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280 Cards in this Set
- Front
- Back
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What does the adneo- prefix mean in cancer?
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Gland
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Definition of sterile?
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Free from all microbiological contaminants (organisms, particles, pyrogens)
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Definition of aseptic?
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Produced from sterile components in a sterile environment, does not guarantee sterility
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What is enteral nutrition support?
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Nutrition via the gut
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What is parenteral nutrition support?
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Nutrition not via the gut, by IV
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What are the three types of enteral tubes?
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Nasogastric, gastronomy, jejunostomy
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Which enteral tubes do not use the oesophagus?
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Gastronomy, jejunostomy
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Typical components of enteral nutrition?
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Water, protein, carbs & fat, electrolytes, trace elements, water & fat sol vitamins, possibly fibre
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What does PEG stand for?
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Percutaneous endoscopic gastronomy
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Osmolarity limit for parenteral nutrition?
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900mOsm/L
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Osmolarity of human plasma?
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285-295 mOsm/L (or per kg)
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Examples of goals in TPN?
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Correct nutritional def or elec/vit/trace balance, maintain weight and lbw, support anabolism/nitro balance and healing
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What are the three seperate compartments in prepared TPN bags?
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Fat emulsion, amino acid soln, glucose soln
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Which type of cabinet are aseptic cytotoxic products prepared in?
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Vertial laminar flow
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Which apoptosis gene is mutated in over 70% of tumors?
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p53 gene
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What telomere based action can tumors exploit?
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Activate telomerase (80-90% of tumors) to stabilise telomere length and extend life of cell, avoiding apoptosis due to age
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What is the role of BRCA1?
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Tumor suppressor gene involved in repairing DNA damage
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HPV genome contains which two oncogenes, which affect which tumor supressor genes?
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E6 (targets p53) and E7 (targets rb)
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What is the rb gene?
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Retinoblastoma gene, a tumor supressor gene, which regulates cell cycle progression
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Which form of viral hepatitis cannot cause cancer?
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HepA (food bourne)
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Which forms of viral hepatitis can cause cancer?
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Chronic infection with B or C
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Other names for EBV?
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Epstein-Barr virus - glandular fever, or mono
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Which stage of the cell cycle is non-proliferative?
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G0
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Which stage of the cell cycle forms proteins for replication?
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G1
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Which stage of the cell cycle forms proteins for mitosis?
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G2
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Which stage of the cell cycle has DNA synthesis?
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S
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Which stage of the proliferative cell cycle is the longest?
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S
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What occurs in cell cycle G0?
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Normal functioning cell - no proliferation
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What occurs in cell cycle G1?
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Creation of proteins/enz needed for replication
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What occurs in cell cycle G2?
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Creation of proteins/enz needed for mitosis
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What occurs in cell cycle M?
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Mitosis
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What occurs in cell cycle S?
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DNA synthesis
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What can cause G1 arrest?
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DNA damage
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DNA damage can stop the cell cycle at which points?
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G1 or G2/M arrest
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What is an APU?
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Aseptic production unit
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What are the five 'rights'?
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Right patient, right drug, right dose, right route, right time
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Technical term for being 'tissued'?
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Extravasation
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What is the term for a drug that causes blistering when extravasation occurs?
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Vesicant
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Type of instructions avoided with cytos?
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Negative ones ('Not for intrathecal use')
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Why is route so important with cytos?
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Dose variation in route has huge impact
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Four most common methods of dose calc with cytos?
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Weight, BSA, AUC kinetic model, GFR
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What is mucositis?
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Lining of the mouth/throat breaking down
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What important dosing factor exists for doxorubicin?
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Cumulative lifetime dose (~550mg/m2 IV)
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Three general 'compartments' of tumours?
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A (continuously dividing cells), B (resting in G0), C (not able to divide)
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Why is the third 'compartment' of tumours hard to kill?
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Not dividing
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Two modes of alkylating agents?
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Crosslinking guanine bases & stopping strand seperation, and attaching alkyl group to guanine bases
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Which mode of alkylating agents may stop cell division but not induce apoptosis?
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Cross-linking guanine bases (stop seperation of strands)
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What are the cytotoxic metabolites of cyclophosphamide?
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Phosphoramide mustard and acrolein
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What is the toxic molecule formed from cyclophosphamide metabolism?
