Human Aspects of Cardiovascular and Renal Pharmacology Deck Flashcards
Atenolol
β1 adrenoreceptor antagonist that has antihypertensive effects. Unclear exact mode of action. Also used to treat angina.
Bisoprolol
β1 adrenoreceptor antagonist that has antihypertensive effects. Unclear exact mode of action. Also used to treat angina.
Pindolol
Partial β1 adrenoreceptor agonist. Due to mild nature has little effect on cardiac output.
Prazosin
α1 adrenoreceptor antagonists. Prazosin is the archetypal example, but Doxazosin is the most commonly used. Lack of presynaptic α2 receptor block means that there is no reflex tachycardia.
Doxazosin
α1 adrenoreceptor antagonist. Doxazosin is the most commonly used and dilates resistance and capacitance vessels. Lack of presynaptic α2 receptor block means that there is no reflex tachycardia.
Phentolamine
Non-selective α adrenoreceptor antagonist. Gives vasodilation accompanied by reflex tachycardia.
Labetolol
α1, β1 and β2 antagonist (more so β than α). Antihypertensive.
Amlodipine
L-Type Ca2+ channel antagonist. Most commonly prescribed dihydropyridine. Antihypertensive effect mainly due to reduction of smooth muscle contraction.
Minoxidil
KCO used to treat hypertension. Acts on ATP-sensitive K+ channels, opening them, causing hyperpolarisation and relaxation of vascular smooth muscle. Can be used in severe refractory hypertension in combination with a β blocker and diuretic. It also causes some hirsutisms so has some use as a topical hair loss treatment.
Clonidine
Centrally acting α2 agonists. Guanfacine is more potent as α2 agonist but has lower efficacy than clonidine as an antihypertensive. Their effect originally thought to be due to decreasing NA release by acting on CNS presynaptic receptors but effect may be through I1 receptor. Clonidine withdrawal has marked effects.
Guanfacine
Centrally acting α2 agonists. Guanfacine is more potent as α2 agonist but has lower efficacy than clonidine as an antihypertensive. Their effect originally thought to be due to decreasing NA release by acting on CNS presynaptic receptors but effect may be through I1 receptor.
Moxonidine
Imidazoline drug that mimics the effects of clonidine and guanfacine. Centrally acting antihypertenive with fewer side effects than α2 agonists.
α-Methyldopa
Converted into α-methylnoradrenaline. False transmitter of NA system. It is less potent at α1 adrenoreceptors but more potent at α2 adrenoreceptors than NA. Centrally acting anti-hypertensive agent.
Hexamethonium
Antihypertensive ganglionic blocker. First used as an antihypertensive in the 1950s. Since they block all ganglionic transmission they were soon superceded by more specific agents. They are only used in certain surgical procedures to control local blood flow.
Trimetaphan
Antihypertensive ganglionic blocker. First used as an antihypertensive in the 1950s. Since they block all ganglionic transmission they were soon superceded by more specific agents. They are only used in certain surgical procedures to control local blood flow.
Sodium Nitroprusside
Directly acting vasodilator, metabolised to NO. However in solution it also hydrolyses to give cyanide, so is used intravenously in hypertensive emergencies.
Hydralazine
Arteriolar vasodilator with unknown mechanism.
Simvastatin
2nd generation statin, most widely prescribed for at risk individuals. It acts by inhibiting HMG-CoA reductase, decreasing cholesterol synthesis so liver has to take up more LDL from the blood. This decreases predisposition to atheroma formation.
Clofibrate
Fibric acid derivative which lowers VLDL and (to a lesser extent) LDL. It stimulates lipoprotein lipase, releasing triglycerides from VLDL and chylomicrons. The lipid can then be taken and stored in fat or metabolised in skeletal muscle.
Rosiglitazone
PPARγ agonist. Induces LXR transcription, leading to indirect induction of ABCA1, which controls the rate limiting step in HDL synthesis. Reported to reduce atherosclerosis in both experimental models and clinical trials.
Colestyramine
Anion exchange resin. It prevents reuptake of bile acids from the intestine by sequestering them in the gut lumen, so causes an increase in cholesterol metabolism to synthesise bile acids in the liver. Unpleasant side effect of chronic diarrhoea.
Nicotinic Acid
Inhibitor of liver triglyceride production and VLDL secretion when used in large doses. Increases levels of t-PA.
Ezetimibe
Inhibits intestinal absorption of cholesterol by targeting NPC1L1 protein which transports sterol across brush border and is also present in the liver where it helps the reabsorption of cholesterol from bile. It circulates enterohepatically so is repeatedly re-delivered to the intestine, can be used in combination with a statin or alone.
Glyceryl Trinitrate
“Nitrovasodilator”. Organic nitroderivatives. Both glyceryl trinitrate and isosorbide dinitrate are commonly used to treat angina, the former especially in acute attacks. Glyceryl trinitrate is poorly absorbed from the stomach and so is taken sub-lingually (absorbed directly into systemic circulation). Causes vasodilation by being converted to NO in vascular smooth muscle cells. The main way that nitrovasodilators work in angina is by causing venous dilation, reducing RAP and decreasing the work done by the heart. They also seems to cause vasodilation in collateral vessels of ischaemic areas preferentially. May cause headache.
Isosorbide Dinitrite
“Nitrovasodilator”. Organic nitroderivative. Both glyceryl trinitrate and isosorbide dinitrate are commonly used to treat angina, the former especially in acute attacks. Isosorbide dinitrate needs to be metabolised to isosorbide mononitrate by the liver for it to work. Causes vasodilation by being converted to NO in vascular smooth muscle cells. The main way that nitrovasodilators work in angina is by causing venous dilation, reducing RAP and decreasing the work done by the heart. They also seems to cause vasodilation in collateral vessels of ischaemic areas preferentially. May cause headache.
Amyl Nitrate
“Nitrovasodilator”. Organic nitroderivative. Causes vasodilation by being converted to NO in vascular smooth muscle cells. The main way that nitrovasodilators work in angina is by causing venous dilation, reducing RAP and decreasing the work done by the heart. They also seems to cause vasodilation in collateral vessels of ischaemic areas preferentially. May cause headache.
Propranalol
Non-specific β antagonist. Less useful than specific β1 antagonists due to unwanted side effects- bronchoconstriction, blocking β2 mediated coronary vasodilation, unmasking α1 mediated vasoconstriction.
Nifedipine
DHP that blocks L-type Ca2+, decreasing Ca2+ entry to vascular smooth muscle. This causes vasodilation, decreasing blood pressure and decreasing the work of the heart. Selectivity for vascular smooth muscle rather than cardiac Ca2+ channels due to less negative resting potential (-50 to -60mV) vs (-80 to -90mV) so a higher proportion of the channels are inactivated.
Ivabradine
Acts on I f current, blocking it and reducing pacemaker activity. Slower HR allows more blood to perfuse the myocardium. Effects are selective due to the location of the HCN channels on which it acts. Very few unwanted side effects.
Ranozaline
Inhibits the late Na+ currents in cardiac myocytes, reducing Ca2+ overload and diastolic wall stress in ischaemic tissue, improving coronary flow.
Nicorandil
KCO that can stimulate a similar protection to ischaemic preconditioning from ischaemic damage by preserving ATP levels during ischaemia. Also a NO donor, which is believed to be involved in preconditioning. May also open vascular Katp channels, improving perfusion by relaxing vascular smooth muscle. The NO it produces may also enhance endothelium-dependent relaxation mechanisms. Used to treat angina.
Vascular Endothelial Growth Factor (VEGF)
A possible future treatment for angina, its expression causes angiogenesis, providing new blood flow to ischaemic tissue. Neo-vascularisation can be achieved through a single injection of a gene transfer vector; however a limited expression can cause abnormal angiogenesis.
Hypoxia-Inducible Factor 1α (HIF-1α)
A transcription factor that regulates the expression of multiple angiogenic genes, including genes, including VEGF. Possible target for future angina treatments.
Sirolimus
Immunosupressant drug that has antiproliferatice effects and is eluted from a type of drug-eluting stents used to revascularise coronary arteries in the treatment of coronary heart disease.
Paclitaxel
A drug eluted by certain stents used to revascularise coronary arteries in the treatment of CHD which interferes with the normal function of microtubule growth. Also an anti-cancer drug.
Quinidine
Class 1A antidysrhythmic, V-gated Na+ channel blocker. Increased AP duration with an intermediate rate of association/dissociation. Greater affinity for open state than for inactivated. Work against atrial and ventricular dysrhythmias and shows use dependence at normal resting potentials. Not in common use.
Flecainamide
Class 1C antidysrhythmic. Very slow to associate/dissociate, good for ectopic beats. However lower long term survival in controlled trials means it is only used in very unusual circumstances.
Lidocaine
Class 1B antidysrhythmic. Greater affinity for inactivated rather than activated states. Influenced by length of the action potential. Kinetics means it is most effective at high firing rates, where the diastolic is depolarised and in parts of the heart where AP is longest. Acting at lower concentrations than needed to be a LA.
Amiodarone
Class III antidysrhythmic. Prolongs AP and refractory period, possibly by inhibiting K+ channels involved in repolarisation. May also affect inactivation of Na+ channels, prolonging their activation. Helps prevent re-entrant and circular dysrhythmias.
Verapamil
Class IV antidysrhythmic, Ca2+ channel antagonist with myocardial selectivity. Useful for many types of dysrhythmia due to the ubiquitous nature of Ca2+ channels in the heart. If given in excess can inhibit contraction (disruption of excitation-contraction coupling). So it is not normally used if cardiac function is compromised.
