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Pharmacology > !pharmacology Of Neurological Infections > Flashcards

!pharmacology Of Neurological Infections Flashcards

1
Q

What is metronidazole

A

Prodrug active against anaerobic bacteria and anaerobic protozoan microorganisms

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2
Q

What agents are lumped together with metronidazole, bc of smiler chemical structures

A

5-nitroimidazoles, tinidazole

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3
Q

Metronidazole and tinidazole

A

Similar MOA, resistance and spectrum, adverse effects

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4
Q

Is tinidazole or metrodinazole better tolerated

A

Tinidazole

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5
Q

MOA metronidazole

A

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

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6
Q

How can metronidazole be catalytically recycled

A

By losing the added electron. This means that metronidazolecan move back and forth between its active and inactive state within a susceptible microorganism.

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7
Q

_ and _ can compete with mtronidazole for electrons

A

oxygen O2

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8
Q

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

A

The inactive metronidazole

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9
Q

How resist metronidazole

A

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

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10
Q

What is metronidazole active against

A

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

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11
Q

Adverse effects metronidazole UNIQUE

A

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

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12
Q

Meningitis

A

Inflammatory process of the leptomeninges and the CSF within the subarachnoid space

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13
Q

What usually causes meningitis

A

Infection

Acute progenitor-bacteria

Acute aseptic-viral

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14
Q

Acute progenitor meningitis pathophysilogy

A

Neutrophils fill the subarachnoid space in severely affected areas

Untreated progenitor meningitis can be fatal-antibiotics reduces mortality

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15
Q

Clinical presentation acute progenitor meningitis

A

Fever, headache, nuchal rigidity

Decreased level of consciousness

Raised intracranial pressure

CF>180 90%
CSF>400 20%

Neutrophils
Increased protein
Decreased glucose

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16
Q

Neonates progenitor meningitis

A

E. coli, group b strop

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17
Q

Infants meningitis progenic

A

H influenza

Strep b

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18
Q

Adolescents acute pyogenic meningitis

A

N meningitidis

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19
Q

Elderly acute pyogenic meningitis

A

S pneumoniae, l monocytogenes

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20
Q

Therapy for acute pyogenic meningitis

A

Penicillin-nonsusceptible strep p interval > 3 hrs between hospital admission and antibiotic treatment

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21
Q

Standard empiric tratment for meningitis

A

(Cefotaxime or ceftriaxone)+ vancomycin

Ampicillin added in older patients >50 years

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22
Q

Treat neonate E. coli or group b strep for acute pyogenic meningitis

A

Cefotaxime or ceftriaxone+vancomycin

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23
Q

Treat infants with h influenza type B acute pyogenic meningitis

A

Hib vaccine cefotaxime or ceftriaxone

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24
Q

Treat N meningitidis in adolescents and young adults with acute pyogenic meningitis

A

Cefotaxime+ceftriaxone+vancomycin

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25
Q

How treat s pneumonia or L monocytogenes in older adults(>50) with acute pyogenic meningitis

A

Cefotaxime or ceftriaxone+vancomycin+ampicillin

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26
Q

What give someone with pyogenic meningitis with beta lactam allergy under 50

A

Vancomycin+moxifloxacin

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27
Q

What is used to treat acute pyogenic meningitis in people with beta lactam allergy over 50

A

Vancomycin+moxifloxacin+TMP/SMX

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28
Q

How treat acute pyogenic meningitis in immunocompromised patient

A

Vancomycin+ampicillin +(cefepime or meropenem)

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29
Q

Pathophysiologu acute aseptic virus meningitis

A

Negative routine bacterial cultures

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30
Q

What viruses cause 80% of acute aseptic virus meningitis

A

Coxsackievirus, echovirus

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31
Q

Clinical presentation acute aseptic meningitis

A

Fever, headache, altered mental status, nuchal rigidity, photophobia, -similar to pyogenic meningitis