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Acrolein (nephrotoxic)
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What factors affect alkylating agent cell lethality?
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Adduct recognition, creation of strand breaks, cell having an intact apoptotic response
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What role does glutathione (GSH) have with alkylating agents?
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Inactivates them (also via GST)
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Main resistance mechanisms against alkylating agents?
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Decr uptake (if req active tx), inactivation (increased GSH/GST or ALDH)
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Mode of action of methotrexate?
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Inhibits dihydrofolate reductase, affecting purine and thymidylate production
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What inhibits dihydrofolate reductase?
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Methotrexate
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What are the purine bases?
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Adenine, guanine
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What are the pyrimidine bases?
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Cytosine, thymine, uracil
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What cell phase do antimetabolites affect?
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S phase (DNA synthesis)
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Main cytotoxic action of anthracyclines?
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Inhibition of topoisomerase-II
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What cytos inhibit topisomerase-II?
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Anthracyclines
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What classes of cytos are cell cycle specific?
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Antimetabolites, antibiotics, taxanes, vinca alkaloids
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What are the two classes of antimitotic cytos?
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Vinca alkaloids and taxanes
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Mode of action for vinca alkaloids?
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Inhibit microtubule polymerisation, prevents mitotic spindle forming
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Mode of action for taxanes?
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Stabilise microtubules in polymerised state
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What classes of cytos are NOT cell cycle specific?
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Alkylating agents, platinum agents, secondary effect of antibiotics
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Advantages of IV for cytos?
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No 1st pass (100%F), accurate dosing, reduces GI harm, allows hydration control, forced compliance
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Complications of cyto IV ppt on admin?
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Phlebitis, extravasation, dose variation, thrombus and emboli
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What organs still have high doses of cytos despite nanoparticle targetting?
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Liver and spleen
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Main benefit of nanoparticle tumor targetting?
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Higher tolerated doses
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What is doxorubicin formulated with to avoid precipitation?
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Cremophor EL (non-ionic polyethoxylated detergents) in 50% ethanol
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Why does doxorubicin have hypersensitivity issues?
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Due to formulation, uses non-ionic polyethoxylated detergents in 50% ethanol
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What is Cremophor EL?
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Doxorubicin formation component, non-ionic polyethoxylated detergents
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Drug issues with drug targeting systems?
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Must retain drug during transit, allow drug to access target site, allow retention at target site, and be released from delivery system
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Drug targeting technologies in development?
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Liposomes, antibodies, polymeric micelles, viral, nanoparticle, polymer-protein conjugates
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Benefits of carrier targeted drug delivery?
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Impr sol & stability, reduced toxicity, incr circ time & bioavail, avoid resistance (PGP)
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What are the three classes of drug targeting?
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1st/2nd/3rd order
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What is 1st order drug targeting?
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Delivery to the target tissue (tumor)
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What is 2nd order drug targeting?
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Delivery to a specific cell type in the target tissue
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What is 3rd order drug targeting?
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Delivery to a specific intracellular site in a specific cell type in the target tissue
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What class of drug targeting is Myocet/Doxil/Caelyx (liposomal doxorubicin)?
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1st order (to tumor tissue)
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How does EPR increase drug delivery?
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More open endothelium allows longer retention of vehicle, and incr chance of drug release
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What effect does the RES have on delivery systems?
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Decr circ time due to recognition of system as invader
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How does Doxil/Caelyx reduce the barrier of the RES?
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Pegylated liposome "hides" from RES
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What are Kupffer cells?
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Specialised macrophages in the liver, part of RES
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What is the rate limiting step with liposomal drug delivery?
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Release of drug from liposomes
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When does peak drug concentration occur with liposomal drug delivery?
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2-3d after admin, due to RLS step of release from liposome
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What environmental conditions in tumours help with targeting?
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Lower pH, more oxidative environment, unique popln of proteases
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What three bio-reversible linkages are used in tumor targeting?
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Acid cleavable, peptide link, disulfide link
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Advantages of prodrug reversible linkages in delivery systems?
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Drug not active until in tumour tissue, and can link to liposome to stop 'leakage'
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Why is Mitomycin C well suited to DDS system?
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Very good at killing cancer cells but also normal cells
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Why is a lipid linkage system used in the Mitomycin C DDS?
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Believed that it still leaks out of DDS before delivery
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What factors allow 3rd order drug targetting via intracellular trigger?
