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Cardiovascular
| Term | Definition |
|---|---|
| Tetracaine | Local anaesthetic -> inhibits Na+ current at pH 8.3 -> pKa of 8.5 |
| Benzocaine | Local anesthetic -> inhibits Na+ current at pKa of 2.6 |
| Local anaesthetic characteristics | Drug must be uncharged to cross membrane -> then becomes charged/activated (intracellular) -> channel must be open -> channel shows use-dependence (some hydrophobic don't show - lodge whilst in PM) -> enhance inactivation |
| Tetrodotoxin | Guanidium derivative of puffer fish organs -> highly selective reversible blockers of neuronal VGNaC (S6 Glu387 COOH) at pore mouth -> less affinity for cardiac Na+ channels |
| Batrachotoxin | Membrane permeant alkaloid from skin of Colombina tree frog -> acts on intracellular channel portions -> irreversibly opens Na+ channels -> lower threshold (more readily open) -> provoke cardiac dysrhythmias |
| Alpha scorpion toxin | Polypeptide acting on outside of VGNaC -> inhibits inactivation -> permanently opens Na+ channel -> voltage dependent binding (enhanced by batrachotoxin - lowers activation potential) |
| Nifedipine | Dihydropyridine -> L-type Ca2+ channel blocker -> less Ca2+ influx -> no muscular contraction -> vascular selective -> manage angina, hypertension, aldosterone antagonist -> bind to inactivated S6 and S5/6 loops |
| Verapamil | Phenylalkylamine -> L-type Ca2+ channel blocker -> relatively selective for myocardium -> less Ca2+ influx -> less muscular contraction -> reduce myocardial O2 demand -> manage angina (less tachycardia/vasodilation) -> bind to open S6 and S5/6 loop |
| Diltiazem | Benzothiazepine -> L-type Ca2+ channel blocker -> IM selectivity for cardiac/vascular -> vasodilation, slow conduction velocity -> manage angina/hypertension -> binds to extracellular portion |
| Sulphonyl urea drugs | Close K-ATP channels -> less K+ efflux -> cell depolarisation -> stimulate insulin secretion in beta pancreatic cells, protect cardiac cells from ischaemia |
| Propranolol | Non-selective beta-blocker -> cardiac beta1 - inhibits AC activation -> less PKA -> less L-type VGCaC Ca2+ influx -> reduce HR/blood Pa -> smooth muscle beta2 -> increase contraction -> hypertension/bronchoconstriction |
| Atenolol | Beta1 selective blocker -> cardiac beta1 -> inhibits AC activation -> less PKA -> less L-type VGCaC Ca2+ influx -> reduce HR/blood Pa, angina |
| Quinidine/procainamide | IA anti-dysrhythmic -> moderate VGNaC blockade -> increased AP duration -> increase ERP in ventricular AP -> increase QT interval -> IM dis/association rate -> high affinity for open Na+ channels (use-dependent) -> no effect on nodal/pacemaker tissue |
| Lidocaine | IB anti-dysrhythmic -> weak VGNaC blockade -> decreased AP duration -> fast dis/association rate (decreases w/ depolarised Vm) -> high affinity for inactivated Na+ channels |
| Flecainide | IC anti-dysrhythmic -> no AP effect -> slow dis/association -> suppress majority of other dysrhythmias (ectopic beats) |
| Type II antidysrhythmics | Beta blockers -> sympathetic antagonists -> -ve ionotropy/chronotropy -> xcs myocardial catecholaminic sensitisation -> MI (enhanced inward current to produce AP creates ectopic foci) |
| Type I antidysrhythmics | VGNaC blockers -> types IA/B/C |
| Amiodarone | Type III antidysrhythmics -> prolong AP/RP -> inhibit GIRK (less repolarisation -> prolong AP/ARP) -> inactivate Na+ channels (lengthen AP/prevent re-entry/dysrhythmias) -> inhibit Ca2+ channel influx (use-dependent - suppress excitability/conductability) |
