L13 - Lung of immunocompromised patient

Question 1

Innate defences

Answer 1

mucociliary, neutrophils and macrophages

Question 2

adaptive defences

Answer 2

B cells, T cells

Question 3

Cystic fibrosis

Answer 3

autosomal recessive disease causes mutations
defective exchange of chloride leads to extracellular dehydration with excessive thick sputum, infection and severe bronchiectasis

Question 4

CF type I

Answer 4

no protein produced

Question 5

CF type 2

Answer 5

protein produced but not transported to the cell membrane

Question 6

CF type 3

Answer 6

protein transported to cell membrane but does not work properly

Question 7

CF type 4

Answer 7

gets to cell membrane and functions, but is less effective than the WT

Question 8

CF type 5

Answer 8

less proteins produced that make it to the cell membrane

Question 9

CF type 6

Answer 9

less stable proems produced so many don’t make it to the cell membrane

Question 10

Ivacaftor

Answer 10

potentiates channel open probability, improvements in lung function, nutrition and CFTR function

Question 11

HIV

Answer 11

lenti/retrovirus that infects cells via CD4 receptors and co-receptors on T helper cells, macrophages and dendritic cells

Question 12

AIDS

Answer 12

Occurs when viral replication kills the infected cells

Question 13

HIV drug resistance

Answer 13

replication is error prone therefore mutations arise that induce resistance

Question 14

HIV mechanism

Answer 14

glycoproteins on HIV allow it to dock and fuse to CD4 and CCR5 receptors
viral capsid enters the cell, enzymes and nucleic acids are released
Using reverse transcriptase ssRNA is converted to dsRNA
Viral DNA is then integrated into the cells own DNA by integrase enzyme
When infected cell divides, viral DNA is read and viral proteins are made
innate virus leaves the cell, taking the cell membrane with it
undergoes maturation

Question 15

HIV maturation protein chains

Answer 15

in the new viral particle are cut by the protease enzyme into individual proteins that combine to form a working virus

Question 16

ARVs

Answer 16

work by interfering with virus replication by preventing HIV docking and interfering with action of the major HIV enzymes

Question 17

major HIV enzymes

Answer 17

reverse transcriptase, integrase and protease

Question 18

Fusion inhibitor drugs

Answer 18

Enfurvitode, T-20

Question 19

Miraviroc

Answer 19

CCR5 receptor blocker

Question 20

NNRTI

Answer 20

non-nucleotide reverse transcriptase inhibitor

Question 21

Efavirennz

Answer 21

NNRTI

Question 22

Nervirapine

Answer 22

NNRTI

Question 23

Rilpivirine

Answer 23

NNRTI

Question 24

NRTI

Answer 24

Nulceotide reverse transcriptase inhibitor

Question 25

3TC Lamivudine

Answer 25

NRTI

Question 26

FTC Emtricitatine

Answer 26

NRTI

Question 27

AZT Zidovurine

Answer 27

NRTI

Question 28

TDF Tenofovir

Answer 28

NRTI

Question 29

ABC Abacavir

Answer 29

NRTI

Question 30

Dolutegravir

Answer 30

integrase inhibitor

Question 31

Raltegravir

Answer 31

integrase inhibitor

Question 32

Elvitegravir

Answer 32

integrase inhibitor

Question 33

Dorunavir

Answer 33

protease inhibitor

Question 34

Atazanavir

Answer 34

protease inhibitor

Question 35

Lopinavir

Answer 35

protease inhibitor

Question 36

HAART

Answer 36

HIV treatment. comprises of combinations of 3 different ARVs, using two NRTIs plus either another NNRTI, protease inhibitor or integrase inhibitor

Question 37

HAART benefits

Answer 37

recommended for all patients as it reduces transmission and increases life expectancy

Question 38

HAART problems

Answer 38

many tablets for life, complex for patients, missed doses encourage treatment failure and resistance, many side effects

Question 39

B cell defects and antibody deficiency

Answer 39

particularly associated with CVID and anti-CD20 monoclonal antibody therapy and other immunosuppression increased risk of encapsulated bacteria and oto-sino-pulmonary infection

