Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology > Lungs > Flashcards

Lungs Flashcards

1
Q

Amphotericin B MOA

A

Complexes with ergosterol to disrupt fungal cell membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Spectrum of activity amphotericin B

A

Very broad

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Amphotericin B and yeasts

A

Candida albicans

Cryptococcus neoformans

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Amphotericin B and organisms causing endemic mycoses

A

Histoplasma capsulatum

Blastomyces dermatitidis

Coccidioides immitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Amphotericin B and pathogenic molds

A

Asperigillus fumigatus

Agents of mucormycosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Resistance amphotericin B

A

Alteration to ergosterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Pharmacokinetics amphotericin B

A

Mainly IV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

AE amphotericin B

A

Most common

Immediate-fever, chills, msucle spasm, vomiting, HA, and hypotension

Long term-renal toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Flucytosine MOA

A

Converted to 5-fluorodeoxyuridine monophosphate (Fdump) and fluorouridine triphosphate (FUTP), which inhibit DNA and RNA synthesis, respectively

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Spectrum of activity flucytosine

A

Narrow

C neoformans and some candida

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Resistance flucytosine

A

Altered drug metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Pharmacokinetics flucytosine

A

Water soluble oral formulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

AE flucytosine

A

Anemia, leukopenia, and thrombocytopenia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Soles MOA

A

Inhibiton of fungal cytochrome P450 enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Spectrum of activity anoles

A

Broad

See individual drugsbelow for specific patterns

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Resistance azoles

A

Upregulation of fungal cytochrome P450

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Pharmacokinetis azoles

A

See below

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

AE azoles

A

Relatively non toxic

Minor GI issues

Abnormalities in liver enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Ketoconazole

A

Greater propensity to inhibit mammalian cytochrome P450 enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Itraconazole

A

Oral and IV

Potent antifungal

Poor penetration into CSF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Spectrum itraconazole

A

Dimorphic fungi histoplasma, blastomyces and sporothrix

Aspergillus
-largely replaced by voriconazole as the azole of choice for aspergillosis

Dermatophytoses and onychomycosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Fluconazole

A

Good cerebral spinal fluid penetration

High oral bioavailability (can be given by IV as well)

Widest therapeutic index of all azoles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Spectrum fluconazole

A

Azole of choice for cryptococcal meningitis

Most commonly used for the treatment of mucocutaneous candidiasis

No activity against aspergillus spp or other filamentous fungi

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Voriconazole

A

IV and oral formulations

Inhibitors of the mammalian CYP3A4

Visual disturbances are common (30%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Spectrum voriconazole

A

Similar to itraconazole

Candida spp( including fluconazole-resistant species such as candida krusei) and the dimorphic fungi

Treatment of choice for invasive aspergillosis and some environmental molds

Enhanced activity against aspergillus spp. Versus other azoles.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Posaconazole

A

Available only as a liquid oral preparation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Spectrum posaconazole

A

Broadest spectrum member of azoles

Activity against most species of candida and aspergillus

Only azole with significant activity against the agents of mucormycosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is posaconazole currently licensed for

A

Salvage therapy in invasive aspergillosis

Prophylaxis of fungal infections during induction chemotherapy for leukemia

Allogeneic bone marrow transplant patients with graft versus host disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Echinocandins

A

These are large cyclic peptides linked to a long chain FA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

MOA echinocandina

A

Inhibit glucan synthase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Spectrum of activity echinocandins

A

Candida
Aspergillus
Not C neoformans or the agents of zygoma oasis and mucormycosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is echinocandina licensed for

A

Disseminated and mucocutaneous candida infections

Empiric antifungal therapy during febrile neutropenia
-replaced amphotericin B for this indication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Resistance echinocandins

A

Point mutations in glucan synthase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Pharmacokinetics echinocandina

A

Only IV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

AE echinocandins

A

Well tolerated!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Caspofungin (echinocandin) specific spectrum

A

Invasive aspergillosis

Only as a salvage therapy in patients that don’t respond to amphotericin B

Not primary treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Half life aspofungin

A

9-11 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Micafungin (echinocandins) spectrum)

A

Mucocutaneous candidiasis

Candidemia

Prophylaxis of candida infections in bone marrow transplant patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

HL micafungin

A

11-15 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Andulafungin spectrum

A

Esophageal candidiasis and invasive candidiasis , including candidemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

HL anidulafungin (echinocandins)

A

24-48 horus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Antifungal

A

Amphotericin B

Flucytosine

Azoles
-ketoconazole, itraconazole, voriconazole, posaconazole

Echinocandins
-caspofungin, micafungin, anidulafungin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Anti viral

A

OK

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

LIFE CYCLE OF HIV

A

Virus binds to host cell and integrates into host genome

Gene transcription of viral proteins, cleavage, and maturation produces new visions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Resistance HIV

A

Resistance quickly develops, espicially with monotherapy

HAART-highly active antiretroviral therapy

CD4 T celll counts, viral load assays, and the patients clinical status must be monitored to assess effectiveness of chosen antiretroviral regimen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Goal of treating HIV

A

To decrease the circulating viral load

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Spectrum of activity HIV

A

HIV-1 (focus on these notes)

Effectiveness to HIV2 varies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs)

A

Used in combination with other agents

NNRTIs, PIs, or integrate inhibitos

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

MOA NRTI

A

Competitive inhibition of HIV1 reverse transcriptase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Resistance NRTIs

A

Point mutations in HIV1 reverse transcriptase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

AE NRTI

A

Mitochondrial toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Abacavir (NRTI)

A

Guanosine analog

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

AE abacavir

A

Hypersensitivity (8%) first 6 weeks therapy

  • fever, fatigue, nausea, vomiting, diarrhea, and abdominal pain
  • respiratory symptoms-dyspnea, pharyngitis, cough
  • skin rash
  • do not reintroduce abacavir if hypersensitivity is observed. Reintroduce could result in severe outcomes including death
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Didanosine (NRTI)

A

Synthetic analog of deoxyadenosine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

AE didanosine

A

Dose dependent pancreatitis

  • conditions or drugs that may cause pancreatitis are contraindicated
  • alcohol abuse, hyperTG

Retinal changes and optic neutiris

  • adults with high doses and children
  • mandate periodic retinal examinations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Etricitabine (NRTI)

A

Fluoridated analog of lamivudine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

AE emtricitabine

A

HA, diarrhea, nausea, and rash

-hyperpigmentation of the palms or soles may be observed particularly in african Americans (13%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Besides HIV, what does emtricitabine treat

A

HBV, s discontinuation could exacerbate HBV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Lamivudine

A

Cytosine analog

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

AE lamivudine

A

Uncommon, hypersensitivity rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Besides HIV what does lamivudine treat

A

HBV so discontinuation could exacerbate HBV symptoms in a patient infected with both

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Stavudine

A

Thymidine analog

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

AE stavudine

A

MAJOR-dose related peripheral sensory neuropathy

-increased by concomitant neurotoxic drug use or in patients with advanced immunosuppression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Tenofovir

A

An acyclic nucleoside phosphonate (nucleotide) analog of adenosine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Tenofovir dinoprostone fumarate

A

Water soluble prodrug of active tenofovir

Recommended for use during preg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

AE tenofovir dinoprostone fumarate

A

GI complaints

-nausea, diarrhea, vomiting, flatulence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Tenofovir alafenamide

A

A phosphonoamidate prodrug of tenofovir

Less renal toxicity than tenofovir dinoprostone fumurate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

AE tenofovir alafenamide

A

Uncommon

May include GI symptoms or HA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

Besides HIV what does tenofovir alafenamide treat

A

HBX, discontinuation may exacerbated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

Zidovudine (NRTI)

A

Deoxythymidine analog

Safe in preg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

AE zidovudine

A

Microcytic anemia 1-4%
Neutropenia (2-8%)
GI intolerance, HA, insomnia may occur
-tend to resolve during therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

Nucleoside reverse transcriptase inhibtiors (NNRTIs) MOA

A

Bind directly to HIV1 reverse transcriptase resulting in allosteric inhibiton of RNA and DNA dependent DNA polymerase activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

First generation NNRTI

A

Delaviridine, efacirenz, nevirapine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Second generation NNRTI

A

Etravirine, rilpivirine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

Resistance NNRTI

A

Baseline genotypes testing is recommended to screen for resistant HIV1 reverse transcriptase mutants (point mutations that alert NNRTI binding )

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

AE NNRTI

A

GI intolerance

Skin rash

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

Metabolism NNRTI

A

Cyp450—many drug drug interaction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Delaviridine

A

Skin rash in 38%

Avoid in preg

CYP3A4 and 2D6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Efavirenz

A

Combined with tenofovir and emtricitabine in the conformation atrial as a once a day combination pill

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

Metabolism efavirenz

A

3a4 and 2B6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

AE efavirenz

A

Main involve CNS 5-%
-dizzy, drowsy, insomnia, nightmares, HA
These dimish with continued therapy
Increase with alcohol and psychoactice drug use

Psychiatric symptoms may necessitate discontinuation
-depression, mania, psychosis

Skin rash 28%

Nauseas, vomiting, diarrhea, crystalluria, elevated liver enzymes, increases in total serum cholesterol by 10-20%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

Efavirenz preg

A

Can be used in pregnancy but only after the first 8 weeks due to birth defects observed ina. Primate study

