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!pharmacology Of Neurological Infections Flashcards

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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
How treat s pneumonia or L monocytogenes in older adults(>50) with acute pyogenic meningitis
Cefotaxime or ceftriaxone+vancomycin+ampicillin
26
What give someone with pyogenic meningitis with beta lactam allergy under 50
Vancomycin+moxifloxacin
27
What is used to treat acute pyogenic meningitis in people with beta lactam allergy over 50
Vancomycin+moxifloxacin+TMP/SMX
28
How treat acute pyogenic meningitis in immunocompromised patient
Vancomycin+ampicillin +(cefepime or meropenem)
29
Pathophysiologu acute aseptic virus meningitis
Negative routine bacterial cultures
30
What viruses cause 80% of acute aseptic virus meningitis
Coxsackievirus, echovirus
31
Clinical presentation acute aseptic meningitis
Fever, headache, altered mental status, nuchal rigidity, photophobia, -similar to pyogenic meningitis
32
CSF in acute aseptic meningitis
Lymphocytic pleocytosis Moderate protein elevation Normal glucose levels Opening pressure can be normal OR elevated
33
Treat acute aseptic meningitis
Self limiting and treated symptomatically
34
Treatment is suspect pyogenic meningitis
Start antibiotics soon after LP
35
Treatment is suspect aseptic meningitis
Observation, may be self limiting
36
Treatment when not sure if pyogenic or aseptic meningitis
Start antibiotics after LP | If bacterial cultures are negative then discontinue antibiotics
37
Cephalosporins 3rd gen
Cefotaxime | Ceftriaxone
38
Glycopeptide
Vancomycin
39
Aminopenicillin
Ampicillin
40
Benzylpyrimidine/sulfonamide
Trimethoprim/sulfamethoxazole
41
Cephalosporin 4th gen
Cefepime
42
Car ape EM
Meropenem
43
Fluoroquinolone
Moxifloxacin
44
Brain abscess
Localized focus of necrosis of brain tissue with accompanying inflammation
45
CSF brain abscess
High white cell count Increased protein concentration Normal glucose content
46
Increased intracranial pressure can lead to __ ___
Fatal herniation
47
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
48
Brain abscess pathogens
Viridans strep | S aureus
49
Brain abscess immunocompetent
Likely bacteria
50
Brain abscess immunocompromised
More possibilities including fungi
51
Brain abscess treatment
Surgery+antibiotics -aspiration, craniotomy to drain Antibiotic Empiric therapy -vancomycin+(ceftriaxone or cefotaxime)+metronidazole
52
Penicillin G brain abscess
Covers aerobic and anaerobic strep (mouth flora)
53
Metronidazole brain abscess
Readily penetrates brain abscesses | Combined with other agents when used to treat brain abscess
54
Ceftriaxone brain abscess
Covers most aerobic and microaerophilic strep -substitute for penicillin G Covers many enterobacteriaceae Interchangeable with cefotaxime
55
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
56
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)
57
Cephalosporins 3rd gen brain abscess
Cefotaxime Ceftriaxone Ceftazidime
58
Glycopeptide brain abscess
Vancomycin
59
5-nitromidazoles brain abscess
Metronidazole
60
Penicillin G brain abscess
Penicillin G
61
Cephalosporin 4th gen brain abscess
Cefepime
62
Carbapenem brain abscess
Meropenem
63
Subdural empyema
Produced by bacteria (and rarely fungal) infections of the skull bones or air sinuses that spread to the subdural space
64
CSF subdural empyema
High white cell count Increased protein concentration Normal glucose content
65
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
66
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
67
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
68
Cephalosporins 3rd gen for subdural epyema
Cefotaxime Ceftriaxone Ceftazidime
69
Glycopeptide for subdural empyema
Vancomycin
70
Carbapenem for subdural empyema
Meropenem
71
5 nitroimidazole for subdural empyema
Metronidazole
72
What is viral meningoencephalitis
Parenchyma infection of the brain. Associated with meningoencephalitis and encephalomyelitis
73
How get viral meningoencephalitis
Arthropod borne viral encephalitis Subacute sclerosing panencephalitis from measles Poliomyelitis
74
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
