Major Concepts of Antimicrobials

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Major Concepts of Antimicrobials
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Special Concepts r/t Anitmicrobials

• Selective toxicity
• Ability to target without harming host
• Susceptibility
• Prophylaxis
• Neutropenia, Surgery, Endocarditis
• Combination Therapy
• Misuse non-specific fevers, viruses

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Resistance
Fig 82-1
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Aminoglycosides Bactericidal Inhibitors of
Protein Synthesis

• Chapter 86

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Aminoglycosides Background

• Resistance is beginning to limit use
• Gentamicin cheaper but commonly used
• 20 diff aminoglycoside-inactivating enzymes (like
  the beta-lactamases for PCN)
• Reserve amikacin (in this class this is big gun,
  save it)
• Bactericidal
• concentration dependent (the more you get, the
  more it kills)
• Post-antibiotic effect several hours (it sticks
  around a lot longer than some other drugs)
• NOT effective against anaerobes

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Gentamicin (Garamycin) (Prototype)

• MOA / Use narrow spectrum for gram- bacilli
  esp. pseud. aerugenosa, E. coli, Klebs., Serratia
• ADME
• Poor CSF
• Not absorbed orally (so?) (typically IV)
• Toxicity w/ wound irrigation
• Needs Peak and Trough
• Binds tightly to renal tissue
• Excretion primarily renal
• Dosage varies widely (0.5 mg/kg to 25 mg/kg)

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• Adverse Effects
• Ototoxic (if it stays above the baseline for
  therapeutic levels too long want the level to
  drop low enough so the body can wash it out)
• r/t excess trough levels sensory hairs
• HA (headache), N, vertigo then high-pitched
  tinnitis (Action?) If you noticed tinnitus, first
  action would be to stop the dose and call the dr!
• Nephrotoxic
• Total cumulative dose
• ATN (acute tubular necrosis, tube in the nephron
  gets necrotic and leads to renal
  failure.(proteinuria (protein in the blood),
  casts (slough big particles), ?BUN (Blood Urea
  Nitrogen), ?Creatinine
• Elderly and young and sick
• Neuromuscular blockade
• Hypersensitivity blood dyscrasias (rare)

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• D?D
• PCNs, Cephs, Vanco used in combo
• PCNs inactivate schedule issue?
• Ethacrynic Acid will potentiate (increase)
  ototoxicity
• Other nephrotoxics
• Skeletal Muscle relaxants (r/t the neuromuscular
  blockade which makes them weak)

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Aminoglycosides Special Concerns

• Neomycin most nephrotoxic (Not ever IM or IV,
  might see it preoperativly to sterilize the gut)
  Will also see it topically.
• Scheduling once daily Safer? (yes, lets trough
  get low to wash out of tissue)
• Post-antibiotic effect
• Washout esp. in vestibule and kidneys
• Typically only measure trough up to 1hr prior
  to next dose level should be ?

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Antifungal Agents

• Chapter 91

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Antifungal Agents

• Systemic mycotic infections
• Opportunistic (r/t infections that set up house
  in debilitated pts) candidiasis, aspergillosis,
  cryptococcosis, mucormycosis
• Nonopportunistic (ones you get because you were
  exposed to it) sporotrichosis, blastomycosis,
  histoplasmosis, coccidioidomycosis
• Superficial mycotic infections
• Candidiasis
• Dermatophytes

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Antifungal Agents

• Systemic mycotic (fungal) infections
• Opportunistic host is sick, debilitated,
  immunocompromised pt
• candidiasis, aspergillosis, cryptococcosis,
• Non-opportunistic
• blastomycosis, histoplasmosis, coccidioidomycosis
• Superficial mycotic infections
• Candidiasis
• Dermatophytes (little bugs with sharp teeth on
  that commercial)

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Antifungals Major Classes

• Polyenes
• Azoles
• Pyrimidine analogs
• Echinocandins

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Amphotericin B Fungizone

• MOA / TE
• Broad spectrum antifungal agent binds to
  ergosterol component of fungal cell wall and
  increases permeability. Fungocidal. DOC for most
  progressive, potentially fatal systemic mycoses
  (you use this one when the bug is going to kill
  the person)
• ADME
• Highly toxic (sterols) (in the bug it breaks down
  ergosterol in the cell wall, you have sterols in
  you, hence, it breaks down the bugs sterols and
  can break down your sterols)
• Poor GI absorption - SLOW IV USE ONLY
• Poor CSF

