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ADRENERGIC AGENTS (atrium) Increased contraction Increased heart rate b Vasodilation (ventricle) a Vasoconstriction EFFECTS OF ADRENERGIC AGENTS ON ARTERIAL PRESSURE b Arterial pressure = cardiac output x vascular tone a ADRENERGIC AGENTS THE GOOD THE BAD Increased blood flow / DO2 Vasodilation (systemic & pulmonary) b Increased spanchnic perfusion Tachycardia Isoproterenol Increased myocardial O2 demand (ischemia) Arterial hypotension Increased blood pressure Increased brain perfusion (CPP) a Increased tissue perfusion pressure Peripheral vasoconstriction Phenylephrine Decreased cardiac output / DO2 Decreased renal / splanchnic perfusion b Adrenergic agents a PRELOAD HEART RATE CONTRACTILITY AFTERLOAD ADRENERGIC AGENTS Isoproterenol Dopexamine b Dobutamine Phenylephrine a DOBUTAMINE increases cardiac output has little influence on pressures (decreases vascular resistances) Systemic Arterial pressure - CVP Vascular = Resistance Cardiac output A decrease in arterial pressure under dobutamine administration suggests some degree of hypovolemia Avoid early dobutamine administration in hypotensive patients (norepinephrine may be safer initially) ADRENERGIC AGENTS inotropes Isoproterenol Dopexamine b Dobutamine Dopamine Epinephrine Norepinephrine Phenylephrine a vasopressors ADRENERGIC AGENTS +++ + PRESSURE 0 norepinephrine dobutamine - (noradrenaline) dopamine isoproterenol epinephrine +++ phenylephrine (adrenaline) HEART RATE + FLOW 0 a b - VASOACTIVE DRUGS IN THE ICU WHAT ABOUT REGIONAL BLOOD FLOW ? EFFECTS OF ISOPROTERENOL ON HEPATIC ARTERY BLOOD FLOW After RICHARDSON et al. mL/min.100g Br J Pharmac 57:581;1976 100 80 60 40 20 0 BASELINE ISOPROTERENOL 0.02-0.05 mcg/min REGIONAL EFFECTS OF DOBUTAMINE IN ENDOTOXIC SHOCK D De Backer, H Zhang, P Manikis et JL Vincent J Surg Res 65: 93-100, 1996 21 pentobarbital-anesthetized dogs endotoxin 2 mg/kg + saline infusion - 7 control - 7 dobutamine 5 mcg/kg/min - 7 dobutamine 10 mcg/kg/min REGIONAL EFFECTS OF DOBUTAMINE IN ENDOTOXIC SHOCK mL/min.kg D De Backer, H Zhang, P Manikis et JL Vincent J Surg Res 65: 93-100, 1996 600 CARDIAC INDEX *+ + 500 * *+ * DOBU 5 400 + * DOBU 10 *+ *+ * 300 200 * CONTROL ** 100 ** 0 BASE ENDO FLUIDS FLUIDS + INTERVENTION *p < 0.05 vs FLUIDS + p < 0.05 vs CTRL MEAN ± SEM REGIONAL EFFECTS OF DOBUTAMINE IN ENDOTOXIC SHOCK D De Backer, H Zhang, P Manikis et JL Vincent mL/min J Surg Res 65: 93-100, 1996 250 LIVER DO2 + + 200 * * * *+ DOBU 5 150 * + DOBU 10 100 + CONTROL 50 * ** 0 BASE ENDO FLUIDS FLUIDS + INTERVENTION * p < 0.05 vs FLUIDS + p < 0.05 vs CTRL MEAN ± SEM DOBUTAMINE IMPROVES GASTROINTESTINAL MUCOSAL BLOOD FLOW IN A PORCINE MODEL OF ENDOTOXIC SHOCK Neviere et al, Crit Care Med 25: 1271-7, 1997 Effects of Norepinephrine on gastric mucosa Norepinephrine + dobutamine Epinephrine in patients with septic shock Duranteau et al, Crit Care Med 27: 893-900, 1999 CARDIAC INDEX, L/min.M² GMP (laser Doppler, U) 6 500 5 400 4 300 3 200 2 1 100 0 0 NE EPI NE EPI N = 12 NE+Dobu NE+Dobu MAP 74 mmHg ADRENERGIC AGENTS If the primary aim Is to increase blood flow Isoproterenol Dopexamine b Dobutamine Dopamine Epinephrine Norepinephrine Phenylephrine a If the primary aim Is to