IBHRE复习资料：III. Basic Pharmacology_2

1、 Basic Pharmacology (2%) Basic Pharmacology (4 Questions) Basic knowledge Types of drugs Major cardiovascular responses; Pharmacokinetics Interaction Metabolism 2 The Autonomic Nervous System 自主神经系统自主神经系统 Consists of motor neurons that control multiple internal organs, including the heart Has 2 divi

2、sions: Sympathetic交感神经 or Adrenergic 肾上腺素 Alpha receptors peripheral arteries Arterial dilatation扩张/ constriction 收缩 Beta receptors central organs 1 Heart: HR, contractility, AV conduction. 2 Lungs: Broncho dilatation Parasympathtic 副交感神经or Cholinergic 胆碱能 Vagal activation: HR, AV conduction 3 Cardi

3、ovascular Drugs Agonists(激动剂) restore or enhance cellular activity by mimicking natural body chemicals than bind to cell receptors Antagonists（拮抗剂） inhibit or block action by occupying a cell receptor Nitrates （硝酸酯类） dilate veins and arteries, for chest pain Inotropes正性肌力药物 (Digitalis洋地黄) the amt of

4、 intercellular Ca+, the contractile force of the myocardium Sympathomimetic (Proterenol拟交感神经类，异丙肾上腺素) mimic sympathic activity Sympatholytic ( blocker副交感神经类) oppose sympathetic activity 4 Antiarrhythmic Drugs Vaughn Williams Classification Change the shape of the action potential by altering the flo

5、w of ions across a cardiac cell membrane Alter the automaticity, conductivity and refractoriness of cardiac tissue reduced the risk of re-entry & automaticity Bind to the channels and gates of a cell membrane Slow-binding drugs block the ioin-specific membrane channels and reduce conduction velocity

6、 Fast-binding drugs unbind quickly and have less effect on blocking a channel. 5 Effect on AP by Anti-arrhythmic Drugs 6 Class I - Na Channel Blockers Ia Quinidine奎尼奎尼 丁丁 A Flut & Fib, reentrant SVTs & VT Blocks Na+ / K+ , slows depolarization, prolong AP/RP QRS, QT prolonged Suppress automaticity o

7、f Purkinje/ can cause torsades de pointes （扭转性室速）（扭转性室速） Hypotension 低血压低血压 Ia Procainamide 普鲁卡因胺 AF with fast Ventricular rate through bypass tract Similar to Q but not as prolong AP & QT interval as Q QRS, QT prolonged torsades de pointes Drug induced SLE Hypotension Ia Disopyramide 丙吡胺 Limited us

8、e, (-)ive inotropic & strong anticholinergic properties QRS, QT prolonged torsades de pointes Ib Lidocaine 利多卡因利多卡因 VT/VF (Popularly use) Slow depolarization & conduction velocity (shorten AP & RP) at fast HR & during ischemia, hypokalemia & acidosis, QRS prolonged QT shortened Suppress automacticit

9、y & ealry & late afterdepolarizations Ib Mexiletine 美西律 Not for emergency VT/VF QRS prolonged QT shortened CNS S.E uncoordinated movements Ib Phenytoin 苯妥英 VT due to digitailis toxicity Hypotension IbTocainide 妥卡尼 Rarely used Class I - Na Channel Blockers IC Flecainide 氟卡尼 AT/VT, effective for PVCs

10、& non- sustained VTs/ AVNRT/AVRT Not 1st choice for VT Slow conduction in all parts of the heart with slow binding automaticity Contraindicated in underlying heart disease (low EF cos life = 12 h) Risk of exacerbation of Re-entry (+) (Proarrythmic) IC Propafenone 普罗帕酮 Similar, a slight in RP Mild &

11、Ca+ blocking properties exacerbation of Re- entry (+) (Proarrythmic) IC Moricizine 莫雷西嗪 Similar as Flecainide, VT/AT Effect on conduction velocity is less pronounced AP & RP exacerbation of Re- entry (+) (Proarrythmic) 8 Class II - Blockers Carvedilol 卡维地洛 Metoprolol 美托洛尔 Terminate or prevent AVNRT,

12、 SANRT, Macro- reentrant tachy Slow the ventricular response to AT, A Flut, AF (All For A) Pronounced effect in areas of rich adrenergic innervation (SAN & AVN) Bradycardia, myocardial depression, bronchoconstrict ion, claudation, Raynauds phenomenon, hypoglycemic effect, depression, impotency 9 Cla

13、ss III - K+ Channel Blockers Amiodarone (Half life 100 days)胺 碘酮 AT , SVT or VT PAF Prolong AP & RP in A & V Has all effects (Class I, II & IV) GI,Pulmonary & Thyroid, neurological & occular S.E Bretylium 溴苄铵 Recurrent VF in emergency Prolong AP in V rather than in A, Initially adrenergic surge and

14、later antiadrenergic effect Need less energy for cardioversion, postural hypotension,体 位性低血压 Sotalol 索它洛尔 Not as effective Interaction with many drugs (antibiotic/ antihistamine) May prolong the QT interval (dose related) Brady, (-)ive inotrophy, torsades de pointes Ibutilide/Dofetilide 伊布利特/多非利特 AF

