!pharmacology Of Neurological Infections Flashcards
What is metronidazole
Prodrug active against anaerobic bacteria and anaerobic protozoan microorganisms
What agents are lumped together with metronidazole, bc of smiler chemical structures
5-nitroimidazoles, tinidazole
Metronidazole and tinidazole
Similar MOA, resistance and spectrum, adverse effects
Is tinidazole or metrodinazole better tolerated
Tinidazole
MOA metronidazole
Dependent on activation of metronidazole by susceptible organisms . Anaerobic pathogenic microorganisms contain electron transport components tat have a high enough negative redox potential to donate electrons to metronidazole. When an electron is donated to metronidazole, a highly reactive nitro radical anion is formed. It is this ion that, in turn, mediates the killing of susceptible organisms by means of radical-mediated DNA damage. T
How can metronidazole be catalytically recycled
By losing the added electron. This means that metronidazolecan move back and forth between its active and inactive state within a susceptible microorganism.
_ and _ can compete with mtronidazole for electrons
oxygen O2
When levels of O2 rise, metronidazole is less likely to enter its active nitro radical anion form. Furthermore increased O2 levels promote recycling of the active nitro back to what
The inactive metronidazole
How resist metronidazole
Increasing intracellular O2
Resistance to metronidazole correlates with impaired O2 scavenging, which leads to increased intracellular O2 levels and decreased activation of metronidazole.
This type of resistance has been reported in T vaginalis, G lamblia, and a variety of different anaerobic bacteria
What is metronidazole active against
Anaerobes
Flagellated protozoa T vaginalis, G lamblia
Brand mane of met is flagyl
Protozoan E histolytica
Anaerobic cocci and anaerobic gram negative bacilli
Helicobacter and campylobacter spp are also susceptible
Gram positive bacilli such as clostridium spp
Adverse effects metronidazole UNIQUE
Metallic taste
Dry mouth
Nausea
Headache
Disulfiram like effect-(disulfiram is an anti alcoholic medication designed to induce vomiting if patient consumes alcohol) similar effect with metronidazole…alcohol during or three days after therapy-vomit flush ab pain or headache
Meningitis
Inflammatory process of the leptomeninges and the CSF within the subarachnoid space
What usually causes meningitis
Infection
Acute progenitor-bacteria
Acute aseptic-viral
Acute progenitor meningitis pathophysilogy
Neutrophils fill the subarachnoid space in severely affected areas
Untreated progenitor meningitis can be fatal-antibiotics reduces mortality
Clinical presentation acute progenitor meningitis
Fever, headache, nuchal rigidity
Decreased level of consciousness
Raised intracranial pressure
CF>180 90%
CSF>400 20%
Neutrophils
Increased protein
Decreased glucose
Neonates progenitor meningitis
E. coli, group b strop
Infants meningitis progenic
H influenza
Strep b
Adolescents acute pyogenic meningitis
N meningitidis
Elderly acute pyogenic meningitis
S pneumoniae, l monocytogenes
Therapy for acute pyogenic meningitis
Penicillin-nonsusceptible strep p interval > 3 hrs between hospital admission and antibiotic treatment
Standard empiric tratment for meningitis
(Cefotaxime or ceftriaxone)+ vancomycin
Ampicillin added in older patients >50 years
Treat neonate E. coli or group b strep for acute pyogenic meningitis
Cefotaxime or ceftriaxone+vancomycin
Treat infants with h influenza type B acute pyogenic meningitis
Hib vaccine cefotaxime or ceftriaxone
Treat N meningitidis in adolescents and young adults with acute pyogenic meningitis
Cefotaxime+ceftriaxone+vancomycin
How treat s pneumonia or L monocytogenes in older adults(>50) with acute pyogenic meningitis
Cefotaxime or ceftriaxone+vancomycin+ampicillin
What give someone with pyogenic meningitis with beta lactam allergy under 50
Vancomycin+moxifloxacin
What is used to treat acute pyogenic meningitis in people with beta lactam allergy over 50
Vancomycin+moxifloxacin+TMP/SMX
How treat acute pyogenic meningitis in immunocompromised patient
Vancomycin+ampicillin +(cefepime or meropenem)
Pathophysiologu acute aseptic virus meningitis
Negative routine bacterial cultures
What viruses cause 80% of acute aseptic virus meningitis
Coxsackievirus, echovirus
Clinical presentation acute aseptic meningitis
Fever, headache, altered mental status, nuchal rigidity, photophobia, -similar to pyogenic meningitis
CSF in acute aseptic meningitis
Lymphocytic pleocytosis
Moderate protein elevation
Normal glucose levels
