I & D exam 5

secondary immunodeficiency

not caused by genetic defect, but rather due to infections, medications, or other external factors that impair the immune system.

nausea, diarrhea, GI issues

common antifungal ADRs

acquired C1 inhibitor dysfunction

late-onset angioedema characterized by recurrent swelling episodes.

primary immunodeficiency

genetic defect that impairs innate or adaptive immunity

hereditary angioadema

example of primary immunodeficiency

late complement defects

reelate to an increased susceptibility to meningococcal disease (defects in C5-C9)

lupus and glomerulonephritis, invasive infections with encapsulated organisms (s. pneumoniae, H. influenzae, n. meningitidis)

examples of early classical pathway defects

bradykinin

small peptide causes blood vessel dilation and increased permeability, causes fluid leak into tissues (edema)

stops production of bradykinin

how does C1 inhibitor effect bradykinin

hereditary angioadema

cause by C1 inhibitor (C1-INH) deficiency/abscence

hereditary angioadema

rapid swelling triggered by trauma, surgery, or emotional stress, hereditary or acquired, dental procedures can cause life-threatening swelling of the airways

neutropenia

low neutrophil count, infections, fever, skin infections, mouth sores, swelling/inflammation of gums

leukocyte adhesion deficiency

elevated WBC count, skin and soft tissue infections, affects tethering/rolling of adhesion of neutrophils, periodontitis, oral ulcers, and poor wound healing

chronic granulomatous disease

defects in componenets of NADPH oxidase complex, neutrophil deficiency cannot make ROS

chronic granulomatous disease

skin and soft tissue infection with catalase + organisms (staph, seratia, aspergillus, burkhoderia)

periodontitis

leukocyte adhesion deficiency could result in

lupus (systemic lupus erythematosus)

early complement deficiency often results in

Neisserria

defects in late complement pathway are associated almost exclusively with infections by which bacteria

neutropenia

Lack of first responders in this immunodeficiency could be due to congenital or acquired causes, but regardless, patients with this condition are susceptible to infections by Gram-negative rods.

type IV

hypersensitivity reaction initiated by antigen-activated T lymphocytes

conjugated vaccines

induce a strong immune response against infections by bacteria with polysaccharide capsules and have contributed to the significant reduction of bacterial meningitis.

nystatin

polyene, forms pores in fungal cell membranes

polyene

nystatin drug class

miconazole/clotrimazoles

azoles (imidazoles), forms pores in fungal cell membranes

azoles (imidazoles)

miconazole/clotimazole drug class

Chlorohexidine mouthwash

bisbiguanides, Disrupts bacterial and fungal membranes with single use; disrupts DNA/RNA function  with chronic use

bisbiguanides

chlorohexidine mouthwash drug class

Fluconazole (and other -conazoles)

azoles (triazoles), block fungal CyP450 enzymes involved in ergosterol synthesis, disrupting cell membrane

azoles (triazoles)

fluconazole drug class

Echinocandins, Flucytosine (pyrimidine analogs), ibrexfungerp (triterpenoids)

fungal membrane and DNA/RNA disrupter

fluconazole

Which antifungal agent has a ADR of QT prolongation

increased risk of TdP (torsades de pointe (arrhythmia))

What  is the risk of taking more than one QT-prolonging drug

echinocandins, Flucytosine, ibrexafugerp

Antifungal agents reserved for immunosuppressed inpatients

replicating viruses (not latent)

What do antiviral agents act on

vaccines

What is the best prevention of viruses

adenovirus, pox virus, herpes virus

DNA virus examples

DNA due to stability

What kind of viruses are easier to prevent with vaccines and why

coronavirus, retrovirus, influenza

Examples of RNA viruses

Viral entry inhibitors

block viral attachment or entry 

CCR-5 antagonists, fusion inhibitors, attachment inhibitors

Examples  of  viral  entry inhibitors

Interferons

block entry into cell via endocytosis

Adamantanes

inhibit uncoating of virus

Nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTI and NNRTI)

block viral DNA or RNA replication

Integrase strand receptor inhibitors

prevent integration of retrovirus DNA into host cell DNA

Protease inhibitors

block viral protein synthesis

Assembly inhibitors

block viral protein capsid assembly

Neuroamisdase inhibitors

block viral exit from cell

Acyclovir/valacyclovir

nucleoside reverse transcriptase inhibits guanosine incorporation into cell

nucleoside inhibitors, competitively bind DNA during transcription (transcription termination) 

