Blood Pressure and DrugsUniversity of Toronto血压和药物多伦多大学.ppt

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1、Blood Pressure and Drugs,Sarah Fu(sarah.fumail.utoronto.ca)Meng Xue Shi(mengxue.shimail.utoronto.ca)Shuhua Situ(shuhua.situlmail.utoronto.ca)Monica Tran(mo.tranmail.utoronto.ca)Presentation Date:Friday,September 21,2012,PHM142 Fall 2012Instructor:Dr.Jeffrey Henderson,Measure of systolic and diastoli

2、c pressurePressure against the blood vesselsProportional to blood flowTransport of nutrients and O2Removal of waste and CO2Distribution of Hormones,Blood Pressure,Blood pressure above 140/90Risk increases with age2011 44%men and women ages 45-642011 45%men and women ages 65+,Hypertension,BlindnessSt

3、rokeHeart attackHeart failureKidney damageHigh salt dietObesityHereditaryStress,Dangers of Hypertension,Causes,Renin-Angiotensin Aldosterone System,Liver,A:Enalapril,ACE Inhibitors,Liver,B,A:EnalaprilB:Esterase,ACE Inhibitors,Liver,B,A:EnalaprilB:Esterase,ACE Inhibitors,Liver,B,A:EnalaprilB:Esterase

4、,ACE Inhibitors,Liver,B,A:EnalaprilB:Esterase,ACE Inhibitors,Liver,B,B:EsteraseC:Enalaprilat,ACE Inhibitors,Action of Benazeprilat,ACE Inhibitors,HypotensionChest painAbdominal painAnemia,Adverse effects,1%during clinical trials,1%during clinical trials,FatigueHeadacheDizzinessNausea,Common in insti

5、tutionalized elderlyOrthostatic Hypotension baroreflex failure or volume depletionSystolic bp decrease 20mm HgDiastolic bp decrease 10mm Hg Associated with hypertension,increased age and diabetes mellitus,Hypotension,Symptoms Blurred vision,headache,nausea,dizziness RisksIncreased incident of cerebr

6、al vascular disease Mild cardio-infarction Coronary heart disease Heart failure Cardio-vascular mortality,Orthostatic Hypotension,Non-MedicinalConsumption of salt Consumption of extra fluidsHead of bed elevatedPhysical Activity Abdominal binder,Treatments,Medicinal Pyridostigmine(Mestinon)Fludrocort

7、isone(Florinef)Midodrine(ProAmatine),VasopressorIncreases standing systolic bp Metabolite desglymidodrine1-agonist Activation of-adrenergic receptors Arterial and venous vasoconstrictionElevates blood pressure,Midodrine,Cytosol,Nucleus,Midodrine Desglymidodrine Glycine,Desglymidodrine,Phospholipase

8、C,1-adrenergic receptor s,Vasoconstriction Increase BP,Enzymatic cleavage,Increase in calcium,Supine hypertension Scalp paresthesias Pilomotor reactions(goosebumps)Urinary urgency Headaches,Adverse Effects,Summary,Hypertension,Hypertension:BP 140/90ACE converts angiotensin I(inactive)into angiotensi

9、n II(active)to increase blood pressureAngiotensin II is responsible for vasoconstriction,thirst,and releases aldosterone for retention of Na+Majority of ACE inhibitors(Enalapril),when activated,bind by the carbonyl groupEnalaprilat(active form)inhibits ACE,which vasoconstriction,thirst,and stops the

10、 release of aldosterone,Hypotension,Systolic BP drop 20mm Hg or diastolic BP drop 10mm HgMidodrine:major metabolite desglymidodrine which activates adrenergic receptorsVasopressor effect that causes activation and constriction of the arterial system,Ace Inhibitors.09/15/12.Adrenal Gland.Barrios,V.,E

11、scobar,C.,(2010).Antihpertensive and organ-protective effects of benazepril.Expert Review of Cardiovascular Therapy,12,1653-1724.Burt,V.L.,Whelton,P.,Roccella,E.J.,Brown,C.,Cutler,J.A.,Higgins,M.,Labarthe,D.(1995).Prevalence of hypertension in the US adult population.Hypertension,25,305-313.Canadian

12、 Health Measures Survey:Blood pressure in adults.09/13/12.eCPS.09/15/12.Figueroa,J.J.,Basford,J.R.,and Low,P.A.,(2010).Preventing and treating orthostatic hypotension:As easy as A,B,C.Cleveland Clinic Journal of Medicine,7(5),298-306 High blood pressure,by age group and sex.09/15/12.Hypertension in

13、Canada,2010.09/15/12.Jabary,N.S.,Sarabia,R.,Sanchez,T.,and Gordillo,R.(2007).Midodrine treatment in the management of severe orthostatic hypotension after hemangioblastoma surgery.Acta Neurochirurgica,149,303-306 Kaplan,N.M.,&Victor,R.G.(2009).Kaplans Clinical Hypertension(10th ed.).Philadelphia:Wol

14、ters KluwerLiver.09/13/12.Nature of Code Blood Vessels.09/13/12.Oldenburg,O.,Kribben,A.,Baumgart,D.,Philipp,T.,Erbel,R.,and Cohen,M.V.,(2002).Treatment of orthostatic hypotension.Current Opinion in Pharmacology,740-746 Perazella,M.A.(2003).Efficacy and safety of midodrine in the treatment of dialysi

15、s-associated hypotension.Expert Opinion Drug Safety,2(1),37-47Sherwood,L.(2007).Human Physiology(6th ed.).Belmont:Thomson Broks/Cole.Swann,P.,Stehouwer,M.,and Tukker,J.,(1995).Molecular mechanism for the relative binding affinity to the intentinal peptide carrier.Comparion of three ACE-inhibitors:enalapril,enalaprilat,and isinopril.Biochimica et Biophysica Acta,1236,31-38.,References,