Drugs Flashcards
Clopidogrel/Ticagrelor/Prasugrel
Indications - ACS/CA Stents/2o Prevention
MOA - Prevent platelet aggregation by binding irreversibly to ADP receptors on the surface of platelets.
AEs - Bleeding/GI Upset/Thrombocytopenia
Warnings - Stop in active bleeding/7 days before elective surgery/Caution in patients with hepato-renal impairment.
Important interactions - Pro-drug that requires metabolism by hepatic cytochrome P450 (CYP) to its active form to have an antiplatelet effect therefore efficacy may be reduced by CYP inhibitors e.g. omeprazole, Abxs and SSRIs.
Aspirin
Indications - ACS/Acute Ischaemic Stroke/2o Prevention
MOA - Irreversibly inhibits cyclooxygenase to reduce production of the pro-aggregatory factor thromboxane from arachidonic acid, thus reducing platelet aggregation.
AEs - GI Upset/Peptic Ulceration/Haemorrhage/Bronchospasm/Tinnitus
Warnings - Should not be given to children under the age of 16 due to the risk of Reye’s syndrome/Aspirin hypersensitivity/Third trimester of pregnancy as PG inhibition may lead to the premature closure of the ductus arteriosis/Caution in those with peptic ulcers or gout.
Important interactions - Acts synergistically with other anti-platelet drugs, which although therapeutically beneficial can lead to increased risk of bleeding.
Apixaban/Edoxaban/Rivaroxaban
Indications - VTE/AF
MOA - Inhibit activated factor X (Xa) preventing conversion of prothrombin to thrombin.
AEs - Bleeding/GI Upset/Anaemia/Dizziness/Elevated liver enzymes.
Warnings - Stop in active bleeding/Dose reduction or alternative agent in those with hepato-renal impairment/CI in pregany and breastfeeding where the risk of harm to offspring is unknown.
Important interactions - Risk of bleeding increased by concurrent therapy with other antithrombotic agents/CYP inducers increase anticoagulant effect e.g. macrolides and decreased by rifampicin and phenytoin.
Dabigitran
Indications - VTE/AF
MOA - Acts directly on thrombin, preventing the conversion of fibrinogen to fibrin.
AEs - Bleeding/GI Upset/Anaemia/Dizziness/Elevated liver enzymes.
Warnings - Stop in active bleeding/Dose reduction or alternative agent in those with hepato-renal impairment/CI in pregany and breastfeeding where the risk of harm to offspring is unknown.
Important interactions - Risk of bleeding increased by concurrent therapy with other antithrombotic agents/CYP inducers increase anticoagulant effect e.g. macrolides and decreased by rifampicin and phenytoin.
Alteplase/Streptokinase
Indications - Acute ischaemic stroke (within 4.5 hours)/Acute STEMI (within 12 hours, PCI largely replaced fibrinolytics in this context)/Massive PE with haemodynamic instability.
MOA - Catalyse the conversion of plasminogen to plasmin, which acts to dissolve fibrinous clots.
AEs - Nausea/vomiting/hypotension/serious bleeding/allergic reaction/cardiogenic shock/cardiac arrest.
Warnings - Bleeding/Intracranial haemorrhage/Previous streptokinase treatment (development of antistreptokinase antibodies can block its effect).
Important interactions - Risk of haemorrhage increased in patients taking anticoagulants and antiplatelet agents.
Heparin (Enoxaparin, Dalteparin and UFH)/Fondaparinux
Indications - 1o prevention of VTE/ACS
MOA - Antithrombin (AT) inactivates clotting factors, particularly factors IIa and Xa, providing a natural break to the clotting process. Heparins and fondaparinux enhance the anticoagulant effect of AT. The size of heparin molecules determines their molecular specificity: UFH (large and small molecules) promotes inactivation of both factors IIa and Xa, whereas LMWH (smaller molecules) is more specific for factor Xa. Fondaparinux is a synthetic pentasaccharide that mimics the sequence of the binding site of heparin to AT and is very specific for factor Xa.
AEs - Haemorrhage/hyperkalaemia (effect on adrenal adolsterone secretion)/Heparin-induced thrombocytopenia (less likely with LMWH than UFH, and does not occur with fondaparinux).