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

Etavirine

A

A diarylpyrimidine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

AE etravirine

A

Most common-rash, nausea, diarrhea

Substrate as well as an inducer of CYP3a4 and an inhibitor of 2C9 and 2C19

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

Nevirapine

A

A single dose administered at the onset of labor followed by another dose to the neonate within 3 days of delivery is effective at preventing transmission of HIV from mother to newborn

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

AE nevirapine

A

Rash 2-%

  • maculopapular eruption that spares palms and soles
  • occurs in the first 4-6 weeks of therapy
  • can be a dose limiting toxicity

Liver toxicity 4%
-more frequent with higher CD4 cell count, in women, and in those with HBV and HCV co infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

Rilpivirine

A

Co formulated with emtricitabine and tenofovir into a singe once daily tablet to increase compliance

A diarylpyramidine (like etravirine)

Can use in preg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

AE rilpivirine

A

Most common-rash, depression, HA, insomnia, increased serum aminotransferase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

Protease inhibtors MOA

A

Block the HIV protease and prevent the maturation of the final structural proteins that make up the mature vision core

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

AE PI

A

IG intolerance (may be dos limiting)

Lipodystrophy
-metabolism-hyperglycemia, hyperlipidemia
Morphological-lipoatrophy, fat depression

Redistribution and accumulation of body fat
-central obesity, dorsocervical fat enlargement (buffalo hump), peripheral and facial wasting, breast enlargement , a cushingoid appearance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

Metabolism PI

A

CYP3A4

-ritonavir has the most pronounced inhibitory effect and saquinavir the least

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

Name PI

A 
Atazanavir
Darunavir
Fosamprenavir
Indinavir
Lopinavir
Nelfinavir
Ritonavir
Saquinavir
Tipranavir
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

Atazanavir

A

Boosted atazanavir is a recommended PI agent for use in pregnant women

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

AE atazanavir

A

Most common-diarrhea, nausea

Skin rash in 20%

Indirect hyperbilirubinemia with overt jaundice (10%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

Darunavir

A

Must be co administered with ritonavir or cobicistat

Boosted darunavir is a recommended PI agent for use in pregnant women

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

AE darunavir

A

Rash 2-7%
-occasionally severe

Darunavir contains a ulfonamide moiety
-may cause a hypersensitivity reaction in a patient with a sulfa allergy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

Fosamprenavir

A

Prodrug of amprenavir, rapidly hydrolyzed by enxymes in the intestinal epithelium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

AE fosamprenavir

A

Most common-HA, nausea, diarrhea, perior Ali paresthesia, depression

Contains a sulfonamide moiety
-may cause a hypersensitivity reaction in a patient with a sulfa allergy
Rash in 19%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

Indinavir AE

A

Most common-unconjugated hyperbilirubinemia and nephrolithiasis due to urinary crystallization of the drug

  • nephrolithiasis can occur days after initiating therapy
  • incidence 10%

Consumption of 48 ounces of water a day is important to prevent kidney stones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

Boosting indinavir with ritonavir

A

Allows for twice daily dosing (as opposed to 3 times a day) but this increases the chance for kidney stones so a higher fluid intake is required (1.5-2L)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

Lopinavir

A

Available only in combination with low dose as a booster

Preferred treatment for pregnant women

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

AE lopinavir

A

Generally well tolerated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

Nelfinavir AE

A

Diarrhea and flatulence

-diarrhea may be dose limiting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

Ritonavir

A

No longer used as a sole PI agent due to its high rate of GU side effects at standard dose
-a lower dose used for inhibiton of CYP3A4

Very potent inhibitor of P450 system
-used primarily as a booster

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

Ritonavir

A

Used primarily as a booster

Prodrug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

Saquinavir

A

Minimal amount of the drug absorbed when taken orally

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

AE saquinavir

A

GI discomfort
-nausea, diarrhea, abdominal discomfort, dyspepsia

When boosted with ritonavir, less dyslipidemia, of GI toxicity than with other boosted regimens

Hypersensitivity (rare)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

Tipranaviir

A

Indicated for use in treatment -experienced patients who harbor strains resistant to other PI agents

Used in combination with ritonavir

Contains sulfonamide moiety and should not be Syed in a patient with a sulfa allergy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

AE tipranavir

A

Most common-diarrhea, nausea, vomiting, ab pain

Urticaria or maculopapular rash 10-14%

Hypersensitivity rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

Fusion inhibitor

A

Viral attachment to host cell

Viral envelope glycoproteins complex gp160 (gp120+gp41) binds to its cellular receptor CD4

This binding changes the structure of gp120 which enables access to the chemokine receptors CCr5 or CxR4

Biding to chemokine receptors again leads to structural changes and exposes gp41

Gp41 leads to the fusion of the viral envelope with the host cell membrane and entry of the viral core into the host cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

Name fusion inhibitor

A

Enfuvitride

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
112
Q

Enfuviritide

A

Synthetic 36 aa peptide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
113
Q

MOA enfuviritide

A

Binds to gp41 preventing the conformational and structural changes needed to allow fusion of the viral envelope with the host cell membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
114
Q

Pharmacokinetics enfuviritide

A

Must be administered with subcutaneous injection (2 x a day)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
115
Q

Resistance enfuviritide

A

Mutations in gp41

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
116
Q

AE enfuviritide

A

Local injection site reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
117
Q

Drug drug enfuviritide

A

Not really

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
118
Q

Entry inhibitor

A

Viral attachment to host cell

Viral envelope glycoproteins complex gp160 (gp120+gp41) binds to its cellular receptor CD4

This binding changes the structure of gp120 which enables access to the chemokine receptors CCR5 or CXCR4

Binding to chemokine receptors again leads to structural changes and exposes gp41

Gp41 leads to fusion of the viral envelope with the host cell membrane and entry of the viral core into the host cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
119
Q

Maraviroc MOA

A

Binds specifically and selectively to CCR5 to prevent viral entry into the host cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
120
Q

Pharmacokinetics maraviroc

A

Oral administration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
121
Q

Resistance maraviroc

A

Mutations in V3 loop of gp120

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
122
Q

AE maraviroc

A

Generally well tolerated

Systemic allergic reaction followed by hepatotoxicity has been reported
-discontinue maraviroc if this occurs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
123
Q

Integrate strand transfer inhibtors (INSTIs) MOA

A

Inhibit strand transfer and prevent integration of reverse transcribed HIV DNA into the chromosomes of the host cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
124
Q

AE INSTIs

A

Well tolerated

HA and GI effects most common

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
125
Q

Dolutegravir

A

Preferred agent for treatment of treatment naive patients when combined:
Tenofovir/emtricitabine
Abacavir/lamivudine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
126
Q

Pharmacokinetics dolutegravir

A

14 hour

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
127
Q

AE dolutegravir

A

Infrequent

Hypersensitivity (rash and systemic symptoms have been reported
-dolutegravir should be discontinued

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
128
Q

Elvitagravir

A

Approved in 2012 only available as part of a combination pill
-s tri il4 (elvitegravir, cobicistat, emtricitabine, and tenofovir)

Requires boosting to be efficacious -combined with cobicistat
-inhibits CYP3A4

AE few

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
129
Q

Raltegravir

A

Pyrimidinone analog

A preferred option for treatment naive persons beginning HAART

Recommended for use during pregnancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
130
Q

HL raltegravir

A

9 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
131
Q

AE raltegravir

A

Uncommon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
132
Q

Oseltamivir MOA

A

Neuramindiase inhibitor

Interferes with release of progeny influenza A and B virus from infected host cells, thus halting the spread of infection within the respiratory tract. They competitively and reversible interact with the active enzyme site to inhibit viral neuraminidase activity at low nanomolar concentrations, resulting in clumping of newly released influenza virions to each other and to the membrane of the infected cell. Early administration is crucial bc replication of influenza peaks 24-72 hours after the onset of illness. Initiation of a 5 day course within 48 hours after the onset of illness modestly decreaseses the duration of TMP TOMS, as well as duration of viral shedding and viral titer. Once day prophylaxis is effective in preventing disease exposure

Oral prodrug that is activated by hepatic esterases and widely distributed through body. Oral available 80%, plasma protein binding is low and concentrations in the middle ear and sinus fluid are similar to plasma.

HL 6-10 hours

Excretion by kidney

Oseltamivir is active metabolite snow serum concentrations increase with declining renal function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
133
Q

Oseltamivir spectrum of activity

A

H1N1, H3N2, influenzae B

Influenza a and b

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
134
Q

Oseltamivir resistance

A

May embrace and be transmissible >98% of H1N1 and H3N2 strains as well as 100% flu B retained susceptibility to both

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
135
Q

Oseltamivir AE

A

N/V, HA (take with food)
Fatigue, diarrhea (more common prophylactic use)
Rash rare

Neuropsychiatric events (self injury and delirium), particularly in Japanese adolescent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
136
Q

Oseltamivir drugs and differences

A

Ok

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
137
Q

Zanamivir MOA

A

Analog of sailing acid, interfere with release of progeny of influenza A and B virus from infected host cells, thus halting the spread of infection within the respiratory tract. These agents competitively and reversible interact with the active enzyme site to inhibit viral neuraminidase activity at low nanomolar concentrations, resulting in clumping of newly released influenza virions to each other and to the membrane of the infected cell. Early administration is crucial bc replication of influenza virus peaks at 24 -72 hours after the onset of illness. Initiation of a 5 day course of therapy within 48 hours after the onset of illness modestly decreases the duration of symptoms, as well as duration of viral shedding and viral titer; some studies have also shown a decrease in the incidence of complications. Once daily prophylaxis is 70-90% effective in preventing disease after exposure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
138
Q

Zanamivir spectrum

A

Influenza a and b

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
139
Q

Zanamivir resistance

A

May emerge and be transmissible >98% of H1N1 and H3N2 strains as well as 100% if influenza B virus tested in 2015 retained susceptibility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
140
Q

Zanamivir ADME

A

Administered directly to the respiratory tract via inhalation. Of the active compound 10-20% reaches the lungs; the remainer is deposited in the oropharyngeal. The concentration of the drug in the respiratory tract is estimated to be more than 1000 times the 50% inhibitory concentration for neuraminidase, and the pulmonary half life is 2.8 hours. Of the total dose, 5015% is absorbed and excreted int he urine with minimal metabolis,.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
141
Q

Zanamivir AE

A

Cough, bronchospasm (occasionally severe), reversible decrease in pulmonary function, and transient nasal and throat discomfort.

