50 Drugs Flashcards
Anti-Platelet Drugs
Example(s) of drugs:Acetylsalicylic acid (Aspirin)
Mechanism of action:
Irreversible inactivation of COX enzyme ⇒ ↓ platelet thromboxane (TXA2) and endothelial prostaglandin (PGI2) production- ↓ TXA2 ⇒ ↓ platelet aggregation and thrombus formation- ↓ PGI2 ⇒ ↓ nociceptive sensitisation and inflammation
Indication(s):
- Secondary prevention of thrombotic events
- Pain relief
Side effects:
- Bleeding (<1% Patients)
- Peptic ulceration
- Angiooedema
- Bronchospasm
- Reye’s syndrome (very rare)
Important pharmacokinetics / pharmacodynamics:
Half life becomes longer with very large doses (pharmacokinetics may be non-linear in overdose)
Patient information:
- Avoid over the counter preparations that contain aspirin.
- Some patients may be advised to take a Proton Pump Inhibitor alongside long-term aspirin.
Anti-Platelet Drugs
Example(s) of drugs:Clopidogrel
Mechanism of action:
Irreversibly blocks ADP-receptor on platelet cell membranes ⇒ inhibits formation of GPIIb/IIIa complex, required for platelet aggregation ⇒ ↓ thrombus formation.Indication(s):Secondary prevention of thrombotic events
Side effects:
- Bleeding (1-10% of Patients)
- Abdominal pain / diarrhoea (1-10% of Patients)
Important pharmacokinetics / pharmacodynamics: Avoid in liver failure
Patient information:
- Patients may be advised to stop clopidogrel before surgical procedures.
- Patients should not stop clopidogrel without consulting their doctor if they have an arterial stent in-situ.
Recombinant Tissue Plasminogen Activator (rtPA)
Example(s) of drugs:TenecteplaseAlteplase
Mechanism of action:
- Recombinant form of tissue plasminogen activator
- Catalyses conversion of plasminogen to plasmin
- Promotes fibrin clot lysis
Indication(s):
- Acute ischaemic stroke within 4.5 hours of onset
- Myocardial infarction within 12 hours of onset
- Massive pulmonary embolism
N.B Not all thrombolytic drugs are licenced for all of these indications
Side effects:
- Bleeding
- Allergic reaction / angiooedema (1%)
Important pharmacokinetics / pharmacodynamics:
- Bolus-infusion regimen is used for alteplase
- Tenecteplase is given as a single bolus
- Pharmacodynamic interactions with other blood thinners (antiplatelets / anticoagulants)
Patient information: When using thrombolytic drugs, patients should be made aware of the risk-benefit ratio, which should include reference to the rate of bleeding complications.
Heparins
Example(s) of drugs:Unfractionated Heparin
Mechanism of action:
- Enhances activity of antithrombin III.
- Antithrombin III inhibits thrombin.
- Heparins also inhibit multiple other factors of the coagulation cascade. This produces its anticoagulant effect.
Indication(s):
- Treatment and prophylaxis of thromboembolic diseases, including induction of vitamin K antagonists.
- Renal dialysis (haemodialysis)
- Acute Coronary Syndrome treatment
Side effects:
- Bleeding (Major haemorrhage risk can be as high as 3.5%)
- Heparin-induced thrombocytopenia
- Osteoporosis
Important pharmacokinetics / pharmacodynamics:
- Administered by continuous intravenous infusion or subcutaneous injection
- Complex kinetics - non-linear relationship between dose / half-life and effect – needs TDM
- Effect monitored using activated partial thromboplastin time (aPTT)
- Anticoagulant effect can be reversed with protamine.- Unfractionated heparin has a shorter duration of action than LMW Heparin.
- Used in preference to LMW Heparin, in selected patients, due to the shorter duration of action and reversability with protamine (for example, Peri-operatively.)
Patient information:
- Risk of bleeding
- Regular blood monitoring required
Heparins
Example(s) of drugs:Low Molecular Weight Heparin
Mechanism of action:
- Enhances activity of antithrombin III.
- Antithrombin III inhibits thrombin.
- Heparins also inhibit multiple other factors of the coagulation cascade. This produces its anticoagulant effect.
Indication(s):
- Treatment and prophylaxis of thromboembolic diseases, including induction of vitamin K antagonists.