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Acidic endo-lysosome, lysosome proteases, high oxidative cytosol
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What are the three components of a drug-polymer conjugate?
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Large polymer for passive targeting (EPR), ligand for active targeting, and a reversible link to the drug
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How does lymphatic drainage affect DDS targetting?
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Lack of tumor tissue lymph adds to interstitial pressure, and reduces EPR effect
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Tumor ECM matrix effects on DDS systems?
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More viscous tumour ECM, more dense, adds to interstitial pressure and reduces EPR effect
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What aspect of tumours can give uneven DDS delivery?
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Uneven perfusion throughout tumor, drug cannot diffuse through to all cells
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What are the two physiological barriers that work against DDS systems?
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Lower convective driving force (incr pressure) and heterogenous blood vessel network (uneven delivery)
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What are Doxil and Caelyx?
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Stealth liposomal DDS for doxorubicin
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PK effects of doxorubicin DDS?
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Signficant: lower clearance, longer half life, higher AUC, smaller Vd
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What type of receptors are VEGFR/HER/EFGR?
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Tyrosine kinase receptors
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What does HER2 stand for?
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Human epidermal growth factor receptor 2
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What are the two cellular roles that most growth factor tyrosine kinases are involved in?
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Apoptosis and cell proliferation
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What does the -inib drug suffix mean?
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Inhibits tyrosine kinase activity intracellularly, inhibits cell growth, enhances apoptosis
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Why are opposing hormone treatments rarely used in hormone-sens tumors?
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Generally not pleasant effects
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What does 'recruiting tumor cells from compartment B to compartment A' mean?
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Stimulating cell division to enable targetting
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What are the three ways to treat hormone sensitive tumors?
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Opposing hormones, hormone antagonists, inhibit synthesis of stimulating hormone
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Why are glucocorticoids used in a supportive role in cancer treatment?
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Inhibit lymphocyte proliferation
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What type of drugs can be used to recruit tumor mammary cancer cells into compartment A, and why?
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Estrogens, stimulate cell division, increase efficacy of cytotoxics
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What is tamoxifen?
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SERM, -ve estrogen effect on ER+ breast cancer, +ve estrogenic effect on bone & CVS (beneficial), and endometrium (cancer risk)
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Negative effect of tamoxifen?
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Increased risk of endometrial cancer
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What is raloxifene?
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SERM, used in prevention of post-menopausal osteoporosis, -ve estrogenic effect on uterine and breast tissue
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What is a SERM?
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Selective estrogen receptor modulator, +/- estrogenic effect depends on tissue
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What is anastrazole?
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Aromatase inhibitor
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What is aromatase?
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Enzyme in peripheral tissue that converts androgens to estrogen, which is main source in post-menopausal women
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Why are aromatase inhibitors and anti-estrogens not useful in pre-menopausal women?
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Large amounts of estrogen produced by ovaries are difficult to reduce
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What is bevacizumab?
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Monoclonal antibody, that inhibits VEGFR and so angiogenesis
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What is cetuximab?
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Monoclonal antibody, that inihibits EGFR
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What is traztuzumab?
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Herceptin, monoclonal antibody that inhibits the HER2 EGFR
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What does EGFR stand for?
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Epidermal growth factor receptor
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What does the -tecan suffix indicate?
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Topoisomerase I inhibitor
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What are the topoisomerase I inhibitors?
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Irinotecan and topotecan
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What is irinotecan?
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Topoisomerase I inihibitor
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What is topotecan?
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Topoisomerase I inihibitor
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What does topoisomerase I do?
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Relieves strain in DNA by producing single strand breaks which are then re-ligated
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What type of dosing generally suits non-cellcycle specific drugs?
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High peak to inflict as much damage as possible to exceed repair capacity
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What type of dosing generally suits cellcycle specific drugs?
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Exposure over at least one cell cycle (2-3d), length of exposure more important than peak conc
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Which type of cytotoxics are more effective with peak concentrations?
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Non cell cycle specific
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Which type of cytotoxics are more effective with duration of exposure?
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Cell cycle specific
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Why is chemotherapy given in pulses?
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Exploit inferior repair mechanisms of tumors, allow just enough time for normal cells to recover
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Why is hormonal therapy given after cytotoxic therapy?
