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

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