Cardiovascular Pharmacology Flashcards
Dyslipidaemia: Statins
Inhibit the enzymatic action of HMG CoA reductase, decreasing cholesterol synthesis. Prevents the conversion of HMG-CoA to mevalonate. ↓↓↓ LDL, ↑ HDL, ↑ TGs Increased expression of LDL receptors ADRs: GI disturbances, insomnia, rashes, rhabdomyolysis CAUTION: Metabolised by CYT P450S Examples: Simvastatin, atorvastatin, fluvastatin, pravastatin
Dyslipidaemia: Fibrates
PPAR, increases lipoprotein lipase activity. Agonists of PPAR alpha, lipid-controlled regulatory elements. Increase transcription for lipoprotein lipase, increase hepatic LDL uptake, reduce plasma CRP and fibrinogen. ↓ LDL, ↑ HDL, ↑↑↑ TGs ADRs: Rhabdomyolysis, GI disturbances Examples: Bezafibrate, fenofibrate
Dyslipidaemia: Resins
MOA: Bind to cholesterol-holding bile acids to create an insoluble complex. Leads to secretion in faeces. Increased expression of LDL receptors on hepatocytes, leading to decreased levels of plasma
LDL. ↓↓ LDL, ↑ slightly HDL, ↑ slightly TGs
ADRs: GI disturbances (constipation), decreased absorption of other drugs, fat soluble vitamin deficiency
Dyslipidaemia: Ezetimibe
MOA: Acts at the brush border, upon enterocytes. Prevents absorption of cholesterol, without affecting absorption of fat soluble vitamins, triglycerides and bile acids.
↓↓ LDL, - HDL, - TGs Increased expression of LDL receptors
ADRs: GI disturbance, headache, rhabdomyolysis (if alongside statins) Example: Ezetimibe used in conjunction with statins
Arrhythmia: Class I
Sodium channel blockers/membrane stabilisers. Bind Sodium channels, in the open state, and some K channels. Decrease the availability of channels for binding, increases the threshold for depolarisation and increases the refractory period. Example: Flecamide, lidocaine ADRs: Visual impairment, dizziness, dyspneoa Subtype III only used for severe ventricular arrhythmia - risk of cardiac arrest
Arrhythmia: Class II
Beta-blockers. Affect rate Decrease automaticity (inotropic and chronotropic) and AV conduction velocity. Refractory period is increased. ADRs: Bradycardia, cold extremities, GI disturbances - Not to be used in heart failure, 2nd/3rd degree heart block Example: Atenolol (relatively selective for B1), propanolol, labetolol (+ vasodilation)
Arrhythmia: Class III
K+ channel blockers Bind potassium channels and prevent movement of potassium back into cells, for repolarisation. Prolongs the refractory period. Delays repolarisation. ADRs: Bradycardia, GI disturbances, corneal deposits Example: Amiodarone, defetilide, sotalol
Arrhythmia: Class IV
Calcium channel blockers Bind calcium channels and prevent the inward movement of calcium. Decrease contractility, automaticity and AV conduction. ADRs: Constipation, flushing and headaches Example: Verapamil, diltiazem
Heart failure: Digoxin
Inhibit the ATPase enzyme, disrupts NA/K exchange. Increases intracellular calcium concentration, increases [calcium] in the SR, increases calcium available for contractile activity. Increased inotropy ADRs: Dizziness, visual distrubances, nausea Indications: AF
Arrhythmia: Adenosine
Opens K+ channels –> Hyperpolarization. Decreases calcium currents. Short and rapid action
Hypertension: ACE inhibitors
Inhibit angotensin converting enzyme (ACE), preventing conversion of angiotensin I to angiotensin II. Ultimately prevents aldosterone release and any subsequent water and salt retention, prevents MAP increase. Examples: Ramipril, captopril, enalopril, lisinopril, perindopril ADRs: Dry cough, hypotension, hyperkalaemia
Hypertension: Renin inhibitors
Inhibit renin preventing the conversion of angiotensinogen to angiotensin, inhibiting the whole of RAAS. No alderosterone release and no rise in MAP. Examples: Aliskiren ADRs: Dry cough, hypotension, hyperkalaemia
Hypertension: Beta-blockers (B1)
Bind and blocks beta 1 receptors, preventing Noradrenaline binding. Blocks the action of the the Gs G protein, Gs –> adenylate cyclase –> cAMP –> PKA and increased Calcium. Decreased calcium means decreased contraction. Examples: Atenolol, bisprolol ADRs: Bronchoconstriction (nonspecific binding), hypotension, cold hands and feet, fatigue Contraindications: Not to be used by severe asthmatics, severe PAD, bradycardia > 50
Hypertension: Alpha-blockers (a1)
Bind to alpha 1 receptors, preventing the binding of noradrenaline to the receptors. Binding to A1 receptors inhibits the Gq G protein, prevents PLC activity and production of DAG and IP3. Decreases calcium concentration. Also acts upon A2, as an agonist. Creates negative feedback loop for noradrenaline. Also acts alpha 2 related Gi proteins. Sees inhibition of adenylate cyclase, preventing cAMP production. Examples: Doxazosin, indoramin, prozosin *Used for benign prostatic hypertrophy* ADRs: Postural hypotension, fatigue, dizziness
Hypertension: Calcium channel inhibitors
Block calcium channels, prevents influx of calcium and therefore reduces muscle contraction. Act on L-voltage gated calcium channels, act on the alpha subunit. Dihydropyridines: Lower BP through vasodilation, more specific for smooth muscle channels (Hypertension, angina, supraventricular arrhythmia, not heart failure) Nondihydropyridines: Act on vascular and also cardiac calcium channels. Also have an effect upon AV and SA nodes. (Hypertension, angina with a beta blocker, not heart failure)
Antiplatelets: ADP receptor inhibitors (P2Y12)
- Clopidogrel
MOA: Bind to ADP receptors. Prevent binding of ADP, subsequent Gi activity, PKA activation and platelet activation.
- Inhibit Gi activity: Cause ↑ cAMP, ↑ PKA activity, decreased platelet activation
