Treatments Exam 3 (no antineoplastics) Flashcards
Bone marrow biopsy
Lay patient on stomach
Palpate iliac crest
Numb skin and periosteum
Use Jamshidi needle; once periosteum is penetrated resistance decreases. Push as far into marrow as needed and retrieve core sample.
Examine cellularity: Decreasing cellularity w/ age, look for abnormalities,
Then do same procedure w/ aspiration needle drawing out bone marrow. (This hurts, but only takes a second or two)
Examine cell morphology and use stains, Wright-Giemsa or Cytochemical stain (non-specific esterase that is specific to monocytes)
Immunophenotyping
Use mechanisms like flow cytometry to detect levels of cells w/ important markers (i.e. CD3 vs CD8 levels to determine proportion of T cells)
Cytogenetics
Isolation and imaging of cell’s chromosomes to look for chromosomal abnormalities (translocations etc.)
This takes a long time.
PCR
Examine cellular DNA. Need to know what you are looking for (i.e. 9:22 translocation)
Add DNA to tube and add primers that flank desired areas. Denature DNA. Add primers. Add dNTPs and Taq polymerase to make new strands. Do this many times to amplify sequence of interest.
Do along w/ cytogenetics.
Chloroquines
Basis for selectivity: parasitized RBC concentrates chloroquine at least 25x unparasatized form.
MOA: Interferes w/ heme handling –> forms FPIX toxic form of hemoglobin preferentially over hemozoin (non-toxic form)
Side effects- few for low doses
acute disease levels- dizziness, headache, itching, vomiting, skin rashes, difficulty in visual accommodation.
Large doses for prolonged periods can cause severe eye damage/blindness
Quinine and Quinidine
More toxic than chloroquine but not a lot of resistance yet.
MOA: unknown; likely similar to chloroquine
Adverse effects - acute doses = cinchonisms –> tinnitus, blurred vision, nausea, headache, decreased hearing acuity, permanent vision damage, balance and hearing can result.
IV for severe malaria
cardiac problems –> cardiac monitoring (qunidine is anti-arrythmic drug)
Quinidine + Doxy parenteral = treatment for severe disease
Mefloquine
MOA: unknown; likely similar to chloroquine
Side effects: n and v, dizziness, visual or auditory disturbances.
Key side effects:disorientation, hallucinations, and depression. Neuropsychiatric reactions.
Indicated only for the treatment and prevention of Chloroquine resistant P. falciparum
Atovaquone
MOA: Depolarized parasitic mitochondria and inhibits their ETC.
Drug interactions
Slow onset. Expensive and needs to be taken daily.
Replacing mefloquine for prophylaxis.
GI disturbances can be a problem.
Proguanil
MOA: Metabolite inhibits DHFR w/ selectivity for malarial . Enhances effects of atovaquone.
Slow onset. Expensive and needs to be taken daily.
Replacing mefloquine for prophylaxis.
GI disturbances can be a problem.
Artesmisinins
Don’t use alone –> plus mefloquine or plus lumefantrine
MOA: Heme iron in the malarial pigment acts on drug to produce free radicals that damage parasite proteins. Inhibits a calcium ion ATPase in P. falciparum.
Rapidand potent activity against MDR organisms
DO NOT USE alone to avoid resistance formation.
Lumefantrine
Unknown mechanism
Rapid initial reduction in parasite biomass.
Often used w/ Artesmisinins
Primaquine
“radical cure”
Drug of choice to eliminate hepatic forms of P. vivax and P. ovale.
MOA: Unkown (possibly ROS or interfering w/ ETC)
Hemolytic anemia in people w/ G^PD
Debate on using all the time to kill hepatic form only –> debate will evolve.
Malarone
Atovaquone and Proguanil
Alternative to chloroquine for chloroquine resistant prophylaxis and acute P. falciparum.
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