NOT recommended if have underlying airway disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
142
Q

Peramivir MOA

A

Neuraminidase inhibitor, a cyclopentane analog,

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
143
Q

Permavir spectrum

A

Influenza. A and b

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
144
Q

Permivir resistance

A

Ok

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
145
Q

Peramivir ADME

A

Treat within 48 hours

Less than 30% is protein bound. Is not significantly metabolized and major route of elimination is kidney. Dose adjustment is required for renal insuffiency. The elimination HL following IV is 20 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
146
Q

Peramivir AE

A

Serious skin or kypersensitivity reaction (Stevens johnson , erythema multiforme) have been rarely reported

Hallucinations, delirium, abnormal behavior in patients with influenza receiving it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
147
Q

Peramivir drug differences

A

Ok

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
148
Q

Amantadine MOA

A

Tricyclic amines of the adamantane family that block the M2 proton ion channel of the virus particle and inhibit uncoating of the viral RNA within infected host cells, thus preventing its replication.

4-10 times less active than rimantadine.

Well absorbed and 67% bound to protein, HL 12-18 hours.

Excreted unchanged in urine

Dose reductions are required in elderly and in patients with renal insuffiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
149
Q

Amantadine spectrum

A

Influenza a

70-90% protective in prevention when initiated before exposure and limit duration of clinical illness by 1-2 days

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
150
Q

Amantadine resistance

A

Ok

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
151
Q

Amantadine ADME

A

Amantadine AE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
152
Q

Amantadine resistance

A

High to H1N1 and H3N2, not recommended anymore for prevention

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
153
Q

AE

A

Teratogenic and embryotoxic

GI
-nausea, anorexia

CNS-nervousness, difficulty in concentrations,, insomnia, light headed

Serious-behavioral changes, delirium, hallucinations, agitation, seizuresmay be due to alteration of dopamine neurotransmisssion )less frequent with R than A and associated with renal insuffiency, seizure disorders, LOF age and may increase with concomitant antihistamines, anticholinergics, hydrochlorothiazide and TMPSMX

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
154
Q

Rimantadine MOA

A

Tricyclic amines of the adamantane family that block the M2 proton ion channel of the virus particle and inhibit uncoating of the viral RNA within infected host cells, thus preventing its replication

4-10 times more active than amantadine.

40% bound to protein HL 24-4 hours

Nasal mucus concentrations average 50% higher than those in plasma, and CSF levels are 52-96% of those in serum.

Extensive metabolism by hydroxylation, conjugation, and glucuronidation before urinary excretion

Dose reduction in elderly or renal insuffiency of with severe hepatic insuffiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
155
Q

Rimantadine spectrum

A

Influenza a

70-90% protective in prevention when initiated before exposure and limit duration of clinical illness by 1-2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
156
Q

Rimantadine resistance

A

High to H1N1 and H3N2, not recommended anymore for prevention

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
157
Q

Rimantadnine AE

A

Teratogenic and embryogenic

GI
-nausea, anorexia

CNS-nervousness, difficulty in concentrations,, insomnia, light headed

Serious-behavioral changes, delirium, hallucinations, agitation, seizuresmay be due to alteration of dopamine neurotransmisssion )less frequent with R than A and associated with renal insuffiency, seizure disorders, LOF age and may increase with concomitant antihistamines, anticholinergics, hydrochlorothiazide and TMPSMX.

158
Q

Tuberculosis pharmacology

A

First line-isoniazid, rifampin, pyrazinamide, and ethambutol

Isoniazid and rifampin most active
Isoniazid-rifampin combo given for 9 months will cure 95-98% of Tb but a intensive phase of treatment is needed for first two months due to prevelance of resistance. Do this by adding pyrazinamide during intensive phase and puts treatment at 6 months will no less efficacy.

Usually use four drug regimen in practice-isoniazid, rifampin, pyrazinamide, and ethambutol until susceptibility is determined. If susceptible continue isoniazid and rifampin for four moths.

Neighbor ethambuto nor other streptomycin add substantially to overall activity of the regimen but the fourth drug provides additional coverage if the isolate proves to be resistant to isoniazid, rifampin or both. If therapy starts after it is known that strain is susceptible to isoniazid and rifampin, ethambutolol does not need to be added.

10% isoniazid resistance. Resistance to both isoniazid and rifampin 1%

Multi drug resistance is more preventlant in other parts of the world. Resistance to rifampin alone is rare

159
Q

Isoniazid MOA

A

Most active drug for treatment of Tb caused by susceptible strains. Small molecule that is freely soluble in water.

Penetrates into macrophages and is active against extracellular and intracellular organisms

Inhibits synthesis of mycotic acids, which are essential components of mycobacteria cel walls. Prodrug that is activated by KatG, the mycobacteria catalase peroxidase. The activated form forms a covalent complex with an axel carrier protein (AcpM) and KasA, a beta ketoacidosis carrier protein synthetase, which blocks mycotic acid synthesis.

160
Q

Isoniazid spectrrum

A

Tb

161
Q

Isoniazid resistance

A

Associated with mutations resulting in overexpression on inhA, which encodes an NADH dependent acyl carrier protein reductase, mutation or deletion of the KatG gene; promoter mutations resulting in overexpression of ahpC, a gene involved in protection fo the cell from oxidative stress and mutations in kasA.

Overproducers of inhA express low level isoniazid resistance and cross resistance to ethionamide. KatG mutatnsts express high level isoniazid resistance and often are not cross reasistnt to ethionamide

Rare will be resistant to both so give both . At least two active agents should always be used to treat active Tb to prevent emergence of resistance during therapy

162
Q

Isoniazid ADME

A

Readil absorbed from the GI tract, optimally on an empty stomach; peak concentrations may be decreased by up to 50% when taken with a fat meal.

Diffuses readily into all body fluids and tissues.

The concentration int he CNS and CSF ranges from 20 to 100% to serum

Metab-acetylation by liver N acetyltransferase, is genetically determined. Tumors rapid excretion by rapid acetylators

Metabolites Excreted in urine. Not need to adjust for renal failure or hepatic insuffiency .

Inhibits several P450 enzymes, leading to increased concentrations of such medications as phenytoin, carbamazepine, and benzodiazepines. However when used in combination with rifampin, a potent CYP enzyme inducer, the concentrations of these meds is decreased

163
Q

Isoniazid AE

A

Immunologic
-fever, skin rash, drug induced SLE

Direct
-hepatitis, increase Aminotransferases (seen in 10-20% but don’t need to stop-stop if hepatitis, not increase in ALT AST).,
Clincial hepatitis with loss of appetite, nausea, vomiting, jaundice, RUQ pain , DEATH, hepatocellular damage and necrosis
Risk of hepatitis depends on age usually over 50. Also alcohol dependence and possible during pregnancy and postpartum…stop use

Peripheral neuropathy
-more likely in slow acetylators , malnutrition, alcohol, diabetes, AIDS< uremia, due to pyridoxine defiency. Isoniazid promotes excretion of pyridozine and this toxicity is readily reversed by administration of pyridoxine in a dosage as low as 01.

CNS_memory loss, psychosis, ataxia, seizures. May respond to pyridoxine

Tinnitus, GI discomfort, Hematologic issues

164
Q

Rifampin MOA

A

Semisynthetic derivative of rifamycin

Binds to the B subunit of bacterial DNA dependent RNA polymerase and thereby inhibits I RNA synthesis . Resistanceresults from any one of several possible point mutations in rpoB, the gene for the B subunit of RNA polymerase. These mutations result in reduced binding of rifampin to RNA polymerase. Human RNA polymerase does not bind rifampin and is not inhibited by it. Rifampin is bactericidal for mycobacteria . It readily penetrates most tissues and penetrates into phagocytic cells. It can kill organisms that are poorly accessible to many other drugs, such as intracellular organisms and those sequestered in abscesses and lung cavities.

165
Q

Rifampin spectrum

A

Gram + organisms, some gram negative such as Neisseria and haemophilus species, mycobacteria and chlamydia.

mycobacteria.

