CIRRHOSIS PUD CHF DIABETES KIDNEY HTN באכב CORRONARY · 2018. 12. 13. · Tramadol Hydrochloride TRAMADEX OD - - TRAMADEX TRAMAL TRAMAL RETARD +/b,c *-- Can be used only at CKD

HTN

| 0

1

KID

NEY

| 0

2

DIAB

ETES

| 0

3

CORR

ONAR

Y / CH

F |

04

PUD

| 0

5

CIRR

HOSI

S |

06

בכאבבחולה המורכב

אמנותהטיפול התרופתי

ינואר 2018

בדבל

אי פו

רות

צול

תוכן עניינים: 01 ........................................................ Pain Treatment + HTN | פרופ׳ אהוד גרוסמן

02 ......................................................... Pain Treatment + Kidney | פרופ׳ עדי לייבה

03 ....................................................... Pain Treatment + Diabetes | ד״ר יצחק ברוך

04 ....................... Pain Treatment + Coronary & CHF | ד״ר זאזא יעקבישוילי

05 ................................................................ Pain Treatment + PUD | פרופ׳ רם דיקמן

06 .................................................. Pain Treatment + Cirrhosis | ד״ר לי גולדשטיין

07 ............ Summary: Phamacologic Pain Treatment In High Risk Patients

60

PAIN TREATMENT + HTNפרופ׳ אהוד גרוסמן

HTN

| 0

1

TREATMENT GROUPS GENERIC NAME NAME OF DRUG HTN REMARKS

NON-OPIOIDSANALGESICS

Dipyrone OPTALGIN +1

Paracetamol ACAMOLDEXAMOL + *

One study showed BP increase with acamol 2

PAIN TREATMENT + HTN References:

1. Grossman A, Messerli FH, Grossman E. Drug induced hypertension - An unappreciated cause of secondary hypertension. Eur J Pharmacol. 2015;763:15-22. Day RO et al. BMJ 2013; f3195.

2. Sudano I, et al. Acetaminophen increases blood pressure in patients with coronary artery disease. Circulation. 2010;122:1789-96.

3. Breivik H. Treat the Whole Patient and Be Aware of Drug Interactions. Journal of Pain & Palliative Care Pharmacotherapy. 2015;29:70-71.

4. Laubie M, et al. Central sites and mechanisms of the hypotensive and bradycardic effects of the narcotic analgesic agent fentanyl. Naunyn Schmiedebergs Arch Pharmacol. 1977;296:255-61.

5. Mitaka C, et al. Comparison of hemodynamic effects of morphine, butorphanol, buprenorphine and pentazocine on ICU patients. Bull Tokyo Med Dent Univ. 1985;32:31-9.

6. Buckley NA, Dawson AH, et al. Br Med J. 2014;348:g1626.7. Boyer EW, Shannon M. N Engl J Med. 2005;352(11):1112-20.8. Jette N, Veregin T, Guberman A. Carbamazepine - induced hypertension.

Neurology 2002;59:275-6 .

MILD pain

Vas 1-3

Use with caution, usual dose Reduce dose Increase dosing interval Safe to use Not recommended Remarks

*- + b a c

PAIN TREATMENT + HTN

˚נייר עמדה לטיפול בכאב סביב ניתוח )ינואר 2017))ישנן תרופות נוספות במאגר התרופות של משרד הבריאות שאינן מופיעות ברשימה זו)

HTN

| 0

1

HTN

| 0

1


NSAIDs & COXIBs

Paracetamol + Ibuprofen COMBODEX - * One study showed BP increase with acamol 1,2

Naproxen NAXYN - 1

DiclofenacABITREN VOLTAREN BETAREN

- 1

IbuprofenIBUFEN NUROFEN ADEX

- 1

Etodolac ETOPAN - 1

Celecoxib CELCOX - * In most studies celcox was better than other NSAIDs 1

Etoricoxib ARCOXIA - 1

Piroxicam as ß-Cyclodextrin BREXIN - 1

Lornoxicam XEFO - 1


WEEKOPIOIDS

Buprenorphine BUTRANS + 1

Tramadol Hydrochloride

TRAMADEX OD TRAMADEX TRAMAL TRAMAL RETARDTRAMADEX DROPS TRAMADEX FLASHTAB

+ 3

Tramadol + Paracetamol ZALDIAR + *One study showed BP increase with acamol 2

Codeine CODEINE + *No study that shows elevation of blood pressure

Codeine Phosphate + Paracetamol

COD ACAMOL COD ACAMOL FORTE CODABROL

+ *One study showed BP increase with acamol 2

Paracetamol + Codeine + Caffeine

ROKACET ROKACET PLUS + *

One study showed BP increase with acamol 2

MODERATE pain

Vas 4-6MODERATE pain

Vas 4-6 PAIN TREATMENT + HTN PAIN TREATMENT + HTN


*- + b a cUse with caution, usual dose Reduce dose Increase dosing interval Safe to use Not recommended Remarks

*- + b a c

HTN

| 0

1

HTN

| 0

1


TRICYCLIC ANTIDEPRESSANTS

Clomipramine /Mianserin /Desipramine /Amitriptyline Dexepin / Nortryptylin / Trimiprane / Imipramine

ANAFRANIL / BONSERIN/ DEPREXAN / ELATROL/ GILEX / NORTYLIN / SURMONTIL / TOFRANIL

- 1

SSRI ANTIDEPRESSANTS

Escitalopram / Citalopram/Fluvoxamine / Sertraline /Paroxetive / Fluoxetine

CIPRALEX / CIPRAMIL / FAVOXIL / LUSTRAL / SEROXAT / PROZAC

+ *May cause serotonin syndrome when used with high dose of opioids 1,6,7

SNRI ANTIDEPRESSANTS

Duloxetine Venlafaxine Milnacipran

CYMBALTA / VIEPAX / EFEXOR / IXEL - * BP increase is dose dependent

(above 300 mg/day of Venlafaxine) 1

ANTI- CONVULSANTS

Pregabalin LYRICA / PREGABALIN DEXCEL + 1

Gabapentinoids GABAPENTIN + 1

Carbamazepine TEGRETOL + *There is a case report of BP increase with Carbamazepine 8