- Renal dialysis (haemodialysis)
- Acute Coronary Syndrome treatment
Side effects:
- Bleeding (Major haemorrhage risk can be as high as 3.5%)
- Heparin-induced thrombocytopenia (Less risk than unfractionated heparin)
- Osteoporosis (Less risk than unfractionated heparin)
Important pharmacokinetics / pharmacodynamics:
- Subcutaneous injection
- More predictable dose-response relationship than Unfractionated Heparin.
- 2-4 times longer plasma half-life than Unfractionated Heparin
- Clearance is mostly via a renal pathway, thus the half-life can be prolonged in patients with renal failure, so dose adjustment may be needed.
- Regular coagulation monitoring is not required.
- Less readily reversed with protamine, than Unfractionated Heparin.
Patient information:
- Risk of bleeding
- Requires injection
- Will need blood testing in prolonged therapy (Full Blood Count, to monitor for thrombocytopenia).
Vitamin K Antagonists
Example(s) of drugs:Warfarin
Mechanism of action:
- Inhibits vitamin K epoxide reductase.
- Prevents recycling of vitamin K to reduced form after carboxylation of coagulation factors II, VII, IX and X.
- Prevents thrombus formation.
Indication(s):
- Treatment of venous thromboembolism
- Thromboprophylaxis in: AF / metallic heart valves / cardiomyopathy
Side effects:
- Bleeding (risk increases with increasing INR)- Warfarin necrosis
- Osteoporosis
Important pharmacokinetics / pharmacodynamics:
- Numerous drug interactions / food interactions
- Reversal by giving vitamin K
- Polymorphisms in key metabolising enzymes (VKORC1 and CYP2C9)
- Needs therapeutic drug monitoring and monitored loading regimen
- Monitored with INR and dose adjusted according to indication
Patient information:
- Need for compliance / attendance at visits for monitoring
- Care needed with alcohol
- Must inform doctor before starting new drugs – avoid over the counter aspirin preparations
Direct Thrombin Inhibitors
Example(s) of drugs:Dabigatran
Mechanism of action:
- Direct thrombin inhibitor; prevents conversion of fibrinogen to fibrin.
- This prevents thrombus formation.
Indication(s):
- Prophylaxis of venous thromboembolism (especially post-operative)
- Thromboprophylaxis in non-valvular AF
Side effects:
- Bleeding
- Dyspepsia
Important pharmacokinetics / pharmacodynamics:
- Rapid onset of action
- No food / few drug interactions (not metabolised via CYP 450)
- No need for therapeutic monitoring
- Currently no available antidote
Patient information:Risk of bleeding
Factor Xa Antagonists
Example(s) of drugs:Rivaroxaban
Mechanism of action:
- Inhibits conversion of prothrombin to thrombin, reducing concentrations of thrombin in the blood.
- This inhibits the formation of fibrin clots.
Indication(s):
- Prophylaxis of venous thromboembolism (especially post-operative)T
- hromboprophylaxis in non-valvular AF
- Treatment of venous thromboembolism
Side effects:
- Bleeding
- Nausea
Important pharmacokinetics / pharmacodynamics:
- Predictable drug interactions (metabolised via CYP 450, inc CYP3A4)
- No need for therapeutic monitoring
- Currently no available antidote
Patient information: Risk of bleeding
Factor Xa AntagonistsExample(s) of drugs:Apixaban
Mechanism of action:- Inhibits conversion of prothrombin to thrombin; reducing concentrations of thrombin in the blood.- This inhibits the formation of fibrin clots.Indication(s):- Prophylaxis of venous thromboembolism following hip or knee replacement surgery.- Thromboprophylaxis in non-valvular AF.Side effects:- Bleeding- NauseaImportant pharmacokinetics / pharmacodynamics:- Predictable drug interactions (metabolised via CYP 450 and substrate for p glycoprotein)- 75% is metabolised by the liver, the rest being renally excreted.- No need for therapeutic monitoring- Currently no available antidote.Patient information:Risk of bleeding
Cardioselective Beta-BlockersExample(s) of drugs:BisoprololAtenolol
Mechanism of action:- Cardioselective beta-1-adrenoceptor antagonist.- Preferentially blocks beta-1 receptors in cardiac and renal tissue.- Inhibits sympathetic stimulation of the heart and renal vasculature.- Blockade of the sino-atrial node reduces heart rate (negative chronotropic effect) and blockade of receptors in the myocardium depresses cardiac contractility (negative inotropic effect).- Additionally, blockade of beta-1 adrenoceptors in renal tissue inhibits the release of renin, depressing the vasoconstrictive effects of the renin-angiotensin-aldosterone system.Indication(s):- Hypertension- Angina- Rate-control in atrial fibrillation- Carvedilol or Bisoprolol may be used as part of supportive therapy for mild / moderate heart failure.Side effects:- Bradycardia- Hypotension- Bronchospasm- Fatigue (Can affect up to 10% of patients)- Cold extremities- Sleep disturbances- Loss of hypoglycaemic awarenessImportant pharmacokinetics / pharmacodynamics:- Avoid higher doses and use with caution in patients with Asthmatic and COPD – risk of bronchospasm.- Avoid in patients with history of frequent hypoglycaemia.- Do not combine Beta-Blockers with rate-limiting Ca2+-Channel-Blockers (Verapamil / Diltiazem) in anti-hypertensive therapy, due to risk of heart-block.Patient information:- Compliance is important – Patients may stop beta-blockers if they do not feel any better. Remind them that hypertension is asymptomatic but nonetheless a dangerous risk factor that needs controlled.- Fatigue and cold extremities are common side-effects.