75
Why has incidence of SSPE dropped
Vaccination
76
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
77
Why has poliomyelitis decreased
Vaccines
78
Few drugs useful against viruses wso we use __
Vaccines
79
Active immunity
Vaccines
80
Passive immunity
Immune globulins
81
Active immunity
Live attenuated virus vaccine -contain live virus whose pathogenicity has been attenuated Killed vaccine -subunit vaccines
82
Why are live vaccines preferred to killed citrus
Protection is greater and longer lasting
83
Live attenuated
``` Longer duration greater strength IgA and IgG produced Cell mediated immunity More effective at interrupting spread Possible reversion to virulence ```
84
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
85
Attenuated viral mutants may revert to virluence either during vaccine production or in immunized person
Polio not measles Can be pathogenic in immunocompromised patients
86
Excretion of live virtue to infect others
Herd immunity | Double edge sword
87
SSPE measles vaccine | MMR
Live attenuated vaccine Long term immunity 99% immunity among individuals who have received two doses of measles vaccine
88
I activated poliovirus vaccine IPV
Killed virus vaccine Only vaccine available in US Does not cause vaccine associated paralytic poliomyelitis
89
Live attenuated oral poliovirus OPV
Can cause polio in a small percentage of adults
90
When was the last polio case in the US
1978-1979
91
Poliovirus remains endemic to where
Nigeria, Pakistan, Afghanistan
92
What causes fungal meningoencephalitis
Cryptococcal meningitis
93
Who gets fungal meningoencephalitis
AIDS
94
CSF of fungal meningoencephalitis
High protein concentration
95
Manifestation of fungal meningoencephalitis
Chronic meningitis affecting the basal leptomeninges Appears as soap bubbles on whole brain sections
96
Clinical presentation fungal meningoencephalitis
Stiff neck, photophobia, vomiting Lethargy and confusion High suspicion with advances HIV CD4<100
97
Treat fungal meningoencephalitis
Amphotericin B Flucytosine (5-fluorouracil) Fluconazole Induction phase therapy -amphotericin B+flucytosine Consolidation phase of therapy -fluconazole
98
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
99
Amphotericin B MOA
-forms a complex with ergosterol and disrupts the fungal cell membrane Leads to cytoplasmic leakage and fungal cell death
100
How is amphotericin B given
IV into CSF Not absorbed orally
101
Adverse effects amphotericin B
Renal toxicity, acute febrile reaction(chills and fever) | Anemia
102
MOA flucytosine (5-FC)
Antimetabolite Converted to 5-FU inside fungal cells Inhibitis DNA and RNA synthesis
103
What happens if flucytosine is used alone
Rapid resistance develops
104
Adverse effects 5-FC
Conversion of 5-FC to 5-FU outside fungal cell Bone marrow depression, nausea, vomiting diarrhea
105
Types of fluconazole
Azole, triazole
106
MOA fluconazole
Inhibits ergosterol synthesis by inhibiting fungal p450 enzymes
107
Fluconazole has good CSF penetration?
Yup
108
Adverse effects fluconazole
Limited, widest therapeutic index of all of the adolescents
109
Cryptococcal meningoencephalitis
Amphotericin B Flucytosine Azole-fluconazole
110
What cephalosporin 1st gen do not treat neuroinfections
Ceftaroline
111
What tetracyclines do not treat neuroinfections
Doxycycline Tertracycline Miniocycline Demeclocycline
112
What macrolides do we not use for neuroinfections
Erythromycin Clarithromycin Azithromycin Fidaoxomicin
113
What aminoglycosides not use in neuroinfections
``` Streptomycin Gentamicin Tobramycin Amikacin Neomycin Paromomycin Kanamycin Netolmicin ```
114
What no class should we not use neuroinfections
Clindamycin
115
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
116
What is they’re allergic to beta lactam
Ceftriaxone+ampicillin Cefotaxime Moxifloxacin+TMP/SMX Moxifloxacin Meropenem+ampicillin
117
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 ```
118
What does metronidazole tresat
``` Giardia lamblia Entamoeba histolytica Trichomonas Gardnerella Anaerobes ```
119
Side effects metronidazole
Metallic taste | Disulfiram like reaction with alcohol

Pharmacology (52 decks)

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