BENZO- DIAZIPINES

Clonazepam / Midazolam /Alprazolam / Diazepam /Clobazam

CLONEX / BUCCOLAM / RIVOTRIL / ALPRALID / ASSIVAL / FRISIUM / VABEN / XANAGIS / XANAX

+ 1


STRONGOPIOIDS

Fentanyl FENTA + 4

Fentanyl Citrate

ABSTRAL ACTIQ BREAKYL FENTORA PECFENT

+ 4

Methadone ADOLANMETHADONE + *

No study that shows elevation of blood pressure

Morphine Sulphate MCRMIR ORAMORPH + 5

OxycodoneOXYCOD OXYCOD FORTE OXYCONTIN

+ *No study that shows elevation of blood pressure

Oxycodone + Naloxone TARGIN + *No study that shows elevation of blood pressure

Oxycodone + Paracetamol PERCOCET + *One study showed BP increase with acamol 2

PAIN TREATMENT + HTN PAIN TREATMENT + HTNSevere pain

Vas 7-10OTHERS



*- + b a c

HTN

| 0

1

HTN

| 0

1

PAIN TREATMENT + KIDNEYפרופ׳ עדי לייבה

KID

NEY

| 0

2

PAIN TREATMENT + KIDNEY References:

1. Stueber T et al. The use of dipyrone in the ICU is associated with acute kidney injury: A retrospective cohort analysis. Eur J Ansthesiol. 2017.

2. Sandler DP, Smith JC, Weinberg CR et al. Analgesic use and chronic renal disease. N Eng J Med 1989;320:1238.

3. Filitz J, Griessinger N, Sittl R, et al. Effect of intermittent hemodialysis on buprenorphine and norbuprenorphine plasma concentration in chronic pain patients treated with transdermal buprenorphine. Eur J Pain 2006; 10:743.

4. Gibson TP.Pharmacokinetics, efficacy and safety of analgesia with a focus on tramadol HCL. Am J Med 1996;101:47S.

5. Lintz W, Erlacin S, Frankus E,Uragg H. Biotransformation of tramadol in man and animal (Author’s trans.). Arzeneimittelforschung 1981;31:1932.

6. Barnes JN, Goodwin FJ. Dihydrocodeine narcosis in renal failure. Br Med J (Clin Res Ed) 1983;286:438.

7. Guay DR, Awni WM, Findlay JW et al. Pharmacokinetics and pharmacodynamics of codeine in ESRD. Clin Pharmacol Ther 1988;43:63.

8. Noels LM, Elseviers MM, de Broe ME. Impact of legislative measures on the sales of analgesics and the subsequent prevalence of analgesic nephropathy: A comparative study in France, Sweden and Belgium. Nephrol Dial Transplant 1995;10:167.

9. Ibanez L, Morlans M, Vidal X et al. Case control study of regular analgesics and NSAID use and ESRD. Kidney Int 2005;67:2393.

10. Bennett WM, Henrich WL, Stoff JS. The renal effects of NSAIDS: summary and recommendations. Am J Kid Dis 1996;28:S56.

11. Wagner EH. NSAIDS and renal disease--Still unsettled. Ann Intern Med 1991;115:227.

12. Schwartz A, Krause PH, Kunzendorf U, et al. The outcome of acute interstitial nephritis: risk factors for the transition from acute to chronic interstitial nephritis. Clin Nephrol 2000;54:179.

13. Perazella MA, Eras J. Are selective COX-2 inhibitors nephrotoxic? Am J Kid Dis. 2000;35(5).937.

14. Gurwitz JH, Avorn J, Ross-Degnan D, et al. NSAIDS associated azotemia in the very old. JAMA 1990,264(4):471-5.

15. Koehntop DE, Rodman JH. Fentanyl pharmacokinetics in patients undergoing renal transplantation. Pharmacotherapy 1997;17:746.

16. Bower S. Plasma protein binding of fentanyl: the effect of hyperlipoproteinemia and chronic renal failure. J Pharm Pharmacol 1982;34:102.

17. Kreek MJ, Schecter AJ, Gutjahr CL, Hecht M. Methadone use in patients with chronic renal disease. Drug Alcohol depend 1980;5:197.

18. Wolff J, Bigler D, Christensen CB, et al. Influence of renal function on the elimination of morphine and morphine glucuronides. Eur J Clin Pharmacol 1988;34:353.

19. Foral PA, Ineck JR, Nystrom KK. Oxycodone accumulation in a hemodialysis patient. South Med J. 2007.

20. Kirvela M, Lindgren L, Seppala T, Olkkola KT. The pharmacokinetics of oxycodone in uremic patients undergoing renal transplantation. J Clin Anesth 1996;8:13.

21. Mclaughlin JK, Lipworth L, Chow WH, Blot WJ. Analgesic use and chronic renal failure: a critical review of the epidemiologic literature: Kidney International 1998;54:679.

22. Pilowsky I, Hallett EC, Bassett DL, Thomas PG, Penhall RK. A controlled study of amitriptyline in the treatment of chronic pain. Pain. 1982; 14(2):169.

23. Aiyer R, Barkin RL and Bhatia A et al. Treatment of neuropathic pain with venlafaxine: A systematic review. Pain Med 2017; 18(10):1999.

24. Randinitis EJ, Posvar EL, Alvey CW, Sedman AJ, Cook JA and Bockbrader HN et al. Pharmacokinetics of pregabalin in subjects with various degrees of renal function. J Clin Pharmacol. 2003; 43(3):277.

25. Tramadol Drug Information.26. MDRD GFR Calculator: http://nephron.org/mdrd_gfr_si.

MILD pain

Vas 1-3

TREATMENT GROUPS GENERIC NAME NAME OF DRUG CKD 3-5 CKD 5 HD/PD REMARKS


Dipyrone OPTALGIN + / a + / a *No drug removal on dialysis 1

Paracetamol ACAMOLDEXAMOL + / a + / a *

No drug removal on dialysis 2



*- + b a c

CKD: Chronic Kidney DiseaseHD: HemodialysisPD: Peritoneal Dialysis

CKD Stage 3 (eGFR) = 30-59CKD Stage 4 (eGFR) = 15-29

CKD Stage 5 (eGFR) < 15CKD Stage 5D (eGFR) < 15 on dialysis

Calculate eGFR in ml/min/1.73m2 according to MDRD formula, using age / sex / race / updated plasma creatinine (http://nephron.org/mdrd_gfr_si): 26

