility of the organism
    • aerobic vs anaerobic, Gram+ vs Gram-, and the different classes of bacteria
  • narrow versus broad spectrum
    • Narrow: Penicillin, erythromycin, Clindamycin
    • Broad: Ampicillin, tetracyclines, cephalosporins 3 and 4 gen, fluoroquinolones
  • MOA(mechanism of action) inhibitors
    • Bactericidal:
      • stop cell wall synthesis
        • Penicillin, cephalosporin, and vancomycin
      • stop protein synthesis which is bactericidal and bacteriostatic.
        • Aminoglycosides, Macrolides, tetracyclines
      • inhibit nucleic acid synthesis
        • Fluoroquinolones and Metronidazole
      • viral enzyme inhibitors? (either maybe)
    • Bacteriostatic:
      • Change cell membrane permeability
        • Antifungal and Amphotericin B
      • stop the metabolites of the bacteria
        • sulfonamides
    • getting a great pt hx is important to the treatment of the disease
    • admin of antimicrobials
      • GI upset is not an allergy
      • IV watch for extravasation, and phlebitis
      • IM can cause necrosis w/ some of the antimicrobials
      • S/E and allergic reactions
        • allergic: penicillins are the most common then cephalosporins and sulfonamides.
          • don’t give the drug if allergic
          • patient should have ID band to show that they are allergic
  • always ask for allergies before giving antibiotic!!
      • Superinfections are most common with broad spectrum antibiotics that are not selective enough and kill the patient’s normal flora as well.
  • PT education
    • complete the entire therapy
    • q12 hr is different than twice a day
  • minimum bactericidal concentration is the least amount of the drug needed to kill the bacteria
  • minimum inhibitory concentration is the least amount of drug needed to inhibit bacterial growth
  • misuses of antimicrobial drugs
    • viral or fungal infections
    • fever, if there is no next step to try and identify the bacteria or source
    • improper dose
    • no culture of the bacteria
    • no surgical drainage of

drugs by MOA

  • drugs that weaken the cell wall through stopping synthesis of the wall
      • Penicillins
        • bactericidal in gram positive bacteria
        • safe to humans b/c we do not have cell walls
        • D/D interactions with anticoags increase bleeding, contraceptives with estrogen can cause PEN to no be effective
        • beta lactam ring weakens the cell wall
          • beta lactamASE is used by some bacteria, breaks up the ring in the drug to make the drug ineffective
        • unstable absorption when taken orally
        • very thick and viscous IM needs to be givin Z track. it is thick and a lot of pressure is needed to administer.
        • few side effects, but 5% of the population has an allergic reaction
        • PenASE (beta lactamase) makes bacteria resistant to Penicillins
        • Classes of Pen.
          • Pen G
            • Benzylpenicillin
              • narrow specturom, and sensitive to penASE
              • Bac-cidal to G+
              • prophylaxis in dental/invasive procedures for endocarditis and syphilis
          • Dicloxacillin
            • Narrow, PenASE resistant
            • Treat staph
          • Aminopenicillins
            • Ampicillin, Amoxicillin (broad spectrum)
            • G+ and some G- are treated
            • S/E: rash and Diarrhea
          • Extended spectrum Penicillins
            • Ticarcillin
            • Piperacillin
            • less important Carbenicillin indanyl, and mezlocillin
        • Ampicillin and sulbactam is Unasyn
        • Amoxicillin and Clavulanic acid is Augmentin
      • Cephalosporins
        • break down cell wall, for G+ and an increasing effectiveness with G-
        • bactericidal, and more resistant to PenASE than penacilin
        • spectrum broadens from gen 1 and 2 (narrow) to gen 3 and 4 are broad
        • ADME: poorly absorbed through PO route, no metabolism, excreted in kidneys and stool
        • allergy in 10% of people w/ the pen allergy
        • four generations: they all have the Cef- or Ceph- prefix.
      • Cabapenems
        • Imipenem (primaxin)
        • broad spectrum
        • resistant to beta lactam break down (penASE resistant)
        • used in Pseudomonas aeruginosa
        • Superinfections are an adverse effect as well and an allergic RXN
      • Aztreonam
        • Narrow, G-, Renal elimination, and given parenterally
      • Vancomycin (Lyphocin)
        • inhibit Cell wall synthesis
        • most used antibiotic in the US
        • for MRAS, C diff, G+, prophylaxis endocarditis
        • ADME: PO is ok with this drug, altered taste, Ototoxicity, redneck syndrome if given to quick IV
  • bacteriostatic inhibitors of protein synthesis
      • Tetracycline
        • Broad spectrum
  • Effective through PO route
        • for acne, lyme Dx, H. pylori, Cholera, Riskettsia, cholera
        • chelation occurs when calcium, Iron, and magnesium containing supplements and foods inactivate the tetracycline and cause it to be inactive
          • do not take with meals!
          • one hour before or two hours after meals to avoid chelation
  • S/E: photosensitivity, brown teeth, not ok for mothers pregnant and breastfeeding moms, do not give to kiddos.