Opening pressure can be normal OR elevated
Treat acute aseptic meningitis
Self limiting and treated symptomatically
Treatment is suspect pyogenic meningitis
Start antibiotics soon after LP
Treatment is suspect aseptic meningitis
Observation, may be self limiting
Treatment when not sure if pyogenic or aseptic meningitis
Start antibiotics after LP
If bacterial cultures are negative then discontinue antibiotics
Cephalosporins 3rd gen
Cefotaxime
Ceftriaxone
Glycopeptide
Vancomycin
Aminopenicillin
Ampicillin
Benzylpyrimidine/sulfonamide
Trimethoprim/sulfamethoxazole
Cephalosporin 4th gen
Cefepime
Car ape EM
Meropenem
Fluoroquinolone
Moxifloxacin
Brain abscess
Localized focus of necrosis of brain tissue with accompanying inflammation
CSF brain abscess
High white cell count
Increased protein concentration
Normal glucose content
Increased intracranial pressure can lead to __ ___
Fatal herniation
Clinical presentation brain abscess
Initially non specific; results in a delay of diagnosis
Pain in localized to the site of the abscess
-gradual or sudden
-not easily relieved with over the counter relief
Headache
Fever
Focal neurological deficits
Seizures
Brain abscess pathogens
Viridans strep
S aureus
Brain abscess immunocompetent
Likely bacteria
Brain abscess immunocompromised
More possibilities including fungi
Brain abscess treatment
Surgery+antibiotics
-aspiration, craniotomy to drain
Antibiotic
Empiric therapy
-vancomycin+(ceftriaxone or cefotaxime)+metronidazole
Penicillin G brain abscess
Covers aerobic and anaerobic strep (mouth flora)
Metronidazole brain abscess
Readily penetrates brain abscesses
Combined with other agents when used to treat brain abscess
Ceftriaxone brain abscess
Covers most aerobic and microaerophilic strep
-substitute for penicillin G
Covers many enterobacteriaceae
Interchangeable with cefotaxime
Ceftazidime, cefepime, or meropenem brain abscess
Often used if a brain abscess complicates a neurosurgical procedure
Covers cases in which the abscess culture grows p aeruginosa
Vancomycin brain abscess
Included in treatment regimen until culture and susceptibility results are available
No MRSA=no vancomycin (oxacillin or nafcillin should be substituted for vancomycin)
Cephalosporins 3rd gen brain abscess
Cefotaxime
Ceftriaxone
Ceftazidime
Glycopeptide brain abscess
Vancomycin
5-nitromidazoles brain abscess
Metronidazole
Penicillin G brain abscess
Penicillin G
Cephalosporin 4th gen brain abscess
Cefepime
Carbapenem brain abscess
Meropenem
Subdural empyema
Produced by bacteria (and rarely fungal) infections of the skull bones or air sinuses that spread to the subdural space
CSF subdural empyema
High white cell count
Increased protein concentration
Normal glucose content
Clinical presentation subdural epyema
Fever and progressively worsening headache
Progressice symptoms-focal neurologic deficits, seizures, nuchal rigidity, and signs of increased ICP
Contralateral hemiparesis
Seizures
Increasing mass effect leads to deterioration in consciousness leading to coma
What causes subdural empyema
Aerobic and anaerobic strep, staph, enterobacteriaceaae, and anaerobic bacteria
Following neurosurgical procedures or head trauma(staph and gram neg bacilli)
333% culture negative
What do when see subdural empyema
Medical emergency
Surgery to evacuate the empyema
Empiric treatment
-(cefotaxime or ceftriaxone)+vancomycin+metronidazole
Or for hostpital acquired P aeruginosa or MRSA
Meropenem+vancomycin
Cephalosporins 3rd gen for subdural epyema
Cefotaxime
Ceftriaxone
Ceftazidime
Glycopeptide for subdural empyema
Vancomycin
Carbapenem for subdural empyema
Meropenem
5 nitroimidazole for subdural empyema
Metronidazole
What is viral meningoencephalitis
Parenchyma infection of the brain. Associated with meningoencephalitis and encephalomyelitis
How get viral meningoencephalitis
Arthropod borne viral encephalitis
Subacute sclerosing panencephalitis from measles
Poliomyelitis
SSPE
Occurs in kids and young adults months to ears after infection with measles
Characterization by
Variable inflammation of white and grey matter
Neurofibrillary tangles
AEDs to cognitive decline, spasticity of limbs, and seizures
Why has incidence of SSPE dropped
Vaccination
Clinical presentation poliomyelitis
Initially mild gastroenteritis
In a small fraction of individuals the virus invades he CNS
-paresis or paralysis follows
—diaphragm and intercostal muscles may be affected
Why has poliomyelitis decreased
Vaccines
Few drugs useful against viruses wso we use __
Vaccines
Active immunity
Vaccines
Passive immunity
Immune globulins
Active immunity