KID

NEY

| 0

2

KID

NEY

| 0

2

MODERATE pain

Vas 4-6


NSAIDs & COXIBs

Paracetamol + Ibuprofen COMBODEX - - 9

Naproxen NAXYN - - 10


- - 2


- - 11

Etodolac ETOPAN - - 12

Celecoxib CELCOX - - 13

Etoricoxib ARCOXIA - - 13

Piroxicam as ß-Cyclodextrin BREXIN - -

Lornoxicam XEFO - - 14


WEEKOPIOIDS

Buprenorphine BUTRANS + / a + / a * No drug removal on dialysis 3


TRAMADEX OD - -

TRAMADEX TRAMALTRAMAL RETARD

+ / b,c * -- Can be used only at CKD 3- Not recommended at CKD 4-5 25

TRAMADEX DROPS TRAMADEX FLASHTAB + / b,c + / b,c

Tramadol + Paracetamol ZALDIAR + / b,c + / b,c 25

Codeine CODEINE - - 6



- - 7


ROKACET ROKACET PLUS - - 8

MODERATE pain

Vas 4-6

KID

NEY

| 0

2

KID

NEY

| 0

2

PAIN TREATMENT + KIDNEY PAIN TREATMENT + KIDNEY



*- + b a c




Calculate eGFR in ml/min/1.73m2 according to MDRD formula, using age / sex / race / updated plasma creatinine (http://nephron.org/mdrd_gfr_si): 26 CKD: Chronic Kidney Disease

HD: HemodialysisPD: Peritoneal Dialysis




KID

NEY

| 0

2

KID

NEY

| 0

2

PAIN TREATMENT + KIDNEYSevere pain

Vas 7-10


STRONGOPIOIDS

Fentanyl FENTA + / a + / a *No drug removal on dialysis 15

Fentanyl Citrate


+ / a + / a *No drug removal on dialysis 16

Methadone ADOLANMETHADONE + / a + / a *

No drug removal on dialysis 17

Morphine Sulphate MCRMIR ORAMORPH - - 18


+ / b + / b *Partial drug removal on dialysis 19

Oxycodone + Naloxone TARGIN + / b + / b *Partial drug removal on dialysis 20

Oxycodone + Paracetamol PERCOCET + / c + / c *Partial drug removal on dialysis 21





- - 22




- * - * No info



CYMBALTA / VIEPAX / EFEXOR / IXEL - - 23

ANTI- CONVULSANTS

Pregabalin LYRICA / PREGABALIN DEXCEL + / b,c + / b,c *

Partial drug removal on dialysis 24

Gabapentinoids GABAPENTIN + / b,c + / b,c *Partial drug removal on dialysis 24

Carbamazepine TEGRETOL + + / b *Minimal drug removal on dialysis 24

BENZO- DIAZIPINES



+ / a * + / a * No drug removal on dialysis

OTHERS PAIN TREATMENT + KIDNEY


*- + b a c




Calculate eGFR in ml/min/1.73m2 according to MDRD formula, using age / sex / race / updated plasma creatinine (http://nephron.org/mdrd_gfr_si): 26CKD: Chronic Kidney Disease

HD: HemodialysisPD: Peritoneal Dialysis





*- + b a c

KID

NEY

| 0

2

KID

NEY

| 0

2

PAIN TREATMENT + DIABETESד״ר יצחק ברוך

DIAB

ETES

| 0

3

DIAB

ETES

| 0

3

DIAB

ETES

| 0

3

TREATMENT GROUPS GENERIC NAME NAME OF DRUG DIABETES REMARKS


Dipyrone OPTALGIN +1,2


Long term use of paracetamol can cause hyperglycemia 3,4,5

References:

1. FDA approved drugs; Feb; 2017. Drugs. Com, Clinical Pharmacology; 2017.2. PLOS One; 2015.3. Drugs.com; 2017. 4. JAMA Pediatrics; Am J Dis Child.1966;112(6).5. Maahs DM et al. Effect of paracetamol on CGM Glucose in an Outpatient

Setting.Diabetes Care: [2 pages], 12 Aug 2015.6. FDA approved drugs; Rxlist; John P. Cunha, 20167. Oman Med J, 2010; Joslin Diabetes Center; 2017.8. Pamela Natalia Bellucci et al. Potential Effects of Nonsteroidal Anti-

Inflamatory Drugs in the prevention and Treatment of type 2 Diabetes mellitus ; Journal of Pharmacy Practice 2017, Vol.30(5):549-556.

9. J Li et al. Non- steroidal anti - inflammatory drugs increase insulin release from beta cells by inhibiting ATP - sensitive potassium channels, Br J of Pharmacology (2007)151:483-493.

10. Br J Clin Pharmacol; 1981. Diab Med. 2015.11. Maahs DM et al. Effect of paracetamol on CGM Glucose in an Outpatient

Setting. Diabetes Care: [2 pages], 12 Aug 2015.12. Simpson et al. Diabetes care 39(9):2016.13. Diabetes News Journal; Jan 2015; Haggstrom 2014; WikiJournal of

Medicine; J Fam Pract. 2012 November; 61(11).14. medicalook.com. J Fam Prac. 2012 Nov;6(11)15. FDA approved drugs; 2017; J Fam Pract. 2012 November: 6(11).

16. Roopan S, Larsen ER et al. Use of Antidepressants in patients with depression and comorbid diabetes mellitus: a systemic review; Acta Neuropsychiatrica 2017, DOI: 10.1017/ neu. 2016.54.

17. Hardy et al. Does treatment with Duloxetine for neuropathic pain impact glicemic control?; Diabetes Care, Jan 2007, Vol.30, Issue1; 21-26.

18. Boyle J et al. Randomized, placebo-controlled comparison of Amitriptyline, Duloxetine, and Pregabalin in patients with chronic diabetic peripheral neuropathic pain. Diabetes Care 2012 Dec;35(12):2451-8. Epub 2012, Sep 18 .

19. Joep H. G. Scholl, Rike van Eekeren and Eugène P. van Puijenbroek et al. Six cases of (severe) hypoglycaemia associated with gabapentin use in both diabetic and non-diabetic patients. BJCP, 2015 May: Vol 79(5); 870-871.

20. Avanish Jha, Kundavaram Paul Prabhakar Abhilash, Rini Bandhyopadhyay, and Peter John Victor et al. Hypoglycemia - A rare complication of carbamazepine overdose. Indian J Pharmacol. 2014 Nov-Dec; 46(6): 651-652.

21. VS Salice FV, Valenza MP, Pizzocri LV, Valenti GC, Chevallard MU, Umbrello SG, Gatti SF, Fargion GI, Iapichno and LG Gattinoni. Benzodiazepines induce hyperglycemia in rats by affecting peripheral disposal of glucose. Crit Care. 2013; 17(Suppl 2): 385.

