Post on 01-Jan-2016
description
Category Systemic BP (mm Hg) Diastolic BP (mm Hg)
Normal <130 <85
High normal 130-139 85-89
HypertensionStage 1 140-159 90-99Stage 2 160-169 100-109
Stage 3 180-209110-119 Stage 4
210 120
Blood Pressure = Blood Pressure = Cardiac Output X Peripheral ResistanceCardiac Output X Peripheral Resistance
Preload Contractility Preload Contractility Heart Heart
RateRate CirculatingCirculatingFluid VolumeFluid Volume
RenalRenalSodiumSodium
HandlingHandling
SympatheticSympatheticNervousNervousSystemSystem
ReninRenin AngiotensinAngiotensinAldosteroneAldosterone
SystemSystem
ArteriolarArteriolarVenousVenousVasoconstrictionVasoconstriction
VenousVenous
Vascular Vascular Smooth Smooth MuscleMuscle
Vascular remodelingVascular remodeling
V VVasomotor center
AfterloadAfterload
VolumeVolumeKidneysKidneys
PreloadPreload
Renin
Ang II
Aldosterone BP= CO x TPVRBP= CO x TPVR
11
22 11
11
Resistance arterioles Capacitance venules
Total Peripheral Vascular Resistance (TPVR)Total Peripheral Vascular Resistance (TPVR)
Ang I
Cardiac Output Cardiac Output HeartHeart
22
TPVRTPVR
VSMCsVSMCsVascularVascularSmooth Smooth MuscleMuscleCellsCells
Adrenergic agents Angiotensin-converting enzyme inhibitors Angiotensin II receptor blockers Calcium channel blockers Diuretics Vasodilators
Adrenergic Agents◦Alpha1 blockers◦Beta blockers (cardioselective and nonselective)
◦Centrally acting alpha blockers◦Combined alpha-beta blockers◦Peripheral-acting adrenergic agents
Mechanism of action of beta-adrenoblockers(anaprilin, atenolol, methoprolol etc.)
in case of arterial hypertension
β-adrenoblockers
β1-adrenoreceptors of heart
Cardiac output
Angiotensine ΙΙ Renin
Aldosterone
Holding sodium and water
Peripheral resist- ance of vessels
Volume of blood circulation
Decreasing of blood pressure
NO production
V VVasomotor center
AfterloadAfterload
VolumeVolumeKidneysKidneys
PreloadPreload
Renin
Ang II
Aldosterone
11
22 11
11
Resistance arterioles Capacitance venules
PVRPVR
Ang I
Cardiac Output Cardiac Output HeartHeart
22
- Blockers- Blockers
VSMCsVSMCs
??
??
V VVasomotor center
AfterloadAfterload
VolumeVolumeKidneysKidneys
PreloadPreload
Renin
Ang II
Aldosterone BP= CO x TPVRBP= CO x TPVR
11
22 11
11
Resistance arterioles Capacitance venules
TPVRTPVR
Ang I
Cardiac Output Cardiac Output HeartHeart
22
- Blockers- Blockers
VSMCsVSMCs
??
??