Non-Cardioselective Beta-BlockersExample(s) of drugs:PropranololCarvedilol
Mechanism of action:- Propanolol: Non-cardioselective beta-1-adrenoceptor antagonist.- Carvedilol: Non-selective beta-1, beta-2 and alpha-1-adrenergic receptor antagonistic effects.- Inhibits sympathetic stimulation in the heart and vascular smooth muscle.N.B Further details under Cardio-Selective Beta-Blockers.Indication(s):- Hypertension- Angina- Anxiety- Migraine prophylaxis- Post-MI prophylaxis- Carvedilol or Bisoprolol may be used as part of supportive therapy for mild / moderate heart failure.Side effects:- Bradycardia- Hypotension- Bronchospasm- Fatigue (Can affect up to 10% of patients)- Cold extremities- Sleep disturbances- Loss of hypoglycaemic awareness Important pharmacokinetics / pharmacodynamics:- Caution in diabetic patients – risk of deranged carbohydrate metabolism- Avoid in patients with Asthma and COPD – risk of bronchospasm- Do not combine Beta-Blockers with rate-limiting Ca2+-Channel-Blockers (Verapamil / Diltiazem) in anti-hypertensive therapy.- Propanolol is lipid-soluble and is predominantly cleared by the liver. Avoid in liver impairment. Avoid abrupt withdrawal – risk of liver impairment.Patient information:- Nightmares and sleep disturbances may occur.- Compliance is important – Patients may stop beta-blockers if they do not feel any better. Remind them that hypertension is asymptomatic but nonetheless a dangerous risk factor that needs controlled.- Fatigue and cold extremities are common side-effects.
ACE InhibitorsExample(s) of drugs:RamiprilEnalaprilLisinoprilPerindopril
Mechanism of action:- Inhibits conversion of Angiotensin I to Angiotensin II (a more potent systemic vasoconstrictor).- This action subsequently inhibits Aldosterone release from the adrenal cortex, depressing renal sodium and fluid retention, thereby decreasing blood volume. Indication(s):- Hypertension- Heart Failure- Nephropathy- Prevention of Cardiovascular events in high risk patientsSide effects:- Dry cough (10% of Patients, causing cessation of treatment in 5%)- Hypotension- Hyperkalaemia- Renal Impairment- AngioedemaImportant pharmacokinetics / pharmacodynamics:- Adverse drug reactions are higher in patients with:High-dose diuretic therapy / Hypovolaemia / Hyponatraemia / Hypotension / Unstable Heart Failure / Renovascular diseasePatient information:- Blood test required at 1-2 weeks to check electrolyte balance.- Dry cough is a common side-effect.
NitratesExample(s) of drugs:Isosorbide MononitrateGlyceryl Trinitrate (GTN)
Mechanism of action:- Converted to Nitric Oxide (NO), a potent vasodilator.- Cardioselective, acting predominantly on coronary blood vessels, enhancing flow of blood to ischaemic areas of the myocardium.- Additionally, reduces myocardial oxygen consumption by reducing cardiac preload and afterload.Indication(s):- Treatment of Angina- Severe hypertension (intravenous GTN is sometimes used in this setting)Side effects:- Headache (incidence varies greatly, between 20-82%, causing cessation of treatment in 10%)- Postural Hypotension / Dizziness- Tachycardia Important pharmacokinetics / pharmacodynamics:- Tolerance develops with long-term use.- In order to avoid tolerance, patients should have a daily nitrate-free period.- Isosorbide Mononitrate: Oral medication, longer duration of action than GTN.- GTN: Rapidly inactivated by first pass (hepatic) metabolism and therefore cannot be digested – sublingual spray/tablet only. It can also be given intra-venously.Patient information:- Headache is a common side effect initially, but incidence decreases the longer the patient is on the drug.- Take GTN before activity that you know will bring on angina.