| Type IV antidysrhythmics | VGCaC blockers -> L-type channels -> nifedipine (dihydropyridine), verapamil (phenylalkylamine), diltiazem (benzothiazepine) -> decrease conduction velocity -> increase ERP/increase PR nodal interval |
| Adenosine | Anti-dysrhythmic -> AV A1 receptors -> Gi -> reduce cAMP -> increase [ATP]i -> activate I K-ACh -> K+ efflux -> hyperpolarise nodal tissue -> slow HR -> treat SVT -> short 1/2 life as natural compound |
| Digoxin | Cardiac glycoside -> anti-dysrhythmic/heart failure -> inhibit Na+/K+ ATPase -> intracellular Na+ increases -> less extracellular Na+ for NCX -> less Ca2+ efflux -> increase SERCA SR Ca2+ -> greater Ca2+ release -> +ve ionotropy -> increase AV RP -> toxic |
| Dobutamine | Beta1 selective DOPA analogue -> +ve ionotropy over chronotropy -> hypovolaemic shock treatment, improve CO after open heart surgery |
| Levosimendan | Calcium sensitisers -> increase cardiac Ca2+ binding efficiency to troponin w/out increase in energy consumption requirement -> inhibit PDE III -> peripheral vasodilation -> treat congestive heart failure |
| Streptokinase | Thrombolytic -> activates plasminogen activator (hydrolyses Arg-Lys bonds) -> plasmin proteolytic enzyme generated -> degrades fibrin (clot formation) and clotting factors II, V, VII (clotting cascade) |
| Alteplase | Thrombolytic -> recombinant human tissue plasminogen activator -> degrades fibrin |
| Aspirin | Antiplatelet -> oral administration (low dose) -> inhibits COX enzymes -> inhibits thromboxane A2 production -> decreased platelet aggregation |
| Clopidogrel | Antiplatelet -> oral administration -> prodrug metabolised in liver -> active metabolite specifically/irreversibly inhibits P2Y12 receptor -> inhibits ADP binding -> prevents platelet activation/fibrin cross-linking |
| Clopidogrel mutation | In Japanese population, some carry 2 non-functioning copies of gene for CYP2C19 (cytochrome P450 enzyme) -> cannot activate prodrug clopidogrel |
| Ticagrelor | Antiplatelet -> allosteric antagonist of P2Y12 receptors -> reversible ADP blocker -> prevents platelet activation |
| Eptifibatide | Antiplatelet -> cyclic heptapeptide reversible inhibitor of glycoprotein IIb/IIIa -> prevent platelet activation/aggregation |
| Tirofiban | Antiplatelet -> non-peptide inhibitor of glycoprotein IIb/IIIa -> prevent platelet activation/aggregation -> prevent MI in patients w/ unstable angina/recent MI |
| Abciximab | Antiplatelet -> mAb inhibitor of glycoprotein IIb/IIIa -> binds to platelet/endothelial/vascular smooth muscle vitronectin receptor (prevents cell adhesion/haemostasis) -> coronary angioplasty when treating coronary artery thrombosis |
| Heparin | Natural anticoagulant -> produced by basophil/mast cells - injection administration -> binds/activates antithrombin III (AT-III) -> inactivates thrombin/blood clotting proteases -> prevents prothrombin conversion to thrombin -> unstable angina after MI |
| Heparin side effects | Heparin-induced thrombocytopenia -> heparin bound platelet has PF4 (platelet factor 4) inside alpha granules -> -ve charged -> DAMP -> B cells produce anti-PF4 heparin IgH -> complex binds to platelet FcgamIIa R -> clot/removal -> platelet deficiency |
| Types of heparin | Low MW and unfractionated |
| Dalteparin | Low MW heparin -> wider application, sub-Q administration, more predictable pharmacokinetics -> anticoagulant -> activates antithrombin III (AT-III) -> prevents prothrombin conversion to thrombin -> venous thromboemboli treatment |
| Warfarin | Anticoagulant -> oral administration -> prevents clotting factor II, VII, IX, X synthesis by inhibiting Vit K epoxide reductase -> prevents efficient clotting cascade |