increase pressure The history of shock therapy DOPAMINE IN THE TREATMENT OF HYPOTENSION AND SHOCK Mac Cannel et al N Engl J Med 275: 1389-98, 1966 ACUTE HEMODYNAMIC EFFECTS OF DOPAMINE IN PATIENTS WITH SHOCK Loeb NS et al Circulation 44: 163-73, 1971 DOPAMINE increases urine and sodium output - in healthy humans McDonald et al, J Clin Invest 43: 1116-24, 1964 - in patients with cardiac failure Goldberg et al, N Engl J Med 269: 1060-4, 1963 DOPAMINE dopaminergic b a 0 5 10 15 20 mcg/kg/min Blood flow distribution Dopaminergic receptors = vasodilation Brain Skin Muscle RV LV Heart Gut Kidney more dopaminergic receptors Renal vasodilatory action of dopamine in patients with heart failure Elkayam et al, Circulation 117: 200-205, 2008 % change from baseline Renal blood flow 70 60 50 40 Cardiac output 30 20 10 0 0 1 2 3 4 5 6 7 8 9 10 11 Dose, mcg/kg/min Intravascular Doppler ? RENAL DOSES OF DOPAMINE ? RENAL DOSE DOPAMINE: FACT AND FICTION Ann Intern Med 115: 153, 1991 DOPAMINE AND THE KIDNEY: TEN YEARS ON Clin Sci 84: 357, 1993 RENAL EFFECTS OF DOPAMINE: CAN OUR DREAM EVER COME TRUE? Crit Care Med 22: 5, 1994 RENAL-DOSE DOPAMINE: A SIREN SONG? Lancet 344: 7, 1994 LOW-DOSE DOPAMINE: WILL THERE EVER BE A SCIENTIFIC RATIONALE ? Br J Anaesth 78: 350, 1997 RENAL DOSE DOPAMINE: LONG ON CONJECTURE, SHORT ON FACT Crit Care Med 28: 1657, 2000 RENAL SUPPORT IN CRITICALLY ILL PATIENTS: LOW DOSE DOPAMINE or LOW DOSE DOBUTAMINE ? Duke et al, Crit Care Med 22: 1919-25, 1994 Creatinine clearance, mL/min ADRENERGIC AGENTS EFFECTS OF ADRENERGIC AGENTS ON HEPATO-SPLANCHNIC CIRCULATION IN SEPTIC PATIENTS D De Backer, J Creteur, JL Vincent ShO2 Crit Care Med 31: 1659-67, 2003 dopamine low doses epi low doses norepi high doses epi high doses norepi ADRENERGIC AGENTS CARDIAC INDEX L/min.m² 5,5 5 +++ Crit Care Med 31: 1659-67, 2003HIGH DOSES 4,5 +++ 4 *** 3,5 3 LOW DOSES 2,5 DOPA NOREPI EPI ADRENERGIC AGENTS FRACTIONAL SPLANCHNIC BLOOD FLOW % 30 Crit25 Care Med 31: 1659-67, 2003 LOW DOSES 20 15 ++ 10 HIGH DOSES 5 DOPA NOREPI EPI VASOPRESSOR AGENTS DOPAMINE The good The bad Increased blood flow Increased renal blood flow Risk of arrhythmias Increased splanchnic blood flow Immunosuppression Increased edema clearance (prolactin release) Improved muscle function NOREPINEPHRINE Strong vasopressor effect Risk of vasoconstriction SOAP Vasoactive drugs in circulatory shock ICU mortality All shock Septic shock (N =1058) (N = 462) Dopamine 42.9 % 52.5 % No dopamine 35.7 % 44.1 % p = 0.02 p = 0.08 Crit Care Med 34: 589-97, 2006 ICU mortality SOAP (multivariable analysis) OR (95 % C.I.) p Mean SOFA score 1.52 (1.39 - 1.67) < 0.001 Mean fluid balance 1.39 (1.19 - 1.63) < 0.001 Age 1.03 (1.01 - 1.04) 0.001 Cancer 3.54 (1.72 - 7.30) 0.001 Dopamine administration 2.05 (1.25 - 3.37) 0.005 Medical admission 1.83 (1.12 - 2.99) 0.016 septic shock CritCrit Care Care Med Med 34:34: 589589-97,-97, 20062006 Dopamine vs norepinephrine in shock states De Backer et al, N Engl J Med 362: 779-89, 2010 40 30 Norepinephrine better 20 10 No difference Z 0 50 100 150 200 -10 -20 -30 Dopamine better -40 V Sequential Trial (1600 patients) Dopamine vs norepinephrine in shock states De Backer et al, N Engl J Med 362: 779-89, 2010 RISK OF DEATH – NOREPINEPHRINE vs. DOPAMINE Conclusions: In a large population-based sample of patients with septic shock in the US, use of dopamine as initial vasopressor was associated with increased mortality among multiple clinical subgroups. VASOACTIVE DRUGS IN THE ICU Abandon dopamine Dopamine vs norepinephrine in shock states De Backer et al, N Engl J Med 362: 779-89, 2010 Early termination (arrhythmia) No of patients 50 5% 45 40 P < 0.001 35 30 25 20 15 1% 10 5 0 DOPAMINEAll centers NOREPINEPHRINE n = 1677 ADRENERGIC AGENTS Isoproterenol Dopexamine b Dobutamine ? Dopamine Epinephrine Norepinephrine Phenylephrine a ADRENERGIC AGENTS EFFECTS OF ADRENERGIC AGENTS ON HEPATO-SPLANCHNIC CIRCULATION IN SEPTIC PATIENTS D De Backer, J Creteur, JL Vincent ShO2 Crit Care Med 31: 1659-67, 2003 dopamine low doses epi low doses norepi high doses epi high doses norepi ADRENERGIC AGENTS CARDIAC INDEX L/min.m² 5,5 5 +++ Crit Care Med 31: 1659-67, 2003HIGH DOSES 4,5 +++ 4 *** 3,5 3 LOW DOSES 2,5 DOPA NOREPI EPI ADRENERGIC AGENTS FRACTIONAL SPLANCHNIC BLOOD FLOW % 30 Crit25 Care Med 31: 1659-67, 2003 LOW DOSES 20 15 ++ 10 HIGH DOSES 5 DOPA NOREPI EPI EPINEPHRINE Epinephrine vs norepinephrine + dobutamine? Annane et al, Lancet 370: 676- 84, 2007 Norepinephrine Epinephrine + (N = 161) dobutamine (N = 169) SOFA score 12 12 Source = lung (%) 46 48 Mech. ventilation (%) 95 94 Blood lactate (mEq/L) 4.0 4.6 30 day mortality (%) 40.0 34.3 ICU mortality (%) 46.6 44.4 Hospital mortality (%) 52.2 48.5 JLV/USI 5/97 The CATS study 2016 Propensity-score matched 2018 Higher lactate levels How I treat shock EPINEPHRINE SHOULD BE AVOIDED Tachyarrhythmias Reduced hepato-splanchnic blood flow Increased blood lactate levels 27 835 patients with septic shock in 26 hospitals Increased hospital mortality 35.9% vs 39.6%, p=0.03 "The decreased use of norepinephrine during periods of shortage was associated with an increase in use of phenylephrine." BASELINE SHORTAGE Nepi Phenylephrine Dopa Vasopressin Adré VASOACTIVE DRUGS IN THE ICU Current recommendations 1- Norepinephrine is the vasopressor agent of choice Norepinephrine Advantages ▪ Natural agent ▪ Short half-life ▪ Easy titration ▪ Wide experience Potential disadvantages ▪ Adverse effects on regional blood flow ▪ Immunomodulatory effects ▪ Increased catabolism VASOACTIVE AGENTS IN SEPTIC SHOCK Dopamine Epinephrine Dopexamine Milrinone Prostaglandin E1 Levosimendan Angiotensin Nitroglycerin Metaraminol Pentoxifyllin Mephentermine Calcium Dobutamine Vasopressin PDE inhibitors Norepinephrine Hydralazine N-acetylcysteine Magnesium Terlipressin Phenylephrine Prostacyclin L-NMMA Calcium antagonists Enoximone Isoproterenol IV Vasopressor IV Vasopressor Only Variables + Midodrine p (n= 140) (n= 135) IV vasopressor 3.8 2.9 < .001 duration, days IV vasopressor 21 (15) 7 (5.2) .007 reinstitution, No. (%) Change in creatinine, 0.8 ± 1.6 0.5 ± 1.3 .048 mg/dL ICU LOS, 9.4 ± 6.7 7.5 ± 5.9 .017 days ICU mortality 26 (18.6%) 15 (11.1%) .08 Gutron 2018 Activation of the renin–angiotensin–aldosterone system (RAAS) Angiotensinogen renin Angiotensin I Endothelial cell dysfunction ACE Adrenergic ACE inhibitors Angiotensin II Vasopressin
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    Drugs-Biologicals FORMULARY for INTERNET PAGE 12 26 18