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32
Q

CSF in acute aseptic meningitis

A

Lymphocytic pleocytosis

Moderate protein elevation

Normal glucose levels

Opening pressure can be normal OR elevated

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33
Q

Treat acute aseptic meningitis

A

Self limiting and treated symptomatically

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34
Q

Treatment is suspect pyogenic meningitis

A

Start antibiotics soon after LP

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35
Q

Treatment is suspect aseptic meningitis

A

Observation, may be self limiting

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36
Q

Treatment when not sure if pyogenic or aseptic meningitis

A

Start antibiotics after LP

If bacterial cultures are negative then discontinue antibiotics

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37
Q

Cephalosporins 3rd gen

A

Cefotaxime

Ceftriaxone

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38
Q

Glycopeptide

A

Vancomycin

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39
Q

Aminopenicillin

A

Ampicillin

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40
Q

Benzylpyrimidine/sulfonamide

A

Trimethoprim/sulfamethoxazole

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41
Q

Cephalosporin 4th gen

A

Cefepime

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42
Q

Car ape EM

A

Meropenem

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43
Q

Fluoroquinolone

A

Moxifloxacin

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44
Q

Brain abscess

A

Localized focus of necrosis of brain tissue with accompanying inflammation

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45
Q

CSF brain abscess

A

High white cell count
Increased protein concentration
Normal glucose content

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46
Q

Increased intracranial pressure can lead to __ ___

A

Fatal herniation

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47
Q

Clinical presentation brain abscess

A

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

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48
Q

Brain abscess pathogens

A

Viridans strep

S aureus

49
Q

Brain abscess immunocompetent

A

Likely bacteria

50
Q

Brain abscess immunocompromised

A

More possibilities including fungi

51
Q

Brain abscess treatment

A

Surgery+antibiotics
-aspiration, craniotomy to drain

Antibiotic

Empiric therapy
-vancomycin+(ceftriaxone or cefotaxime)+metronidazole

52
Q

Penicillin G brain abscess

A

Covers aerobic and anaerobic strep (mouth flora)

53
Q

Metronidazole brain abscess

A

Readily penetrates brain abscesses

Combined with other agents when used to treat brain abscess

54
Q

Ceftriaxone brain abscess

A

Covers most aerobic and microaerophilic strep
-substitute for penicillin G

Covers many enterobacteriaceae

Interchangeable with cefotaxime

55
Q

Ceftazidime, cefepime, or meropenem brain abscess

A

Often used if a brain abscess complicates a neurosurgical procedure

Covers cases in which the abscess culture grows p aeruginosa

56
Q

Vancomycin brain abscess

A

Included in treatment regimen until culture and susceptibility results are available

No MRSA=no vancomycin (oxacillin or nafcillin should be substituted for vancomycin)

57
Q

Cephalosporins 3rd gen brain abscess

A

Cefotaxime
Ceftriaxone
Ceftazidime

58
Q

Glycopeptide brain abscess

A

Vancomycin

59
Q

5-nitromidazoles brain abscess

A

Metronidazole

60
Q

Penicillin G brain abscess

A

Penicillin G

61
Q

Cephalosporin 4th gen brain abscess

A

Cefepime

62
Q

Carbapenem brain abscess

A

Meropenem

63
Q

Subdural empyema

A

Produced by bacteria (and rarely fungal) infections of the skull bones or air sinuses that spread to the subdural space

64
Q

CSF subdural empyema

A

High white cell count
Increased protein concentration
Normal glucose content

65
Q

Clinical presentation subdural epyema

A

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

66
Q

What causes subdural empyema

A

Aerobic and anaerobic strep, staph, enterobacteriaceaae, and anaerobic bacteria

Following neurosurgical procedures or head trauma(staph and gram neg bacilli)

333% culture negative

67
Q

What do when see subdural empyema

A

Medical emergency

Surgery to evacuate the empyema

Empiric treatment
-(cefotaxime or ceftriaxone)+vancomycin+metronidazole

Or for hostpital acquired P aeruginosa or MRSA
Meropenem+vancomycin

68
Q

Cephalosporins 3rd gen for subdural epyema

A

Cefotaxime
Ceftriaxone
Ceftazidime

69
Q

Glycopeptide for subdural empyema

A

Vancomycin

70
Q

Carbapenem for subdural empyema

A

Meropenem

71
Q

5 nitroimidazole for subdural empyema

A

Metronidazole

72
Q

What is viral meningoencephalitis

A

Parenchyma infection of the brain. Associated with meningoencephalitis and encephalomyelitis

73
Q

How get viral meningoencephalitis

A

Arthropod borne viral encephalitis

Subacute sclerosing panencephalitis from measles

Poliomyelitis

74
Q

SSPE

A

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

75
Q

Why has incidence of SSPE dropped

A

Vaccination

76
Q

Clinical presentation poliomyelitis

A

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

77
Q

Why has poliomyelitis decreased

A

Vaccines

78
Q

Few drugs useful against viruses wso we use __

A

Vaccines

79
Q

Active immunity

A

Vaccines

80
Q

Passive immunity

A

Immune globulins

81
Q

Active immunity

A

Live attenuated virus vaccine
-contain live virus whose pathogenicity has been attenuated

Killed vaccine
-subunit vaccines

82
Q

Why are live vaccines preferred to killed citrus

A

Protection is greater and longer lasting

83
Q

Live attenuated

A 
Longer duration greater strength
IgA and IgG produced
Cell mediated immunity
More effective at interrupting spread
Possible reversion to virulence
84
Q

