calcineurin inhibitors (Cs, Tacrolimus) Flashcards
MOA of both
inhibitors production and release of lymphokines, thereby suppressing cell-mediated immune response
Inhibit Tcell mediated immune response
important safety info re prescribing and dispensing for Cs
must be prescribed and dispensed by brand name
pt need to be stabilised on one brand because switching between formulations without close monitoring may lead to clinically important changes in blood-ciclosporin conc
Why do pt need to be maintained on a particular brand for Cs
switching between formulations without close monitoring may lead to clinically important changes in blood-ciclosporin concentration
is Cs used for malignancy
no, contraindicated in malignancy with systemic use (in non transplant indications)
What are they mainly indicated for
Transplantation and Autoimmune
3 CI for ciclosporin
Malignancy (in non-transplant indications); uncontrolled hypertension (in non-transplant indications); uncontrolled infections (in non-transplant indications)
Can patient who has uncontrolled hypertension be put on ciclosporin
No, contraindicated in non transplant indications
Food & drink interactions - juices
CICLOSPORIN
POMELO and GRAPEFRUIT juice predicted to INCREASE exposure to ciclosporin
PURPLE GRAPE juice predicted to DECREASE ciclosporin exposure
Effect of pomelo juice on Cs
predicted to increase ciclosporin exposure
Effect of purple grape juice on Cs
predicted to decrease ciclosporin exposure
name a common SE (to do with eye) of Cs
eye inflammation
Cs trough level is dependent on…
indication.
monitor whole blood ciclosproinc conc
tacrolimus - what has been reported to occur primarily in children with tacrolimus blood trough conc much higher than recommended max levels?
Cardiomyopathy
Patients should be monitored by echocardiography for hypertrophic changes—consider dose reduction or discontinuation if these occur.
Hypertrophic heart changes on an ECG (electrocardiogram) are indicative of hypertrophic cardiomyopathy (HCM), a condition where the heart muscle thickens abnormally. This can lead to various electrical changes observable in an ECG reading
tacrolimus is contraindicated if Hx hypersensitivity to this abx drug class!
macrolides
monitoring tacrolimus
after initial dosing and for maintenance, tacrolimus doses should be adjusted according to whole blood tacrolimus trough conc, esp during diarrhoea
pt from this ethnic background may require higher doses of tacrolimus
black African or afto Caribbean
monitoring patient parameters for tacrolimus
Monitor blood pressure, ECG (for hypertrophic changes—risk of cardiomyopathy), fasting blood-glucose concentration, haematological and coagulation parameters, plasma protein, electrolytes, neurological (including visual) status, hepatic and renal function.
Monitor for posterior reversible encephalopathy syndrome (PRES).
advice to give to pt about what to avoid for tacrolimus
Advise patients to avoid excessive exposure to UV light including sunlight and to report symptoms of eye disorders for prompt evaluation by an ophthalmologist.
do they cause bone marrow suppression?
no
incidence of neurotoxicity is greater with
tacrolimus
Effect of tacrolimus on blood glucose
Commonly causes hyperglycaemia and DM (also hyperlipidaemia)
Uncommonly causes HYPOglycaemia
Effect of ciclosporin on blood glucose
Commonly causes HYPERglycaemia and DM (also hyperlipidaemia)
interactions
- drugs plus drinks
hyperkalaemia drugs increased hyperkalaemia
increased levels if inhibitors given
grapefruit juice and pomelo juice increases
reduced levels with inducers
increased nephrotixicty with nephrotoxic drugs
what effect does tacrolimus have on BP
can cause hypo or hypertension
what electrolye disturbances can ciclosporin and tacrolimus cause
cs: hyperglycaemia, hyperuricaemia, hyperkalaemia, hypomagesnium
tacrolimus: hyperglycaemia, hyperuricaemia, hyperkalaemia
ciclopsorin monitoring pt parameters
Dermatological and physical examination, including BP pressure and RFTs required at least 2x before starting treatment for psoriasis or atopic dermatitis.
LFTs
Monitor serum potassium, especially in renal dysfunction (risk of hyperkalaemia).
Monitor serum magnesium.
Measure blood lipids before treatment and after the first month of treatment.
Investigate lymphadenopathy that persists despite improvement in atopic dermatitis.
Monitor kidney function—dose dependent increase in serum creatinine and urea during first few weeks may necessitate dose reduction in transplant patients (exclude rejection if kidney transplant) or discontinuation in non-transplant patients.
Monitor blood pressure—discontinue if hypertension develops that cannot be controlled by antihypertensives.
Monitor hepatic function if concomitant NSAIDs given.
ciclosproin - counsel pt to avoid ….
Manufacturer advises avoid excessive exposure to UV light, including sunlight. In psoriasis and atopic dermatitis, avoid use of UVB or PUVA.
Are they nephrotoxic or hepatotoxic?
nephrotoxic
Signs of toxicity
Nephro
Neuro
Immune
(e.g., changes in urine output, persistent headache, signs of infection)
What effect can they have on BP
can cause HTN - monitor, discontinue if it develops and can’t be controlled by drugs
Interactions
Inhibitors, anti arrhythmics increase levels
Inducers decrease levels
Nephrotoxicity
Hyperkalaemia - NSAIDs, SEAT, ACE
