calcineurin inhibitors (Cs, Tacrolimus)

Question 1

MOA of both

Answer 1

inhibitors production and release of lymphokines, thereby suppressing cell-mediated immune response

Inhibit Tcell mediated immune response

Question 2

important safety info re prescribing and dispensing for Cs

Answer 2

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

Question 3

Why do pt need to be maintained on a particular brand for Cs

Answer 3

switching between formulations without close monitoring may lead to clinically important changes in blood-ciclosporin concentration

Question 4

is Cs used for malignancy

Answer 4

no, contraindicated in malignancy with systemic use (in non transplant indications)

Question 5

What are they mainly indicated for

Answer 5

Transplantation and Autoimmune

Question 6

3 CI for ciclosporin

Answer 6

Malignancy (in non-transplant indications); uncontrolled hypertension (in non-transplant indications); uncontrolled infections (in non-transplant indications)

Question 7

Can patient who has uncontrolled hypertension be put on ciclosporin

Answer 7

No, contraindicated in non transplant indications

Question 8

Food & drink interactions - juices

CICLOSPORIN

Answer 8

POMELO and GRAPEFRUIT juice predicted to INCREASE exposure to ciclosporin

PURPLE GRAPE juice predicted to DECREASE ciclosporin exposure

Question 9

Effect of pomelo juice on Cs

Answer 9

predicted to increase ciclosporin exposure

Question 10

Effect of purple grape juice on Cs

Answer 10

predicted to decrease ciclosporin exposure

Question 11

name a common SE (to do with eye) of Cs

Answer 11

eye inflammation

Question 12

Cs trough level is dependent on…

Answer 12

indication.

monitor whole blood ciclosproinc conc

Question 13

tacrolimus - what has been reported to occur primarily in children with tacrolimus blood trough conc much higher than recommended max levels?

Answer 13

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

Question 14

tacrolimus is contraindicated if Hx hypersensitivity to this abx drug class!

Answer 14

macrolides

Question 15

monitoring tacrolimus

Answer 15

after initial dosing and for maintenance, tacrolimus doses should be adjusted according to whole blood tacrolimus trough conc, esp during diarrhoea

Question 16

pt from this ethnic background may require higher doses of tacrolimus

Answer 16

black African or afto Caribbean

Question 17

monitoring patient parameters for tacrolimus

Answer 17

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).

Question 18

advice to give to pt about what to avoid for tacrolimus

Answer 18

Advise patients to avoid excessive exposure to UV light including sunlight and to report symptoms of eye disorders for prompt evaluation by an ophthalmologist.

Question 19

do they cause bone marrow suppression?

Answer 19

no

Question 20

incidence of neurotoxicity is greater with

Answer 20

tacrolimus

Question 21

Effect of tacrolimus on blood glucose

Answer 21

Commonly causes hyperglycaemia and DM (also hyperlipidaemia)

Uncommonly causes HYPOglycaemia

Question 22

Effect of ciclosporin on blood glucose

Answer 22

Commonly causes HYPERglycaemia and DM (also hyperlipidaemia)

Question 23

interactions

• drugs plus drinks

Answer 23

hyperkalaemia drugs increased hyperkalaemia

increased levels if inhibitors given

grapefruit juice and pomelo juice increases

reduced levels with inducers

increased nephrotixicty with nephrotoxic drugs

Question 24

what effect does tacrolimus have on BP

Answer 24

can cause hypo or hypertension

Question 25

what electrolye disturbances can ciclosporin and tacrolimus cause

Answer 25

cs: hyperglycaemia, hyperuricaemia, hyperkalaemia, hypomagesnium

tacrolimus: hyperglycaemia, hyperuricaemia, hyperkalaemia

Question 26

ciclopsorin monitoring pt parameters

Answer 26

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.

Question 27

ciclosproin - counsel pt to avoid ….

Answer 27

Manufacturer advises avoid excessive exposure to UV light, including sunlight. In psoriasis and atopic dermatitis, avoid use of UVB or PUVA.

Question 28

Are they nephrotoxic or hepatotoxic?

Answer 28

nephrotoxic

Question 29

Signs of toxicity

Answer 29

Nephro
Neuro
Immune

(e.g., changes in urine output, persistent headache, signs of infection)

Question 30

What effect can they have on BP

Answer 30

can cause HTN - monitor, discontinue if it develops and can’t be controlled by drugs

Question 31

Interactions

Answer 31

Inhibitors, anti arrhythmics increase levels
Inducers decrease levels
Nephrotoxicity
Hyperkalaemia - NSAIDs, SEAT, ACE