Rate-limiting Calcium Channel BlockersExample(s) of drugs:VerapamilDiltiazem
Mechanism of action:- Prevent cellular entry of Ca2+ by blocking L-type calcium channels.- Myocardial and Smooth muscle contractility depressed. Cardiac contractility will be reduced. - Dilate coronary blood vessels and reduce afterload.- Antidysrhythmic actions due to prolonged atrioventricular node conduction – depresses heart rate.Indication(s):- Supraventricular arrhythmias- Treatment of angina- HypertensionSide effects:Verapamil- Constipation (up to 11.7% of patients)- Flushing / Headache / Dizziness / Hypotension (up to 2.5% of patients) Diltiazem- GI disturbances (up to 6% of patients)- Bradycardia (up to 3.6% of patients)- Peripheral oedema (up to 15% of patients)- Dizziness / Headache / Hypotension (up to 4.3% of patients) Important pharmacokinetics / pharmacodynamics:- Contra-indicated in heart failure and left ventricular dysfunction due to potent negative inotropy.- Avoid in bradycardia and hypotension.- Do not use with beta-blockers.Patient information:- Constipation is a common side effect with Verapamil.- Ankle swelling is a common side effect with Diltiazem, hot weather making it worse.- Compliance is important – Patients may stop Calcium-channel blockers if they do not feel any better. Remind them that hypertension is asymptomatic but nonetheless a dangerous risk factor that needs controlled.
Non Rate-limiting Calcium Channel BlockersExample(s) of drugs:AmlodipineNifedipineFelodipine
Mechanism of action:- Prevent cellular entry of Ca2+ by blocking L-type calcium channels.- Myocardial and smooth muscle contractility depressed – these drugs mainly affect smooth muscle.- Dilate coronary blood vessels and reduce afterload- These drugs do not lower heart rate (heart rate may increase)Indication(s):- Hypertension- Treatment of AnginaSide effects:- Ankle oedema (up to 15% of patients)- Abdominal pain / Nausea- Palpitations (up to 4.5% of patients)- Flushing / Headache / DizzinessImportant pharmacokinetics / pharmacodynamics:Avoid in: Cardiogenic shock, Unstable Angina, Significant Aortic Stenosis.Patient information:- Compliance is important – Patients may stop Calcium Channel Blockers if they do not feel any better.- Remind them that hypertension is asymptomatic but nonetheless a dangerous risk factor that needs controlled.- Ankle swelling is a common side effect, hot weather making it worse.
HMG CoA Reductase InhibitorsExample(s) of drugs:SimvastatinAtorvastatinPravastatin
Mechanism of action:- Competitively inhibits HMG CoA Reductase; the rate-determining enzyme in the mevalonate pathway synthesis of cholesterol.- This causes an increase in LDL-receptor expression, on the surface of hepatocytes.- Increases hepatic uptake of cholesterol, reducing plasma cholesterol levels.- Reduces development of athersclerotic plaques. Statins may have additional pleotropic effects.Indication(s):- Familial hypercholesterolaemia- Prevention of cardiovascular events in high-risk patients.Side effects:- Myalgia (5-7% of patients)- Myopathy (with creatine kinase elevation) and rhabdomyolysis are rare.- GI disturbances (Varied symptoms; up to 6% of patients affected)- Liver abnormalities – deranged LFT’sImportant pharmacokinetics / pharmacodynamics:Myalgia and Rhabdomyolysis are dose-related, begin with low dose, especially in patients with previous side-effects. Patient information:- Report any unexplained muscle pains to their GP, who will check a creatine kinase blood level.- Diarrhoea and abdominal pain may be present initially. Other information:Hypothyroidism should be corrected before assessing need for statin use.
