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  • Nikolai SergeyevichKorotkov (also romanized Korotkoff; Russian: Николай Сергеевич Коротков) (26 February [O.S. 14 February]1874 – 14 March 1920) was a Russian surgeon, a pioneer of 20th century vascular surgery, and the inventor of auscultatory technique for blood pressure measurement.Korotkoff method is a non-invasive auscultatory technique for determining both systolic and diastolic blood pressure levels. The method requires а sphygmomanometer and а stethoscope. Due to ease and accuracy, it is considered a "gold standard" for blood pressure measurementKorotkoff sounds are pulse-synchronous circulatory sounds heard through the stethoscope in auscultation of blood pressure using Riva-Rocci's sphygmomanometer.Korotkoff test or Korotkoff sign is a collateral circulation test: in aneurysm, if the blood pressure in the peripheral circulation remains fairly high while the artery above the aneurysm is compressed, the collateral circulation is good.The cuff of Riva-Rocci is placed on the middle third of the upper arm; the pressure within the cuff is quickly raised up to complete cessation of circulation below the cuff. Then, letting the mercury of the manometer fall one listens to the artery just below the cuff with a children's stethoscope. At first no sounds are heard. With the falling of the mercury in the manometer down to a certain height, the first short tones appear; their appearance indicates the passage of part of the pulse wave under the cuff. It follows that the manometric figure at which the first tone appears corresponds to the maximal pressure. With the further fall of the mercury in the manometer one hears the systolic compression murmurs, which pass again into tones (second). Finally, all sounds disappear. The time of the cessation of sounds indicates the free passage of the pulse wave; in other words at the moment of the disappearance of the sounds the minimal blood pressure within the artery predominates over the pressure in the cuff. It follows that the manometric figures at this time correspond to the minimal blood pressure.

terminating the terminator terminating the terminator Presentation Transcript

  • DR. ABDUL RAB SHAIKH MD CARDIOLOGY (UK) DIP CARD (UK) Consultant Interventional Cardiologist Red Crescent Institute Of CardiologyTERMINATING THE TERMINATOR
  • Nikolai Korotkov
  • Distribution of Hypertension Subtype in the untreated Hypertensive Population in NHANES III by Age ISH (SBP 140 mm Hg and DBP <90 mm Hg) SDH (SBP 140 mm Hg and DBP 90 mm Hg) IDH (SBP <140 mm Hg and DBP 90 mm Hg) 17% 16% 16% 20% 20% 11% 100 80Frequency of hypertension 60subtypes in all untreated 40hypertensives (%) 20 0 <40 40-49 50-59 60-69 70-79 80+ Age (y) Numbers at top of bars represent the overall percentage distribution of untreated hypertension by age. Franklin et al. Hypertension 2001;37: 869-874.
  • Hypertension: A Significant CV and Renal Disease Risk Factor CAD CHF Stroke LVH Hypertension Renal disease Morbidity Disability Peripheral vascular diseaseNational High Blood Pressure Education Program Working Group. Arch Intern Med. 1993;153:186-208.
  • Treating and Managing blood pressure
  • ESH–ESC: Algorithm for Treatment of HypertensionTask Force for ESH–ESC. J Hypertens 2007;25:1105–87
  • Antihypertensive Therapy: Number of Agents Required to Achieve BP Goal UKPDS (<85 mm Hg, diastolic) MDRD (<92 mm Hg, MAP) HOT (<80 mm Hg, diastolic) AASK (<92 mm Hg, MAP) RENAAL (<140/90 mm Hg) IDNT ( 135/85 mm Hg) 1 2 3 4 Number of BP MedicationsBakris et al. Am J Kidney Dis. 2000;36:646-661; Bakris et al. Arch Intern Med. 2003;163:1555-1565; Lewis et al. N Engl J Med.2001;345:851-860.
  • Are All ARB’s the same??
  • Olmesarta Losarta Candesarta Irbesarta Telmisarta Eprosarta Valsarta n n n n n n nProdrug Yes Yes Yes No No No NoReceptor Non- Competitiv Non- Non- Non- Competitiv Non-antagonism competitive e competitive competitive competitive e competitiv (active e metabolite is non- competitiv eAT1:AT2 12,500 1,000 >10,000 8,500 >3,000 1,000 20,000affinityt1/2 (hours) 10-15 6-9 9 11-15 >20 5-9 9Tmax (hours) 1-2 3-4 3-4 1.5-2 0.5-1 1-2 2-4Vd (L) 16-29 34 0.1 L/kg 53-93 500 ~13 ~23Bioavailability 25.6 ~33 14 60-80 50 13 23(%)
  • ARB’s and half-life
  • Better Blockade of Ang II Receptor by irbesartan than valsartan, losartan Single administration 6 days administration IRBESARTAN SHOWED SUPERIOR ANTAGONISTIC ACTIVITY AS COMPARE TO VALSARTAN AND LOSARTAN Belz GG et al. Clin Pharmacol Ther 1999;66:367-373
  • Irbesartan Blood Pressure Efficacy is Superior to Losartan At Maximum QD Doses Systolic blood pressure Diastolic blood pressure Irbesartan Irbesartan Losartan Irbesartan Irbesartan Losartan 300 mg 150 mg 100 mg placebo 300 mg 150 mg 100 mg placebo (n=134) (n=129) (n=131) (n=138) (n=134) (n=129) (n=131) (n=138) 0 -2 -3.7 Mean Change From Baseline -4 -4.9 at Week 8 (mm Hg) -6 -8 -8.7 -9.7 -10 -11.3 -11.7 -12.1 -12 -14 -16 -16.4 (p<0.01) -18 Δ 3.0 mm Hg -20 (p<0.01) Δ 5.1 mm Hg Both drugs were well tolerated 8-week, randomized, double blindmild-moderate HTN (95-110 mmHg) Kassler-Taub K et al. Am J Hypertens 1998;11:44–53.
