First Aid 173-196 Flashcards
Why administer imipenem with cilastin?
Cilastin inhibits renal dehydropeptidase I which would otherwise inactivate imipenem in the renal tubules
Aztreonam clinical use
Gram negative rods only;
Use in penicillin allergic patients or patients who cannot handle the nephrotoxicity of aminoglycosides
Gentamicin; Neomycin; Amikacin; Tobramycin; Streptomycin; What drug class?
Aminoglycosides;
Ototoxicity (esp when used with loop diuretics);
Severe gram neg infections;
Require oxygen for uptake
Minocycline - what drug class?
Tetracycline
Why do infants get “gray baby syndrome” with chloramphenicol use?
They lack liver UDP-glucuronyl transferase
Use what for anaerobes above the diaphragm?
Clindamycin (and Metronidazole for anaerobes below the diaphragm)
Use Linezolid for:
Gram positives like MRSA and VRE;
Binds 50S
SE: thrombocytopenia, peripheral neuropathy, serotonin syndrome, optic neuritis
When to use dapsone, when not to use dapsone
Use dapsone for MRSA if patient is allergic to vancomycin;
Do not use dapsone for pneumonia bc it is inactivated by surfactant;
SE: rhabdomyloysis
MOA Ethambutol
Anti-cell wall - mycobacteria;
Inhibits Arabinosyl transferase –> No arabinoglycan synthesis
MOA Isoniazid
Anti-cell wall - mycobacteria;
Inhibits mycolic acid synthesis
Why is rifabutin preferred over rifampin for use in HIV-infected patients?
Rifabutin has less cytochrome P-450 induction
How is isoniazid activated in the body?
By bacterial catalase-peroxidase (encoded by KatG)
Use for Streptogramin class - Quinupristin, Dalfopristin
VRE
Use for tigecycline
MRSA
The azole class inhibits what enzyme in the formation of fungal cell membranes?
14-alpha-demethylase
Use: Nifurtimox
Chagas disease
MOA Chloroquine
Blocks detoxification of heme to hemozoin –> build up of heme is toxic to plasmodia
Function of RBC receptors CD55 and CD59
Prevent MAC from attacking RBCs;
CD55 missing in PNH because no glycan anchoring protein made (GPI) –> lysis and release of free hemoglobin
Recurrent infections that worsen with age;
Easy bleeding;
Eczema;
Dx?
Wiskott-Aldrich Syndrome
Recurrent Neisseria infection;
Dx?
Terminal complement deficiency
Severe bacterial and viral infections in infancy;
Chronic diarrhea;
Mucocutaneous candidiasis;
Dx?
Severe combined immunodeficiency
very low or absent CD3+ T-cells
Congenital heart disease;
Dysmorphic facies;
Hypocalcemia;
Dx?
DiGeorge syndrome
Severe bacterial and fungal infections;
Granuloma formation;
Dx?
Chronic granulomatous disease
Oculocutaneous albinism;
Pyogenic infections;
Progressive neurologic dysfunction;
Dx?
Chediak-Higashi syndrome
CVID is similar to SCID but
no thymic aplasia;
infections present after infancy
Immunohistochemistry staining of the complete moles is p-57 negative due to
absence of a maternal genome
The type of mutation in fragile X syndrome
Loss of function mutation;
Long arm of X chromosome;
FMR1 (fragile X mental retardation) gene
Tetanospasmin is what kind of toxin?
Exotoxin;
Prevents release of glycine and GABA from spinal inhibitory interneurons that regulate LMNs
Dolutgravir
Raltegravir
Elvitegravir
Class? SE?
HIV Integrase inhibitors
SE: increase in creatine kinase
Acyclovir, Famciclovir, Valacyclovir are analogs of
guanosine
So is Ganciclovir (for CMV)
Main SE of ganciclovir/valganciclovir
Bone marrow suppression
Renal toxicity
Pyrophosphate analog that is both HIV RT inhibitor and DNA/RNA polymerase inhibitor
Foscarnet - like Cidofovir, does not require phosphorylation by viral thymidine kinase
Coadminister what antiviral with probenecid an IV saline to reduce nephrotoxicity
Cidifovir
What is the usual HIV tx cocktail?
2 NRTIs and 1 integrase inhibitor (standard)
What is the only NRTI that is already a nucleotide and therefore need not be phosphorylated to activate?
Tenofovir
What can be administered to reverse the bone marrow suppression associated with NRTI therapy?
G-CSF (granulocyte colony-stimulating factor) and EPO
What NNRTIs are contraindicated in pregnancy?
Delavirdine
Efavirenz - associated with CNS symptoms and vivd dreams
What NRTI has a SE of pancreatitis?
Didanosine
What is the difference between NRTIs and NNRTIs?
The NNRTIs bind RT at a different site and do not need to be phosphorylated
What HIV protease inhibitor is also a CYP450 inhibitor?
Ritonavir
What HIV treatment class is associated with lipodystrophy?
Protease inhibitors (-navir)
result in Cushing-like fat redistribution
Hyperglycemia is another SE
What potent CYP/UGT inducer is contraindicated with HIV protease inhibitors?