    AVG ITEM Average Patient Item Charge Code Description BIL AWP /pkg COST Price 25000041 SODIUM and POTASSIUM BICARBONATE TBEF UD $3.61 $0.12 $1.00 25000054 GLIMEPIRIDE TAB 1 MG UD $8.25 $0.11 $1.30 25000086 amLODIPine TAB 5 MG UD $8.65 $0.06 $1.00 25000087 AMMONIA AROMATIC SOLN 15 % (W/V) UD $3.53 $0.17 $1.00 25000090 AMOXICILLIN CAP 500 MG UD $20.12 $0.19 $1.00 25000102 ABACAVIR TAB 300 MG UD $507.10 $8.45 $16.90 25000103 ACAMPROSATE TBEC 333 MG UD $182.38 $0.80 $1.76 25000104 ACARBOSE TAB 25 MG UD $16.70 $0.27 $1.00 25000106 ACETAMINOPHEN SUPP 120 MG UD $5.09 $0.42 $1.00 25000108 ACETAMINOPHEN SUPP 325 MG UD $4.91 $0.44 $1.00 25000109 ACETAMINOPHEN TAB 325 MG UD $12.39 $0.02 $1.00 25000111 ACETAMINOPHEN TAB 500 MG UD $2.34 $0.02 $1.00 25000112 ACETAMINOPHEN SUPP 650 MG UD $3.83 $0.17 $1.00 25000113 ACETAMINOPHEN SOLN 650 MG/20.3 ML UD $75.74 $0.48 $1.22 25000117 ACETAMINOPHEN-CODEINE TAB 300-30 MG UD $12.41 $0.09 $1.00 25000121 ACETYLCYSTEINE SOLN 200 MG/ML (20 %) UD $18.18 $7.66 $15.32 25000140 ALBUTEROL SULFATE NEBU 2.5MG/3ML (0.083 %) UD $8.58 $0.29 $1.00 25000147 ALLOPURINOL TAB 100 MG UD $18.45 $0.12 $1.00 25000150 ALPRAZolam TAB 0.25 MG UD $8.87 $0.09 $1.00 25000151 ALPRAZolam TAB 0.5 MG UD $4.16 $0.04 $1.00 25000182 AMIODARONE TAB 200 MG UD $15.70 $0.20 $1.00 25000184 AMITRIPTYLINE TAB 10 MG UD $8.73 $0.06 $1.00 25000186 AMITRIPTYLINE TAB 25 MG UD $17.46 $0.08 $1.00 25000188 AMITRIPTYLINE TAB 50 MG UD $34.90 $0.16 $1.00 25000205 HYDROCORTISONE ACETATE SUPP 25 MG UD $127.30 $5.75 $11.50 25000206 HEMORRHOIDAL SUPPOSITORY SUPP 0.25
  • Wednesday, July 10, 2019 4:00Pm

    Wednesday, July 10, 2019 4:00Pm

    Wednesday, July 10, 2019 4:00pm Oklahoma Health Care Authority 4345 N. Lincoln Blvd. Oklahoma City, OK 73105 The University of Oklahoma Health Sciences Center COLLEGE OF PHARMACY PHARMACY MANAGEMENT CONSULTANTS MEMORANDUM TO: Drug Utilization Review (DUR) Board Members FROM: Melissa Abbott, Pharm.D. SUBJECT: Packet Contents for DUR Board Meeting – July 10, 2019 DATE: July 3, 2019 NOTE: The DUR Board will meet at 4:00pm. The meeting will be held at 4345 N. Lincoln Blvd. Enclosed are the following items related to the July meeting. Material is arranged in order of the agenda. Call to Order Public Comment Forum Action Item – Approval of DUR Board Meeting Minutes – Appendix A Update on Medication Coverage Authorization Unit/SoonerPsych Program Update – Appendix B Action Item – Vote to Prior Authorize Jornay PM™ [Methylphenidate Extended-Release (ER) Capsule], Evekeo ODT™ [Amphetamine Orally Disintegrating Tablet (ODT)], Adhansia XR™ (Methylphenidate ER Capsule), and Sunosi™ (Solriamfetol Tablet) – Appendix C Action Item – Vote to Prior Authorize Balversa™ (Erdafitinib) – Appendix D Action Item – Vote to Prior Authorize Annovera™ (Segesterone Acetate/Ethinyl Estradiol Vaginal System), Bijuva™ (Estradiol/Progesterone Capsule), Cequa™ (Cyclosporine 0.09% Ophthalmic Solution), Corlanor® (Ivabradine Oral Solution), Crotan™ (Crotamiton 10% Lotion), Gloperba® (Colchicine Oral Solution), Glycate® (Glycopyrrolate Tablet), Khapzory™ (Levoleucovorin Injection), Qmiiz™ ODT [Meloxicam Orally Disintegrating Tablet (ODT)], Seconal Sodium™ (Secobarbital