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Can reduce effectiveness of cytos due to cytostatic effect
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Why can trastuzumab be given with chemo, but not tamoxifen?
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Tamoxifen is hormonal treatment and can work against chemo (as it is cytostatic)
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What are the factors that can increase polypharmacy in oncology?
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Treatment for analgesia, nausea, anxiety, weightloss
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Examples of cancer cell resistance mechanisms?
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Increased glutathione inactivation, reduced folate carriers (affects methotrexate), increased efflux pump expression, changing drug target (eg topoisomeraseII), superior repair mechanisms
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Four modes of cytotoxics on DNA?
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Antimetabolites, modification of DNA bases (alkyl group), cross linking, nucleotide mispairing
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What are the classes of non-cycle specific cytos?
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Alkylators, anthracyclines, protein inhibitors
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What are the classes of cycle specific cytos?
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Antimetabolites, vinca alkaloids, taxanes, tecans
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Which group of cytos work best with high peak dosing?
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Non-cycle specific
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Which group of cytos work best with prolonged exposure?
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Cycle specific
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Typical cancer 'sanctuary' sites?
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CNS and testes
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What enzyme is inhibited by 5-FU?
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Thymidylate synthase - covalent/irreversible
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What percent of morphine is ionised at physiolog pH?
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80%
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Components of the morphine rule?
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Tertiary N, 2C chain, quatern C, aromatic/polar group
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Anagesic level of pethidine cf morphine?
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A tenth
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How is methadone metabolised?
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By 2C19 and alcohol dehydrogenase (textbook: 3A4/2B6 mainly)
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Reasons for long effect of methadone?
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Slow metabolism and multiple active metabolites
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What enables the regioisomers in conotoxins?
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Cysteine residues allowing different disulphide joins
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What channels do conotoxins affect to induce analgesia?
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N-type voltage gated calcium channels on presynaptic membrane of neurons
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What technique is used to examine the SAR in conotoxins?
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Alanine scan, changing one aa at a time to alanine and examining activity
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Reasons to use conotoxins?
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Patient unresponsive/allergic/sensitive to opioids
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How does capsaicin work?
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Agonist of TRPV1 receptor (transient receptor potential vanolloid 1)
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What antibody is crucial in t-cell activaton?
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IL-2
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Role of IL-2?
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Activation and proliferation of T-cells, stimulates cytokine prodtn to stim prolif of B/T cells, macrophages
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Steps to produce IL-2?
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APC & antigen to T-cell TCR, activate calcineurin, which activates NFAT (nuclear factor of activated Tcell), which upregulates IL-2 mRNA in nucleus
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What pathway is activated by IL-2 receptors?
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mTOR, increases T-cell proliferation
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Activated glucocorticoid receptor inhibits what?
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NFkB transcription factor for cytokines
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How does cyclosporin work?
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Binds to cytosolic cyclophilin (an immunophilin), forms complex that inhibits calcineurin (and NFAT), blocks production of IL-2
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Common adverse effects of cyclosporin?
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Nephrotoxicity (75%, dose-dependant, reversible), hirsutism, hypertension
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How does tacrolimus work?
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Binds to cytoplasmic immunophilin FKBP, complex inhibits calcineurin
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Which drugs inhibit calcineurin?
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Cyclosporin, tacrolimus, via different immunophilin complexes
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Which is the more potent calcineurin inhibitor?
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Tacrolimus
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Which adverse effect is the opposite for tacrolimus and cyclosporin?
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Alopecia (tacrolimus) vs hirsutism (cyclosporin)
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Mode of action of mycophenolate?
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Prodrug for mycophenolic acid, inhibits inosine monophosphate dehydrogenase, reduces purine synthesis in T and B cells, induces apoptosis
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How is mycophenolate selective?
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T and B cells unable to use alternative pathways to inosine monophosphate dehydrogenase to produce purines
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Other name for sirolimus?
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Rapamycin
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Mode of action of sirolimus?
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Forms complex with FKBP to inihibit mTOR pathway, cell arrest in G1
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Mode of action of basiliximab and daclizumab?
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Monoclonal antibodies to IL-2 receptor alpha chain, prevents T-cell activation
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When are basiliximab and daclizumab used?
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Organ transplant to prevent rejection, given just before and after transplant
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Three types of "novel proteins" associated with tumors?