Cardiac GlycosidesExample(s) of drugs:Digoxin
Mechanism of action:- Increases vagal parasympathetic activity and inhibits the Na+/K+ pump, causing a buildup of Na+ intracellularly.- In an effort to remove Na+, more Ca2+ is brought into the cell by the action of Na+/Ca2+ exchangers.- The buildup of Ca2+ is responsible for the increased force of contraction and reduced rate of conduction through the AV node. Indication(s):- Heart Failure- Rate control in Atrial fibrillationSide effects:- Nausea- Vomiting- Diarrhoea- ConfusionImportant pharmacokinetics / pharmacodynamics:- Digoxin has a narrow therapeutic index.- Symptoms of digoxin toxicity are similar to effects of clinical deterioration.- Additionally, the plasma-concentration is not a reliable indicator of toxicity.- Digoxin-specific antibody fragments are used for life-threatening digoxin overdose.- Digoxin has a long half-life and maintenance doses may only be required once-daily.- Renal function, age and heart disease are major determinants for safe digoxin dosage.Patient information:Risk of toxicity.
Anti-Arrhythmic DrugsExample(s) of drugs:Amiodarone
Mechanism of action:- Amiodarone blocks cardiac K+ channels, prolonging repolarization of the cardiac action potential.- Restores regular sinus rhythm.- It also slows atrioventricular nodal conduction.Indication(s):Supraventricular / ventricular arrhythmias.Side effects:- Photosensitivity skin reactions (up to 75% of patients)- Hypersensitivity reactions- Hyper / Hypothyroidism (linked to high iodine content)- Pulmonary fibrosis- Corneal deposits (69-100% of patients)- Neurological disturbances- GI disturbances / HepatitisImportant pharmacokinetics / pharmacodynamics:- Very long half-life, once daily dosing, can take weeks-months to achieve steady-state amiodarone-plasma concentrations.- Thyroid function tests should be performed before treatment and every six months, or where symptomatic.- LFTs should be taken during treatment.Patient information:- Requires good compliance and attendance for monitoring blood tests.- Avoid exposure to the sun, wear protective clothing and sunscreen.- Report presence of rash after use – hypersensitivity risk
Beta-lactams - PenicillinsExample(s) of drugs:FlucloxacillinAmoxicillinBenzylpenicillinPenicillin V
Mechanism of action:- Attaches to penicillin-binding-proteins on forming bacterial cell walls.- This inhibits the transpeptidase enzyme which cross-links the bacterial cell wall.- Failure to cross-link induces bacterial cell autolysis. - Amoxicillin provides some amount of gram-negative cover in addition to gram-positive drugsIndication(s):Different penicillins have different indications for use because of a different spectrum of cover.Flucloxacillin provides Staphylococcus aureus cover whereas Amoxicillin does not. For example:Flucloxacillin:- Soft tissue infection- Staphylococcal endocarditis- Otitis externaAmoxicillin:- Non-severe community acquired pneumoniaSide effects:- Diarrhoea- Vomiting- Liver function impairment- Hypersensitivity reactions (severe reactions are rare; <0.05% are true hypersensitivity reactions)Important pharmacokinetics / pharmacodynamics:Good oral absorption.Flucloxacillin: Beta-lactamase stable/insensitive. This means Beta-lactamase producing bacteria are vulnerable to this drug. Amoxicillin: Beta-lactamase susceptible. This means Beta-lactamase producing bacteria are resistant to this drug. it is often combined with clavulinic acid, a beta-lactamase inhibitor.Patient information:- Return if symptoms persists after the course of antibiotics, may be infected with resistant organism.- Diarrhoea is a common side effect.- Report any incidence of a rash after use – risk of hypersensitivity reactions.Other information:- To overcome resistance in bacteria that secrete Beta-lactamase, a Beta-lactamase inhibitor is given with the penicillin. - An example is Clavulonic Acid. When combined with amoxicillin, it forms co-amoxiclav.
Beta-lactams - CephalosporinsExample(s) of drugs:CeftriaxoneCephalexin
Mechanism of action:- Attaches to penicillin-binding-proteins on forming bacterial cell walls.- This inhibits the transpeptidase enzyme which cross-links the bacterial cell wall.- Failure to cross-link induces bacterial cell autolysis.- Less susceptible to beta-lactamases than penicillins. - Provides both gram-positive and gram-negative cover.Indication(s):- Serious infection: septicaemia / pneumonia / meningitisSide effects:- Hypersensitivity reactions (Low cross-reactivity in patients with true penicillin allergy – can be as low as 3-7%)- Antibiotic-associated C.Difficile diarrhoea- Liver function impairmentImportant pharmacokinetics / pharmacodynamics:- Renal excretion.- Longer half-life, needs to be given once daily.Patient information:- Diarrhoea is a common side effect.- Report any incidence of a rash after use – risk of hypersensitivity reactions.