Live attenuated virus vaccine
-contain live virus whose pathogenicity has been attenuated
Killed vaccine
-subunit vaccines
Why are live vaccines preferred to killed citrus
Protection is greater and longer lasting
Live attenuated
Longer duration greater strength IgA and IgG produced Cell mediated immunity More effective at interrupting spread Possible reversion to virulence
Killed virus
Shorter duration
Lower strength
IgG
Weakly or no cell mediated immunity
Lesseffective ta interrupting the spread of virulent virus
No reversion to virluence
Attenuated viral mutants may revert to virluence either during vaccine production or in immunized person
Polio not measles
Can be pathogenic in immunocompromised patients
Excretion of live virtue to infect others
Herd immunity
Double edge sword
SSPE measles vaccine
MMR
Live attenuated vaccine
Long term immunity
99% immunity among individuals who have received two doses of measles vaccine
I activated poliovirus vaccine IPV
Killed virus vaccine
Only vaccine available in US
Does not cause vaccine associated paralytic poliomyelitis
Live attenuated oral poliovirus OPV
Can cause polio in a small percentage of adults
When was the last polio case in the US
1978-1979
Poliovirus remains endemic to where
Nigeria, Pakistan, Afghanistan
What causes fungal meningoencephalitis
Cryptococcal meningitis
Who gets fungal meningoencephalitis
AIDS
CSF of fungal meningoencephalitis
High protein concentration
Manifestation of fungal meningoencephalitis
Chronic meningitis affecting the basal leptomeninges
Appears as soap bubbles on whole brain sections
Clinical presentation fungal meningoencephalitis
Stiff neck, photophobia, vomiting
Lethargy and confusion
High suspicion with advances HIV CD4<100
Treat fungal meningoencephalitis
Amphotericin B
Flucytosine (5-fluorouracil)
Fluconazole
Induction phase therapy
-amphotericin B+flucytosine
Consolidation phase of therapy
-fluconazole
Ergosterol
Vital part of the celll membranes of fungi
Not found inthecell membranes of humans
-selective toxicity
Most anti-fungal agents bind ergosterol with a higher affinity than cholesterol
Amphotericin B MOA
-forms a complex with ergosterol and disrupts the fungal cell membrane
Leads to cytoplasmic leakage and fungal cell death
How is amphotericin B given
IV into CSF
Not absorbed orally
Adverse effects amphotericin B
Renal toxicity, acute febrile reaction(chills and fever)
Anemia
MOA flucytosine (5-FC)
Antimetabolite
Converted to 5-FU inside fungal cells
Inhibitis DNA and RNA synthesis
What happens if flucytosine is used alone
Rapid resistance develops
Adverse effects 5-FC
Conversion of 5-FC to 5-FU outside fungal cell
Bone marrow depression, nausea, vomiting diarrhea
Types of fluconazole
Azole, triazole
MOA fluconazole
Inhibits ergosterol synthesis by inhibiting fungal p450 enzymes
Fluconazole has good CSF penetration?
Yup
Adverse effects fluconazole
Limited, widest therapeutic index of all of the adolescents
Cryptococcal meningoencephalitis
Amphotericin B
Flucytosine
Azole-fluconazole
What cephalosporin 1st gen do not treat neuroinfections
Ceftaroline
What tetracyclines do not treat neuroinfections
Doxycycline
Tertracycline
Miniocycline
Demeclocycline
What macrolides do we not use for neuroinfections
Erythromycin
Clarithromycin
Azithromycin
Fidaoxomicin
What aminoglycosides not use in neuroinfections
Streptomycin Gentamicin Tobramycin Amikacin Neomycin Paromomycin Kanamycin Netolmicin
What no class should we not use neuroinfections
Clindamycin
32 year old presents with complaints of headache with joint and muscle pain. Patient admits that pain has persisted for the past 3 days. PE reveals nuchal rigidity. A gram stain of her spinal fluid shows many neutrophils and many gram negative, bean shaped diplodocus.
Which of the following pharmacological agents would be best to treat this patients infection
Tetracyclines
Cefotaxime+vancomycin
Erythromycin
Metronidazole
Meropenem+ampicillin+vancomycin
What is they’re allergic to beta lactam
Ceftriaxone+ampicillin
Cefotaxime
Moxifloxacin+TMP/SMX
Moxifloxacin
Meropenem+ampicillin
A 31 year old male presents with fever, headache, confusion, muddles thinking, and vomiting. Has aids with 90 CD4 PE shows nuchal rigidity and photophobia and an India ink stain of the spinal fluid shows budding organisms
Fluconazole Clindamycin Colistin Ampicillin+erythromycin Emphotericin B+flucytosine
What does metronidazole tresat
Giardia lamblia Entamoeba histolytica Trichomonas Gardnerella Anaerobes
Side effects metronidazole
Metallic taste
Disulfiram like reaction with alcohol