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Amphotericin B (contd)

• Adverse effects almost 100 - varying
• Phlebitis (slow IV helps prevent this)
• Fever, chills, nausea (common) pre-treat w/
  benadryl / acetaminophen so they dont suffer so
  much
• Nephrotoxicity residual if ?4 g/day, 1 L NS
  (keep them hydrated with saline), Monitor urine
  q 3-4 days (looking from protein, cast, and serum
  Creatinine)
• Hypokalemia (lowered potassium)
• Bone marrow suppression (will lower reds, whites,
  and browns (platelets))
• D?D nephrotoxics - flucytosine

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Itraconazole (Sporanox)

• MOA / TE
• Azole group of antifungal agents that inhibits
  sythesis of ergosterol fungistatic to treat
  histoplamosis, meningitis of cryptococcus
  neoformans disseminated candidiasis
• ADME
• PO or IV
• Food ? abs. capsules, ? abs. of suspension
• Metabolized in liver
• 40 excreted unchanged in urine

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Itraconazole (Sporanox) contd

• Adverse effects
• Common N, V, and D, rash, HA, edema
• Rare - Hepatic necrosis, transient
  cardiosuppression
• D?D
• Inhibits cytochrome P450 isozymes (if system is
  impaired, your drug levels are going to rise,
  will also raise other drug levels)
• Increases levels of warfarin, digoxin,
  sulfonylureas (antidiabetic drug-watch blood
  sugar), cyclosporine, quinidine and many other
  drugs
• Acid reduces decrease drug levels
• Pepsid, prilosec, etc. will impair absorption of
  Itraconazole

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Azoles Special Considerations

• Fluconazole Diflucan
• Lower toxicity level
• Can be taken orally
• SJS syndrome (Stevens johnson Syndrome is a side
  effect of this medication. Looks like a chemical
  burn)
• Ketoconazole Nizoral
• Effect on sex hormones inhibits production
  (will impair fertility)

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Drugs for Superficial Mycoses

• Dermatophytic infections (e.g., ringworm)
• Tinea pedis, tinea corporis, t. cruris, t.
  capitis
• Drugs
• Clotrimazole (Gyne-Lotrimin) DOC for topical
  dermatophytic and candida infections of skin,
  mouth, vagina
• Vulvovaginal candidiasis
• Griseofulvin (Grifulvin) - oral
• Onychomycosis (fungal infection of the toes
  (toenails)

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Griseofulvin (Grifulvin V)

• MOA / TE
• Superficial mycoses only inhibits fungal
  mitosis incorporates into keratin (thats how
  is suppresses the bugs)
• Adverse effects
• Transient headache, rash, GI upset
• Contraindicated in hepatocellular disease (this
  is liver intensive medication, like most of the
  antifungals)
• D?D
• Decreases warfarin

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Antiviral Agents I Drugs for Non-HIV Viral
Infections

• Chapter 92
• They mutate readily, they live in your cells (so
  theyre hard to get to). They are harder to treat
  b/c they are harder to target...

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Viral Infections

• Dilemma (see previous slide)
• Types
• HSV (Herpes-simplex) More sensitive to antivirals
  
• Genitalia, mouth, face (HSV-2)
• VZV (Varicella Zoster) Moderately sensitive to
  antivirals. Relative to HSV
• Chicken pox Shingles
• CMV (Cytomegalovirus) Less sensitive to
  antivirals more resistant

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Herpes

• Look in book for some box on herpes. There is no
  cure for viral infections like Herpes. All we can
  do is treat them an live around them
• Just get that the same antivirals are used over
  and over again

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Drugs for Non-HIV Viral Infections

• Prototype Acyclovir Zovirax
• MOA / TE Suppress synthesis of viral DNA and is
  useful in treating HSV1,2 VZV no cure
• Adverse Effects
• Intravenous reversible nephrotoxicity, phlebitis
• Infuse slowly hydration (trying to protect the
  kidneys) during 2 hr after
• Oral GI, vertigo
• Topical stinging