| Warfarin interactions and dosing | Interacts w/ many common food/drink drugs/chemicals -> may enhance/reduce warfarin anticoagulation effect -> when dosed over long periods, blood levels carefully/continuously monitored |
| Dabigatran | Anticoagulant -> thrombin inhibitor -> prevent fibrinogen conversion to fibrin -> patients w/ atrial fibrillation/stroke risk factor for clot development, short term prophylactic to prevent thromboembolism in individuals w/ recent knee/hip replacement |
| Vit K epoxide reductase | Reduces oxidised Vit K -> more reduced Vit K -> more inactive prozymogens converted to active zymogens -> more clotting factor II, VII, IX, X synthesis |
| Babies and Vit K | Vit K mainly introduced via diet -> Vit K injection after birth to synthesise clotting factors II, VII, IX, X -> prevent cranial haemorrhage |
| Rivaroxaban, apixaban, edoxaban | Anticoagulant -> indirect thrombin inhibitors -> inhibit factor Xa -> prevent prothrombin conversion to thrombin |
| Fondaparinux | Anticoagulant -> indirect inhibitor of activated Xa -> prevent prothrombin conversion to thrombin -> treat acute coronary syndromes |
| Argatroban | Anticoagulant -> synthetic direct thrombin inhibitor -> prevent fibrinogen conversion to fibrin -> used for HIT patients (platelet deficiency) |
| Bivalirudin | Anticoagulant -> natural hirudin analogue -> thrombin inhibitor in medicinal leech saliva -> prevents fibrinogen conversion to fibrin |
| Danaparoid | Anticoagulant -> indirect inhibitor of factor Xa -> prevents conversion of prothrombin to thrombin, direct inhibitor of factor IX -> prevents thrombin activation -> used for HIT patients |
| Tranexamic acid | Coagulant -> inhibits xcs clot lysis leading to severe haemorrhage -> inhibits plasminogen activation -> prevents plasmin formation -> prevents fibrinogen/fibrin proteolysis -> increase clotting -> suppress bleeding in traumatic injury/postpartum |
| Furosemide | Loop diuretic -> blocks NKCC in apical membrane of ThAL -> hypokalaemia (less K+ reabsorption) -> metabolic alkalosis (H+/K+ exchanger to compensate hypokalaemia) |
| Hydrochlorothiazide | Thiazide diuretic -> blocks Na+/Cl- cotransporter in apical membrane of ThAL/DCT -> hypokalaemia (significant if combined w/ digoxin -> less competition for Na+/K+ ATPase -> myocardial sensitivity -> toxic) -> metabolic alkalosis |
| Amiloride | K+ sparing diuretic -> blocks ENaC in apical membrane of DCT |
| Spironolactone | K+ sparing diuretic -> aldosterone antagonist -> competes w/ aldosterone for cytoplasmic receptor -> prevents upregulation of Na+/K+ ATPase and ENaC |
| Acetazolamide | CA inhibitor -> inhibits CA in brush border for PCT/DCT -> prevents H2CO3 conversion to H2O and CO2 -> prevents H2O absorption -> less Na+ influx via apical NHE -> filtrate alkalosis -> hypokalaemia |
| Ramipril | ACE inhibitor -> prodrugs -> prevent AgII production (prevent vasoconstriction) and prevents bradykinin hydrolysis (increase vasodilation) -> treat hypertension, high RAAS activation |
| Saralasin | AgII R peptide antagonist -> not suitable for oral administration (stomach pepsins) -> partial agonist -> treat hypertension |
| Losartan | AgII R non-peptide antagonist -> blocks AT1 -> AT2 activation generates NO to increase cGMP and vasodilation -> treat hypertension |
| Phentolamine | Non-selective alpha AR blocker -> vasodilation (alpha1 - baroreceptor reflex) but marked reflex tachycardia (alpha2 - decrease sympathetic outflow) -> treat hypertension |
