shevyatiwari's version from 2015-10-26 05:52


Question Answer
An alkylating agentF. Antimetabolite
Mechanism of action similar to MtxF. Similar to Azt
Rapid and complete absorption from GITF. Incomplete and unpredictable absorption
Converted by the liver to 6-TGT
Half life of 25 daysF. 80 minutes
Peak plasma levels vary 10 fold and occur 2-4 hours post ingestionT
It is affected by allopurinolF. Not metaobolised by XO
TPMP levels are not as important as in aztF. More
Broad TIF. Narrow
BA similar to cyclosporinT. 30%
Protein binding similar to AztT.
Metabolism is hepatic and excretion is renalT
Decreases T lymphocyte counts in skin lesionsT
Yields nucleoside analgouesT
C/I include allergy, history of hepatovenular occlusive disease, pregnancy, infection, haematological disordersT
Approx 50% experience myelosuppressionT
GI effects include excessive flatulenceT
Quite hepatotoxicF
Aminosalicylates interact and cause decreased toxicityF. INhibit TPMT causing increased toxicity


Question Answer
Well absorbedT and widely distributed XBBB
Peak levels in 1-2 hoursT
Works for up to 2 daysF. 20 hours
Undergoes saturable hepatic metabolismT
Predominant renal excretionT. 80% renal excretion
Urease may help in degradationT- urease in intestinal bacteria may play a part in degradation but primarily renally excreted 80%
Short plasma half life of 60 minutesF. Short - 4-5 hours
At 24 hours is completely clearedT
Inhibits ribonucleotide diphosphate reductaseT
Limits DNA bases for synthesisT
No radiation sensitising effectsF
Alters gene expression through hypermethylationF. HYPOmethylation
Concentration in hepatocytesF. Preferentially concentrates in leukocytes
Acts in S phaseT. Acts upon cells entering S phase p. 216
Third line agent in psoriasisT
C/I in allergy, cardiopulmonary disease, haematological disorders, hepatic disease, renal disease and infectionT
Category DT
C/I in pancytopeniaT
The most common adverse effects are GIF. myelosuppression
Anaemia seen in up to 1/3 of patientsT
Taking with antacids doesn't affect absorptionT. Can also take with milk or food to reduce dyspepsia. Bioavailability 100%
A rare cause of dermatomyositis-like eruptionF. Hydroxyurea is the most common drug to cause dermatomyositis-like eruption. Also can cause Lichenoid eruption resembling a chronic GVHD, leg ulcers , limited ad reversible alopecia, photosensitivity and radiation recall, hyper pigmentation of skin and nails. Also, drug - induced lupus and flu-like illness, GI upset
Risk of NMSCT
Risk of drug induced lupusT
Patients should have monthly urinalysisT. Can get haematuria
Most responses occur quicklyT. Within 8 weeks
Megaloblastic changes are commonT
Megaloblastic changes respond to folateF
Limited and irreversible alopecia is a S/EF, reversible alopecia
Lichenoid drug eruptions, leg ulcers, photosensitivity, radiation recall, hyper pigmentation of skin and nails are all possibleT
Safe to use with other myelosuppressives or cytarabineF


Question Answer
A member of nitrogen mustard familyT. A derivative
Acts in the S phase of the cell cycleF. is an alkylating agent. Cross links DNA -> cell death by apoptosis
Low bioavailabilityF. 75%
Peak plasma in 1-2 hoursT
Undergoes metabolism in the plasmaF. Hepatic. Requires hepatic activation . CYP
Half life of 5-9 hoursT
Children and those with increased CYP activity demonstrate short t1/2T
Cyclophoshpamide is the active drugF. Is a pro drug of 4-hydroxycyclophosphamide, exists in equilibrium with aldophosphamide
Aldophoshpamide is cleaved on the cell membrane to phosphor amide mustardF. Intracellularly
Aldophosphamide creatives an active metabolite acroleinF. Active metabolite is cytotoxic phosphoramide mustard. Acrolein is highly reactive and depletes glutathione stores
Alcohol dehydrogenase is involved in converting aldophosphamide to inactive metabolitesF. Aldehyde dehydrogenase converts aldophosphamide to a second inactive metabolite carboxyphosphamide - 30-60 % of which, excreted in the urine
Cyclophosphamide is 50% protein boundF 13%. Its metabolites are 50%
Excretion is renalF. Mostly hepatic
Affects B and T cells equallyF. Greater effect on B cells. B>T
Affects T suppressor and helper cells equallyF. Greater effect on suppressor cells
Resistance occurs via a plasmidF. Occurs due to decreased cellular penetration, increased competition from other nucleophilic substances, improved DNA repair, or increased drug metabolism
C/I in bladder cancerT
C/I includedrug allergy, myelosuppression, lactation, pregnancy (cat D) , infection, poor liver/renal function
haemorrhagic cystitis is commonT. Occurs in up to 41% of patients, due to acrolein
Mesna can cause hypersensitivity or FDET
Exposure is associated with Hodgkin's lymphomaF. NHL, leukaemia and SCC
GI S/E are commonT. Up to 70-90%
Effects menstrual cycleT. Amenorrhoea
Premature ovarian failure is rareF. Amenorrhea occurs in 27-60% of women treated with cyclophosphamide with 80% of those affected present with premature ovarian failure. Most important risk factors for frank gonadal failure are cumulative dose and age at dosing. Leuprolide acetate may provide some partial protection. Not a first line for women who wish to conceive following treatment .
Co administration with testosterone is not beneficial in MF. Can reduce risk of azoospermia
Anagen effluvium, permanent pigmented bands on teeth, hyper pigmentation of skin and nails can occurT
Urinalysis and cytological exam are indicated every 12 monthsF. when dose exceeds 50g and 6 monthly thereafter or with any evidence of hemorrhagic cystitis - STOP
Pulse IV dosing has less S/E than oral dosingT
Hydration must start as soon as therapy has begunF. Should start 24 hours before


Question Answer
An antimetaboliteF. alkylating
Derivative of nitrogen mustardT
BA of 87%T
Not affected by foodF. Food reduces BA by 10-20%
High protein bindingT. 99%
Half life of 1.5 hoursT
Metabolised and activated in the liverF. Metabolised but not activated
<1% excreted in kidneysT.
Faster but more toxic than cyclophoshpamideF. Opposite. less toxic, less effective, slower
Yields acrolein and therefore can cause hemorrhagic cystitisF
Pulmonary fibrosis is a S/ET
Hepatotoxicity, seizures, azoospermia and amenorrhe are all S/ET. Differs as has mood alterations - sleep disturbance, anxiety, restlessness, irritability and depression and SEIZURES. SIGNIFICANT EPILEPTIFORM POTENTIAL
Increased risk of leukaemia and SCCT
Safe with AZTF. Increased immunosuppressive, carcinogenic and myelosuppressive
Safe with CyclosporinF. Increased immunosuppressive, carcinogenic and myelosuppressive


Question Answer
An alkylating agentT
Absorption not affected by foodF. Variable oral BA greatly affected by food
Food increases BAF. Decreases from 85% to 58%
Doesn't require hepatic activationT
Highly protein boundT. 60-90% bound to albumin
Half life of 90 minutesT
Only 10-15% renal excretionT. Mostly hepatic excretion - 10-15% unchanged in the urine
C/I include allergy, pregnancy, lactationT
S/E: BM suppression, GIT distress, reproductive consequences, cutaneous reactions and carcinogenesisT