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Tumor specific antigens, tumor associated antigens (wrong context, eg fetal), viral antigens
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What are the broad tumor related reasons for a lack of immune response?
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Fail to provide a target, or tumor is immunosuppressive
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Specific ways a tumor fails to provide a target to immune system?
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No tumor antigens, shut down antigen pres, MHC-I expr, costim/adhes molecules
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Specific ways a tumor is immunosuppressive?
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Express apoptosis molecules (FasL), or secrete anti-inflam molecules (TGF-beta, IL-10, PGE2)
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What are the broad host related reasons for a lack of immune response to a tumor?
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Immunosupression, or inappropriate response
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Specific ways immunosupression occurs in tumor response?
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Drug/radiation, and age
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Specific ways an inappropriate response to a tumor can occur?
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Induced tolerance
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Three components needed for an immune response to a tumor?
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Host capable of responding, overcome tumor induced immunosupression, tumor needs to express MHC and tumor specific antigens
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What is the cause of 75% of FN infections?
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Gram positive infections
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General effect of GCSF in FN?
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Reduce morbidity but not mortality - incr recovery rate, best used as prophylaxis in those with >20% risk inf
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Which cytos frequently cause alopecia?
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Anthracyclines, taxanes, cyclophos, *mycins, etoposide
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Which cytos frequently cause emesis?
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Platins, doxorubicin, cyclophosphamide
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What are the two classes/types of cancer vaccines used?
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Therapeutic (for those with cancer) and prophylactic
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What are the three types of therapeutic cancer vaccines?
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Adoptive Tcell, cell based (whole cell and DC), sub unit based
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Advantages of adoptive t-cell vaccine?
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Individualised, low toxicity, self renewing, autologous, can prolif++
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Disadvantages of adoptive t-cell vaccine?
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Resource and cost expensive, unproven efficacy, risk of autoimmune reaction, difficult to collect TIL
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Advantages of whole cell vaccines?
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Individualised, autologous or allogenic(someone else's tumor), don't need to define tumour antigens
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Outline of a whole cell vaccine?
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Remove tumour cells, grow, kill (w/necrosis), inject back in
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Disadvantages of a whole cell vaccine?
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Requires chunk of tumor, risk of autoimmune, may need immunostim help
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Outline of a DC vaccine?
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Strip antigens from tumor, introduce to cultered dendritic cells, inject into patient
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Advantages of a DC vaccine?
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Don't need to define tumor antigens, individualised, low toxicity
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Disadvantages of a DC vaccine?
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Req blood and tumor, high cost/difficulty, unproven efficacy, autoimmune risk
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Outline of cancer subunits vaccines?
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Purified tumor proteins/peptides/DNA with a good delivery system
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Advantages of cancer subunit vaccine?
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Can mass produce, safe
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Disadvantages of cancer subunit vaccine?
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Requires defined antigens, unproven efficacy
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Two ways to use cytokine cancer therapy?
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Target tumor directly, or activate immune system
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Disadvantages of cytokine cancer therapy?
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Short half lives, risk of systemic toxicity
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Causes of secondary immune deficiency?
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Drug induced, chemicals (eg benzene), radiation, cancer (squeezes out normal cells), HIV
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What is aplastic anemia?
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Complete loss of bone marrow
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Symptoms of aplastic anemia?
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Fatigue, pale, SOB, infections, easy bruising, bleeding gums/nose/prolonged
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What is HSCT?
|
Haematopoetic stem cell transplantation
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Diseases that HSCT is used for?
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SCID, aplastic anemia, leukaemias, lymphomas
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Outline of autologous HSCT?
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Take patient's stem cells, ablate patient cells, replace
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Two main donor sources of HSCT?
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Autologous (self) and allogenic (family, or other match)
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Three different types of HSCT transplants?
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Bone marrow, peripheral blood stem cells, umbilical cord stem cells
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Where is bone marrow taken from on the body in a donor?
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From the hip bone (under GA)
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Outline of a peripheral blood HSCT?
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Donor treated with GCSF, which mobilises stem cells into peripheral, then blood taken and cells harvested (no GA)
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Advantages of using cord blood for transplants?
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Reduced chance of viral contamination or graft vh (naive blood)
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Disadvantages of using cord blood for transplants?
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Small volume, takes longer to engraft
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How do cytokine adjuvants differ between immunosupressive therapy and cancer vaccines?