With isoniazid or other antitb drugs to patients with active Tb

Meningococcal carriage. Staph carriage. Osteomyelitis (staph) prosthetic joint infections, prosthetic valve endocarditis

166
Q

Rifampin resistance

A

Resistant mutants present in all microbial populations and readily selected out if rifampin is used as a single drug,

No cross resistance to other drug classes of antimicrobial drugs, but there is cross resistsance to other rifamycin derivatives rifabutin and rifapentine

167
Q

Rifampin ADME

A

Well absorbed after oral administration and excreted mainly through the liver into bile. It then undergoes enterohepatic recirculating, with the bulk excreted as a deacylated metabolite in feces and a small amount excreted int he urine. Dosage adjustment for renal or hepatic insuffiency is not necessary. Usual doses result in serum levels 5-7 mcg/mL. Rifampin is distributed widely in body fluids and tissues . The drug is relatively highly protein bound, and adequate CSF concentrations are acheived onyl in presence of meningeal inflammation

168
Q

Rifampin AE

A

Strong inducer P450, which increases the elimination of numerous other drugs

Co administration results in significantly lower serum levels of drugs

Harmless ORANGE URINE, SWEAT AND TEARS. Rash, thrombocytopenia, nephritis

Cholestatic jaundice and hepatitis, light chain proteinuria,

Flu like syndrome

169
Q

Ethambutol MOA

A

Synthetic water soluble , heat stable compound ,

Inhibits mycobacteria arabinosyl transferase, which are encoded by the embCAB Operon. Arabinosyl transferase are involved in the polymerization reaction of arabinosyl an, an essential component of the mycobacteria cell wall.

170
Q

Ethambutol spectrum

A

Tb and other mycobacteria

Mycobacterium avium complex -given with other agents

171
Q

Ethambutol resistance

A

Mutations resulting in overexpression of emb gene products or within the embB structural gene.

Rapid when drug used alone. Always given with another antiTb drug. (Isnoazis, rifampin, pyrazinamide during intima treatment),

172
Q

Ethambutol ADME

A

Well absorbed from gut.
HL 2-4 horus

20% excreted in feces 50% urine unchanged.
Accumulated INR enal failure, and does reduced 3x if creatine clearance less than 30 ml/min.

Crosses BBB only when meninges inflamed

Concentrations in CSF range depending on meningeal infallmmamtion

173
Q

Ethambutol AE

A

Hypersensitivity rare

Common-retrobulbar neuritis, resulting in loss of visual acuity and red green color blindness. (Usually when used for several months)

Visual disturbances occur in 3% after at least 1 month.
Get baseline monthly visual acuity and color discrimination testing with attention if high doses or renal issues

CONTAINDCATED IN YOUNG BC OF VISION AND RED GREEN COLOR DISCRMINIAOTN

174
Q

Pyrazinamide MOA

A

Relative nicotinamide, and it is used only for treatment of Tb. Stable and slightly water soluble. Inactive at neutral pH, but at 5.5 it inhibits Tb. Taken up by macrophages and exerts its activity against mycobacteria residing within the acidic environment

Converted to pyrazinamide acid-the active form of the drug-by mycobacteria pyrazinamide seems, which is encoded by pncA. Pyrazinamide acid disrupts mycobacteria cell membrane metabolism and transport function

175
Q

Pyrazinamide spectrum

A

Ok

176
Q

Pyrazinamide resistance

A

May be due to impaired uptake of pyrazinamide or mutations in pncA that impair conversion of PZa to its active form

177
Q

Pyrazinamide ADME

A

well absorbed from the GI tract and widely distributed in body tissues, including inflamed meninges.

HL 8-11 hours. The parent compound is metabolized by the liver, but metabolites are really cleared; therefore, PZA should be administered at 25-35 mg/kg is unused for thrice weekly or twice weekly treatment regimens.

178
Q

Pyrazinamide AE

A

Major adverse effects of PZA include hepatoxocity , nausea, vomiting, drug fever, photosensitivity, and hyperuricemia. The latter occurs uniformly and is not a reason to halt therapy if patients are asymptomatic.

179
Q

Pyrazinamide resistance

A

Tubercle bacilli develop resistance to pyrazinamide fairly readily, But there is no cross resistance with isoniazid or other anti mycobacteria drugs

180
Q

First line agents TB

A

Isoniazid, rifampin, ethambutol, pyrazinamide

181
Q

Second line agents Tb

A

Streptomycin, ethionamide, capreomycin, cyclosporine, aminosalicylic acis, kanamycin and amikacin, fluoroquinolones, linezolid, rifabutin, rifapentine, bedauiline

182
Q

Streptomycin MOA

A

Aminoglycosides. Lessen dose if on dialysis of creatinine clearance less than 30ml/min

183
Q

Streptomycin spectrum

A

TB, MAC, mycobacterium kansassi

Others are resistant

184
Q

Streptomycin resistance

A

All large populations of Tb contain some streptomycin resistant mutants. 1 in 10^9 are resistant .
Due to point mutation in either rpsL gene encoding the S12 ribosomal protein or the respiratory gene encoding 16S ribosomal RNA, which alters the ribosomal binding sit.

185
Q

ADME streptomycin

A

Penetrates into cells poorly and is active mainly against extracellular tubercle bacilli. The drug crosses the bbb and achieves therapeutic concentrations with inflamed meninges

186
Q

Clinical streptomycin

A

Streptomycin sulfate is used when an injectable drug is needed or desirable and in the treatment of infections resistant to other drugs.

187
Q

AE streptomcin

A

Ototoxicity and nephrotoxicity.

Vertigo and hearing loss are the most common AE and may be permanent. Dose related. And increased in elderly.

Adjust with renal prob.

Reduce to no more than 6 months

188
Q

Ethionamide

A

Chemically related to isoniazid and similarly blocks the synthesis of mycotic acids. It is poorly water soluble and available only for oral use. Metabolized by liver

189
Q

Spectrum ethionamide

A

Tubercle bacilli

-CSF equal to serum

190
Q

ADME ethionamide

A

CSF same as serum

Administered at an intima dose which is increased

Hepatotoxicity. Neurologic symptoms may be alleviated by pyridoxine

191
Q

Resistance ethionamide

A

Rapidly in vitro in Vito. There can be low level cross resistance between isoniazid and ethionamide

192
Q

Capreomycin

A

Peptide protein synthesis inhibitor antibiotic obtained from strep capreomycin.

193
Q

Capreomycin spectrum

A

Mycobacteria, including multidrug resistant strains of M tuberculosis (when resistant to streptomycin)

194
Q

Resistance capreomycin

A

Some cross resistance with amikacin and kanamycin.

Associated with rss , EUS, or tlyA gene mutations

195
Q

AE capreomycin

A

Nephrotoxicity and ototoxicity

Tinnitus, deafness, vestibular disturbances

Injection pain and sterile abscess

196
Q

How minimize ris of toxicity of capreomycin

A

Intermittent dissing

197
Q

Cyclosporine

A

Structural analog of D alanine-inhibits cell wall synthesis

Two oral doses,

198
Q

ADEM cyclosporine

A

Two oral doses

Cleared renally, and the dose should be reduced by half if creatinine clearances is less than

Widely distributed to tissues, including the CNS

199
Q

AE cycloserine

A

Peripheral neuropathy and CNS dysfunction, including depression and psychoses.

Pyridoxine should be given with cycloserine bc this ameliorates neurologic toxicity.
Most common first 2 weeks of therapy,

200
Q

Aminosalicyclic acid (PAS)

A

Folate synthesis antagonist that is active almost exclusively against M tuberculosis. Structurally similar to PABA and is thought to have a similar MOA to the sulfonamides.

must be administered sprinkled over applesauce or yogurts or fruit

201
Q

Spectrum aminosalicycic acid

A

Tubercle bacilli

202
Q

ADME aminosalicyclic acid

A

Granule formulation results in improved absorption from GI

Widely distributed in tissues and body fluids except the CSF

Rapidly excreted in urine, in part as active PAs and in part as the acetylated compound and other metabolic products. To avoid accumulation in renal impairment lessen with creatine clearance less than 30

Very high in urine can give crystsalluria

203
Q

Aminosalicylic acid infrequently used in USA

A

Other oral drugs are better tolerated . GI symptoms are common but occur less frequently with the delayed release granules; they ma be dimished by giving the drug with meals and with antacids. Peptic ulceration hemorrhage may occur. Hypersensitivity reactions manifested by fever, joint pains, skin rashes, hepatosplenomegaly, hepatitis, adenopathy, and granulocytes Elia often occur after 3-8 weeks of PAS therapy. Making it necessary to stop administration temporarily or permanently

204
Q

Kanamycin and amikacin

A

Aminoglycoside antibiotics .
Kanamycin has been used for treatment of Tb caused by streptomycin resistant strains but is no longer available in USA and less toxic alternatives taken its place (capreomycina nd amikacin)

205
Q

Amikacin

A

Treat Tb due to prevelance of multidrug resistant strains. Prevelance of amikacin resistant strains is low and most multidrug resistant strains remain amikacin susceptible. M Tb is inhibited at concentrations 1mcg or less

Active against atypical mycobacteria.

206
Q

Resistance amikaricin

A

No cross resistance between streptomycin and mikacin, but kanamycin resistance often indicated resistance o amikacin as well.

207
Q

Spectrum amikacin

A

Tb suspected or known to be caused by streptomycin resistant or multidrug resistant strains. This drug must be used in combination with at least one a preferably two or three other drugs to which the isolate is susceptible for treatment of drug resistant cases.

208
Q

FLUOROQUINOLONES

A

In addition to their activity against many gram positive and gram negative bacteria, ciprofloxacin, levofloxacin, gatofloxacin and moxifloxacin inhibit strains of M Tb .