Question 40

Primary antibody deficiency

Answer 40

immunoglobulin replacement has dramatically increased survival, reduces infections including pneumonia

Question 41

secondary antibody deficiency

Answer 41

immunoglobulin replacement indications are less clear, only might be used

Question 42

Immunoglobulin replacement

Answer 42

prepared from pooled plasma from healthy donors, can be administered by intravenous and subcutaneous lifelong

Question 43

Infection prophylaxis

Answer 43

prophylactic agents need to be taken continuously

Question 44

decision to institute prophylaxis depends on many factors...

Answer 44

nature and severity of underlying condition, risk of infection, previous infection history, evidence it will benefit situation, availability of agents, route, frequency and side effects, treatment burden, antimicrobial stewardship

Question 45

Antibiotic prophylaxis

Answer 45

used in myelotoxic chemotherapy with neutropenia, can be predicted in both time and severity

Question 46

Antibiotic and anti fungal prophylaxis

Answer 46

in chronically neutropenic patients, e.g. bone marrow transplant or those with inherited defects

Question 47

Pneumocystic pneumonia prophylaxis

Answer 47

used in HIV and immunosuppression

Question 48

Pneumocystic pneumonia

Answer 48

life-threatening opportunistic lung infection of immunocompromised individuals

Question 49

Pneumocystic pneumonia cause

Answer 49

by pneumocystis jinvecii, a fungus with some protozoal features

Question 50

Pneumocystic pneumonia occurs in..

Answer 50

patients with reduced Th cell number of function, e.g. HIV, chronic high dose steroids, solid organ or bone marrow transplantation

Question 51

Co-trimoxazide

Answer 51

Oral inhibit folate biosynthesis rashes, bone marrow suppression and GI problems, extremely effective

Question 52

Nebulised pentamidine

Answer 52

Nebulised monthly uncertain mode of action, anti-parasitic, cough, bronchospasm and need to protect staff effective but some failures

Question 53

pulmonary infection presentation in immunocompromised patients

Answer 53

may be non-specific chest X-ray or CT, blood tests investigation of sputum samples

Question 54

PCP

Answer 54

fungus with some protozoan features, usually killed by alveolar macrophages, requiring CD4+ activated Th cells progressive breathlessness and dry cough with ground glass opacity on CTs

Question 55

PCP treatment

Answer 55

high dose co-trimoxazole toxicity: fluid load, rash, renal/liver toxicity, low blood K+, neutropenia and low blood glucose Adjunctive corticosteroid therapy for moderate to severe PCP enhances survival in HIV - reduces inflammation to dying organisms

Question 56

Invasive aspergillosis

Answer 56

environmental fungus affecting neutropenic or immunocompromised patients can be progressive and fatal pulmonary nodules or infiltrates on CT

Question 57

Echinocandins

Answer 57

inhibit synthesis of B glycans

Question 58

Trizoles

Answer 58

inhibit lanosteol-14a-demethylase, which converts lanasterol into ergosterol

Question 59

Polyenes

Answer 59

bind ergosterol to weather the membrane and make i t'leaky'

Question 60

Invasic aspergillosis treatments

Answer 60

echinocandins, amphatericin B and nephrotoxic

Question 61

Echinocandins side effects

Answer 61

well tolerated but there is GI disturbance, hepatotoxicity, allergic reactions, not very effective alone

Question 62

Amphotericin B

Answer 62

IV only but lipsomal formulation to reduce toxicity

Question 63

Neprhotoxic

Answer 63

hypokalaemia, chills and allergic reactions

Question 64

Voricanazole

Answer 64

fist line invasive aspergillosis treatment reduces immunosuppression oral or intravenous

Question 65

Voricanazole side effects

Answer 65

visual disturbance, cardiac rhythm disturbance, hepatotoxic rash, convulsions

Question 66

Voricanazole response rates

Answer 66

50-90% as fungal resistance is emerging