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Vaccines want to provoke immune reponse, other wants to reduce immune response
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What type of transplants does GvH occur with?
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HSCT or solid organs contaminated with leukocytes
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What are the two types of immunotherapies used with transplants?
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Anti-T-cell antibodies, and co-stimulation blockades
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Disadvantages of using anti-T-cell antibodies as immunosupressive therapy in transplant?
|
Anaphylaxis risk, and non-specifically kills all T-cells (shotgun - memory loss)
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Advantages of using costimulation blockade as immunosupressive therapy in transplant?
|
Memory responses unaffected
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Symptoms of acute GvH?
|
Dermititis, hepatitis, gastroenteritis ("acute triad")
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Symptoms of chronic GvH?
|
Dermititis, alopecia, weight loss, debility - liver, lung, joint, GI involvement
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What is the rate of GvH with HSCT?
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30-50%
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Risk factors for GvH?
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MHC mismatch (<10% with ident siblings, 75% with one MHC mismatch), composition of transplant (may contain T-cells), gender mismatch, age, donor has had children
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How many MHC molecules are there to match in transplant?
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12
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Why are infusions of donor lymphocytes sometimes given to diffuse cell cancer patients after HSCT?
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To induce graft vs tumor, which lowers relapse rates
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More simple forms of cytotoxic prodrugs?
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Hydrolysis (ester, amide, phophatase), reduction (azo, nitro, disulphide), self eliminating (p-aminobenzylcarbonyl linker)
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Outline of metalloproteinase prodrug cyto?
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Drug linked via specific amino acid that can be cleaved by specific overexpressed/overactive metalloproteinase
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What does ADEPT stand for?
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Antibody directed enzyme prodrug therapy
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Outline of ADEPT?
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Tumor-specific antibody linked to enzyme, and drug is given glucuronidated, cleaved at tumor
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Outline of bioorthogonal prodrugs?
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Tumor-specific antibody linked via specific shaped linkage to drug, correct inert molecule reacts and drug is cleaved at site
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What prodrug method is used to combat tumor resistance?
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Polycationic peptides help avoid efflux pumps
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Where do VEGFR inhibitors bind?
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To ATP site of VEGFR tyrosine kinase receptor
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What are the hypoxia related tumor enzyme drug targets?
|
Carbonic anhydrase IX and XII
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Outline of carbonic anhydrase targeting?
|
Coumarin inhibitors are isoform selective, sulfocoumarins most selective
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New methods of tumor targeting?
|
Hydrolysis/reduction, self elim, metabolic (peptide, silicate esters), ADEPT, bioorthogonal, polycationic, VEGFR inhibitors, carbonic anhydrase
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Difference between analgesic and narcotic?
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Analgesic considered pain relief only, narcotic vague generally covers analgesia and sedation
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Main effects of activated kappa opioid receptors?
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Sedation and dysphoria
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What type of receptors are opioid receptors?
|
Inhibitory GCPRs, that inhib AC, and decrease cAMP levels
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Two molecular effects activation of opioid receptors has on cells?
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Inhibit AC and decrease cAMP, facilitate opening K+ channels, and block voltage sens Ca channels
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Which opioid receptor mediates pupil constriction?
|
Mainly mu, a small amount of kappa
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Which opioid receptor mediates respiratory depression?
|
Mu
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How does opioid respiratory depression work?
|
Mu receptor mediates a decrease to sensitivity of CO2 levels
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Which opioid receptor mediates consitpation?
|
All three involved (mu, kappa, delta)
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Two side effects of opioids not affected by tolerance?
|
Pupil constriction and constipation
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|
Symptoms of opioid withdrawal?
|
Nausea, sweating, fever, diarrhoea, piloerection, insomnia
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Which opioids have the most severe withdrawal?
|
Short acting lipid soluble and potent opioids
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Which opioid receptor mediates dependance?
|
Mu
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|
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Characteristics of fentanyl?
|
Potent, short duration (0.5-2h), IM/IV/patches, patches can give 72h action but have slow onset
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Why is methadone used in addiction?
|
Similar analgesia to morphine, but better bioavail, longer half life, giving leaks peaks/troughs (imp w/addicts)
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|
Adverse effects of tramadol?
|
Nausea and vomiting common, serotonin syndome possible with other 5HT drugs
|
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|
Other effects of tramadol?