22. Takeda; PI; Medicines.ie. J Fam Pract .2012.Nov;6 (11).

MILD pain

Vas 1-3


PAIN TREATMENT + DIABETES


*- + b a c

DIAB

ETES

| 0

3

DIAB

ETES

| 0

3


NSAIDs & COXIBs

Etodolac ETOPAN + *

- Caution is needed in diabetic patients who suffer from kidney failure

- Use for short period of time - Use with glocose-lowering compounds can induce

hypoglycemia 3,8,9

Celecoxib CELCOX + *



hypoglycemia 3,8,9

Etoricoxib ARCOXIA - *



hypoglycemia 8,9,14

Piroxicam as ß-Cyclodextrin BREXIN + *



hypoglycemia 3,8,9

Lornoxicam XEFO + *



hypoglycemia 8,9,22


NSAIDs & COXIBs

Paracetamol + Ibuprofen COMBODEX + *



hypoglycemia - Long term use of paracetamol can cause

hyperglycemia 5,7,8,9

Naproxen NAXYN + *



hypoglycemia 8,9,10

DiclofenacABITRENVOLTARENBETAREN

+ *



hypoglycemia 3,8,9

IbuprofenIBUFENNUROFENADEX

+ *



hypoglycemia 7,8,9

MODERATE pain

Vas 4-6 PAIN TREATMENT + DIABETESMODERATE pain

Vas 4-6 PAIN TREATMENT + DIABETES



*- + b a c

DIAB

ETES

| 0

3

DIAB

ETES

| 0

3


STRONGOPIOIDS

Fentanyl FENTA + 1

Fentanyl Citrate


+ 1

Methadone ADOLANMETHADONE + 3



+ 15

Oxycodone + Naloxone TARGIN + 1

Oxycodone + Paracetamol PERCOCET + *Long term use of paracetamol can cause hyperglycemia 3,5

MODERATE pain

Vas 4-6


WEEKOPIOIDS




+ 13

Tramadol + Paracetamol ZALDIAR + *Long term use of paracetamol can cause hyperglycemia 3,5

Codeine CODEINE + 6



+ *Long term use of paracetamol can cause hyperglycemia 1,5


ROKACET ROKACET PLUS + *

Long term use of paracetamol can cause hyperglycemia 1,5

Severe pain

Vas 7-10 PAIN TREATMENT + DIABETES PAIN TREATMENT + DIABETES



*- + b a c

DIAB

ETES

| 0

3

DIAB

ETES

| 0

3

OTHERS PAIN TREATMENT + DIABETESTREATMENT GROUPS GENERIC NAME NAME OF DRUG DIABETES REMARKS

ANTI- CONVULSANTS

Pregabalin LYRICA PREGABALIN DEXCEL + *

Long term use in high doses can cause hyperglycemia (600 mg only) 18

Gabapentinoids GABAPENTIN + * Can cause hypoglycemia 19

Carbamazepine TEGRETOL + * High doses can cause hypoglycemia (rare) 20

BENZO- DIAZIPINES

Clonazepam CLONEXBUCCOLAMRIVOTRILALPRALIDASSIVAL FRISIUMVABEN XANAGIS XANAX

+ * Can cause hyperglycemia in rats 21

MidazolamAlprazolamDiazepamClobazamOxazepam

OTHERS



ClomipramineMianserinDesipramineAmitriptylineDexepinNortryptylinTrimipraneImipramine

ANAFRANILBONSERIN DEPREXAN ELATROLGILEXNORTYLIN SURMONTIL TOFRANIL

+ *Long term use in high doses can cause hyperglycemia

16


EscitalopramCitalopramFluvoxamineSertralineParoxetive

CIPRALEXCIPRAMIL FAVOXIL LUSTRALSEROXAT PROZAC

+ 16



CYMBALTAVIEPAXEFEXOR IXEL

+ *- Risk of increase in nocturnal blood glucose- Duloxetine can cause hyperglycemia- Long term use may increase A1C levels 17,18

PAIN TREATMENT + DIABETES



*- + b a c

PAIN TREATMENT + Corronary/ CHFד״ר זאזא יעקבישוילי

CORR

ONAR

Y / CH

F |

04

TREATMENT GROUPS GENERIC NAME NAME OF DRUG Coronary / CHF REMARKS


Dipyrone OPTALGIN +1,2


New clinical study RCT from Spain- sodium salts cause increase in blood pressure 3

References:

01. Schmitz et al., Dipyrone (metamizole) markedly interferes with platelet inhibition by aspirin in patients with acute and chronic pain: A case-control study.

(https://insights-ovid-com.beilinson-ez.medlcp.tau.ac.il/pubmed? pmid=28030443)

02. Polzin et al., Prevention of dipyrone (metamizole) induced inhibition of aspirin antiplatelet effects.

(https://insights-ovid-com.beilinson-ez.medlcp.tau.ac.il/pubmed? pmid=25789542&isFromRelatedArticle=Y)

03. Fanelli et al, Ther Adv Drug Saf 2017, Vol. 8(6) 173-182 (https://www-ncbi-nlm-nih-gov.beilinson-ez.medlcp.tau.ac.il/pmc/articles/

PMC5455842/pdf/10.1177_2042098617690485.pdf)04. BMJ 2016 (http://www.bmj.com.beilinson-ez.medlcp.tau.ac.il/content/354/

bmj.i4857.long)05. https://www-ncbi-nlm-nih-gov.beilinson-ez.medlcp.tau.ac.il/pubmed/21516735.06. Joseph P et al. DOI: 10.111/j.1533-2500.2008.00204.x; Opioids and the

management of chronic severe pain in the elderly.

07. http://onlinelibrary.wiley.com.beilinson-ez.medlcp.tau.ac.il/doi/10.1111/j. 1533-2500.2008.00204.x/epdf

08. HYPERLINK “https://www-ncbi-nlm-nih-gov.beilinson-ez.medlcp.tau.ac.il/pubmed/28616956” \o “The Cochrane database of systematic reviews.” Cochrane Database Syst Rev. 2017 Jun 15;6:CD003726. DOI: 10.1002/14651858.CD003726.pub4.