Warnings - Patients at increased risk of bleeding including clotting disorders, severe uncontrolled HTN, and recent surgery or trauma/Witheld immediately before and after invasive procedures particularly LP and spinal anaesthesia/LMWH and fondaparinux accumulate in those with renal impairment therefore a lower dose or UFH should be used instead.
Important interactions - Additive effect with other antithrombotic drugs.
Warfarin
Indications - VTE prevention and treatment/AF
MOA - Inhibits hepatic production of vitamin-K-dependent coagulation factors (II, VII, IX and X, and proteins C and S). It does this by inhibiting vitamin K epoxide reductase, the enzyme responsible for restoring vitamin K to its reduced form, necessary as a co-factor in the synthesis of these clotting factors.
AEs - Bleeding - warfarin can be revered with phytomenadione (Vitamin K1)
Warnings - CI immediate risk of haemorrhage and pregnancy (teratogenic)/Caution in patients with liver disease who are less able to metabolise the drug.
Important interactions - CYP inducers (phenytoin, carbamazepine, rifampicin) increase warfarin metabolism and risk of clots/CYP inhibitors (Fluconazole and macrolides) decrease warfarin metabolism and increase bleeding risk.
Iron
Indications - Prophylaxis and treatment of IDA.
MOA - Iron required for the synthesis of the haem component of haemoglobin, which gives RBCs the ability to carry oxygen.
AEs - GI upset/Black bowel motions/Anaphylaxis
Warnings - May exacerbate bowel symptoms in patients with intestinal disease/IV iron should be used with caution in those with an atopic predisposition due to the risk of anaphylactic reaction.
Important interactions - Oral iron salts can reduce the absorption of other drugs, including levothyroxine and bisphosphonates. These medications should therefore be taken at least 2 hours before oral iron.
Thiamine
Indications - Thiamine (Vitamin B1) is used in the treatment and prevention of Wernicke’s encephalopathy and Korsakoff’s psychosis, which are manifestations of severe thiamine deficiency.
AEs - High-dose may rarely cause anaphylaxis.
Folic Acid
Indications - Folic acid is used in megaloblastic anaemia as a result of folate deficiency, and in the first trimester of pregnancy to reduce the risk of neural tube defects.
Hydroxocobalamin
Indications - Hydroxocobalamin is used in the treatment of megaloblastic anaemia and subacute combined degeneration of the cord as a result of vitamin B12 deficiency.
Phytomenadione
Indications - Recommended for all new born babies to prevent vitamin K deficiency bleeding, and is used to reverse the anticoagulant effect of warfarin.
AEs - High-dose may rarely cause anaphylaxis.
Alpha-Blockers e.g. Doxazosin, tamsulosin and alfuzosin.
Indications - Benign prostatic enlargement/Resistant hypotension.
MOA - Highly selective for alpha-1-adrenoceptors which are found mainly in the smooth muscle of blood vessels and urinary tract (bladder neck and prostate in particular). Blockade of these receptors induces relaxation, therefore cause vasodilation and a fall in BP, and reduced resistance to bladder outflow.
AEs - Postural hypotension/dizziness/syncope.
Warnings - Should not be used in patients with existing postural hypotension.
Important interactions - Combining anti-HTN drugs results in an additive effect.
Adenosine
Indications - Supraventricular tachycardia.
MOA - Agonist of adenosine receptors on cell surfaces. In the heart, activation of these G-coupled protein receptors induces several effects, including reducing the frequency of spontaneous depolarisations (automaticity) and increasing resistance to depolarisation (refractoriness). In turn, this transiently slows the sinus rate and conduction velocity and increases AV node refractoriness.
AEs - Bradycardia/asystole cause the patient to have a sinking feeling in their chest, often accompanied by breathlessness and a sense of impending doom. Due to the drug’s short lived effect, this feeling is only brief.
Warnings - CI in those with hypotension, coronary ischaemia or decompensated heart failure/May induce bronchopasm in susceptible individuals, so should be avoided in patients with asthma or COPD/Heart transplant patients are very sensitive to the effects of adenosine.
Important interactions - Dipyridamole, an antiplatelet agents, blocks cellular uptake of adenosine. This prolongs and potentiates its effect, so the dose adenosine should be halved/Theophylline and aminophylline are competitive antagonists of adenosine receptors and reduce its effect therefore higher dose required.