Mechanism of action for most agents used to treat herpesviruses

acyclovir 

Herpes antiviral safe to use during pregnancy

acyclovir/valacyclovir, famciclovir

agents used to treat HSV (herpes simplex virus)

supportive care only (no antiviral agent approved) 

Treatment of Epstein barr virus

 block viral RNA replication (baloxavir) or inhibit virus exit (amivers)

MOA of influenza agents

within 2 days of symptoms onset 

When to start influenza treatment

baloxavir

Influenza antiviral taken as single oral dose

nausea, vomiting, headache

ADRs of influenza antiviral agents (reduced with baloxavir)

niramatrelvir and ritonavir (paxlovid)

What agents confer 89% relative risk reduction (RRR) of COVID hospitalization/death

block DNA/RNA replication and protein synthesis

MOA of COVID anti viral treatments

remdesivir

What agent confers 87% RRR of COVID hospitalization/death

dysgeusia, diarrhea, nausea

ADRs of Covid antiviral

NSAIDs (non steroidal anit-inflammatory drugs)

inhibits prostaglandin, prostacyclin and thromboxane production (Cox pathway)

Corticosteroids

inhibit prostaglandin, prostacyclin, thromboxane, leukotriene, and interleukin production, (blocks arachidonic acid production)

prednisone, dexamethasone, triacinolone

Corticosteroid examples

autoimmunity

 immune system attacks it’s own healthy cells (rheumatoid arthritis) 

celecoxib

NSAID with lowest risk of GI effects

ibuprofen, naproxen, celecoxib

NSAID examples

Direct immunosuppressants

block IL-2 production and interfere with T cell function 

infection, hypertension 

ADRs of direct immunosupressants

Biological response modifiers

target specific step in immune process

prolonged bleeding, effects on GI tract

Concern in patients taking chronic NSAIDs

delayed wound healing, hyperglycemia (corticosteroid only)

Concern in patients taking corticosteroids or direct immunosupressants

 polio (IPV), hepatitis A, influenza (shot)

Inactivated vaccine examples

tetanus, diptheria

Toxoid vaccine examples

Hep B, HPV, shingles, pertussis, Hib, pneumococcal polysac, meningococcal polysac

Subunit vaccine examples

Ebola, COVID-19

Viral vector vaccine examples

 MMR, varicella, rotavirus, influenza (nasal spray), polio

Live-attenuated vaccine example

 inactivated vaccine 

Relatively easy and inexpensive to make, safe

toxoid vaccine

Typically requires intermittent boosters to maintain antibody level

subunit vaccine

Suitable for those who should not receive “live” vaccine

Pneumococcal polysaccharide vaccine

created from mixed polysaccharides from 23 diff strep pneumoniae serotypes

Recombinant vaccine (subunit)

 Hep B vaccine, created from portion of HBsAG expressed recombinantly in yeast

 live-attenuated vaccine

Has potential to revert to fully pathogenic form

live-attenuated

Long term immunization in which host cell processes viral antigens to allow T and B cell response

Conjugated vaccine

isolating polysaccharide capsule and adding protein component, Hib

Type I

immediate, IgE/mast cell meditaed

Type II

Ab-mediated, IgG or IgM

Type III

 immune complex-mediated, IgG or IgM and antigen complex

Type IV

delayed-type, T Cell mediated

systemic anaphylaxis, Bronchial asthma, urticaria (hives), atopic dermatitis, allergic rhinitis (hay fever), food allergies

Allergic disease of Type I

Transfusion reactions, Autoimmune hemolytic anemia, Goodpasture syndrome, Drug hypersensitivity reactions, graves disease (thyroid disease), Pemphigus vulgaris

Type II hypersensitivites

systematic lupus erythematosus, hypersensitivity pneumonitis, post streptococcal glomeronephritis 

hypersensitivities of Type III

granulomatous, contact dermatitis, rheumatoid arthritis, drug fever

Allergic disease  of Type IV

Corticosteroids

supresses inflammation, suppress synthesis of prostaglandins and leukotriense by mast cells

Antihistamine

blocks histamine, reduce inflammation, type I hypersensitivity treatment

Epinephrine

relax bronchial muscle and constriction of blood vessels, systematic anaphylaxis treatment

Albuterol

used for asthma, opens bronchioles, type I hypersensitivity treatment

Pseudoephedrine

nasal decongestant, hay fever treatment

Type I

Latex allergy that requires immediate action

type IV

Hypersensitivity not affected by agammaglobulinemia (failure to develop mature B cells)

Patients never vaccinated nor had COVID infection

what group of patients newly diagnosed with a COVID infection would most benefit from nirmatrelvir + ritonavir (Paxlovid)?