Negative ChronotropicNegative Chronotropic& Inotropic Effects& Inotropic Effects
Inhibition ofInhibition ofRenin ReleaseRenin Release
____________________________________________________________
- Reduction in cardiac output- Reduction in cardiac output- Inhibition of renin release- Inhibition of renin release- CNS effects- CNS effects- Reduction in venous return - Reduction in venous return and plasma volumeand plasma volume- Reduction in peripheral resistance- Reduction in peripheral resistance- Improvement in vascular - Improvement in vascular compliancecompliance- Resetting of baroreceptor levels- Resetting of baroreceptor levels- Effects on - Effects on prejunctionalprejunctionalreceptorsreceptors
- Attenuation of pressor response to - Attenuation of pressor response to catecholamines (stress, exercise) catecholamines (stress, exercise) ____________________________________________________________
Cardioselectivity (Beta-1 vs Beta-2 )
Intrinsic Sympathomimetic Activity (ISA; partial agonistic activity)
Affinity for alpha-1 adrenergic receptors (Labetalol, Carvedilol)
Beta BlockersBeta Blockers
Beta-1,2-Non-Selective Propranolol [INDERAL] Nadolol [CORGARD] Carteolol [CARTROL] * Timolol [BLOCADREN] Pindolol [VISKEN] * Sotalol [BETAPACE] Penbutol [LEVATOL] *
Beta-1-Selective Acebutolol [SECTRAL] * Atenolol [TENORMIN] Betaxolol [KERIONE] Bisoprolol [ZEBETA] Esmolol [BREVIBLOC] Metoprolol [LOPRESSOR ]
Beta-1,2/Alpha 1SelectiveBeta-1,2/Alpha 1Selective LabetalolLabetalol [TRANDATE, NORMODYNE] [TRANDATE, NORMODYNE]
Carvedilol Carvedilol [COREG][COREG]
* - ISA
XX
Side Effects: Bronchospasm Bradicardia/heart block Mask and prolong the symptoms of hypoglycemia Abrupt withdrawal can precipitate MI Cold extremities, Raynaud’s phenomenon,
intermittent claudication Decreased exercise tolerance; fatigue, depression
and impotence CNS: sleep disturbance, vivid dreams, nightmares Effects of plasma lipids
Beta BlockersBeta Blockers
Adrenergic AgentsAlpha1 Blockers (peripherally acting) Block the alpha1-adrenergic receptors The SNS is not stimulated
Result: DECREASED blood pressure
Stimulation of alpha1-adrenergic receptors causes HYPERtension
Blocking alpha1-adrenergic receptors causes decreased blood pressure
V VVasomotor center
AfterloadAfterload
VolumeVolumeKidneysKidneys
PreloadPreload
Renin
Ang II
Aldosterone BP= CO x TPVRBP= CO x TPVR
11
Resistance arterioles Capacitance venules
TPVRTPVR
Ang I
Cardiac Output Cardiac Output HeartHeart
22
11 Receptors Receptors
BlockersBlockers
11
11
11
11
11
Inhibition of VasoconstrictionInhibition of VasoconstrictionInduced by EndogenousInduced by Endogenous
Catecholamines atCatecholamines atArterioles and VeinsArterioles and Veins
Reduced Peripheral ResistanceReduced Peripheral Resistanceandand
Reduced PreloadReduced Preload
Adrenergic AgentsAlpha1 Blockers doxazosin (Cardura) prazosin (Minipress) terazosin (Hytrin)
Adrenergic AgentsCentral-Acting Adrenergics clonidine (Catapres) methyldopa (Aldomet)
(drug of choice for hypertension in pregnancy)
V VVasomotor center
AfterloadAfterload
VolumeVolumeKidneysKidneys
PreloadPreload
Renin
Ang II
Aldosterone BP= CO x TPVRBP= CO x TPVR
11
Resistance arterioles Capacitance venules
TPVRTPVR
Ang I
Cardiac Output Cardiac Output HeartHeart
22
CentralCentralAgonistsAgonists
11
VSMCVSMC
X
X X
X
X
Diminished CNSDiminished CNSSympathetic OutflowSympathetic Outflow
Alpha-2 AgonistAlpha-2 Agonist
NE & EPINE & EPI
Pre-synaptic NeuronPre-synaptic Neuron
Alpha-2 ReceptorAlpha-2 Receptor
Alpha-1 ReceptorAlpha-1 ReceptorBeta ReceptorBeta Receptor
Post-synapticPost-synapticEffectorEffector
Activation of Pre-synapticActivation of Pre-synapticAlpha-2 Receptors ReducesAlpha-2 Receptors Reduces
NE & EPI Release at SynapseNE & EPI Release at Synapse
RostralRostralVentrolateralVentrolateral
MedullaMedulla
Central Central 22–Agonists–AgonistsCentral Central 22–Agonists–Agonists
