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浙江大学医学院:(血液)循环系统(Circulation system)Chapter 6 心血管药物 Cardiovascular Drugs

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jugular pulmonary atrum vonnie aorta Section Ill Circulation system Trunk and Legs

Section III Circulation system

Overview of Cardiovascular Diseases a Common Cardiac Diseases n Abnormal contractility: Heart failures Abnormal rhythms Arrhythmias u Abnormal blood supply Ischemic heart diseases u Myocardial disorders n Common vascular diseases u Abnormal systematic resistance Hypertension o Dysfunction of coronary vessels Coronary vascular diseases u Dysfunction of cerebral vessels Cerebral ischemia, hemorrhage a Dysfunction of pulmonary vessels Pulmonary hypertension u Dysfunction of peripheral vessels: Peripheral vasculardisorder d Arteriosclerosis

Overview of Cardiovascular Diseases Common Cardiac Diseases Abnormal contractility:Heart failures Abnormal rhythms:Arrhythmias Abnormal blood supply:Ischemic heart diseases Myocardial disorders Common vascular diseases Abnormal systematic resistance:Hypertension Dysfunction of coronary vessels:Coronary vascular diseases Dysfunction of cerebral vessels:Cerebral ischemia, hemorrhage Dysfunction of pulmonary vessels:Pulmonary hypertension Dysfunction of peripheral vessels: Peripheral vascular disorder Arteriosclerosis

Overview of Cardiovascular Drugs u Classification based on target organs/tissues o Heart: Heart failures, arrhythmias, cardiac ischemia. over-load of the heart a Vessels: Vasodilatation vasoconstriction arteriosclerosis n Classification based on the mechanisms o Ion channels. Cal+. Nat. Kt channels o Receptors Adrenoreceptors, AT, receptors, etc. D Enzymes ACEL, Nat-K-ATPase, HMG-CoA reductase o Others. Diuretics

Overview of Cardiovascular Drugs Classification based on target organs/tissues Heart:Heart failures, arrhythmias, cardiac ischemia, over-load of the heart Vessels:Vasodilatation, vasoconstriction, arteriosclerosis Classification based on the mechanisms Ion channels:Ca2+, Na+ , K+ channels Receptors:Adrenoreceptors, AT1 receptors, etc. Enzymes:ACEI, Na+ -K+ -ATPase, HMG-CoA reductase Others:Diuretics

Chapter 6 Cardiovascular drugs Voltage-gated Ca channe/ Caa Part 1 Plasma membrane Calcium ion Drugs affecting ion channels in cvs Ryanodine recept embrane Ca of the SER

Chapter 6 Cardiovascular Drugs Part 1 Drugs affecting ion channels in CVS

Passive Active Nonmediated Transporter mediated A C on智n nne C D (b) Modes ofsolute transmembrane transport

Modes of solute transmembrane transport ion channel

A. General properties of ion channels in CVS u Properties of ion channels a Permeation o Selectivity 0 Gating voltage-gatee chemically gated: ligand-gated phospharylation-gated mechanosensitive nongated background /leak channels

A. General properties of ion channels in CVS Properties of ion channels Permeation Selectivity Gating voltage-gated chemically gated: ligand-gated phospharylation-gated mechanosensitive nongated background / leak channels

cR head group on 0=P-0 transmembrane transpor 66000000000

Ion transmembrane transport

Chemically gated Bind ligand Ligand-gated B Phosphorylation- ga Chemically gated Phosphorylate Phosphrylation- gated: G protein/ secona massagers Dephosphorylate Gating mechanisms C Voltage-gated membrane Voltage-gated of ion channels potential D Stretch or pressure- gated Mechanosensitive Stretch

Gating mechanisms of ion channels Chemically gated Ligand-gated Chemically gated Phospharylation￾gated: G protein / second massagers Voltage-gated Mechanosensitive

A. General properties of ion channels in CVS u Voltage-gated ion channels d Nat channels a Ca2+ channels K+ channels

A. General properties of ion channels in CVS Voltage-gated ion channels Na+ channels Ca2+ channels K+ channels

Outside cell Inside ce‖ filte voltage sensor General structure of ion channels Pore Structure of electivity filter a-subunit

Structure of -subunit General structure of ion channels voltage sensor filter

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