Alsoactive against atypical mycobacteri

209
Q

Moxifloxacin

A

Most active against M Tb

210
Q

Levofloxacin

A

Slightly more active than ciprofloxacin against M Tb, whereas ciprofloxacin is slightly more active against atypical mycobacteria

211
Q

Spectrum fluoroquinolones

A

When strains are resistant to first line.

Use moxifloxacin or levofloxacin

212
Q

Resistance fluoroquinolones

A

Point mutations in grade A subunit, develops rapidly if a fluoroquinolones is used as a single agent; thus the drug must be used in combination with two or more additional active agents

Resistance to one indicates resistant to all

However moxifloxacin may retain some activity in strains resistant to ofloxacin

213
Q

Linezolid

A

Inhibits strains of Mtb

Good intracellular concentrations and is active in murine models of Tb

In combo with other second and third line drugs to treat multidrug resistant Tb . Conversion of sputum cultures to negative was associated with it

214
Q

AE linezolid

A

Bone marrow suppression and irreversible peripheral and optic neuropathy, have been reported with the prolonged courses of therapy that are necessary for treatment of Tb.

Low -prevent AE and supplement pyridoxine

215
Q

When use linezolid

A

Only multidrug resistant

216
Q

Who should not have linezolid

A

Patients on concomitant serotonergic agents due to concern for serotonin syndrome

217
Q

Rifabutin

A

Derived from rifamycin and is related to rifampin.

218
Q

Rifabutin spectrum

A

M tuberculosis, MAC, and mycobacterium fortuitous.

219
Q

Resistance in rifabutin

A

Cross resistance with rifampin is virtually complete
Some resistant strains may appear susceptible to rifabutin in vitro but a clincal response is unlikely bc the molecular basis of resistance, rpoB mutation, is the same

220
Q

ADME rifabutin

A

Both subrate and inducer of cytochrome p450 enzymes. Because it is a less potent inducer, rifabutin is often used in place of rifampin for treatment of Tb in patients with HIV infection who are receiving antiretroviral therapy with a protease inhibition, a nonnucleoside reverse transcriptase inhibitor or an integrate strand transfer inhibit, drugs that also cytochrome p450 or UDP glucuronosyltransferases substrates

221
Q

AE rifabutin

A

May accumulate in severe renal impairment, and the dose should be reduced by half if creatinine clearance is less than 30ml.min. Rifabutin is associated with similar rates of hepatotoxicity or rash compared to rifampin; it can also cause leukopenia, thrombocytopenia, andoptic neuritis

222
Q

Rifapentine MOA

A

Another analog of rifampin.

As with all rifamycin, it is a bacterial RNA polymerase inhibitor, and cross resistance between rifampin and rifapentine is complete.

223
Q

Spectrum rifapentine

A

M Tb and MAC

224
Q

ADME rifapentine

A

Potent inducer of P450 enzymes, and it has the same drug interaction profile; however when is given intermittently, induction of metabolism of other medications is less pronounced compared to rifampin.

HL 13 hours

Not given at high risk of failure patients or positive cultures at the end of the intensive treatment phase and those with evidence of cavitation on chest radiographs.

DONT use to treat active Tb in patients with HIV bc unacceptable high relapse rate with rifampin resistant organisms.

Combined with isoniazid

Effective for latent Tb

225
Q

AE rifapentine

A

Similar to rifampin.

226
Q

Bedaquiline

A

Diarylquioline-first drug with a novel mechanism of action against M Tb to be approved since 1971.

Inhibits adenosine 5-triphosphate synthase in mycobacteria, has in vitro activity against both replicating and nonreplicating bacilli, and has bactericidal and sterilizing activity in the murkiness model of Tb .

227
Q

Resistance bedaquiline

A

Cross resistance has been reported between bedaquiline and clofazimine, likely via upregulation of the multisubstrate efflux pump, mmpL5

228
Q

ADME bedaquiline

A

Peak plasma concentration and plasma exposure increase twofold when given with high fat foot.

Highly protein bound>99%, is metabolized chiefly through the cytochrome p450 system, and is excreted primarily via the feces.

HL bedaquiline -5.5 months

Long elimination phase probably reflects slow release of bedaquiline and M2 (major metabolite) from peripheral tissues

3a4 is major isoenzymes involved int he metabolism and potent inhibitors or inducers of this enzyme cause CLINCIALLY significant drug interactions

229
Q

When use bedaquiline

A

In combination with at least three other active medications, may be used for 24 weeks of treatment in adults with laboratory confirmed pulmonary Tb if the isolate is resistant to both isoniazid and rifampin .

230
Q

AE bedaquiline

A

25% or more

Nausea, arthralgias, and headache.

Hepatotoxicity and cardiac toxicity.

Black box warning related to QT prolongation and mortality .

Reversed for patients who do no have other treatment options and used with caution in patients with other risk factors for cardiac conduction abnormalities

231
Q

Pharmacology of asthma and COPD drugs

A

Ok

232
Q

Components of asthma management

A

Routine monitoring of symptoms and lung function
Patient education to create a partnership between clinical and patient

Controlling environmental factors (trigger factors) and comorbid conditions that contribute to asthma severity

Pharmacological therapy

233
Q

Goals of asthma management

A

Reduction in impairment and reduction of risk

234
Q

How manage asthma

A

Can usually be managed with rescue inhalers to treat symptoms and controller inhalers that prevent symptoms. Severe cases may require longer acting inhalers that keep the airways open, as well as oral steroids.

235
Q

Air of asthma therapy

A

Minimal chronic symptoms, including nocturnal

Minimal exacerbations

No emergency visits

Minimal use of a required B2 agonist

No limitations on activities, including exercise

Peak expirations flow circadian variation<20%

Near normal peak expirations flow

Minimal AR from medicine

236
Q

Treat mild intermittent asthma

A

SABA

237
Q

Mild persistent asthma

A

ICS low dose

SABA

238
Q

Moderate persistent asthma

A

SABA

LABA ICS low dose

239
Q

Severe persistent asthma

A

LABA

ICS high dose

SABA

240
Q

Treat very persistent asthma

A

OCS, LABA, ICS high dose, SABA

241
Q

Step 1 persistent asthma

A

Rescue inhaler

242
Q

Persistent asthma step 2

A

Low dose inhaled corticosteroid plus LABA

Rescue inhaler

243
Q

Persistent asthma step 3

A

Low dose inhaled corticosteroid plus a LABA

Rescue inhaler as needed

Consider seeing an asthma specialist

244
Q

Step 4 persistent asthma

A

Medium dose inhaled corticosteroid plas a LABA
Rescue inhaler as needed

See an asthma specialist

245
Q

Step 5 persistent asthma

A

High dose inhaled corticosteroid plus a LABA

Consider amalizumab

Rescue inhaler as needed

See an asthma specialist

246
Q

Step 6 persistent asthma

A

High dose inhaled corticosteroid plus a LABA plus oral corticosteroid and consider amalizumab

Rescue inhaler as needed

See an asthma specialist

247
Q

Drugs for asthma

A

Bronchodilators
Anti inflammatory drugs

Leukotriene antagonist

Monoclonal antibody

248
Q

Bronchodilators

A

B2 agonists

Anticholinergic drugs

Methylxanthines

249
Q

Anti inflammatory drugs

A

Inhaled corticosteroids

250
Q

Bronchodilators therapy

A

Bronchodilators act primarily on airway smooth muscle to reverse the bronchoconstriction of asthma. This gives rapid relief of symptoms but has little or no effect on the underlying inflammatory process. Thus, bronchodilators are not sufficient to control asthma in patients with persistent symptoms. There are three classes of bronchodilator in currentt use:

B2 adrenergic agonists, anticholinergics, and theophylline of these, B2 agonists are by far the most effective.

251
Q

2 agonists

A

B2 agonsits activate B2 adrenergic receptors, which are Woden expressed int he airways. B2 receptors are coupled through a stimulators G protein to adenylyl cyclase, resulting in increased intracellular cyclic adenosine monophosphate (AMP), which relaxes smooth muscle cells and inhibits certain inflammatory cells, particularly mast cells. The primary action of b2 agonists is to relax airway smooth muscle cells of all airways, where they act as functional antagonsits, reversing and preventing contraction of airway smooth muscle cells by all known bronchoconstrictors. This generalized action is likely to account for their great efficacy as bronchodilators in asthma. There are also additional non bronchodilator effects that may be CLINCIALLY useful , including inhibition of mast cell mediator release, reduction in plasma exudation, and inhibition of sensory nerve activation. Inflammatory cells express small numbers of B2 receptors but these are rapidly down regulated with B2 agonist activation so that, in contrast to corticosteroids, there are no effects on inflammatory cells in the airways and there is no reduction in airway hyper responsiveness.