A n g i o t e n s i n II
Peripheral resistance Renal function
Cardiovascular structure
RapidPressor Response
1. Direct vasoconstriction
2. Enhancement of peripheral noradrenergic neurotransmission 3. Increased central (CNS) sympathetic discharge
4. Release of catecholamines from adrenal medulla
1. Increases Na+ reabsorption
2. Releases aldosterone from adrenal cortex
3. Altered renal hemodynamics: - renal vasoconstriction - increased noradrenergic neurotransmission in kidney - Increased renal sympathetic tone (CNS)
SlowPressor Response
Cardiovascular Hypertrophy and Remodeling
1. Non-hemodynamic effects: - Increased expression of proto-oncogenes - Increased production of growth factors - Increased synthesis of extracellular matrix proteins
2. Hemodynamic effects: - Increased afterload (cardiac) - Increased wall tension (vascular)
V VVasomotor center
AfterloadAfterload
VolumeVolumeKidneysKidneys
PreloadPreload
Renin
Ang II
Aldosterone BP= CO x TPVRBP= CO x TPVR
11
22 11
11
Resistance arterioles Capacitance venules
TPVRTPVR
Ang I
Cardiac Output Cardiac Output HeartHeart
22
ACE IACE Inhibitorsnhibitors
VSMCsVSMCs
Angiotensinogen Ang IAng II
Renin (renal)
Renin
Angiotensinogen
Angiotensinogen Ang I
mRNA
AT1
Ang II
AT1
A C E
ACE
(autocrine)
(paracrine)
(endocrine)
mRNARenin
mRNAA C E
endothelialcell
tissuetissue
(VSM cells)(VSM cells)
(myocyte ) (myocyte )
(liver)
mRNAA C E
mRNAmRNA
Renin
Angiotensinogen
Angiotensinogen
Ang IACE
Ang II
Local (tissue) RAS:Local (tissue) RAS:Intrinsic; Extrinsic
blood vessel
Bradykinin
A C E A C E
Kallikrein Renin
Angiotensin II
Angiotensin I
Angiotensinogen
Angiotensin Converting Enzyme
ACEIsACEIs
Kininogens
Inactive Peptides
BK receptorsBK receptors AT-1 receptorsAT-1 receptors
ACEIsACEIs
20 mmHg
Afferentarteriole
Bowman’scapsule
Efferentarteriole
Arterialpressure +
Angiotensin II+
Angiotensin II+ +
INTRAGLOMERULAR PRESSUREINTRAGLOMERULAR PRESSURE
excess glomerular pressure
hyperfiltration microalbuminuria
ACEIs : ACEIs : Prevention of renal disease Prevention of renal disease
ACE Inhibitors
RAAS: Renin Angiotensin-Aldosterone System
When the enzyme angiotensin I is converted to angiotensin II, the result is potent vasoconstriction and stimulation of aldosterone
Result of vasoconstriction: increased systemic vascular resistance and increased afterload
Therefore, increased BP
ACE Inhibitors Aldosterone stimulates water and sodium
resorption. Result: increased blood volume, increased
preload, and increased B
ACE Inhibitors ACE Inhibitors block the angiotensin-
converting enzyme, thus preventing the formation of angiotensin II.
Also prevent the breakdown of the vasodilating substance, bradykinin
Result: decreased systemic vascular resistance (afterload), vasodilation, and therefore, decreased blood pressure
ACE Inhibitors captopril (Capoten) Short half-life, must be dosed more frequently
than others enalapril (Vasotec) The only ACE inhibitor available in oral and
parenteral forms lisinopril (Prinivil and Zestril) and quinapril
(Accupril) Newer agents, long half-lives, once-a-day
dosing Several other agents available
Kininogens
Bradykinin
Inactive PeptidesA C E A C E
Kallikrein Renin
Endothelial Cell
Plasminogen Activators
Angiotensin II
Angiotensin I
Angiotensinogen
PAI-1 +
ACE Inhibitors vs AT1 Antagonists
++
tPA
A C E Is
PAI-1
Example: Fibrinolytic SystemExample: Fibrinolytic System
V VVasomotor center
AfterloadAfterload
VolumeVolumeKidneysKidneys
PreloadPreload
Renin
Ang II
Aldosterone BP= CO x TPVRBP= CO x TPVR
11
22 11
11
Resistance arterioles Capacitance venules
TPVRTPVR
Ang I
Cardiac Output Cardiac Output HeartHeart
22
Ang II ReceptorAng II ReceptorBlockersBlockers
VSMCsVSMCs
Ang II
Ang II
Angiotensin II Receptor Blockers Allow angiotensin I to be converted to
angiotensin II, but block the receptors that receive angiotensin II
Block vasoconstriction and release of aldosterone
