PCC2 Cardiovascular Drugs

How do GPIIb/IIIa receptors work ? - Found on platelet membranes, which have high affinity for fibrinogen - Binding to fibrinogen in this way = cross links can form between platelets - Intra-platelet increases in Ca2+ ion concentration causes activation of GPIIB/IIIa receptors. - It is a hybrid murine-human monoclonal antibody GPIIb/IIIa receptor inhibitors - Abciximab - Can bind to and inactivate platelet GPIMOA Ib/IIIa receptors - Prevents platelet aggregation GPIIb/IIIa receptor inhibitors - Tirofiban MOA - reversibly antagonises fibrinogen - binds to platelet GP11b/IIIa receptors How is Abciximab administered ? Intravenously GPIIb/IIIa receptor inhibitors - Epitifibatide MOA Binds to and antagonises GP11b/IIIa receptors with high affinity. Antiplatelet drugs: Clopidogrel MOA - Inhibits ADP-induced activation of platelets at the GPIIb/IIIa receptor - Prevents further platelet aggregation and subsequent thrombus formation - Inhibits ADP-induced activation of platelets at the GPIIb/IIIa receptor Antiplatelet drugs: Prasugrel MOA - Prevents further platelet aggregation by irreversibly binding to ADP P2Y12 receptor - Greater antiplatelet effect than clopidogrel because it is metabolised more efficiently 1/5 Antiplatelet drugs: Ticagrelor MOA A cyclopentyltriazolopyrimidine - inhibits platelet activation and aggregation mediated by reversible inhibition of P2Y12 ADP-receptor. Antiplatelet drugs: Dipyridamole MOA Increases cAMP concentration in platelets. Fibrinolytic (thrombolytic) drugs MOA - They are drugs that can lyse thrombi by converting plasminogen (found in blood) into plasmin - Plasmin = proteolytic enzyme whose substrate is polymerised fibrin so thrombi are broken down - Restores patency of the vessel that was obstructed, tissue can be reperfused with blood before necrosis occurs. Intravenously - can be given with aspirin How are Fibrinolytic (thrombolytic) drugs - Maximum benefit is obtained by adminadministered ? istration within 90mins following MI, with effectiveness decreasing over 24hrs. Fibrinolytic (thrombolytic) drugs - Streptokinase An enzymatic protein extracted from streptococcal bacteria. - Plasminogen becomes deposited on fibrin polymers Fibrinolytic (thrombolytic) drugs - Strep- Streptokinase binds to circulating plastokinase MOA minogen = forms a plasmin activating complex that converts more plasminogen into plasmin. Streptokinase - Side effects - Nausea - Vomiting - Allergic reaction = it is also antigenic, so the production of streptococcal antibodies precludes repeated use - Bleeding/occasional stroke - Hypotension = necessitating slowing of 2/5 infusion rate or raising of the patient's legs Streptokinase - Contra indications - Recent haemorrhage - Trauma - Dental extractions - Surgery - Pregnancy Tissue-type plasminogen activators (t-PAs) - Alteplase - Recombinant human t-PA (not allergenic) - Can be used in patients previously treated with streptokinase - much more affordable Aim of Stroke treatment ? - Achieve best possible recovery of function - To avoid secondary complications - To prevent further events (secondary prevention) A computerised tomography (CT) scan What diagnostic tool is commonly used of the brain/head to exclude or confirm a to differentiate between types of stoke? haemorrhage. - For patients with a diagnosis of ischaemic stroke causing a measurable neurological deficit, thrombolysis with alteplase is indicated. What drugs should be given within 4.5hrs of the onset of symptoms in patients with ischaemic stroke? - Treatment effect of alteplase is time-dependent so earlier treatment increases the chance of a favourable outcome for the patient. - Patients with ischaemic stroke should receive aspirin 300mg daily for 2 weeks. Describe the drugs that are used in the treatment of ischaemic stroke and why - This can be given orally but may also they are used - NICE reccomendations be given rectally in suppository form if ? the patient is unable to take medication enterally. 3/5 - After this clopidogrel is recommended at a dose of 75mg daily to prevent further events - Clopidogrel = recommended at a dose of 75mg daily to prevent further events Secondary prevention of Stroke drugs ? - Stains = if the patient was already taking a statin prior to the stroke, this can continue but if one is to be newly initiated then it should be started at least 48 hours after the stroke. - Antihypertensives (should be used cautiously initially unless the patient is severely hypertensive) = patients with severe hypertension following a stroke can be given intravenous labetalol or intravenous GTN (if beta-blockers are contraindicated). - NICE recommend dipyridamole (modTransient Ischemic Attack (TIA) - treat- ified-release) and aspirin in combinament tion for prevention of occlusive vascular events. - It is a humanised monoclonal antibody fragment (reversal agent) Haemorrhagic stroke treatment - idaru- - It has a highly specific binding affinity cizumab MOA with dabigatran - Therefore reversing the anticoagulant activity of it and its metabolites - One of the main complications of a SAH is secondary cerebral ischaemia = can be cause by cerebral vasospasm Subarachnoid haemorrhage - Nimodipine - Nimodipine has selectivity for cerebral vasculature - Patients suffering with a SAH can also 4/5 be given nimodipine prophylactically to try and prevent cerebral vasospasm. Explain the treatment modalities used in patients with atherosclerotic PVD ? - Prophylactic antiplatelet - Antihypertensive agents - Lipid lowering agents - Thrombolytic drugs and vascular surgery = severe disease 5/5