Flashcards
Seen Q day 2
Cards in this deck (96)
- 1optimise treatment, selecting, maximises, desired effects whilst minimizing the risk of toxicity. C conc, blood, low or excessive thus potentially toxic, maintain a THERAPEUTIC LEVELsafe + effective, narrow range of serum concs
minimizing, risk, under- or over-dosing due to DRUG/FOOD INTERACTION OR GENETIC POLYMORPHISM OF EZS + TRANSPORTERS INVOLVED IN C'S METABOLISM - 2DRUG/FOOD INTERACTION ORGENETIC POLYMORPHISM OF EZS + TRANSPORTERS INVOLVED IN C'S METABOLISM
ASSESS, AS PRESCRIBED - 3reducing abnormal electrical activity, brain. chewable, long-acting, suspension seizure d, bipolar d, chronic nerve pain THERAPEUTIC RANGE = 4 TO 10 mg / lnausea, vision changes, swelling, swallowing, breathing, severe rash w/ fever, muscle or joint aches
symptoms of OD: unconsciousness, vomiting, rapid or pounding Hbeat, abnormal movements - 4within the therapeutic range, adequatebroken down, liver, could interact or be affected, other meds, also
induces its own metabolism. Thus, although STEADY STATE is achieved 2 weeks after initiating therapy, - 5any dosage change during chronic therapy will take 1 week to produce a new steady state conc. limited solubility in aq + by a feedback system involving its ability to INDUCE HEPATIC OXIDASE EZS + hence increase its own metabolismLIMITED SOLUBILITY IN AQ
FEEDBACK SYSTEM, ABILITY TO INDUCE HEPATIC OXIDASE EZS - 6THIS METABOLISM CONVERTS IT TO A 10,11-epoxide, still pharmacologically active. then deactivated by conjugation10,11-epoxide
- 7elimination half-life35 hrs after single dose
- 8major route of eli98% hepatic metab w/ some active metabolites
- 9factors affecting plasma concINCREASED in hepatic disease + by concurrent use w/ erythromycin
- 10b. immunoassay measures total C, both protein-bound + free portions of the drugdraw volume 0.6 ml, vein
serum + plasma (lithium heparin)
turnaround time: 2hrs
above 12 microgram / mL, toxic - 11SINCE G6PDH activity falls upon binding to the antibody, C's conc is measured in terms of EZ activity Active G6PDH reduces NAD to NADH, resulting in an absorbance change that's measured spectrophotometrically.G6PDH activity FALLS upon BINDING TO THE ANTIB, conc, measured in terms of EZ activity.
Active G6PDH reduces NAD to NADH, resulting in an absorbance change that is measured spectrophotometrically. - 12mix tubes containing anticoagulant by gentle inversion sample at TROUGH LEVEL right before next dose, when you have the least amount of drug in bod, in order to avoid overdosingtime of collection isn't critical but due to the relatively short half life, C levels can vary quite markedly across the dosage interval; collection at a similar time, usually before next dose, may help LT monitoring
- 13COLLECTION AT A SIMILAR TIME, USUALLY BEFORE NEXT DOSE, MAY HELP LT MONITORINGadults, started at 100 to 200 mg daily. slowly increased every 1 to 2 weeks
Usually, amount taken is increased by 100 or 200 mg at a time - 14venepuncture, glass or plastic tubes. ENSURE COMPLETE CLOT FORMATION HAS OCCURRED PRIOR TO CENTRIFUGATION OF SERUM.FOR PLASMA, ANTICOAGS INC LITHIUM HEPARIN + SODIUM HEPARIN
- 15longer, complete, clotting. FIBRIN CLOTS MAY SUBSEQUENTLY FORM IN THESE SERA + THE CLOTS COULD CAUSE ERRONEOUS TEST RESULTSERRONEOUS TEST RESULTS
- 16Some sample dilution may occur, collected in tubes containing CITRATE ANTICOAG. THE AMOUNT OF DILUTION, considered, interpretating assayeffective treatment, some pats may require SERUM LEVELS OUTSIDE, RANGES. expected range, provided only as a GUIDE, + individual pat results should be interpreted in light of other clinical signs + symptoms
- 17C test may also be requested when a pat's condition doesn't appear to be responding to therapy. concs, too low, irregularly, ineffective for that persontroublesome level of side effects +/or develops complications
Seizure protection, best assessed in the context of trough levels, + toxicity potential, context of peak levels. - 18a. desired effects. maintain, therapeutic level. serum concs. drug/food interaction or genetic polymorphism of EZs + transporters involved, metab. prescribedbipolar, chronic nerve pain
THERAPEUTIC RANGE: 4 - 10 mg / L - 19THERAPEUTIC RANGE, adequate vision changes, swelling, breathing OD: abnormal movementsbroken down, liver, affected, other meds. induces its own metab. Thus, although steady state, achieved 2 weeks after initating therapy, any change in dosage during chronic therapy will take 1 week to produce, new SS conc.