Rifampin
What interferon treats:
Multiple sclerosis
IFN-beta
What interferon treats:
CGD
IFN-gamma
What interferon treats:
chronic hep B and C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, renal cell carcinoma, malignant melanoma
IFN-alpha
What Hep C therapy inhibits synthesis of guanine nucleotides?
Ribavarin
severe teratogen
SE hemolytic anemia
inhibits inosine MP dehydrogenase
MOA Sofosbuvir
inhibits HCC RNA-dependent RNA pol
acts as a chain terminator
must use in combination with ribavarin +/- peginterferon-alpha
MOA Simprevir
HCV protease inhibitor
must use with Ledipasvir (NS5A inhibitor)
What infection control techniques can be sporocidal?
Autoclave
H2O2
Iodine and iodophors
“SAFe Children Take Really Good Care”
Antimicrobials to avoid in pregnancy: Sulfonamides - kernicterus Aminoglycosides - Ototoxic Fluoroquinolones - Cartilage damage Clarithromycin - Embryotoxic Tetracyclines - discolored teeth and inhibition of bone growth Ribavarin Griseofulvin Chloramphenicol - gray baby syndrome
Medullary sinuses of lymph nodes contain
reticular cells and macrophages;
they interact with efferent lymphatics
Where are T cells found in the lymph node?
Paracortex
Between follicles and medulla;
not well developed in patients with DiGeorge syndrome;
enlarges in extreme cellular immune response ie viral infection
The superior mesenteric lymph node drains
lower duodenum, jejunum, ileum, colon to splenic flexure
The para-aortic lymph node drains
testes, ovaries, kidneys, uterus
The vagina (middle third) and cervix are drained by
Internal iliac lymph node
Vulva - superficial inguinal
Right lymphatic duct drains everything from where?
on the right side of the body above the diaphragm
The thoracic duct drains everything on the left side of the body, and the right side of the body below the diaphragm, into where?
the junction of the left subclavian and internal jugular veins
Where are T-cells found in the spleen?
Periarteriolar lymphatic sheath (PALS) within the white pulp;
B cells are found in the follicles of the white pulp
What is the function of the marginal zone of the spleen?
APCs capture blood-borne antigens for recognition by lymphocytes;
contains macrophages and specialized B cells;
Marginal zone between red and white pulp
What are the effects of lowered IgM levels in splenic dysfunction (or absence)
low IgM --> low complement activation --> low C3b opsonization --> increased susceptibility to encapsulated organisms: Pseudomonas Strep pneumo Haemophilus Neisseria E Coli Salmonella Kelbsiella Group B strep
The thymus is derived from the:
third pharyngeal pouch
“Th”ymus - “th”ird
Of what embryological origin are lymphocytes?
Mesenchymal
Lyzozyme, complement, C-reactive protein and defensins are all what?
proteins secreted by the innate immune system
Examples of PAMPS recognized by TLRs
LPS of gram negative bacteria;
Flagellin;
Viral nucleic acids
MHC is encoded by
HLA genes;
MHC presents antigen fragments to T cells and binds T-cell receptors
HLA-A
HLA-B
HLA-C
are
MHC I (one letter)
HLA-DR
HLA-DP
HLA-DQ
are
MHC II (2 letters)
MHC I is expressed on all nucleated cells except
RBCs
Where is MHC II expressed?
Surfaces of APCs
Where are MHC I antigen peptides loaded?
RER - then transported to membrane
How are MHC II antigen peptides loaded?
After endocytosies –> endosome –> release of invariant chain in an acidified endosome –> back to surface
MHC I has what associated protein?
Beta-2-microglobulin
“PAIR” for HLA-B27
Psoriatic arthritis Ankylosing spondylitis IBD-associated arthritis Reactive arthritis aka the seronegative arthropathies
What is the only lymphocyte-derived member of the innate immune system?
NK cells
use perforin and granzymes to induce apoptosis of virally infected and tumor cells
IL-2, IL-12, IFN-alpha and IFN-beta enhance the activity of
NK cells
How are NK cells activated? 3 ways…
- Absence of MHC I on a cell
- Exposure to a nonspecific activation signal on a target cell
- Also kill via antibody-dependent cell-mediated cytotoxicity where CD16 binds Fc region of bound Ig
B cella become what to secrete immunoglobulins?
plasma cells
T-cells are involved in what hypersensitivity reaction?
type IV - delayed cell-mediated
What is positive selection?
Thymic cortex;
Can T cells bind self?
What is negative selection?
Thymic medulla
Too high self-affinity gets destroyed
AIRE deficiency leads to
Polyendocrine syndrome I
APCs are:
B cells, macrophages, dendritic cells
B7 proteins on APCs that make up the costimulatory signal have what CD?
CD80/86
Interacts with CD28 on naive T cell
CD40 receptor on B cell binds
CD40L on Th cell –> cytokine release determines class switching, ab production/maturation
Fc part of ab binds
complement and macrophages
F”c” for complement, carboxy terminal, constant, carbohydrate side chains
