Cardiac Output, Venous Return, and Their Regulation
ย
CKD MBD - Drug Related Issues - Dr. Gawad
1. CKD โ MBD
Drug Related Issues
Case Scenarios
Mohammed Abdel Gawad
Nephrology Specialist
Kidney & Urology Center (KUC) - Alexandria โ EGY
drgawad@gmail.com
2. CKD - MBD CKD - MSDCKD - MVD
Please refer also to this lecture on www.NephroTubeCNE.com
3. CKD patients may develop any intercurrent
primary or secondary disorders rather than the
excepted course and complications of CKD
Please refer also to this lecture on www.NephroTubeCNE.comPlease refer also to this lecture on www.NephroTubeCNE.com
5. Case 1
40 years old female. ESRD and HTN following
delivery in 2010. She is on maintenance
haemodialysis.
Her main major complaint was
bone pain allover her body.
โข Ca: 11.2 mg/dl
โข Phosphrous: 9 mg/dl
โข PTH: 1900 pg/ml
โข Discussion regarding
the probability of
parathyroidectomy: the
patient refused
โข Cinacalcet 30 mg/d
โข Ca carbonate
โข Alphacalcidol
โข Follow up after 4 weeks
โข Ca: 11 mg/dl
โข Phosphrous: 8 mg/dl
โข PTH: 1750 pg/ml
โข + Persistent Nausea
โข Cinacalcet 60 mg/d
โข Ca carbonate
โข Alphacalcidol
โข Follow up after 2 weeks
6. Case 1
โข After 2 weeks:
๏ผ PTH: 1200 pg/ml
๏ผ Ca: 9 mg/dl
๏ผ PO4: 5.5 mg/dl
But
โข Severe Nausea.
โข Vomited twice through
the previous week.
โข The patient didnโt omit any dialysis
sessions.
โข The dialysis adequacy is within
recommended targets.
โข Blood pressure and other vital signs are
within accepted ranges.
โข No evidence of infection or septicemia.
โข No abdominal tenderness or rigidity.
โข No change in bowel habits (constipation
or diarrhea).
40 years old female. ESRD and HTN following
delivery in 2010. She is on maintenance
haemodialysis.
โข What is the suspected
cause of N&V
7. Case 1
โข After 2 weeks:
๏ผ PTH: 1200 pg/ml
๏ผ Ca: 9 mg/dl
๏ผ PO4: 5.5 mg/dl
But
โข Severe Nausea.
โข Vomited twice through
the previous week.
โข The patient didnโt omit any dialysis
sessions.
โข The dialysis adequacy is within
recommended targets.
โข Blood pressure and other vital signs are
within accepted ranges.
โข No evidence of infection or septicemia.
โข No abdominal tenderness or rigidity.
โข No change in bowel habits (constipation
or diarrhea).
40 years old female. ESRD and HTN following
delivery in 2010. She is on maintenance
haemodialysis.
โข What is the suspected
cause of N&V
Gastrointestinal adverse events (mostly
nausea and vomiting) are frequently
associated with cinacalcet
European Medicines Agency: Mimpara: EPAR product information:
Summary of product characteristics. Accessed April 30, 2015
8. Cinacalcet GIT Adverse Effects
โข Nausea (30% to 66%)
โข Vomiting (26% to 52%)
โข Diarrhea (21%)
โข Anorexia (6% to 21%)
โข Constipation (5% to 18%)
โข Abdominal pain (11%)
2015
9. Cinacalcet Induced N&V
Mechanism
Cinacalcet stimulate the CaR present in:
โข Hypothalamus & other brain regions controlling vomiting.
โข Gastrointestinal tract.
CaR
CaR
Cinacalet
Massy ZA et al. Semin Nephrol 34: 648โ659, 2014
10. Cinacalcet Induced N&V
How to avoid?
โข Incidence of gastrointestinal adverse events is
lower when Cinacalcet is administered:
๏ผwith the first main meal after dialysis.
๏ผin the evening.