- 20limited solubility in aq feedback system involving its ability to INDUCE HEPATIC OXIDASE EZS This metab converts it to a 10,11-epoxide, still pharmacologically active. Then deactivated by conjugation.eli half-life = 35 hrs after single dose
major route of eli = 98% hepatic metabolism w/ some active metabolites
plasma conc: increased, in hepatic d + by concurrent use w/ erythromycin - 21total C, both protein-bound + free portions of the drug. 0.6 ml, vein serum + plasma for plasma, anticoagulants inc lithium heparin + sodium heparin. Mix tubes containing anticoag by gentle inversion.2hrs. above 12 microg / mL. G6PDH activity falls upon binding to the antib, C's conc is measured, EZ activity. Active G6PDH reduces NAD to NADH, resulting in an absorbance change that is measured spectrophotometrically.
- 22SAMPLE AT TROUGH LEVEL RIGHT BEFORE NEXT DOSE, AVOID OVERDOSING, HAVE THE LEAST AMOUNT OF DRUG, BODtime of collection, not critical but, relatively short half-life, C levels can vary quite markedly across the dosage interval. collection at a similar time, usually before, next dose, may help LT monitoring.
- 23adults, 100 or 200 mg daily. slowly increased by 100 or 200 mg at a time, every 1 to 2 weeksvenepuncture. complete clot formation, prior, centrifugation of serum. longer, complete, clotting. FIBRIN CLOTS, SERA, ERRONEOUS TEST RESULTS. Some sample dilution may occur when samples are collected in tubes containing citrate anticoag. dilution, considered, interpreting
- 24effective, serum levels outside, ranges. guide, indi pat results, interpreted in light of other clinical signs + symptoms.condi does not appear to be responding to therapy. too low, irregularly, ineffective for that person. troublesome level of side effects +/or develops complications.
SEIZURE PROTECTION, BEST ASSESSED IN THE CONTEXT OF TROUGH LEVELS, + TOXICITY POTENTIAL, BEST ASSESSED IN THE CONTEXT OF PEAK LEVELS - 25Lithium heparin is added to blood collection tubes tostop clot formation
- 26role of glucagonstimulating the liver to breakdown glycogen
stimulating the cs to take up aas
inhibiting the prod of ketone bods - 27role of glucagon isn'tinhibiting the phosphofructokinase I EZ in the liver
- 28glucagon roles:stimulating the liver to breakdown glycogen
stimulating the cs to take up aas
inhibiting the prod of keton bods - 29lithium heparin, added to blood collection tubes tostop clot formation
stop clot formation - 30haptoglobinan acute phase protein, released in response to tissue damage
- 31haptoglobinan acute phase protein, released in response to tissue damage
- 32HbA1c has an advantage for monitoring bglevels bcit has a defined life-span as a component of a rbc
- 333-isopentenyl pyrophosphate is a precursor for (all of the above)3-isopentenyl pyrophosphate is a precursor for:
vitamin K
ubiquinone
cholesterol - 34Statins reduce plasma cholesterol as theyinhibit the EZ HMG CoA reductase
- 35Isoforms of an EZall have dif post-translational processing
all have dif post-translational processing - 36isoforms of an EZsame aa sequence
cat the same r
have dif post-translational processing - 37development, atherosclerotic plaque:endothelium, damaged
low density lipoprotein (LDL) is oxidised
macrophage scavenger receptors take up oxLDL - 38notneutrophils + platelets adhere to the damaged area
- 39basophilsleast abundant wbcs in the blood
- 40unlikely consequence from this metabolic blockprod of D is increased