      • Macrolides (Erythromycin)
        • Broad spectrum
        • inhibits bacterial protein synthesis
        • use is allergic to penicillin
        • for G+
        • long QT interval
        • S/E: GI upset, cholestatic hepatitis, superinfection
        • D/D: interacts with CCB, HIV protease inhibitors, and antifungal increase the serum levels of erythromycin
      • Clindamycin (Cleocin)
        • inhibits protein synthesis
        • only for anaerobic infections such as in the gums, colon, sepsis
          • not effective in the CNS
        • Can give orally (IM,IV as well)
        • S/E: pseudomembranous colitis severe bloody diarrhea, Hepatic and renal toxicity, hypersensitivity
  • inhibit protein synthesis and are bactericidal
      • Aminoglycosides
  • can cause injury to ear and kidney
  • oto-(nonreversible) and nephrotoxicity
        • narrow spectrum G-
  • Draw peak and trough
  • Draw peak at 30mins after administration
  • trough at 1 hour before the next dose is given
        • bactericidal
      • Types:
        • Gentamicin
          • for G- serious infections
          • nephro and ototoxicity
        • Neomycin is the most toxic and causes rash as well
  • Amikacin patient may respond better to this drug if other aminoglycosides are not working.
  • Disrupt synthesis of folic acid, Antimetabolites
      • TMP/SMZ
        • Bactrim or Septra
  • Sulfa drug
            • inhibits folic acid
          • broad spectrum
          • collect urine sample before giving any antibiotic
          • used in UTI G+ or G-
          • Hypersensitivity reaction results in stevens- johnson syndrome
            • Bc it is a sulfa drug
        • UTI is usually caused by e. coli
          • some elderly pts can have bacteria in the bladder and be asymptomatic and done not necessarily need to be treated.
      • Phenazpyridine
        • turns urine and contact lenses reddish orange
    • MAC: mycobacterium avium complex infection.
      • people with HIV have this ½ the time
      • 2 bacteria: M. avium, and M. intracellulare
      • -thromycin for prophylaxis  
    • Fluoroquinolones:
      • CiproFLOCACIN
        • Broad spectrum
        • inhibits DNA gyrase in bacteria
        • Tendon rupture!!! do not give to kiddos under 18
        • undergo chelation just like
    • antibacterial and antiprotozoal drug
      • flagyl
        • works in anaerobes, breaking the DNA helix
          • H. pylori, protazoa
        • parenteral route
        • adverse effects
          • neurotoxicity, allergy, superinfections, disulfiram reaction if take w/ alcohol life threatening nausea and vomiting
  • nephrotoxic, infusion rxn,
    • Amphotericin B
      • used for mycoses that are potentially fatal, admin parenterally
      • it is very toxic
      • binds -sterols which are also found in the human body (cholesterol) which causes the renal dammage.
      • S/E: infusion reaction fever and chills, nephrotoxic
      • ADME: can be found up to a year later in the pt body
    • Nystatin
      • Candidiasis only
      • alters the permeability of the membrane
    • KetoCONAZOLE (Nizoral)
      • antifungal
      • used in less severe fungal reactions
      • MOA is it inhibits the synthesis of ergosterol which is a part of the fungal cell membrane
        • this also affects the body’s sterols (sex hormones)
  • drugs for ringworm
    • Clotrimazole—topical
    • Griseofulvin—oral
      • still in the -azole class
        • just for superficial (skin infections), not systemic
        • inhibits fungal mitosis
  • anti-viral
    • very specific to viruses
      • Acyclovir (Zocirax)
        • similar to a purine nucleoside, and suppresses protein synthesis
        • S/E: phlebitis, nephrotoxic, stinging sensations.
    • Hep B
      • there is a vax
      • transmission through blood and semen
      • Drugs:
        • interferon Alpha 2b – to treat the symptoms, but also causes flu like symptoms
        • Lamicudine (Epivir-HBV) hep b is not resistant to this
        • Tenofovir (viread)
    • Hep C
      • 6 genotypes
      • transmission same as B
      • cause flu like symptoms
      • treat with interferons as well
        • plus these three interferon, ribavirin, and a protease inhibitor
    • Influenza
      • prevention is better than treatment
      • no Vax for people with egg allergy
    • Measles
      • outbreak in 2015 dt unvaxed kiddos
        • 1:20 will develop viral pneumonia
    • HIV
      • Reverse transcriptase, protease, and intefrase are main targets of treatment to disrupt the virus.
      • HAART therapy – highly active antiretroviral therapy. two nucleoside reverse transcriptase inhibitors, and a protease inhibitor.
      • six classes of drugs to treat HIV
        • Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Nucleoside reverse transcriptase inhibitors (NRTIs) Protease inhibitors (PIs) Fusion inhibitors, CCR5 antagonists or entry inhibitors (CCR5s) Integrase strand transfer inhibitors (INSTIs)
        • focus on the first three plus the fusion inhibitors
          • examples
            • NRTI: Zidovudine (Retrovir)
              • stops replication, slows the Dx, and increases the white blood cell (CD4) levels
            • NNRTI: Nevirapine (Viramune) Efavirenz (sustiva)
              • binds reverse transcripase and stops the transcription
            • PI: Indinavir (Crixivan)
              • very effective
            • FI: Fuzeon, T-20
              • stops HIV from fusing with a CD4 cell
        • ELISA test for HIV
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