252
Q

AE B2 agonists

A

Usually associated with b agonists are not problematic when given by inhalation. The most common-muscle tremor and palpitations, which are seen more commonly in elderly patients. There is a small fall in plasma K due to increased uptake by skeletal muscle cells, but this effect does not usually cause any clincial proble,. Tolerance is a potential problem with any agonist given chronically, but while there is down regulation of b2 receptors, this does not reduce the bronchodilator response as there is a large receptor reserve in airway smooth msucle cells. By contrast mast cells become rapidly tolerant, but their tolerance may be prevented by concomitant administration of inhaled corticosteroids

253
Q

Albuterol

A

SABA

254
Q

Indications albuterol

A

Asthma, acute bronchitis, COPD, bronchiolitis

255
Q

AE albuterol

A

HA, dizziness, insomnia, dry mouth, cough

256
Q

Interactions albuterol

A

BB, digoxin, diuretics, monoamine oxidase inhibtiors, tricyclic antidepressants

257
Q

Contraindications albuterol

A

Paradoxical bronchospasm, deterioration of asthma, use of anti inflammatory agents, cardiovascular effects, do not exceed recommended dose, immediate hypersensitivity reactions

258
Q

Terbutaline

A

Beta adrenergic agonist with preferential effects on the beta 2 receptos resulting in smooth muscle relaxation. Only b2 drug available by subcutaneous injection (terbutaline sulfate inj» patients with sulfur allergy, not recommended)

259
Q

Indications terbutaline

A

FDA approved for the treatment or prophylaxis of bronchospasm associated with asthma, bronchitis and emphysema in patients 12 years old and older

260
Q

AE terbutaline

A

HA, nausea, tachycardia and palpitations. However, more serious maternal AE that can occur include cardiac ischemia, hypotension and tachycardia

261
Q

Cautions terbutaline

A

BBW (black box warning) not recommended as a medication for tocolysis

262
Q

Metaproterenol indications

A

Used as a bronchodilator for bronchial asthma and for reversible bronchospasm which may occur in association with bronchitis and copd

263
Q

AE metaproterenol

A

Nervousness, HA, dizziness, palpitations, GI distress, tremor, throat irritation, nausea, vomiting, cough and asthma exacerbation

264
Q

Interactions metaproterenol

A

Beta adrenergic aerosol bronchodilators should not be used concomitantly with metaproterenol bc they may have additive effects. Beta adrenergic agonists should be administered with caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, since the action of beta adrenergic agonists on the vascular system may be potentiated

265
Q

Cautioned/warning metaproterenol

A

Can produce a significant cardiovascular effect in some patients , as measured by pulse rate, bp, symptoms, and/or ECG changes. As with other beta adrenergic aerosols, metaproterenol can produce paradoxical bronchospasm (which can be life threatening0

266
Q

Pirbuterol indications

A

Used int he prevention and reversal of bronchospasm in patients 12 years of age and older with reversible bronchospasm including asthma. It may be used with or without concurrent theophylline and/or corticosteroids

267
Q

AE pirbuterol

A

CNS: nervousness, tremor, HA, dizzy,

Cardio: palpitations, tachycardia

Respiratory: cough

GI: nausea

268
Q

Interactions pirbuterol

A

Other short acting beta adrenergic aerosol bronchodilators should not be used concomitantly with pirbuterol bc they may have additive effects

269
Q

Cautions warnings pirbuterol

A

Cardiovascular: like other inhaled beta adrenergic agonists, can produce a CLINCIALLY significant cardiovascular effect in some patients, as measured by pulse rate, bp and/or symptoms

270
Q

Levalbuterol indications

A

Used in treatment or prevention of bronchospasm in patients 4 years of age and older with reversible obstructive airwaydisease

271
Q

AE levalbuterol

A

Accidental injury, bronchitis, dizzy, pain, pharyngitis, rhinitis, vomiting

272
Q

Interactions levalbuterol

A

Potentiation the effect of other SABA drugs

273
Q

Cautions warnings levalbuterol

A

Life threatening paradoxical bronchospasm may occur

274
Q

Fomoterol

A

LABA

275
Q

Indications fomoterol

A

Treatment of asthma in patients>5 years as an add on to long term asthma control medication such as an inhaled corticosteroid. Prevention of exercise induced bronchospasm (EIB) in patients > 5 years. Maintence treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease

276
Q

AE fomoterol

A

Asthma: viral infection, bronchitis, chest infection, dyspnea, chest pain, tremor, dizzy, insomnia, tonsillitis, rash, dysphagia, and serious asthma exacerbation

COPD: upper respiratory tract infection, back pain, pharyngitis, chest pain, sinusitis, fever, leg cramps, muscle cramps, anxiety, pruritis, increased sputum and dry mouth

277
Q

Interactions fomoterol

A

Adrenergic agents: use with caution. Additional adrenergic drugs may potentiation sympathetic effects

Canthine derivatives, systemic, corticosteroids, and non K sparing diuretics: use with caution. May potentiation hypoK or ECG changes

mAO inhibits, tricyclic antidepressants, macrolides, and drugs that prolong QT: use with extreme caution. May potentiation effect on CVD

BB: use with caution and only when medically necessary. May decrease effectiveness and produce severe bronchospasm.

278
Q

Contraindications/warning fomoterol

A

CVD: like other inhaled beta adrenergic agonsits, can produce a CLINCIALLY significant cardiovascular effect in some patients, as measured by pulse rate, bp and/or symptoms

279
Q

Levalbuterol indications

A

Used in treatment or prevention of bronchospasm in patients 4 years of age and older with reversible obstruction=Clive airway disease

280
Q

AE levalbuterol

A

Accidental injury, bronchitis, dizzy, pain pharyngitis, rhinitis, and vomiting

281
Q

Interactions levalbuterol

A

May potentiation and effect of other Saba drugs

282
Q

Cautions/warning levalbuterol

A

Life threatening paradoxical bronchospasm may occur

283
Q

Salmeterol

A

LABA

284
Q

Indication LABA

A

Treatment of asthma in patients aged 4 years and older. Prevention of exercise induced bronchospasm in patients aged 4 years and older. Maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease

285
Q

AE salmeterol

A

Asthma: HA, influenza, nasal/sinus congestion, pharyngitis, rhinitis, trachietis/bronchitis.

COPD: cough, HA, musculoskeletal pain, throat irritation, viralrespiratory infection

286
Q

Salmeterol LABA interactions

A

Strong cytochrome P450 3a4 inhibtors : use not recommended. May increase risk of cardiovascular effects

Monoamine oxidase inhibitors and tricyclic antidepressants: use with extreme caution. May potentiation effect of salmeterol on vascular system
BB: use with caution. May block bronchodilators effects of beta agonists and produce severe bronchospasm.

Diuretics: use with caution. ECG changes and/or hypokalemia associated with non K sparing diuretics may worsen with concomitant beta agonists

287
Q

Contraindicationswarning salmeterol

A

Asthma: without concomitant use of a long term asthma control medication such as an inhaled corticosteroid. Primary treatment of status asthmaticus or acute episodes of asthma or COPD requiring intensive measures

Severe hypersensitivity to milk proteins

*LABA increase the risk of asthma related death and asthma related hospitalizations.

Prescribe for asthma only as concomitant therapy with an inhaled corticosteroid. Do not initiate in acutely deteriorating asthma or COPD

Do not use to treat acute symptoms.

Not a substitute for corticosteroids

Patients with asthma must take a concomitant inhaled corticosteroid.

Do not use in combination with an additional medicine containing a LABA bc of risk of overdose. If paradoxical bronchospasm occurs, discontinue and institute alternative therapy

288
Q

Indacaterol indications

A

LABA used to treat breathing problems caused by COPD including chronic bronchitis and emphysema

289
Q

AE indacaterol

A

Most common adverse reactions are cough, oropharyngeal pain, nasopharyngitis, HA, nausea

290
Q

Interactions indacaterol

A

Other adrenergic drugs may potentiation effect. Xanthing derivatives, steroids, diuretics or non K sparing diuretics may potentiation hypoK or ecg changes

291
Q

Cautions/warning

A

BBW long acting beta 2 adrenergic agonists (LABA) increase the risk of asthma related death

292
Q

Olodaterol (LABA) indications

A

Used in the long term once daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema

293
Q

AE olodaterol

A

Most common AE reactions are nasopharyngitis, Upper respiratory tract infection, bronchitis, urinary tract infection, cough, dizzy, rash, diarrhea, back pain and arthralgias

294
Q

Interactions olodaterol

A

Other adrenergic drugs may potentiation effect. Xanthine derivatives , steroids, diuretics or non K sparing diuretics may potentiate effect on cardiovascular system. Use with extreme caution. Bb may decrease effectiveness

295
Q

Cautions/warning olodaterol

A

BBW, long acting beta 2 adrenergic agonists increase the risk of asthma related death

296
Q

Anticholinergic agents

A

Anticholinergics block acetylcholine from binding to it receptors on certain nerve cells. They inhibit parasympathetic nerve impulses. These nerve impulses are responsible for involuntary msucle movements in the GI tract, lungs, urinary tract, and other parts of your body

297
Q

Anti muscarinic agents most widely used in asthma/COPD

A

Atropine
Ipratropium
Tiotropium
Aclidinium

298
Q

ATROPINE INDICATIONS

A

ATROPINE IS A MUSCARINIC ANTAGONIST INDICATED FOR TEMPORARY BLOCKADE OF SEVERE OR LIFE THREATENING MUSCARINIC EFFECTS

299
Q

AE ATROPINE

A

MOST ADVERSE REACTIONS ARE DIRECTLY RELATED ATROPINES ANTIMUSCARINIC ACTION. DRYNESS OF THE MOUTH, BLURRED VISION, PHOTOPHOBIA AND TACHYCARDIA COMMONLY OCCUR WITH CHRONIC ADMINISTRATION OF THERAPEUTIC DOSES

300
Q

INTERACTIOSN ATROPINE

A

ATROPINE DECREASES THE RATE OF MEXILETINE ABSORPTION WITHOUT ALTERING THE RELATIVE ORAL BIOAVAILABILITY; THIS EDLAY IN MEXILETINE ABSORPTION WAS REVERSED BY THE COMBINATION OF ATROPINE AND IV METOCLOPRAMIDE DURING PRETREATMENT FOR ANESTHESIA

301
Q

CAUTION.WARNSING ATROPINE

A

When the recurrent use of atropine is essential in patients with CAD. The total dose should be restricted to 2-3 mg to avoid the detrimental effects of atropine induced tachycardia on myocardial oxygen demand

302
Q

Ipratopium indications

A

Used as a bronchodilator for maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease, including chronic bronchitis and emphysema

303
Q

AE ipratropium

A

As an anticholinergic drug, cases of precipitation or worsening of narrow angle glaucoma, mydriasis, acute eye pain, hypotension, urinary retention, tachycardia, constipation, bronchospasm, including paradoxical bronchospasm have been reported

304
Q

Caution/warning ipratropium

A

Caution is advised in the co administration of ipratropium with other anticholinergic containing drugs

305
Q

Tiotropium indications

A

Is an anticholinergic indicated for long term, once daily, maintenance treatment of bronchospasm associated with COPD, and for reducing COPD exacerbations

306
Q

AE tiotropium

A

The most common adverse reactions were upper respiratory tract infection, dry mouth, sinusitis, pharyngitis, and rhinitis.