09. Tramadol for neuropathic pain in adults.10. http://onlinelibrary.wiley.com/doi/10.1002/phar.1646/

abstract;jsessionid=600D3406268896A1F9A7F3C76EEC3F1A.f04t03.11. http://www.eurekaselect.com/120174/article.12. DOI: 10.1016/j.pcad.2015.11.003. Epub 2015 Nov 10.13. DOI: 10.2147/PPA. S16358.14. DOI: 10.1002/pds.2186.15. DOI: 10.1016/j.clinthera.2013.10.11.16. DOI: 10.3904/kjim.2016.282. (https://doi-org.beilinson-ez.medlcp.tau.ac.il/10.1016/j.

atherosclerosis.2014.05.918)

MILD pain

Vas 1-3


PAIN TREATMENT + CORRONARY / CHF


*- + b a c

CORR

ONAR

Y / CH

F |

04

CORR

ONAR

Y / CH

F |

04

PAIN TREATMENT + CORRONARY / CHFTREATMENT GROUPS GENERIC NAME NAME OF DRUG Coronary / CHF REMARKS

NSAIDs & COXIBs

Paracetamol + Ibuprofen COMBODEX - 4

Naproxen NAXYN - 4


- 4


- 4

Etodolac ETOPAN - 4

Celecoxib CELCOX - 4

Etoricoxib ARCOXIA - 4

Piroxicam as ß-Cyclodextrin BREXIN - 4

Lornoxicam XEFO - * One positive Russian study, but no western studies 5

MODERATE pain

Vas 4-6


WEEKOPIOIDS




+ 7,8,9

Tramadol + Paracetamol ZALDIAR + 7,8,9

Codeine CODEINE + 10



+ 10


ROKACET ROKACET PLUS + 10

MODERATE pain

Vas 4-6 PAIN TREATMENT + CORRONARY / CHF



*- + b a c

CORR

ONAR

Y / CH

F |

04

CORR

ONAR

Y / CH

F |

04

OTHERS PAIN TREATMENT + CORRONARY / CHFTREATMENT GROUPS GENERIC NAME NAME OF DRUG Coronary / CHF REMARKS

STRONGOPIOIDS

Fentanyl FENTA + 11

Fentanyl Citrate


+ 11

Methadone ADOLANMETHADONE + 11



+ 11

Oxycodone + Naloxone TARGIN + 1

Oxycodone + Paracetamol PERCOCET + 6

Severe pain

Vas 7-10





- 12




+ *Sertraline most safe, others are associated with greater QTc prolongation, all of them potentiate bleeding risk of antiplatelets 12



CYMBALTA / VIEPAX / EFEXOR / IXEL + *

Hypertension may be the problem, hepatic and renal disease are problem for duloxetine at least 12,13

ANTI- CONVULSANTS

Pregabalin LYRICA / PREGABALIN DEXCEL + *

Pregabalin in a large cohort of older patients with a seizure disorder, was not associated with an increased risk of heart failure relative to Gabapentin 14

Gabapentinoids GABAPENTIN + * Gabapentin safe in terms of QTc 15

Carbamazepine TEGRETOL + * Carbamazepine is relatively safe for CV system,but valproate may be better - observational data 14

BENZO- DIAZIPINES



+ *Even may decrease CV mortality and heart failure 16

PAIN TREATMENT + CORRONARY / CHF



*- + b a c

CORR

ONAR

Y / CH

F |

04

CORR

ONAR

Y / CH

F |

04

PAIN TREATMENT + PUDד״ר לי גולדשטייןפרופ׳ רם דיקמן

PUD

| 0

5

1. Epidemiology. 12:570-576 2001.2. Am J Gastroenterol 2009;104:728-38. 3. Clinical Medicine & Research Volume 5, Number 1: 19-34.4. N Engl J Med 2000;343:1520-8. 5. Clin Gastroenterol Hepatol. 4:1082-1089 2006.6. Drug Saf. 35 (2012) 1127-1146.7. Lancet 2004;364:665-74. 8. JAMA 2000;284:1247-1255. 9. Am J Gastroenterol 2005; 100:664-671.10. Prim Care Companion J Clin Psychiatry. 2001 Feb; 3(1): 22-2711. Am J Gastroenterol 2014; 109:811-819.12. J Clin Psychiatry. 2010 Dec; 71(12):1565-75. Medicine (Baltimore).13. 2015 Nov; 94(46), Psychother Psychosom 2016; 85:270-288.

14. PLoS Medicine. 2017;14(8):e1002369. doi:10.1371/journal.pmed.1002369.15. J Pain Res. 2017 Nov 1;10:2547-2563.16. Expert Opinion on Orphan Drugs (2015) 14(11):1703-1724. 17. Aliment Pharmacol Ther 10, 151-156.18. Drug Safety, 14:11, 1703-1724.19. Am J Gastroenterol 2011; 106:835-842.20. PHYSICIAN’S LEAFLET TRAMADEX OD 100 / 200 /300 – Prolonged Released

Tablets.21. Medicines and Healthcare Products Regulatory Agency.22. United European Gastroenterology Journal 2017, Vol. 5(4) 588-600. 23. US Drug Enforcement Administration Automation of Reports and Consolidated

Orders System (ARCOS); (www.deadiversion.usdoj.gov/ arcos/retail_drug_summary/index.html)

TREATMENT GROUPS GENERIC NAME NAME OF DRUG PUD REMARKS


Dipyrone OPTALGIN +1

Paracetamol ACAMOLDEXAMOL + 1

PAIN TREATMENT + PUD References:

MILD pain

Vas 1-3



*- + b a c

PUD

| 0

5

PUD

| 0

5

MODERATE pain

Vas 4-6MODERATE pain

Vas 4-6


NSAIDs & COXIBs

Paracetamol + Ibuprofen COMBODEX + *May cause dyspepsia, upper and lower GI bleeding or ulceration and exacerbation of quiescent IBD 2,3

Naproxen NAXYN + *May cause dyspepsia, upper and lower GI bleeding or ulceration and exacerbation of quiescent IBD 2,3,4,5


+ *May cause dyspepsia, upper and lower GI bleeding or ulceration and exacerbation of quiescent IBD 2,5,6


+ *Most safe non selective NSAID but still may cause dyspepsia, upper and lower GI bleeding or ulceration and exacerbation of quiescent IBD 2,3,7

Etodolac ETOPAN + *May cause dyspepsia, upper and lower GI bleeding or ulceration and exacerbation of quiescent IBD 3

Celecoxib CELCOX + *Cox-2 loose their protective effect if co-administrated with Aspirin 2,3,8

Etoricoxib ARCOXIA + *May cause dyspepsia, upper and lower GI bleeding or ulceration and exacerbation of quiescent IBD 2,3,6

BREXIN

Piroxicam as Beta-Cyclodextrin (Brexin) is safer than Piroxicam alone should be viewed as a CV safe anti-inflmmatory compound and a GI safer alternative to Piroxicam. Piroxicam alone is the most dangerous non selective NSAID. Piroxicam causes dyspepsia, upper and lower GI bleeding or ulceration and exacerbation of quiescent IBD. Head to head comparisons between Piroxicam as Beta-Cyclodextrin (Brexin) and other NSAID’s are limited. 2,3,5