Killed virus

A

Shorter duration
Lower strength
IgG
Weakly or no cell mediated immunity

Lesseffective ta interrupting the spread of virulent virus

No reversion to virluence

85
Q

Attenuated viral mutants may revert to virluence either during vaccine production or in immunized person

A

Polio not measles

Can be pathogenic in immunocompromised patients

86
Q

Excretion of live virtue to infect others

A

Herd immunity

Double edge sword

87
Q

SSPE measles vaccine

MMR

A

Live attenuated vaccine
Long term immunity
99% immunity among individuals who have received two doses of measles vaccine

88
Q

I activated poliovirus vaccine IPV

A

Killed virus vaccine
Only vaccine available in US
Does not cause vaccine associated paralytic poliomyelitis

89
Q

Live attenuated oral poliovirus OPV

A

Can cause polio in a small percentage of adults

90
Q

When was the last polio case in the US

A

1978-1979

91
Q

Poliovirus remains endemic to where

A

Nigeria, Pakistan, Afghanistan

92
Q

What causes fungal meningoencephalitis

A

Cryptococcal meningitis

93
Q

Who gets fungal meningoencephalitis

A

AIDS

94
Q

CSF of fungal meningoencephalitis

A

High protein concentration

95
Q

Manifestation of fungal meningoencephalitis

A

Chronic meningitis affecting the basal leptomeninges

Appears as soap bubbles on whole brain sections

96
Q

Clinical presentation fungal meningoencephalitis

A

Stiff neck, photophobia, vomiting

Lethargy and confusion

High suspicion with advances HIV CD4<100

97
Q

Treat fungal meningoencephalitis

A

Amphotericin B

Flucytosine (5-fluorouracil)

Fluconazole

Induction phase therapy
-amphotericin B+flucytosine

Consolidation phase of therapy
-fluconazole

98
Q

Ergosterol

A

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

99
Q

Amphotericin B MOA

A

-forms a complex with ergosterol and disrupts the fungal cell membrane

Leads to cytoplasmic leakage and fungal cell death

100
Q

How is amphotericin B given

A

IV into CSF

Not absorbed orally

101
Q

Adverse effects amphotericin B

A

Renal toxicity, acute febrile reaction(chills and fever)

Anemia

102
Q

MOA flucytosine (5-FC)

A

Antimetabolite
Converted to 5-FU inside fungal cells
Inhibitis DNA and RNA synthesis

103
Q

What happens if flucytosine is used alone

A

Rapid resistance develops

104
Q

Adverse effects 5-FC

A

Conversion of 5-FC to 5-FU outside fungal cell

Bone marrow depression, nausea, vomiting diarrhea

105
Q

Types of fluconazole

A

Azole, triazole

106
Q

MOA fluconazole

A

Inhibits ergosterol synthesis by inhibiting fungal p450 enzymes

107
Q

Fluconazole has good CSF penetration?

A

Yup

108
Q

Adverse effects fluconazole

A

Limited, widest therapeutic index of all of the adolescents

109
Q

Cryptococcal meningoencephalitis

A

Amphotericin B

Flucytosine

Azole-fluconazole

110
Q

What cephalosporin 1st gen do not treat neuroinfections

A

Ceftaroline

111
Q

What tetracyclines do not treat neuroinfections

A

Doxycycline
Tertracycline
Miniocycline
Demeclocycline

112
Q

What macrolides do we not use for neuroinfections

A

Erythromycin
Clarithromycin
Azithromycin
Fidaoxomicin

113
Q

What aminoglycosides not use in neuroinfections

A 
Streptomycin
Gentamicin
Tobramycin
Amikacin
Neomycin
Paromomycin
Kanamycin
Netolmicin
114
Q

What no class should we not use neuroinfections

A

Clindamycin

115
Q

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

A

Tetracyclines

Cefotaxime+vancomycin

Erythromycin

Metronidazole

Meropenem+ampicillin+vancomycin

116
Q

What is they’re allergic to beta lactam

A

Ceftriaxone+ampicillin

Cefotaxime

Moxifloxacin+TMP/SMX

Moxifloxacin

Meropenem+ampicillin

117
Q

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

A 
Fluconazole
Clindamycin
Colistin
Ampicillin+erythromycin
Emphotericin B+flucytosine
118
Q

What does metronidazole tresat

A 
Giardia lamblia
Entamoeba histolytica
Trichomonas
Gardnerella
Anaerobes
119
Q

Side effects metronidazole

A

Metallic taste

Disulfiram like reaction with alcohol

Pharmacology (52 decks)

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