Angiotensin II Receptor Blockers losartan (Cozaar) eposartan (Teveten) valsartan (Diovan) irbesartan (Avapro) candesartan (Atacand) telmisartan (Micardis)
Calcium Channel Blockers Benzothiazepines Dihydropyridines Phenylalkylamines
V VVasomotor center
AfterloadAfterload
VolumeVolumeKidneysKidneys
PreloadPreload
Renin
Ang II
Aldosterone BP= CO x TPVRBP= CO x TPVR
11
Resistance arterioles Capacitance venules
TPVRTPVR
Ang I
Cardiac Output Cardiac Output HeartHeart
22
Calcium Channel Calcium Channel BlockersBlockers
CaCa++++
L-type CaL-type Ca++++ channelschannels
AV
11
Calcium Channel Blockers Cause smooth muscle relaxation by
blocking the binding of calcium to its receptors, preventing muscle contraction
This causes decreased peripheral smooth muscle tone, decreased systemic vascular resistance
Result: decreased blood pressure
Negative Inotropic andNegative Inotropic andChronotropic EffectsChronotropic EffectsProduce VasorelaxationProduce Vasorelaxation
at Arteriolesat Arterioles
Reduced Peripheral ResistanceReduced Peripheral Resistance
Verap+Dilti>NifedVerap+Dilti>NifedNifed>Dilti+VerapNifed>Dilti+Verap
Block transmembrane entry of calcium into arteriolar smooth Block transmembrane entry of calcium into arteriolar smooth muscle cells and cardiac myocytes thus inhibiting excitation-muscle cells and cardiac myocytes thus inhibiting excitation-contractioncontraction
L-type CaL-type Ca++++ channels channels
Calcium Channel Blockers Benzothiazepines:
◦ diltiazem (Cardizem, Dilacor)
Phenylalkamines:
◦ verapamil (Calan, Isoptin)
Dihydropyridines:
◦ amlodipine (Norvasc), bepridil (Vascor), nicardipine (Cardene)
◦ nifedipine (Procardia), nimodipine (Nimotop)
Calcium Channel Blockers Angina Hypertension Dysrhythmias Migraine headaches
Calcium Channel Blockers Cardiovascular
◦ hypotension, palpitations, tachycardia
Gastrointestinal◦ constipation, nausea
Other◦ rash, flushing, peripheral edema, dermatitis
V VVasomotor center
AfterloadAfterload
VolumeVolumeKidneysKidneys
PreloadPreload
Renin
Ang II
Aldosterone BP= CO x TPVRBP= CO x TPVR
11
22 11
11
Resistance arterioles Capacitance venules
TPVRTPVR
Ang I
Cardiac Output Cardiac Output HeartHeart
22
DIURETICSDIURETICS
VSMCsVSMCs
Inhibition ofInhibition ofSodium ReabsorptionSodium Reabsorption
Reduced Circulating VolumeReduced Circulating VolumeReduced PreloadReduced PreloadReduced Cardiac OutputReduced Cardiac Output
DiureticsDiuretics DiureticsDiuretics
Carbonic anhydrase inhibitors Loop diuretics Osmotic diuretics Potassium-sparing diuretics Thiazide and thiazide-like diuretics
Act directly on the ascending limb of the loop of Henle to inhibit sodium and chloride resorption.
Increase renal prostaglandins, resulting in the dilation of blood vessels and reduced peripheral vascular resistance.
Potent diuresis and subsequent loss of fluid
Decreased fluid volume causes:◦ Reduced BP
◦ Reduced pulmonary vascular resistance
◦ Reduced systemic vascular resistance
◦ Reduced central venous pressure
◦ Reduced left ventricular end-diastolic pressure
Potassium depletion
Edema associated with CHF or hepatic or renal diseaseControl of hypertensionBody System EffectHematologic Agranulocytosis,
neutropenia, thrombocytopenia
Metabolic Hypokalemia, hyperglycemia,
hyperuricemia
Used in the treatment of patients in the early, oliguric phase of ARF
To promote the excretion of toxic substances
Reduction of intracranial pressure Treatment of cerebral edema
Convulsions Thrombophlebitis Pulmonary congestion
Also headaches, chest pains, tachycardia,
blurred vision, chills, and fever
amiloride (Midamor) spironolactone (Aldactone) triamterene (Dyrenium)
V VVasomotor center
AfterloadAfterload
VolumeVolumeKidneysKidneys
PreloadPreload
Renin
Ang II
Aldosterone BP= CO x TPVRBP= CO x TPVR
11
22 11
11
Resistance arterioles Capacitance venules
TPVRTPVR
Ang I
Cardiac Output Cardiac Output HeartHeart
22
Aldosterone Aldosterone AntagonistsAntagonists
VSMCsVSMCs