- 41likely consequence from this metabolic blockEZ is produced but not active
conc of B increased
EZs involved in the regeneration of co-enzymes maybe deficient - 42not a response to a blood vessel injuryvascular dilation
- 43A response to a blood vessel injuryFactor IX is activated
platelets aggregate around exposed collagen
binding of von Willebrand factor to exposed subendothelial collagen - 44Factor IX is activated platelets aggregate around exposed collagen binding of von Willebrand factor to exposed subendothelial collagenFactor IX is activated
platelets aggregate around exposed collagen
binding of von Willebrand factor to EXPOSED SUBENDOTHELIAL COLLAGEN - 45Lithium heparin haptoglobin = an acute phase pro, released in response to tissue damageHbA1c has an advantage from monitoring bg levels bc it has a defined life-span as a component of a rbc
- 463-isopentenyl pryophosphate is a precursor for: vitamin K, ubiquinone, cholesterolStatins reduce plasma cholesterol as they inhibit the EZ HMG CoA reductase
- 47feature of chronic myeloid leukamia is a chromosomal translocation t(9,22) Vitamin K is required for the coagulation cascade as itis a co-EZ in the gamma-carboxylation of glutamic acid residues for some of teh coagulation factors
- 48albumin:supports oncotic pressure
binds cations
transports: drugs, HMs, fatty acids, bilirubin - 49differ w/ respect to the transport of sugars? GLUT1glucose, galactose, mannose, + glucosamine substrate, rbc, brain fetal tissue
- 50GLUT1glucose, galactose, mannose, glucosamine substrate, rbc, brain fetal tissue
- 51GLUT4:glucose + glucosamine Km up to plasma glucose level, insulin responsive, adipose/ skeletal/ cardiac tissue
- 52GLUT5:FRUCTOSE ONLY , HIGHER Km, not insulin responsive, small intestine/ kidney
- 53gluconeogenesispathway stimulated by the absence of F 2,6-bis P
- 54stimulated by the absence of F 2,6-bis P type 1 = type of diabetes, presence of antibodies to glutamic acid decarboxylase (GAD) + possibly other proteinsdif forms of creatine kinase, source:
- 55MM muscle BB brain MB cardiac muscleMM
BB
MB - 56alanine aminotransferase (AAT) is involved in the metabolism of aastissue AAT is predominantly found in LIVER
- 57aas, liveraas, liver
- 58main protein found in LDL ms: ApoB100 role of ApoB100to deliver cholesterol to cs
to deliver cholesterol to cs - 59Lipoprotein (a) is a small lipoprotein that contains 1 molecule of apoprotein a + ApoB100ApoB100
- 60increasing density of lipoproteins involved in lipid movement around the blood: chlomicrons = v low density L intermediate density lipoprotein (IDL) = low density L lipoprotein (a)= high density L-enia = low no. of a given C type
-plasia = formation
-osis = increased no. of c type - 61dif globins create dif affinities for O2. Affinity decreases as foetus develops, w/ adult Hb having the lowest affinity. developing foetus can gain as much O2 as possible in a low O2 environment + it has a higher affinity than in the mother's blood passing through the placenta.iron deficiency anaemia =
reduced MCHC, increased free intracellular protoporphyrin + the blood film showed rbcs which hypochromic + microcytic. - 62haematinics haematinics, measured in a pat w/ suspected anaemia:iron
vitamin B12
folate
ferritin, transferrin, vitamin B6 - 63iron absorbed most rapidly = ferrous state (Fe2+)iron absorption in duodenum + jejunum
duodenum + jejunum