| Doxazosin | Selective alpha1 AR blocker -> dilates resistance/capacitance vessels and no marked tachycardia (no alpha2 blockage - no increase in sympathetic outflow) -> treat hypertension |
| Minoxidil | Vascular smooth muscle K-ATP channel opener -> K+ efflux -> re/hyperpolarisation -> prevent VGCaC opening and vasoconstriction -> treat hypertension/counteract reflex tachycardia |
| Nicorandil | Vascular smooth muscle mito K-ATP channel opener -> K+ efflux while preserving ATP levels during ischaemia, NO donor -> endothelium-dependent relaxation for ischaemic preconditioning (able to withstand longer periods of ischaemia) -> treatment for angina |
| Clonidine/guanfacine | Presynaptic alpha2 CNS R agonist -> imidazoline I1 receptor -> Gi -> DAG/AA generation -> decrease catecholamine release -> treat hypertension |
| alpha-methyldopa | Converted in adrenergic neuron vesicles into alpha-methylNA -> released as false transmitter -> less potent on alpha1 (less vasoconstriction), more potent on alpha2 (decrease sympathetic outflow) |
| Atorvastatin | Statin -> inhibit HMG-CoA reductase -> liver must take up more plasma LDL to top up enterohepatic circulation cholesterol pool -> lower intracellular [LDL] -> set off LDLR gene transcription via SCAP protein |
| Evolocumab/alirocumab | PCSK9 inhibitor -> enhance internalisation and recycling of LDLR -> increase liver uptake of plasma LDL |
| Inclisiran | siRNA inhibiting PCSK9 mRNA -> prevent internalisation and degradation of LDLR -> increase # LDLR on PM |
| Bezafibrate | Stimulates PPAR alpha/gamma (LXR expression for ABCA-1 expression for reverse cholesterol transport) and stimulates lipoprotein lipase (TAG release from VLDL/chlomicrons for uptake into skeletal muscle) |
| Pioglitazone | Stimulates PPAR alpha/gamma (LXR expression for ABCA-1 expression for reverse cholesterol transport) -> used in T2DM to reduce atherosclerosis |
| Colestyramine | Forms insoluble complexes w/ intestinal bile acid -> prevents reuptake into enterohepatic circulation -> bile/cholesterol excreted in faeces |
| Ezetimibe | Binds to GI tract brush border Niemann-Pick C1-like 1 protein (NPC1L1) -> prevents sterol reabsorption across intestinal epithelial cells -> more sterol excretion in faeces |
| Bempedoic acid | Inhibits ATP citrate lyase (converts TCA citrate to acetyl CoA) -> less acetyl CoA for HMG-CoA reductase for de novo cholesterol synthesis) -> liver must uptake more LDL from plasma |
| Nitrovasodilators MoDA and side effect | Glyceryl trinitrate/nitroglycerin, isosorbide mononitrate, amyl nitrite -> treat angina but can change cerebral blood flow -> migraine headaches |
| Glyceryl trinitrate/nitroglycerin | Poorly absorbed from stomach -> lingual vein injection -> IJV -> converted to NO in vascular smooth muscle cells by ecNOS -> NO stimulates GC -> cGMP increases -> PKG -> venous/collateral coronary vasodilation -> treat angina |
| Dipyridamole | Stimulates adenosine receptors -> dilates all vessels (ischaemic/well-O2 tissues) -> diverts blood away from ischaemic region (coronary steal) -> treat angina |
| Ivabradine | If blocker -> reduce depolarisation to threshold in nodal tissue -> reduce HR -> more time in diastole -> selective for HCN channels in SA/AV node -> no effect on myocardial conduction/contractility/ventricular repolarisation -> treat angina |
| Ranolazine | Late Na+ current blocker -> inhibit late phase of Na+ current in myocytes -> increase [Na+]e -> increase NCX -> decrease Ca2+ influx -> reduce diastolic wall stress -> improve coronary blood flow -> treat angina |
Created by:
vykleung
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