307
Q

Interactions tiotropium

A

May interact additively with concomitantly used anticholinergic medications. Avoid administration fo tiotropium with other anticholinergic containing drugs

308
Q

Cautions/warning tiotropium

A

Not for acute use. Not a rescue medication. Immediate hypersensitivity reactions may include; angioedema, urticaria, rash, bronchospasm, or anaphylaxis can occur. Use with caution in patients with severe hypersensitivity to milk proteins

309
Q

Aclidinium indication

A

Indicated for the long term maintenance treatment of bronchospasm associated with COPD, including chronic bronchitis and emphysema

310
Q

AE aclidinium

A

Include but are not limited to paradoxical bronchospasm, worsening of narrow angle glaucoma, worsening of urinary retention

311
Q

Interactions aclidinium

A

In vitro studies suggest limited potential for CYP450 related metabolic drug interactions, thus no formal interaction studies have been performed. Drug performance is still highly monitored since the drug was approved in 2012.

312
Q

Caution/warning aclidinium

A

Not for acute use. This drug is intended as a twice daily maintenance treatment for COPD and is not indicated for the initial treatment of bronchospasm

313
Q

Methylxanthines

A

Methylxanthines are a unique class of drug that are derived from the purine base xanthine. Xanthine is produced naturally by both plants and animals. The methylxanthines, theophylline, and dyphylline are used int he treatment of airways obstruction caused by conditions such as asthma, chronic bronchitis, or emphysema. Caffeine and theobromine (in chocolate) are also methylxanthines

314
Q

Theophylline

A

Has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation (bronchodilator) and suppression of the response of airways to stimuli (non bronchodilator prophylactic effects)

315
Q

Indications theophylline

A

Used in the treatment of asthma and other lung problems, such as emphysema and chronic bronchitis

316
Q

AE theophylline

A

cNS excitement, hAA, insomnia, irritability, restlessness, seizure, diarrhea, nausea, vomiting, urinary retention

317
Q

Interactions theophylline

A

Theophylline interacts with a wide variety of drugs. The interaction is increased or decreased based on serum theophylline concentrations. Theophylline only rarely alters the pharmacokinetics of other drugs

318
Q

Caution/warning theophylline

A

Theophylline should be used with extreme caution in patients with the following clinical conditions due to the increased risk of exacerbation of the concurrent condition: active PUD, seizure disorder cardiac arrhythmias (not including Brady arrhythmia)

319
Q

Inhaled corticosteroids

A

By far most effective controllers for asthma, and their early use has revolutionized asthma therapy. Most effective anti inflammatory agents used in asthma therapy, reducing inflammatory cell numbers and their activation in the airways.

320
Q

What do ICS do

A

Reduce eosinophils int he airways and sputum, and numbers of activated T lymphocytes and surface mast cells in the airway mucosa. These effects may account for the reduction in AHR that is seen with chronic ICS therapy.

321
Q

MOA ICS

A

Several effects both einflammatory process

The major effect-corticosteroids is to switch off the transcription of multiple activated genes that encode inflammatory proteins such as cytokines, chemokines, adhesion molecules, and inflammatory enzymes.

This effect involves several mechanisms, including inhibiton of the transcription factors NF KB but an important mechanism is recruitment of histone deacetyation 2 inhibitor to the inflammatory gene complex, which reverses the histone acetylation associated with increased gene complex, which reverses the histone acetylation associated with increased gene transcription.

Also activated anti inflammatory genes such as nitrogen-activated protein kinase phosphatase 1, and increase the expression of B2 receptors.

322
Q

Side effects ICS

A

Most metabolic and endocrine side effects of corticosteroids are also mediated through transcriptional activation.

323
Q

Most effective controllers in asthma

A

ICS
Beneficial in treating asthma of any severity and age. Usually given twice daily but some may be effective once daily in mildly symptomatic patients.

ICS rapidly improve symptoms of asthma, and lung function improves over several days.

They are effective in preventing asthma symptoms, such as exercise induced asthma and nocturnal exacerbations, but also prevent severe exacerbations

324
Q

ICS reduce AHR, but maximal improvement may take several months of therapy.

A

Early treatment with ICS appears to prevent irreversible changes in airway function that occur with chronic asthma.

325
Q

Withdrawal ICS

A

Results in slow deterioration of asthma control, indicating that they suppress inflammation and symptoms, but do not cure the underlying condition.

326
Q

Who gets ICS

A

First line for patients with persistent asthma, but if they do not control symptoms at low doses, it si usual to add a LAB as the next step

327
Q

Inhaled corticosteroids

A

Beclomethasone

Budesonide

Ciclesonide

Flunisolide
Fluticasone

Mometasone

Triamcinolone

328
Q

Beclomethasone indications

A

Prescribed as a maintenance treatment for asthma and as prophylactic therapy in patients 5 years of age and older. Also used in the treatment of asthma in patients who require oral corticosteroid therapy to reduce or eliminate the need for the systemic corticosteroids

329
Q

AE beclomethasone

A

Most common AE include HA, pharyngitis, oral symptoms (inhalation route) and sinusitis

330
Q

AE beclomethasone

A

Most common AE include HA, pharyngitis, oral symptoms(inhalation route) and sinutisit

331
Q

Interactions beclomethasone

A

Other drugs may interact with beclomethasone inhalation, including prescription and OTC medicines, vitamins and herbal products

332
Q

Cautions/warning beclomethasone

A

Particular care is needed in patients who are transferred from systemically active corticosteroids to beclomethasone bc deaths due to adrenal insuffiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic pituitary function

333
Q

Budesonide indications

A

Maintenance treatment of asthma as prophylactic therapy in adult and pediatric patients six years of age or older

334
Q

AE budesonide

A

Most common AE are nasopharyngitis, nasal congestion, pharyngitis, rhinitis allergic, viral URI, nausea, viral gastroenteritis, otitis media, oral candidiasis

335
Q

Interactions budesonide

A

The main route of metabolism of corticosteroids ,including budesonide, is via 3a4

336
Q

Cautions/warning budesonide

A

This drug should not be used where primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required. Severe hypersensitivity to milk proteins and any of the ingredients in budesonide is contraindicated

337
Q

Ciclesonide indications

A

Prescribed as an inhaled corticosteroid indicated for maintenance treatment of asthma as prophylactic therapy in adult and adolescent patients 12 years of age and older

338
Q

AE ciclesonide

A

Most common are HA< nasopharyngitis, sinusitis, pharyngolaryngeal pain, upper respiratory infection, arthralgia, nasal congestion, pain in extremity and back pain

339
Q

Interactions ciclesonide

A

In clincial studies, concurrent administration of ciclesonide and other drugs commonly used in the treatment of asthma (albuterol, formoterol) had no effect on pharmacokinetics of desciclesonide

340
Q

Cautions/warning ciclesonide

A

Ciclesonide is not indicated for the relief of acute bronchospasm. Use is not recommended in presence of Candida albicans infection of the mouth and pharynx, tb, fungal , bacterial , viral, or parasitic infection

341
Q

Fluniolide indications

A

Indicated for the maintenance treatment of asthma as prophylactic therapy in adult and pediatric patients 6 years of age and older. Also indicated for asthma patients requiring oral corticosteroid therapy where adding flunisolide therapy may reduce or eliminate the need for oral corticosteroids

342
Q

AE flunisolide

A

The most common are pharyngitis, rhinitis, HA, sinusitis, and increased cough

343
Q

Flunisolide interactions

A

No significant drug interactions with other drugs used in asthma therapy. However the effects of some other drugs can change if you take other drugs or herbal products at the same time

344
Q

Caution/warning flunisolide

A

Contraindications in patients for primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required

345
Q

Fluticasone indications

A

Maintenance treatment of asthma as prophylactic therapy in patients aged 4 and older. Not indicated for relief of acute bronchospasm

346
Q

AE fluticasone

A

Most common adverse reactions are upper respiratory tract infections or inflammation , throat irritation, sinusitis, dysphagia, candidiasis, cough, bronchitis, and HA

347
Q

Interactions fluticasone

A

Strong p450 3a4 inhibtiors use not recommended. May increase risk of systemic corticosteroid effects