  • Greater BP Reduction Observed in Monotherapy with irbesartan 150mg than valsartan 80mg ABPM Self Measurement Office Measurement (Trough) (Morning values) (Trough) ADBP ASBP DBP SBP DBP SBP BP / Baseline (mm Hg) 0 0 -4 -4 -3.8 -4.8 -8 -6.7 -6.3 -7.0 -8 -7.5 -7.3 Δ1.9(40%) Δ2.5(66%) -12 (P<0.01) -10.2 -12 -10.5 -10.0 (P=0.035) -11.6 Δ3.2(46%) Δ4.1(55%) Δ3.2(44%) (P<0.01) -16 (P<0.01) (P<0.01) -16.2 irbesartan 150 mg valsartan 80 mg Δ6.2(62%) (P<0.01)3-week washout, 8-week follow-up, randomized, double Mancia G, et al. Blood Press Monit 2002 ;7: 135–142 blind, mild-moderate HTN (95-110 mmHg)
  • Power to Achieve BP Goals in Uncontrolled Hypertensive Patients
  • Irbesrartan/HCTZ and JNCVII goal BP
  • Why Irbesartan is Unique?• Irbesartan’s specific targeting of the AT1 receptor completely blocking of the renin-angiotensin system than that offered by angiotensin-converting enzyme inhibitors.(1)• Irbesartan is well absorbed, does not require biotransformation to an active metabolite .• Irbesartan is associated with a strong and consistent dose-response and has been demonstrated to provide a level of angiotensin II antagonism that is statistically superior to that offered by some other ARBs.(1)• Shows better compliance than ACE Inhibitors 1. Adams MA, Trudeau L. Can J Clin Pharmacol. 2000 Spring;7(1):22-31. Irbesartan: review of pharmacology and comparative properties.
  • ICE: Persistence with initial antihypertensive monotherapy after 12 months 70 60 † 60.8 * 50 Proportion * * * 51.3 49.7 of patients 40 43.6 44.7 persistent * 42.0 with initialmonotherapy 30 34.4 (%) 20 10 0 Diuretics ACEIs CCBs Losartan Beta- AIIRAs‡ Irbesartan Univariate analysis blockers * p < 0.05; † p = 0.009 vs. irbesartan ‡ Excluding irbesartan Hasford J et al. J Human Hypertension 2002;16:569–75.
  • UNSURPASSED ECONOMY VS BRANDED ARBs Price Comparison Saving in comparison with COZAAR 50 mg 60 51.67 50Price (Rupees) 39 40 PKR 26 per day 30 26 20 Saving in comparison with DIOVAN 80 mg 10 0 50mg 80mg 150mg PKR 13 per day Cozaar Diovan Aprovel Product Cozaar 50mg Diovan 80mg Aprovel 150mg
  • UNSURPASSED ECONOMY VS BRANDED ARBs Daily Cost of Therapy (Higher doses) 90 80 Saving in comparison with 80 COZAAR 100 mgPrice (PKR) 70 60 57.14 50 39 40 PKR 41 per day 30 20 10 Saving in comparison with 0 DIOVAN 160 mg 100 mg 160mg 300mg Cozaar Diovan Aprovel PKR 19 approx. per day Products Cozaar 100 mg Diovan 160mg Aprovel 300mg
  • We can conclude that APROVEL• has superior AT 1 receptor blockade activity as compared to Losartan and Valsartan• Even Aprovel initial prescribing dose (150mg) is superior in Blood Pressure lowering efficacy when compared with maximum dose of Losartan (100mg)• Aprovel is superior to Valsartan in Blood Pressure lowering efficacy in monotherapy as well as in combination with HCTZ
  • We can conclude that APROVEL (Cont.)• Controls 8 out of 10 patients who were uncontrolled on any monotherapy achieved their Blood Pressure goal with CoAprovel• Patients were remained controlled on Aprovel even after 02 years of therapy demonstratrating PERSISTENCE• Along with efficacy, Aprovel is most economical branded ARB available in Pakistan