Piroxicam as ß-Cyclodextrin + *

Lornoxicam XEFO + * Safer than Naxin, limited data 17


WEEKOPIOIDS

Buprenorphine BUTRANS + * May cause constipation, nausea, abdominal pain, bloating

and vomiting 19



+ * As compared to strong opioids, this drug causes less

pronaunced constipation, nausea, abdominal pain, bloating and vomiting 20

Tramadol + Paracetamol ZALDIAR + *May cause constipation, nausea, abdominal pain, bloating and vomiting 21

Codeine CODEINE + * May cause constipation, nausea, abdominal pain, bloating

and vomiting 19,22



+ *May cause constipation, nausea, abdominal pain, bloating and vomiting 19


ROKACET ROKACET PLUS + May cause constipation, nausea, abdominal pain, bloating

and vomiting 22

PAIN TREATMENT + PUD PAIN TREATMENT + PUD



*- + b a c

PUD

| 0

5

PUD

| 0

5

Severe pain

Vas 7-10

PUD

| 0

5

PUD

| 0

5





+ * May cause constipation 9




+ *May cause upper GI bleeding, ulceration and diarrhea 10,11,12,13



CYMBALTA / VIEPAX / EFEXOR / IXEL + *

May cause upper GI bleeding, ulceration and diarrhea 13

ANTI- CONVULSANTS

Pregabalin LYRICA / PREGABALIN DEXCEL + * No common GI side effects 14

Gabapentinoids GABAPENTIN + *Common (1% to 10%): diarrhea, dry mouth or throat, constipation, nausea, vomiting, dyspepsia, dental abnormalities, gingivitis, abdominal pain, flatulence 15

Carbamazepine TEGRETOL + * Very common (10% or more): nausea (29%), vomiting (18%), constipation (10%)16

BENZO- DIAZIPINES



+ * No common GI side effects 18

OTHERS PAIN TREATMENT + PUDPAIN TREATMENT + PUDTREATMENT GROUPS GENERIC NAME NAME OF DRUG PUD REMARKS

STRONGOPIOIDS

Fentanyl FENTA + *

- As a rule for all opioids: regular use of strong opioids - More side effects. Thus, use the lowest dose & the shortest

duration, possibly - As a rule for all opioids: these drugs may cause constipation,

nausea, abdominal pain, bloating and vomiting 22

Fentanyl CitrateABSTRAL / ACTIQ / BREAKYL / FENTORA / PECFENT

+ *May cause constipation, nausea, abdominal pain, bloating and vomiting 22,23

Methadone ADOLANMETHADONE - *

In addition to constipation, nausea, abdominal pain, bloating and vomiting, this drug has unpredictable effects due to undesired accumulation effects 23

Morphine Sulphate MCRMIR ORAMORPH + *

More pronounced constipation, nausea and vomiting as compared to Oxycodine 23


+ *This drug may cause constipation, nausea, abdominal pain, bloating and vomiting 23

Oxycodone + Naloxone TARGIN + *Cause less constipation than oxycodone without naloxone but still may cause constipation, nausea, abdominal pain, bloating and vomiting 22

Oxycodone + Paracetamol PERCOCET + * May cause constipation, nausea and vomiting 22



*- + b a c

PUD

| 0

5

PUD

| 0

5

PAIN TREATMENT + CIRRHOSISד״ר לי גולדשטייןד״ר לי גולדשטיין

CIRR

HOSI

S |

06

References:1. Kotb HI, el-Kabsh MY, Emara SE, Fouad EA. Pharmacokinetics of controlled release

morphine (MST) in patients with liver cirrhosis. Br J Anaesth. 1997;79(6):804-806. 0

2. Mazoit JX, Sandouk P, Zetlaoui P, Scherrmann JM. Pharmacokinetics of unchanged morphine in normal and cirrhotic subjects. Anesth Analg. 1987;66(4):293-298.

3. Bosilkovska M, Walder B, Besson M, Daali Y, Desmeules J. Analgesics in patients with hepatic impairment: pharmacology and clinical implications. Drugs. 2012;72(12):1645-1669.

4. Tegeder I, Lotsch J, Geisslinger G. Pharmacokinetics of opioids in liver disease. Clin Pharmacokinet. 1999;37(1):17-40.

5. Hasselstrom J, Eriksson2 S, Persson ’ A, Rane3 A, Svensson J 0, Sawe J. The metabolism and bioavailability of morphine in patients with severe liver cirrhosis. Br J clin Pharmac. 1990;29:289-297.

6. Malhotra, PhD BK, Schoenhard, PhD GL, de Kater, PhD AW, Friedmann, PhD, MD N. The pharmacokinetics of oxycodone and its metabolites following single oral doses of Remoxy®, an abuse-deterrent formulation of extended-release oxycodone, in patients with hepatic or renal impairment. J Opioid Manag. 2015;11(2):157-169.

7. Tallgren M, Olkkola KT, Seppälä T, Höckerstedt K, Lindgren L. Pharmacokinetics and ventilatory effects of oxycodone before and after liver transplantation. Clin Pharmacol Ther. 1997;61(6):655-661.

8. Chandok N, Watt KDS. Pain management in the cirrhotic patient: the clinical challenge. Mayo Clin Proc. 2010;85(5):451-458.

9. Lee CR, McTavish D, Sorkin EM. Tramadol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states. Drugs. 1993;46(2):313-340.

10. Frye R, Zgheib N, Matzke G, et al. Liver disease selectively modulates cytochrome P450–mediated metabolism. Clin Pharmacol Ther. 2006;80(3):235-245.

11. Clària J, Kent JD, López-Parra M, et al. Effects of celecoxib and naproxen on renal function in nonazotemic patients with cirrhosis and ascites. Hepatology. 2005;41(3):579-587.

12. Lill JS, O’Sullivan T, Bauer LA, et al. Pharmacokinetics of diclofenac sodium in chronic active hepatitis and alcoholic cirrhosis. J Clin Pharmacol. 2000;40(3):250-257.

13. Juhl RP, Van Thiel DH, Dittert LW, Albert KS, Smith RB. Ibuprofen and sulindac kinetics in alcoholic liver disease. Clin Pharmacol Ther. 1983;34(1):104-109.