15、 or Fluttertorsades de pointes 10 Class IV Ca+ Channel Blockers Verapamil 维拉帕米 SVT(WPW), Multifocal AT, Macro reentrant VT Exercise induced and idiopathic VTs Control v rate in AF/ Flu refractoriness, depress automaticity, slow conducting in SAN & AVN (-)ive inotropic, hypotension, bradycardia, AV b

16、lock, Respi failure Contraindicate d for HOCM, Pul disease Diltiazem 地尔硫卓 SVT, AT, AVNRT, macro reentrant VT 11 Pharmacokinetics Bioavailability:生物利用度 The degree to which a drug becomes available to a target tissue after administration Affected by drug formulation, absorption, protein binding and fi

17、rst pass clearance in the liver 12 General Pharmacology (Exam Favorites!) Loading doses do not affect time to steady state or raise concentration of steady sate Elderly patients and patients with CHF have smaller volumes of distribution and thus mandate smaller loading doses Drugs that are renally e

18、xcreted require either dose reduction or less frequent dosing in renal insufficiency Cirrhosis does not increase volume of distribution, so loading doses should not be changed CHF results in decreased volume of distribution, decreased renal and hepatic blood flows, and increased risk of proarrhythmi

19、a use lower doses 13 Routes of Drug Administration 14 Elimination Half- Life (t1/2) Time required for elimination of 50% of the drug from the plasma Essentially completely eliminated (90%) after 4-5 half lives Diseases that affect the organs that metabolize and excrete the drug will alter t1/2 15 St

20、eady State When rate of drug elimination = rate of administration (i.e. drug effects are stable and predictable) Time to steady state is determined by the t1/2, typically 4-5 elimination half lives 16 Volume of Distribution Theoretical space of drug distribution which accounts for the amount of drug

21、 that is taken up by the body tissues Affected by the affinity of different tissues for the drug and by the tissue perfusion (i.e. CHF, Elderly)和组织对药物的青睐性及组织灌注度有 关 17 Renally excreted AADs Class Ia Procainamide普鲁卡因胺 Disopyramide丙吡胺 Class Ic Flecainide氟卡尼 Class III Sotalol心得安, Dofetilide多非利特 Other Di

22、goxin地高辛 All require dose reduction in RF 18 AADs with Pure Hepatic Metabolism Class Ib Lidocaine利多卡因 Mexiletine美西律 Class Ic Propafenone普罗帕酮 Class II Propranolol普纳罗尔 Esmolol艾思 Class III Amiodarone胺碘酮 Class IV Verapamil维拉帕米 Diltiazem地尔硫卓 All require dose reduction in CHF and Hepatic Disease 19 Drugs

23、that affect the Pacing Threshold PacingPacing Quinidine Procainamide at high doses Flecainide氟卡尼氟卡尼 blockers Sotalol Verapamil Amiodarone Propafenone Digitalis洋地黄 20 Drugs that affect the DFT 除颤阈值除颤阈值 DFTDFT Lidocaine Quinidine Flecainide 佛卡尼 Proparanolol Diltiazem 地尔硫卓 Verapamil Amiodarone with chr

24、onic oral, but IV - Digitalis 洋地黄 Bretylium溴苄铵 Sotalol reliably Dofetilide reliably 多多 菲利特菲利特 21 Proarrhythmia 致心律失常作用致心律失常作用 Low EF, CHF & Structural heart disease predict AAD efficacy and proarrhythmia Genetic predisposition based on pattern of metabolism and forme-fruste channelopathy 遗传倾向影响药物代谢

25、Ischemiarisk of proarrhythmia Proarrhythmia with one AADrisk of proarr with any AAD (except amiodarone) Electrolyte abnormality and other drugs may risk Qunidine can cause idisyncratic (non-dose related) Torse de pointe 22 Common S.E of Antiarrhythmic Drugs Hypotension IV Procainamide/ quinidine/ ph

26、enytoin 苯妥英/bretylium溴苄 铵 (-)ive Inotrophy 消化道 反应 blockers/ flecainide 佛卡尼/ disopyramide丙比安/ Verapamil Bradycardia blockers/ ca+ blockers (verapamil)/amiodarone CNS 中枢神经 effects All class IB/ amiodarone/ blockers/ flecainide 佛卡尼 GI effects 免疫 All/ quinidine/ procainamide/ class IB Hepatic effects Am

27、iodarone/ Phenytoin Pneumonitis 肺炎 Amiodarone Tocainide妥卡尼 Blood dyscrasias 不调 Quinidine Tocainide Phenytoin ANS 自主神经系统 effects Disopyramide Quinidine blockers/ digitalis/ sotalol 23 Drugs/ Electrolytes that increase the digoxin level : Quinidine奎尼丁奎尼丁 Flecainide 佛卡尼 Propafenone 普罗帕酮 Amiodarone Verapamil Hypercalcimia 高血钙 Hypokalemia 低钾血症 24 AF Maintenance Yes 25 No Heart D/S Flecainide Propafenon Sotalol Hypt LVH 高血压左心室肥大高血压左心室肥大 Amiodarone Dofetilide Or Ablation No Amiodaro