348
Q

Caution/warning fluticasone

A

Candida albicans infection of the mouth and pharynx may occur monitor patients periodically. Advise the patient to rinse his/her mouth with water without swallowing after inhalation to help reduce the risk

349
Q

Mometasone indications

A

Maintenance treatment of asthma as prophylactic therapy in patients 4 years of age and older

350
Q

AE mometasone

A

The most common adverse reactions are HA< allergic rhinitis, pharyngitis, URI, sinusitis, oral candidiasis, dysmenorrhea, musculoskeletal pain, back pain, and dyspepsia

351
Q

Interactions mometasone

A

In clincial studies, the concurrent administration of mometasone and other drugs commonly used int he treatment of asthma was not associated with any unusual adverse reactions

352
Q

Caution/warning mometasone

A

Use of this drug is contraindicated in patients with status asthmaticus or other acute episodes of asthma where intensive measures are required. Also contraindicated in patients with a known hypersensitivity to milk proteins or any ingredients of mometasone

353
Q

Triamcinolone indications

A

Indicated in the maintenance treatment of asthma patients who require systemic corticosteroids administration , where adding this agent may reduce or eliminate the need for the systemic corticosteroids. Not indicated for the relief of acute bronchospasm

354
Q

AE triamcinolone

A

Diarrhea, oral minilia, toothache, vomiting , weight gain, bursitis, myalgia, dry mouth, rash, chest congestion, voice alteration

355
Q

Triamcinolone interactions

A

The concurrent administration of triamcinolone and other drugs commonly used in the treatment of asthma was not associated with any unusual adverse reactions

356
Q

Caution/warning triamcinolone

A

Contraindications in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required. Particular care is needed in patients who are transferred from systemically active corticosteroids to triamcinolone bc deaths due to adrenal insuffiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to aesolized steroids in recommended doses

357
Q

Combination ICS and LABA drugs

A

Fluticasone+salmeterol

Budesonide+fomoterol

358
Q

Oral and parenteral corticosteroid

A

Oral corticosteroids are used in combination with SABA to treat moderate to severe asthma flare ups. Oral corticosteroids are more likely to cause side effects than inhaled corticosteroids

359
Q

Prednisone indications

A

Used as an antiinflammatory or immunosuppressive agent for certain allergic, Dermatologic, GI, hematologic, ophthalmologist, nervous system, renal respiratory, rheumatologist, specific infectious diseases or conditions and organ transplatation. Also used for the treatment of certain endocrine conditions and for palliation of certain neoplastic conditions

360
Q

AE prednisone

A

Common include fluid retention, alteration in glucose tolerance, elevation in bp, behavioral and mood changes, increased appetite and weight gain

361
Q

Interactions prednisone

A

Anticoagulant agents may enhance or dimish anticoagulant effects. May increase blood glucose concentrations. Use of NSAIDS including aspirin and salicylate increased the risk of GI side effects

362
Q

Caution/warning prednisone

A

May lead to hypothalamic pituitary adrenal axis suppression. Monitor patients for Cushing syndrome and hyperglycemia with chronic use and taper doses gradually for withdrawal after chronic use

363
Q

Leukotriene antagonists

A

Among most prescribed drugs for the management of asthma, used both for treatment and prevention of acute asthmatic attacks. This class of drugs acts by binding to cysteine leukotriene (CysL T) receptors and blocking their activation and the subsequent inflammatory cascade which cause the symptoms commonly associated with asthma and allergic rhinitis. This cysteinyl leukotrienes (LTC4, LTD4, LTE4) are products of arachidonic acid metabolism and are released from various cells, including mast cells and eosinophils. These eicosanoids bind to cysteinyl leukotriene (CysL T) receptors. THe CysL T type 1 receptor is found in the human airway (including airway SM cells and macrophages) and on other pro inflammatory cells (including eosinophils and certain myeloid stem cells). CysLts have been correlated with the pathophysiology of asthma and allergic rhinitis. In asthma, leukotriene mediated effects include airway edema, smooth msucles contraction, and altered cellular activity associated with the inflammatory process)

364
Q

Montelukast

A

Orally active compound that binds with high affinity and selectivity to the CysLT1 receptor (in preference to other pharmacologically important airway receptors, such as the prostatis, cholinergic, or B adrenergic receptor). Montelukast inhibits physiologic actions of LTD4 at the cysLT1 receptor without any agonist activity. More specifically, montelukast causes inhibition of airway cysteinyl leukotriene receptors as demonstrated by the ability to inhibit bronchoconstriction due to inhaled LTD4 in asthmatics

365
Q

Indications montelukast

A

Primaryily prescribed to treat allergies and prevent asthma attacks

366
Q

AE montelukast

A

URI, fever, HA, sore throat, cough, stomach pain, diarrhea, earache, ear infection, flu, runny nose, sinus infection

367
Q

Interaction montelukast

A

The concurrent administration of montelukast and other drugs commonly used int he treatment of asthma was not associated with any unusual adverse reactions

368
Q

Caution/warning montelukast

A

Not indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus. Therapy with montelukast can be continued during acute exacerbations of asthma. Patients who have exacerbations of asthma after exercise should have available for rescue a short acting inhaled B agonist

369
Q

Zafirlukast

A

Selective and competitive receptor antagonist of leukotriene D4 and E4 (LTD4 and LTE4) components of slow reacting substance of anaphylaxis (srsa0 cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth msucle constriction and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma

370
Q

Indications zafirlukast

A

Prophylaxis and chronic treatment of asthma in adults and children 5 years of age and older.

371
Q

AE zafirlukast

A

Coadminstration with warfarin results in a CLINCIALLY significant increase in prothrombin time. Patients on oral warfarin anticoagulant therapy and zafirlukast should have their prothrombin times monitored closely and anticoagulant dose adjusted accordingly

372
Q

Cautions/warning zafirlukast

A

Hepatotoxicity: cases of life threatening hepatic failure have been reported in patients treated with safirlukast. Cases of liver. Injury without other attributable cause have bee reported from ost marketing adverse event surveillance zafirlukast

373
Q

Sileuton

A

Immediate relase tablts were withdrawn from US market in 2008

Controlled release still avail early a

Inhibitor of 5 lipoxygenase and thus inhibits leukotriene (LTB4, LTC4, LTD4, and LTE4) formation

374
Q

Zileuton indicatiosn

A

Leukotriene synthesis inhibitor indicated for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older and not used to treat an acute asthma

375
Q

AE zileuton

A

Most common AE include sinusitis, nausea, and pharyngolaryngeal pain

376
Q

Interactions zileuton

A

Increases theophylline evils and increases warfarin levels. Monitor prothrombin time and adjust warfarin dose accordingly. Zileuton increases propranolol levels and bb activity

377
Q

Cautions/warning zileuton

A

Not recommended in cases where active liver disease or persistent hepatic function enzyme elevations are over 3 times the upper limit of normal

378
Q

Monoclonal antibody

A

Omalizumab

379
Q

Indications for omalizumab

A

Anti IgE antibody indicated for moderate to severe persistent asthma in patients 6 yers of age and older with a positive stint est or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids. Also, indicated in the treatment for chronic idiopathic urticaria in adults and adolescents 12 years of age and older who remain symptomatic despite H1 antihistamine treatment

380
Q

AE omalizumab

A

The most common adverse reactions in clincial studies with adult and adolescent patients>12 with arthralgia, pain, leg pain, fatigue, dizzy, fracture, arm pain, pruritis, dermatitis, and earache

381
Q

Interactions omalizumab

A

No formal drug interaction studies have been performed with omalizumab. In patients with asthma the concomitant use of this agent and allergen immunotherapy has not been evaluated

382
Q

Caution warning omalizumab

A

BBQ anaphylaxis: administer only in a healthcare setting prepared to manage anaphylaxis that can be life threatening and observe patients for an appropriate period of time after administration

383
Q

Asthma COPD overlap

A

Although distinct syndromes , some patients with asthm have features of COPD and some patients with COPD have features of asthma with more reversibility and increased airway and blood eosinophils. This may represent to coincidence of two common diseases, or these may be distinct phenotypes. ACO patients tend to have more symptoms and exacerbations. They may benefit from triple therapy with ICS, LABA and LAMA

384
Q

Goal of chronic asthma management

A

Reduction in impairment

Reduction risk

385
Q

Precipitating or aggravating factors of asthma

A

Viral respiratory infections
Exercise

Endocrine factors

Drugs: asprin, bb

Weather changes: cold air

Allergens

Emotional expression: anger, laughing

Food additives: sulfite

Environmental changes

Exposure to irritant and occupational chemicals

386
Q

Comorbid conditions and asthma

A

Hormonal changes

COPD

Upper airway

Rhinitis

GERD

Fat
Sleep apnea

387
Q

What are the 2 categories of asthma therapy

A

Anti inflammatory drugs

Bronchodilators

388
Q

Muscarinic antagonist and theophylline

A

Decrease acetylcholine (muscarinic) and adenosine (theophylline) which increase bronchial tone

389
Q

Beta agonist

A

Increase AC and cAMP for bronchodilator

390
Q

Theophylline

A

Decrease PDE which increase cAMP and increase bronchodilation

391
Q

Zafirlukast and montelukast

A

Selective reversible antagonsits of CysLT1 receptors)

Taken orally
Are bronchodilators

Have antiinflammatory action
Less effective than ICS

Have glucocorticoids sparing effect(potentiate corticosteroids)

Pharmacology (52 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions