24/05 Flashcards
ticagrelor
Ticagrelor belongs to a class of drugs known as thienopyridines (which also contains clopidogrel). Ticagrelor is a P2Y12 receptor antagonist. The P2Y12 receptor normally couples with Gi proteins which inhibit adenylyl cyclase and also activate PI3K, Akt, Rap1b, and potassium channels. These actions all lead to signalling to activate platelet aggregation. Thus, antagonism of the P2Y12 receptor reduces platelet aggregation and thrombus formation, which can reduce the risk of myocardial infarction and ischemic stroke.
Indications
Ticagrelor is primary used following acute coronary syndrome or percutaneous coronary intervention
Side effects
Increased risk of bleeding
Dyspnoea
Bradyarrhythmia
Negative Chronotopes
A number of drugs have negative chronotropic effects on the heart.
Digoxin exerts its negatively chronotropic effects via an increase in vagal outflow. This slows AV conduction, leading to a decreased heart rate. It is also a positive inotrope
Beta-blockers (such as bisoprolol) exert their negatively chronotropic effects via a direct action on cardiac tissue.
Chronotropic drugs may change the heart rate and rhythm by affecting the electrical conduction system of the heart and the nerves that influence it, such as by changing the rhythm produced by the sinoatrial node. Positive chronotropes increase heart rate; negative chronotropes decrease heart rate.
ACE inhibitors
Ramipril, Lisinopril, Captopril
Look for “pril” ending
Mechanism of action
These drugs reduce the activity of the renin–angiotensin–aldosterone system (RAAS). Angiotensin coverting enzyme (ACE) is found in the pulmonary circulation and endothelium of blood vessels, it removes two residues from angiotensin I, converting it into angiotensin II. Normally, angiotensin II causes vasoconstriction, vascular smooth muscle hypertrophy, ventricular remodelling and hypertrophy, and aldosterone and vasopressin release which both conserve water in the kidneys. All these actions will increase blood pressure. ACE inhibitors block this conversion, so these effects do not happen.
Indications Hypertension Angina Post myocardial infarction Symptomatic heart failure Diabetic nephropathy Prevention of cardiovascular events
Side effects Cough: this is due to increased bradykinin levels in the respiratory tract Angioedema First dose hypotension Hyperkalaemia
Cautions/Contra-indications Pregnancy and breast feeding Aortic stenosis Renovascular disease (such as renal artery stenosis) Idiopathic angioedema
Monitoring
When commencing an ACE inhibitor, it is important to monitor creatinine and potassium. You do expect to see an insignificant rise in both of these. An increase in serum creatinine of 30% from baseline and an increase in potassium of up to 5.5mmol/L are acceptable.
cholestyramine
Cholestyramine can reduce cholesterol absorption by sequestering bile acids in the intestine to prevent their reabsorption and enterohepatic re-circulation.
They can be used for patients with hypercholesterolaemia who do not tolerate statins or as an adjunct to statin therapy. Furthermore, they are often used in patients with jaundice secondary to hyper-bilirubinaemia for symptomatic relief of pruritis.
Common side effects are constipation and increased plasma triglycerides.
Statins are competitive HMG-CoA reductase inhibitors. Fibrates are PPARα agonists. Vitamin A, D,E, and K are fat-soluble vitamins that may not be absorbed if there is a lack of bile due to with defective bile acid synthesis or excretion. Patients suffering from biliary disease may suffer from deficiency of these vitamins.
Angiotensin receptor blockers
Candesartan, Losartan, Irbesartan
Mechanism of action
These drugs block the activation of angiotensin-II receptors which are found in smooth muscle cells in vessels, adrenal gland cortical cells and adrenergic nerve synapses. This leads to vasodilation, decreased vasopressin secretion and decreased production and secretion of aldosterone, which all leads to decreased blood pressure.
Indications
Hypertension (in patients who cannot tolerate ACE inhibitors)
Diabetic nephropathy
Chronic heart failure
Side effects
Hypotension
Hyperkalaemia
Angioedema
Cautions/Contra-indications
Reno-vascular disease (such as renal artery stenosis)
Aortic and mitral stenosis
Hypertrophic cardiomyopathy
Medical management of peripheral vascular disease
clopidogrel + statin
Similar drugs
Prasugrel, Ticagrelor
Mechanism of action Clopidogrel is part of the thienopyridines class of drugs (anti-platelet drugs). These drugs are irreversible antagonists of the P2Y12 adenosine diphosphate (ADP) receptor. This means that platelets cannot bind to this receptor and the glycoprotein IIb/IIIa complex is not activated. As this is not activated, platelet aggregation cannot take place, and so thrombus formation will not happen.
Indications
Ischaemic stroke (after two weeks of aspirin therapy)
Peripheral arterial disease
Side effects Headache Nausea Increased risk of bleeding Dyspepsia Diarrhoea
Cautions/Contra-indications
Some proton pump inhibitors such as Omeprazole and Esomeprazole may make clopidogrel less effective, but others such as Lansoprazole do not appear to have this effect.
Propanolol
beta-blockers, inhibiting the action of (nor)adrenaline on beta-adrenoceptors.
Propranolol is non-selective, and hence are contraindicated in asthma patients, as there are beta-2 receptors in the lungs, which when inhibited, cause bronchoconstriction. Hence, propranolol can precipitate an asthma attack in asthma patients. For this same reason, it is also contraindicated in people with chronic obstructive pulmonary disease (COPD).
It is used to treat hypertension, slow down heart rate for atrial fibrillation, anxiety and is a preventative therapy for migraine headaches.
Process of atherosclerosis
Endothelial dysfunction – results in altered synthesis of nitrous oxide
Endothelial cell injury - leads to expression of adhesion molecules
Foam cell formation -low-density lipoproteins (LDL) are oxidized by endothelial cells and macrophages and are subsequently taken up by macrophages which are then known as foam cells due to their histological appearance
Fatty streak formation - accumulation of these foam cells leads to fatty streak formation
Proliferation of smooth muscle and connective tissue deposition – leads to the development of an atheromatous plaque
Plaque rupture – following plaque rupture platelet adhesion leads to thrombosis and potential vessel blockage
Mechanism Of Action of Loop Diuretics
Furosemide, Bumetanide
Mechanism of action
Loop diuretics inhibit the sodium-potassium-chloride (Na-K-Cl) cotransporters (NKCC) which are found in the thick ascending limb of the loop of Henle. Specifically, they act on a type of Na-K-Cl cotransporters called NKCC2s. They inhibit these, which reduces the absorption of sodium, potassium and chloride ions. Water follows sodium, so if sodium is not being reabsorbed, neither is water, leading to increased urine production, which decreases blood pressure.
Loop diuretics also inhibit NKCC2s in the macula densa which reduces sodium transported into these cells. This stimulates renin release, which increases fluid retention in the body (through the renin-angiotensin system) and increases glomerular perfusion which leads to an increased (so better) glomerular filtration rate.
Indications
Resistant hypertension (especially in renally impaired patients)
Acute and chronic heart failure
Fluid overload
Side effects Hypotension Electrolyte disturbances (hyponatraemia, hypokalaemia, hypomagnesaemia, hypocalcaemia) Hypochloraemic alkalosis Ototoxicity Gout
Cautions/Contra-indications
Loop diuretics can exacerbate diabetes, though hyperglycaemia is less likely than in thiazide diuretic treatment.
Electrolyte abnormalities in the context of Digoxin Toxicity
Mechanism of action
Digoxin decreases conduction through the atrioventricular node, which means delayed signals from the atria to the ventricles, meaning ventricular rate is slowed (which is helpful for rate control of atrial fibrillation and flutter). Digoxin also inhibits the sodium potassium ATPase pump which increases the force of cardiac muscle contraction (this helps with improving symptoms of heart failure).
Indications
Atrial fibrillation rate control
Improving symptoms of heart failure
Digoxin Toxicity
It is important to remember that toxicity can occur even when the concentration is within the therapeutic range, but the likelihood of toxicity increases progressively from 1.5 to 3 mcg/L.
Precipitants Hypokalaemia (and drugs which can induce this such as thiazides) Hypomagnesaemia Hypercalcaemia Hypernatraemia Acidosis Amiodarone Quinidine Calcium channel blockers (Verapamil, Diltiazem) Spironolactone Renal failure Hypothermia Hypothyroidism
Signs and symptoms Confusion Yellow-green vision Lethargy Nausea & vomiting Anorexia Gynaecomastia Bradyarrhythmias
Management
Monitor potassium (+ correct)
Correct arrhythmias
Digibind: this is the reversal agent for digoxin, it contains antibodies specific for digoxin which neutralise it and prevent its action