14. Ackerman Z, Cominelli F, Reynolds TB. Effect of misoprostol on ibuprofen-induced renal dysfunction in patients with decompensated cirrhosis: results of a double-blind placebo-controlled parallel group study. Am J Gastroenterol. 2002;97(8):2033-2039.

15. Laffi G, Daskalopoulos G, Kronborg I, Hsueh W, Gentilini P, Zipser RD. Effects of sulindac and ibuprofen in patients with cirrhosis and ascites. An explanation for the renal-sparing effect of sulindac. Gastroenterology. 1986;90(1):182-187.

16. Brater DC, Lasseter KC. Profile of etodolac: Pharmacokinetic evaluation in special populations. Clin Rheumatol. 1989;8(S1):25-35.

17. Davies NM, McLachlan AJ, Day RO, Williams KM. Clinical pharmacokinetics and pharmacodynamics of celecoxib: a selective cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet. 2000;38(3):225-242.

18. Agrawal NGB, Matthews CZ, Mazenko RS, et al. Pharmacokinetics of Etoricoxib in Patients with Renal Impairment. J Clin Pharmacol. 2004;44(1):48-58.

19. Zapater P, Llanos L, Barquero C, et al. Acute Effects of Dipyrone on Renal Function in Patients with Cirrhosis: A Randomized Controlled Trial. Basic Clin Pharmacol Toxicol. 2015;116(3):257-263..

20. Zylber-Katz E, Caraco Y, Granit L, Levy M. Dipyrone metabolism in liver disease*. Clin Pharmacol Ther. 1995;58(2):198-209.

21. Khalid SK, Lane J, Navarro V, Garcia G, Tsao –. Use of Over-the-Counter Analgesics Is Not Associated With Acute Decompensation in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2009;7(9):994-999.

22. Dwyer JP, Jayasekera C, Nicoll A. Analgesia for the cirrhotic patient: A literature review and recommendations. J Gastroenterol Hepatol. 2014;29(7):1356-1360.

23. Benson GD. Acetaminophen in chronic liver disease. Clin Pharmacol Ther. 1983;33(1):95-101.

24. Mullish BH, Kabir MS, Thursz MR, Dhar A. Review article: Depression and the use of antidepressants in patients with chronic liver disease or liver transplantation. Aliment Pharmacol Ther. 2014;40(8):880-892.

25. Andrade C, Sandarsh S, Chethan KB, Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry. 2010;71(12):1565-1575.

26. Skop BP, Brown TM. Potential Vascular and Bleeding Complications of Treatment With Selective Serotonin Reuptake Inhibitors. Psychosomatics. 1996;37(1):12-16.

27. Weinrieb RM, Auriacombe M, Lynch KG, Chang K-M, Lewis JD. A critical review of selective serotonin reuptake inhibitor-associated bleeding: balancing the risk of treating hepatitis C-infected patients. J Clin Psychiatry. 2003;64(12):1502-1510.

28. Suri A, Reddy S, Gonzales C, Knadler MP, Branch RA, Skinner MH. Duloxetine pharmacokinetics in cirrhotics compared with healthy subjects. Int J Clin Pharmacol Ther. 2005;43(2):78-84.

29 Greenblatt DJ, Wright CE. Clinical Pharmacokinetics of Alprazolam. Clin Pharmacokinet. 1993;24(6):453-471.

30. Gershkovich P, Wasan KM, Ribeyre C, Ibrahim F, McNeill JH. Effect of variations in treatment regimen and liver cirrhosis on exposure to benzodiazepines during treatment of alcohol withdrawal syndrome. Drugs Context. 2015;4:212287.

31. Klotz U, Avant GR, Hoyumpa A, Schenker S, Wilkinson GR. The effects of age and liver disease on the disposition and elimination of diazepam in adult man. J Clin Invest. 1975;55(2):347-359.

32. Physician Insert.33. Child-Turcotte-Pugh Class Calculator: https://www.hepatitisc.uw.edu


CHILD-turcotte-pugh classification for severity of cirrhosis

POINTS *1 2 3

ENCEPHALOPATHY - Grade 1-2(or precipitant included)

Grade 3-4(or chronic)

ASCITES - Mild to moderate(diuretic responsive)

Severe(diuretic refractory)

BILIRUBIN (mg/dL) < 2 2-3 > 3

ALBUMIN (g/dL) > 3.5 2.8 - 3.5 < 2.8

INR < 1.7 1.7 - 2.3 > 2.3

LIver dysfunction severity is difficult to estimate33

Child-Turcotte-Pugh Class obtained by adding score for each parameter (total points):33

CLASS A = 5-6 (least severe liver disease)CLASS B = 7-9 (moderately severe liver disease)CLASS C = 10-15 (most severe liver disease) https://www.hepatitisc.uw.edu

CIRR

HOSI

S |

06

CIRR

HOSI

S |

06

TREATMENT GROUPS GENERIC NAME NAME OF DRUG CHILD A CHILD B CHILD C REMARKS


Dipyrone OPTALGIN +/ a +/ a -19,20

Paracetamol ACAMOLDEXAMOL +/ a * +/ a * +/ a * 8,21,22,23

MILD pain

Vas 1-3 PAIN TREATMENT + CIRRHOSISPAIN TREATMENT + CIRRHOSISMODERATE pain

Vas 4-6



*- + b a c

CHILD A: Well compensatedCHILD B: Significant functional impairmentCHILD C: Decompensated liver function https://www.hepatitisc.uw.edu


CLASS A = 5-6 (least severe liver disease)CLASS B = 7-9 (moderately severe liver disease)CLASS C = 10-15 (most severe liver disease)

CHILD A: Well compensatedCHILD B: Significant functional impairmentCHILD C: Decompensated liver function







NSAIDs & COXIBs

Paracetamol + Ibuprofen COMBODEX +/ a +/ a - 8,32

Naproxen NAXYN +/ b +/ b - 11,32

Diclofenac ABITREN / VOLTAREN / BETAREN +/ b +/ b - 12,32

Ibuprofen IBUFEN / NUROFEN / ADEX +/ a +/ a - 3,13,14,15

Etodolac ETOPAN +/ a +/ a - 16,32

Celecoxib CELCOX +/ a +/ b * - CHILD B: 50% dose reduction 11,17,32

Etoricoxib ARCOXIA +/ b * +/ b * - CHILD A: 60 mg/d maxCHILD B: 30 mg/d max 18,32