|
NA and serotonin reuptake inhibitor
|
|
|
Advantage of using mEslon over LA Morph?
|
mEslon caps can be sprinkled over non-chewed food (elderly)
|
|
|
How to calculate breakthrough pain dose?
|
Divide total dose for day by six
|
|
|
Why is fentanyl used in renal failure?
|
No active metabolites
|
|
|
What type of virus is HIV?
|
RNA single strand lentivirus
|
|
|
What receptors are involved in HIV cell entry?
|
GP120 binds to CD4, then GP120 binds to CCR5 and CXCR4, GP41 penetrates cell surface
|
|
|
What is the largest risk factor for transmission of HIV, for those infected?
|
HIV plasma titre
|
|
|
What is "the window" in HIV?
|
Period between infection and antibodies produced (seroconversion), anywhere from 10d to 6mo - negative test but actually infected
|
|
|
What are the four stages of HIV?
|
Primary infection (seroconversion), latent/asymptomatic phase, HIV progresson, AIDS
|
|
|
Duration of latent phase of HIV?
|
2-10 years, variable
|
|
|
Why does the CD8 response drop off in the latent phase of HIV?
|
Viral mutation
|
|
|
AIDs defining illnesses?
|
Mycobacterium (incl TB), Pneumocystis jiroveci, Karposi's sarcoma, Candidiasis of lungs, CMV
|
|
|
What is CMV?
|
Cytomegalovirus, Herpes viral family
|
|
|
General approach to HIV monitoring?
|
CD4 counts, viral load monitoring (PCR, slow), screening for prone diseases, immunisations when CD4 population large enough, prophylaxis against opp inf
|
|
|
What factors are associated with poor HIV treatment adherence?
|
Low literacy, psychosocial factors, substance abuse, complex regimes, adverse drug effects, treatment fatigue
|
|
|
Fusion inhibitor for HIV?
|
Enfuvirtide (protein, SC, hypersens issues) or maraviroc (not protein)
|
|
|
Integrase inhibitor for HIV?
|
Raltegravir (rash common)
|
|
|
Four main categories of HIV treatment?
|
Reverse transcriptase inhibitors (N and NN), protease inhibitors, fusion inhibitors, integrase inhibitors
|
|
|
When to start HAART?
|
CD4+ count < 500/mL, preg/BF, active TB, HBV or chronic liver disease, AIDS
|
|
|
Which strain of HIV is more virulent?
|
HIV-1
|
|
|
Why is HIV-1 more virulent?
|
High mutation rate
|
|
|
What is enfuvirtide?
|
HIV fusion inhibitor
|
|
|
What is raltegravir?
|
HIV integrase inhibitor
|
|
|
What is maraviroc?
|
HIV entry inhibitor
|
|
|
What mutation gives people high resistance to HIV?
|
Mutations in CCR5 receptor
|
|
|
Difference between maraviroc and enfuvirtide?
|
Maravoc is a non-protein entry inhibitor, enfuvirtide is a protein based fusion inhibitor
|
|
|
What is azidothymidine?
|
Reverse transcriptase inhibitor
|
|
|
What is nevirapine?
|
Non-nucleoside reverse transcriptase inhibitor
|
|
|
HIV entry inhibitors?
|
Maraviroc and enfuvirtide
|
|
|
HIV nucleoside reverse transcriptase inhibitors?
|
Emtricitabine, tenofivir, azidothymidine
|
|
|
HIV non-nucleoside reverse transcriptase inhibitors?
|
Efavirenz, nevirapine
|
|
|
Mechanism of HIV reverse protease inhibitors?
|
Transition state isosteres, mimic substrate
|
|
|
HIV reverse protease inhibitors?
|
Atazanavir, ritonovir, saquinovir
|
|
|
What are the two steps that HIV integrase performs?
|
Removes 3' dinucleotide from viral DNA, then links 3' ends to cellular DNA
|
|
|
What is saquinovir?
|
Reverse transcriptase inhibitor
|
|
|
Normal range of CD4 cell count?
|
500-1200/mL
|
|
|
Unique side effect of atazanivir?
|
Elevated bilirubin
|
|
|
Why are some NRTIs not used in older males?
|
Increased MI risk
|
|
|
Outline of what HIV protease does?
|
Cleaves proteins to produce GAG/POL/ENV structural/viral/envelope proteins needed
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