Schaefer RM et al. The SENSOR Study. Clin Nephrol 70: 126โ134, 2008
Bioavailability of Cinacalcet
increases by 50%โ80% with food
Martin KJ et al. Kidney Int 85: 191โ197, 2014
11. Cinacalcet Induced N&V
How to avoid?
โข Incidence of gastrointestinal adverse events is
lower when Cinacalcet is administered:
๏ผwith the first main meal after dialysis.
๏ผin the evening.
โข If symptoms do not abate:
๏ผreduction to the previous tolerated dose
is often sufficient.
Jordi Bover et al. Clin J Am Soc Nephrol. Jul 29, 2015
Schaefer RM et al. The SENSOR Study. Clin Nephrol 70: 126โ134, 2008
14. Case 2
50 years old male. ESRD secondary to chronic
uncontrolled HTN. He is on maintenance
haemodialysis.
โข The patient medications:
โข Cinaclacet 60mg/d
โข Ca acetate
โข After 2 weeks:
๏ผ PTH: 1200 pg/ml
๏ผ Ca: 8.5 mg/dl
๏ผ PO4: 5.5 mg/dl
โข Severe Nausea.
But
โข Domperidone was prescribed as
a prokinetic
โข Cincalcet was administered with
meals
โข After 2 days:
โข Patient present with
3 syncopal attacks
(especially with
exercise).
โข A syncopal attack was
witnessed during clinic
examination.
15. Case 2
50 years old male. ESRD secondary to chronic
uncontrolled HTN. He is on maintenance
haemodialysis.
16. Case 2
50 years old male. ESRD secondary to chronic
uncontrolled HTN. He is on maintenance
haemodialysis.
Bradycardia:
60 beat/m
17. Case 2
50 years old male. ESRD secondary to chronic
uncontrolled HTN. He is on maintenance
haemodialysis.
Bradycardia:
60 beat/m
18. Case 2
50 years old male. ESRD secondary to chronic
uncontrolled HTN. He is on maintenance
haemodialysis.
Bradycardia:
60 beat/m
What predisposes long QT syndrome in this
patient?
19. Case 2
50 years old male. ESRD secondary to chronic
uncontrolled HTN. He is on maintenance
haemodialysis.
โข Serum Ca: 6.8mg/dl (the patient omitted his Calcium
carbonate supplement, which aggravates the
hypocalcemic effect of Cinacalcet).
โข The physician prescribed Domperidone for nausea
symptomatic management.
What predisposes long QT syndrome in this
patient?
20. Risk of Long QT with Cinacalcet Use
Hypocalcemia
โข Cinacalcet is not on the list of all drugs that can affect QT
interval.
โข BUT hypocalcemia that may be associated with Cinacalcet use
can prolong the QT interval.
โข QT evaluation is not mandatory, BUT QT evaluation is advised
in high-risk patients:
๏ผFamilial history
๏ผBradycardia
๏ผRecent cardiac ablation
๏ผHypokalemia / Hypomagnesemia
European Medicines Agency: Mimpara: EPAR product information:
Summary of product characteristics. Accessed April 30, 2015
21. Risk of Long QT with Cinacalcet Use
Hypocalcemia
โข Cinacalcet should not be initiated if the
calcium is <8.4 mg/dL.
โข The dose should be increased based on
monthly or quarterly PTH results, provided the
corrected calcium is >7.8 mg/dL.
Block GA et al. Nephrol Dial Transplant. 2008 Jul;23(7):2311-8.
22. Risk of Long QT with Cinacalcet Use
Anti-emetic / Prokinetic
Nausea & Vomiting are very common with the use of
Cinacalcet
Jordi Bover et al. Clin J Am Soc Nephrol. Jul 29, 2015
Take care
Antiemetic drugs (mainly metoclopramide)
Gastroprokinetic drugs (domperidone, cisapride, or
ondansetron)
affect the electrocardiographic QT interval
24. Case 3 55 years old male. DM, HTN, CHF, ESRD and he is
on maintenance HD.