duodenum + jejunum - 64XS iron stored as FERRITIN OR HAEMOSIDERINdifferentiates an acute leukaemia from a chronic leukaemia:
the % of blasts
at least 20% blasts in bone marrow = acute
less than 20% = chronic - 65type of c accumulates in lymph nodes in Hodgkin's disease: mutated B cell derived from Reed-Sternbergmutated B cell
Reed-Sternberg
mutated B cell
Reed-Sternberg - 66dif globins create dif affinities for O2. affinity falls as foetus develops, w/ adult Hb having the lowest affinity. the developing foetus can gain as much O2 as possible in a LOW O2 ENVIRONMENT + IT HAS A HIGHER AFFINITY THAN IN THE MOTHER'S BLOOD PASSING THROUGH THE PLACENTAproteins that anchor the skeletal pros within rbcs to the mem:
Band 3, ankyrin, protein 4.2
Band 3, ankyrin, protein 4.2 - 67ELLIPTOCYTES = shape, rbcs take if there are Ms in the proteins involved in the horizontal interactions between the cytoskeleton pros in rbcsB-lymphocyte generates antibs
neutrophil: phagocytosis of bacteria/ viruses - 68rbcs are reliant on glycolysis whereas platelets contain mitochondria where OXIDATIVE PHOSPHORYLATION OCCURS SO PLATELETS CAN PRODUCE MORE ATPrbcs are reliant on glycolysis whereas platelets contain MITOCHRONDRIA WHERE OXIDATIVE PHOSPHORYLATION OCCURS SO PLATELETS CAN PRODUCE MORE ATP
- 69HbA1 c can now also be used to assist w/ diagnosis of DNA= glycated Hb
glycation = non-enzymatic addition of sugar residues to proteins
HbA1c = glycation of the N-terminal valine residue of the beta chains in HbA - 70blood HbA1c conc depends onLIFESPAN ON RBCS - 120DAYS AVERAGE
BGCONC
HbA1c reps the average bg level over the last 8-12 weeks - 71HbA1c measurement must be repeated to confirm diagnosis unless pat has symptoms + plasma glucose > 11.1People diagnosed via HbA1c may not be identified as diabetic using glucose, + vice versa
- 72HBA1c :) :) NO PATIENT PREP WHOLE BLOOD EDTA, LESS RAPID PROCESSING NEEDED DOESN'T VARY WIDELY FROM DAY TO DAY, CHANGES TAKE LONGER UNAFFECTED BY EXERCISE OR FOOD INTAKELOWER WITHIN SUBJECT BIOLOGICAL VARIATION
:( HAEMOGLOBINOPATHIES CAN INTERFERE W/ SOME ASSAYS
MORE EXPENSIVE - 73Safer for pats than fasting or OGTT more expensive but cost effective in terms of screening to get early diagnosis + reducing LT complicationsCation exchange HPLC
POCT method - 74haem: synthesis in all tissues greater synthesis in bone marrow + liver Haem: mainly planar, v stable, Fe2+/Fe3+ in cytochromes, always Fe2+ in HbHaem biosynthesis:
8 succinyl COA
+
8 glycine
=
4 pyrrole rings - 75formation of a pyrrole ring: 2 ALA molecules ...... PBG + 2H20complete inefficiency of any EZ in the synthetic pathway = fatal
- 76autosomal dominant mutations in genes for EZs, about 50% normal EZ activity in affected heterozygotePORPHYRIA = ERRORS IN HAEM SYNTHESIS
- 77Aminolaevulinic acid synthase (ALA synthase) 1st EZ in the pathway rate limiting step activated by many drugs e.g.barbiturates
oestrogens
sulphonamides - 78inhibited by haem + lack of pyridoxal phosphateALA dehydratase
-SH essential for activity
inhibition of EZ by heavy metals can give same symptoms + consequences as an inborn error - 79Acute intermittent poryphyria (AIP): autosomal dominant (11q23.3) partial deficiency prophobilinogen deaminase (PBG)cholesterol synthesis:
- 803 stages: 1. SYNTHESIS OF ISOPENTYL PYROPHOSPHATE 2. condensation of 6 molecules of isopentyl pyrophosphate to form squalene 3. cyclization of squalene to a tetra cyclic product (steroid nucleus) + modification4 stages:
1. SYNTHESIS OF MEVALONATE FROM ACETATE
2. CONVERSION OF MEVALONATE TO ACTIVATED ISOPRENE (ISOPENTYL PYROPHOSPHATE) - 813. condensation of 6 molecules of isopentyl pyrophosphate to form squalene4. cyclization of squalene to a tetra cyclic product (steroid nucleus) + modification
- 82coEZ providing protons + es = NADPH + H+isopentyl pyrophosphate. activated precursor of many biomolecules. e.g. vitamin K, ubiquinone, cholesterol
also vitamin A, isoprene, vitamin D - 83cholesterol source: diet, 30% 80%: liver, small intestine, other tissueschronic myeloid leukaemia:
a chromosomal translocation t(9,22)
CM abnormality. BCR-ALB1 positive aka
Philadelphia chromosome der(22) - 84translocation between CMs 99 & 22 Translocation between CMs 9 and 22BCR-ALB1 combination results in:
increased proliferation rate
apoptopic failure
increased wbc count - 85Burkitt's lymphoma: t(8:14)(q24:q32) Non-Hodgkin lymphoma form seen in young children in Africamyeloid: rbc, neutrophil, monocyte, eoisinophil, basophil platelets
lymphoid: B, T, natural killer (NK), plasma cs - 86acute. clinically aggressive. death within weeks/ months post diagnosis w/o treatment evid of maturational arrestchronic. accumulation of blasts less than 20% of nucleated cs in the bone marrow
no evid of maturational arrest
less aggressive. death within years - 87Non-leukaemic lymphoproliferative disorders: Hodgin's Disease = mutated B cell. Reed-Sternberg cell in lymph node malignant cells move around via lymphatic circulation male>femaleNon Hodgkin lymphoma (NHL)
solid lymphoid tumour, increases after 40 yrs, 4 x more common than HD - 88MM Multiple myeloma (MM) disease of old age, 70 yrs. male > female proliferation of malignant plasma cells, activate osteoclasts. weaken bone leads to fractures, cells produce monoclonal antibodiesmost abundant:
neutrophil 70%
lymphocyte 20
monocyte 7
eosinophil 2
basophil 1 - 89neutrophil 70 lymphocyte 20 monocyte 7 eosinophil2 basophil 1glucose anabolism: gluconeogenesis
final r in a separate compartment = endoplasmic reticulum in the liver - 90plasma protein roles: albumin source = livermost abundant protein in blood plasma:
supports oncotic pressure
binds cations - metal ions
transports: fatty acids, HMs, bilirubin, drugs (dosage) - 91Lipoproteins: decreasing lipids, increasing density:chylomicrons (transport dietary lipid)
v low density L (VLDL)
intermediate density L (IDL)
low density L (LDL) (carries most cholesterol in blood)
high density L (HDL) - 92development of lipoproteins: small dense LDL stays in circulation longer modified LDL particle is an oxidised LDL particle modified LDL picked up by SCAVENGING RECEPTORSIsoforms dif in structure:
creates difs in mobility in electrophoresis;
dif epitopes (antigenic determinant) so will be recognised by dif antibs - 93inborn errors of aa metabolism: albinism: tyrosinase EZ deficiency. symptom: absence of pigmentation albinismtyrosinase
absence of pigmentation - 94albinismtyrosinase
absence of pigmentation - 95tyrosinemia tyrosinemia tyrosinemia. various EZs of tyrosine degradation. weakness, self-mutilation, liver damage, mental retardationtyrosinemia. various EZs of tyrosine degradation. weakness, self-mutilation, liver damage, mental retardation
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- Flashcards on Seen Q day 2, created by Angela Samonte on 14/01/2019.
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