Piroxicam as ß-Cyclodextrin BREXIN + * + * - * 32

Lornoxicam XEFO +/ a +/ b * - * CHILD B: 12 mg/d maxCHILD C: No info

CIRR

HOSI

S |

06

CIRR

HOSI

S |

06

PAIN TREATMENT + CIRRHOSISMODERATE pain

Vas 4-6Severe pain

Vas 7-10 PAIN TREATMENT + CIRRHOSISTREATMENT GROUPS GENERIC NAME NAME OF DRUG CHILD A CHILD B CHILD C REMARKS

STRONGOPIOIDS

Fentanyl FENTA +/ a +/ a +/ a 32

Fentanyl CitrateABSTRAL / ACTIQ / BREAKYL / FENTORA / PECFENT

+/ a +/ a +/ a 32

Methadone ADOLANMETHADONE +/ a +/ a +/ a 32

Morphine Sulphate MCRMIR ORAMORPH +/ a +/ a +/ b,c *

- Decrease dose and dosing interval X 1.5-2- Avoid in hepatorenal syndrome - The same in Morphine IV 1,2,3,4,5


+/ b - - 6,7, 32

Oxycodone + Naloxone TARGIN +/ b - - 6,7, 32

Oxycodone + Paracetamol PERCOCET +/ b * - - CHILD A: Start with 5 mg X 2/d, max 3gr acetaminophen 6,7,8


*- + b a c





*- + b a c





WEEKOPIOIDS

Buprenorphine BUTRANS +/ a - - 32



+/ c * +/ c * + *Increase dosing interval X 2.5 3,9,32

CHILD C: Oral contraindicated, IV use with caution

Tramadol + Paracetamol ZALDIAR +/ c +/ c - Increase dosing interval X 2.5 32

Codeine CODEINE +/ a - * - * CHILD B+C: Not recommended due to possible ineffectiveness 10



+/ a - * - * CHILD B+C: Not recommended due to possible ineffectiveness 8,10


ROKACET ROKACET PLUS +/ a - * - * CHILD B+C: Not recommended due to possible

ineffectiveness 8,10

CIRR

HOSI

S |

06

CIRR

HOSI

S |

06

PAIN TREATMENT + CIRRHOSISPAIN TREATMENT + CIRRHOSIS OTHERSOTHERS





+/ a * +/ a * +/ a *Not much info Desipramine and nortriptyline preferable 3,8,22




+/ b * +/ b * + *

Reduce maintenance and starting dose by 50%CHILD C: No info.

- Use with extreme caution- Could cause GI bleeding - Sertraline contraindicated 24,25,26,27,32



CYMBALTA / VIEPAX / EFEXOR / IXEL +/ b * +/ b * + *

Reduce maintenance and starting dose by 50%CHILD B+C: Don't use Cymbalta CHILD C: Venlafaxine caution for use, Milnacipran usual doses 24,28,32


ANTI- CONVULSANTS

Pregabalin LYRICA / PREGABALIN DEXCEL +/ a +/ a +/ a 3,22,32

Gabapentinoids GABAPENTIN +/ a +/ a +/ a 3,22,32

Carbamazepine TEGRETOL - - - 3,8,22,32

BENZO- DIAZIPINES



+/ b * +/ b * +/ b *

- Oxazepam and Lorazepam usual dose. All other benzodiazepines 50% dose reduction at least

- Refer to doctors insert- No info for clonazepam, Rivotril- CHILD C: Diazepam and midazolam contraindicated.

All benzodiazepines may precipitate encephalopathy 29,30,31,32



*- + b a c







CIRR

HOSI

S |

06

CIRR

HOSI

S |

06

פברואר 2018

העורכים:

- יו"ר האגודה הישראלית לכאב, מנהל היח׳ לשיכוך כאב, המרכז הרפואי הדסה עין-כרם פרופ' אליעד דוידסון - מנהל החטיבה האורתופדית, המרכז הרפואי ת"א פרופ' משה סלעי

- יו"ר איגוד הכירורגים בישראל, מנהל המערך לכירורגיה כללית, המרכז הרפואי רמב״ם פרופ' יורם קלוגר - יו”ר האיגוד הישראלי לרפואה פנימית, מנהל מחלקה פנימית ג’, המרכז הרפואי רבין, ביה”ח בילינסון פרופ’ אבישי אליס

- מנהל המכון לשיכוך כאב, המרכז הרפואי ת"א ד״ר סילביו בריל - מנהל המכון לשיכוך כאב, המרכז הרפואי שיבא, תה״ש ד״ר איתי גור-אריה

- יו”ר החוג לטיפול בכאב, איגוד רופאי המשפחה בישראל, מומחית ברפואת משפחה, מנהלת רפואית ד״ר ורד סימוביץ׳ של חטיבת התפעול, מכבי שירותי בריאות

- מנהל מחלקה פנימית ד’ והיח׳ ליל״ד, המרכז הרפואי שיבא, תה״ש, דיקן הפקולטה לרפואה, אוניברסיטת ת”א פרופ׳ אהוד גרוסמן - יו״ר החברה ליל״ד, מנהל המכון לנפרולוגיה ויל״ד, בית החולים הציבורי אסותא, אשדוד פרופ׳ עדי לייבה

- מומחה ברפואת משפחה, יועץ סוכרת ורכז סוכרת, שירותי בריאות כללית, מרחב חיפה ד״ר יצחק ברוך - יו״ר החוג לטיפול נמרץ לב האיגוד הקרדיולוגי בישראל, מומחה בקרדיולוגיה ומחלות פנימיות, ד״ר זאזא יעקבישוילי רכז תחום קרדיולוגיה, מחוז ת״א יפו, מנהל מכון הלב, מרכז רפואי חולון שירותי בריאות כללית

- סגן מנהל המערך לגסטרואנטרולוגיה ומנהל השירות לתנועתיות מערכת העיכול, המרכז הרפואי רבין פרופ׳ רם דיקמן - יו”ר האיגוד הישראלי לפרמקולוגיה קלינית ומנהלת היח׳ לפרמקולוגיה קלינית, מומחית ברפואה פנימית, ד״ר לי גולדשטיין

המרכז הרפואי העמק- מנהל היחידה לחקר הכאב, המרכז הרפואי רמב”ם פרופ’ אילון איזנברג

- מנהל מחלקת אורתופדית ב’, המרכז הרפואי אסף הרופא פרופ׳ יגאל מירובסקי

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Documents

CIRRHOSIS PUD CHF DIABETES KIDNEY HTN באכב CORRONARY · 2018. 12. 13. · Tramadol Hydrochloride TRAMADEX OD - - TRAMADEX TRAMAL TRAMAL RETARD +/b,c *-- Can be used only at CKD