โข The patient medications:
โข ESA (Hb: 8.5 g/dl)
โข Alphaclacidol
โข Ca carbonate
โข Carvidolol
โข Lisinopril
โข Digoxin (modified to
renal impairment)
โข DM is well controlled on
insulin therapy
โข Before the start of the
traditional HD session, the
patient complaints of:
โข Drowsiness
โข Headache
โข Anorexia
โข Diarrhea
โข Palpitation
โข Symptoms were attributed to
anemia and uremia.
โข After 30 min of HD session:
โข Patient C/O of exacerbation
of palpitation.
โข BP: 80/50 mmHg
โข Loss of consiusness
โข Resuscitation was done.
โข ECG & Lab Ix were done.
25. Case 3 55 years old male. DM, HTN, CHF, ESRD and he is
on maintenance HD.
26. Case 3 55 years old male. DM, HTN, CHF, ESRD and he is
on maintenance HD.
`
Reverse
tick sign
27. Case 3 55 years old male. DM, HTN, CHF, ESRD and he is
on maintenance HD.
`
Reverse
tick sign
Salvador Dali's mustache
(saddle shape)
28. Case 3 55 years old male. DM, HTN, CHF, ESRD and he is
on maintenance HD.
`
Reverse
tick sign
Salvador Dali's mustache
(saddle shape)
What predisposes digoxin toxicity in this
patient?
29. Case 3 55 years old male. DM, HTN, CHF, ESRD and he is
on maintenance HD.
What predisposes digoxin toxicity in this
patient?
โข Serum Ca: 13.5mg/dl (the patient said that he
increased the dose of Alphacalcidol and Ca carbonate
by his own because he felt bony pains).
31. J Am Soc Nephrol 21: 1418โ1420, 2010.
โข Narrow therapeutic window
โข Long half-life
โข Potential for lethal arrhythmias (especially in
the context of HD-induced hypokalemia)
34. Case 4 52 years old female. HTN, Hypothyroidisn, ESRD
on maintenance HD.
โข The patient medications:
โข ESA
โข Ca carbonate
โข Felodipine
โข L-Thyroxine 75 mcg/d
(Last Ix 2 months ago:
TSH โค 2 mIU/L, FT4 = 1.5
ng/dL)
โข The patient started to complaint
of:
โข Drowsiness
โข Headache
โข Anorexia
โข Constipation
โข Somnolence
โข TSH = 9.8 mIU/L mIU/L
โข FT4 = 0.2 ng/dL
โข Reassessment after 4 weeks:
โข Persisting symptoms
โข Persisting Lab indication of
hypothyroidism
โข L-Thyroxine dose increased to
100 mcg/d
โข L-Thyroxine dose increased to
150 mcg/d
35. Case 4 52 years old female. HTN, Hypothyroidisn, ESRD
on maintenance HD.
โข The patient medications:
โข ESA
โข Ca carbonate
โข Felodipine
โข L-Thyroxine 75 mcg/d
(Last Ix 2 months ago:
TSH โค 2 mIU/L, FT4 = 1.5
ng/dL)
โข The patient started to complaint
of:
โข Drowsiness
โข Headache
โข Anorexia
โข Constipation
โข Somnolence
โข TSH = 9.8 mIU/L mIU/L
โข FT4 = 0.2 ng/dL
โข Reassessment after 4 weeks:
โข Persisting symptoms
โข Persisting Lab indication of
hypothyroidism
โข L-Thyroxine dose increased to
100 mcg/d
โข L-Thyroxine dose increased to
150 mcg/d
What is the cause of ineffective L-thyroxine
therapy?
36. What is the cause of ineffective L-thyroxine
therapy?
Case 4 52 years old female. HTN, Hypothyroidisn, ESRD
on maintenance HD.
โข The patient was taking Ca carbonate & L-Thyroxine
pills at the same time
37. L-Thyroxine & Ca Carbonate
L-Thyroxine adsorbs to calcium carbonate
in an acidic environment, which may reduce
its bioavailability
Separate the doses of the thyroid product
and the oral calcium supplement by at least
4 hours.
P V Eligar. The West London Medical Journal. Vol 3 No 4 pp 9 -14, 2011
2015