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Acyclovir Zovirax

• Nursing Implications
• Resistance type of clients (seen in just about
  everybody that is on the drug long term)
• IV indicated for immunocompromised pt
• STI control (just b/c your partner is on
  antivirals doesnt mean that you wont get it or
  that youre safe) STI is new acronym for STD
  (Changed it to infection)
• Treatment for VZV in elderly and children (w/i 24
  hr)

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Acyclovir Zovirax contd

• Nursing Implications (contd)
• po (low availability), topically or IV
• NO IV bolus (you cant take a big piece of the
  drug and stick it in fast), NO IM, or NO SubQ
  injections
• Valacyclovir Valtrex prodrug that increases
  oral bioavailability (of acyclovir) by 55
• Without regard to meals

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Ganciclovir Cytovene, Vitrasert

• MOA / TE
• Suppresses replication of viral DNA to treat CMV
  retinitis of immune compromised clients prevent
  CMV in transplant patients
• Adverse effects
• Granulocytopenia (a piece of your wbcs)
  thrombocytopenia
• Mutagenesis, carcinogenesis
• Teratogenisis and infertility (90d following
  cessation)
• valganciclovir (Valcyte) prodrug for oral use
  (of ganciclovir)
• Take intact with food

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Hepatitis C (HCV)

• Transmissionblood and semen
• Typically asymptomatic
• Leading cause for liver transplants
• Among most common causes of liver cancer
• Drugs
• Pegylated interferon alfa combined with ribavirin
  (Used in combination to treat HepC)

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Interferon alfa (Peg-Intron)immune modulatory,
antineoplastic, antiviral

• MOA / TE
• Blocks entry of virus, synthesis of viral m-RNA
  and proteins, and viral assembly. Tx of chronic
  Hep B (first choice is to vaccinate) C
• ADME
• Pegylated - longer acting
• Only parenterally (subQ usually)
• Adverse Effects
• Flu-like (fever, myalgia, HA, fatigue)
  depression (makes you feel real bad)
• Long/High dose thyroid dysfunction, heart
  damage, bone marrow suppression
• Alopecia, GI, injection site pain, bruising

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Ribavirin (Rebetol)

• MOA unclear (Goes with Interferon)
• Used with Interferon A - together are DOC for Hep
  C (HCV).
• Therapy 24 to 48 weeks. Goal is SVR sustained
  virologic response (loss of detectable viral RNA)
• Adverse effects
• Hemolytic anemia (anemia due to broken blood
  cells)
• Teratogenic (Category X) two forms of BC
• Dosage based on weight

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Hepatitis B - HBV

• Transmissionblood and semen
• Drugs
• HBV vaccine
• Interferon alfa-2b PEG-Intron
• Lamivudine Epivir-HBV (high resistance)
• Adefovir Hepsera
• Duration of treatment and relapse
• They really dont know yet if it has to be
  lifelong but probably.

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Flu Vaccines

• 3 strains selected by CDC, FDA, WHO
• Inactivated
• IM
• Live attenuated LAIV (Flumist) 2003
• Intranasally
• MUST BE FROZEN
• Only ages 5-49 (r/t to ability to do something
  about immune response)

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Flu Vaccine (cont)

• Efficacy Who should receive it? Most people
• 1-2 wks lasts for 6 mo
• Adverse effects
• Fever, malaise, myalgia
• Guillain-Barré syndrome Swine flu vac. 1976
• LAIV (inhaled version) runny nose, HA, cough
  rare GBS, anaphylaxis
• Precautions and contraindications
• Acute febrile illness, hypersensitivity to eggs

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Flu Vaccine (cont)

• Who should NOT without MD approval?
• Allergy to egg
• Previous severe reaction
• GBS
• Moderate, severe illness w/ fever
• Children under 6 months
• LAIV not for adults over 50, children under 5,
  preggers, children or adolescents on long-term
  ASA therapy, chronic heart, lung disease

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Drugs for Influenza

• Prototype oseltamivir (Tamiflu)
• MOA / TE inhibit viral replication of Inf AB
  and is used to prevent and treat same effective
  if implemented within 2 days of sxms
• Adverse effects
• NV
• Confusion, self injury
• Expensive must be started prior to 48 hr (must
  be given quickly or its ineffective...)