Drugs Of The Day Flashcards
Spirinolactone
Class - potassium sparing diuretics
Mechanism of actions - aldosterone antagonist - prevents aldosterone from inc expression of ENAC and ROMK channels in principal cell of CD.
Uses - in step 4 resistant hypertension (1st is ARB/ACEi or CCB. Then it’s add one of the previous or thiazide diuretic. Then it’s all 3. Then it add Spirinolactone or alpha/b blockers). Used as a possible diuretic in chronic heart failure with reduced ejection fraction.
Side effects - # Hyperkalaemia, gynaecomastia (by converting testosterone to oestrogen), severe cutaneous adverse reactions
Warnings - X Hyperkalaemia, Addison’s, anuria
Drug interactions - Δ ↑K+ drugs (monitoring), pregnancy, alcohol, amiloride, ACEi, ARBs
α and β blockers would be considered instead of spironolactone if high [K+] (in step 4 hypertension).
Centrally acting drugs – labetalol (pregnancy, hypertensive emergency i .v. ) - reduce sympathetic outflow - not typically in primary practice but p.o. labetalol in pregnancy
Atarvostatin
Atorvastatin - first pass metabolism – active metabolites – t1/2 ~24h
Competitive inhibition of HMG-CoA reductase
Contributes to upregulation of hepatic LDL receptors so inc clearance of circulating LDL
• # GI disruption, nausea and headache, diffuse muscle pain
Rarely – rhabdomyolysis
Increased liver enzymes
• X renal or hepatic impairment, pregnancy! and breastfeeding
• Δ CYP 3A4 important – amiodarone, diltiazem, macrolides - increases [plasma] statin
Guidelines:
Primary prevention 20 mg atorvastatin once daily (10 year CVD risk of >10% using QRISK 3). Target= >40% reduction in non HDL-C at ~ three months.
Secondary prevention 80 mg atorvastatin once daily
LDL 2.0 mmol per litre or less, or non-HDL cholesterol levels of 2.6 mmol per litre or less
Combination of ezetimibe with statin benefit in CKD and in some for secondary CVD prevention.
Amlodipine
Mechanism of action - binds to alpha subunit on L-type Ca2+ channel (VOCC) so prevents Ca2+ influx prevented so prevents vasoconstriction.
• # Ankle swelling, flushing, headaches (vasodilation), Palpitations (compensatory tachycardia)
• X Unstable angina, severe aortic stenosis, cardiogenic shock
• Δ amlodipine + simvastatin (increased effect of statin)
dihydropyridines selective for peripheral vasculature (little chronotropic or inotropic effects).
cerebral vs peripheral selectivity dictates which are used for hypertension
• CCBs – often primary choice antihypertensive in low renin patients
Ramipril
ACE inhibitors
• To treat : hypertension & heart failure (2nd line and dec ejection fraction).
• Stops ang 2 so production so dec aldosterone so dec Na+ and h2o. Dec ADH so dec water and thirst.
Ang 2 also causes Vasoconstriction of efferent arteriole so inhibited and dec na+ reabsorption from PCT via Na+/H+ exchanger.
• # dry cough, angioedema, hypotension, renal impairment, tinnitus, vertigo
• X hereditary angioedema
• Δ K+ sparing diuretics, alcohol
Furosemide
• Inhibit N+/K+/2Cl-co-transporter. Reduced N+K+2Cl-into epithelium. H2O follows ions concentration by osmosis.
• Direct dilation of capacitance veins –reduces preload.
First line For acute pulmonary oedema, fluid overload in HF, adjunct in nephrotic syndrome
• # Dehydration, hypotension, hypokalaemia, hyponatraemia, hyperuricemia with chronic treatment, arrhythmia, tinnitus –ototoxicity, ↑cholesterol & TG
• X hypokalaemia, hyponatraemia, gout, hepatic encephalopathy
• Δ aminoglycosides, digoxin, lithium
Verapamil
Phenylalkylamines
• Class IV anti-arrhythmic agent/prolongs the action potential/effective refractory period. AF
• Less peripheral vasodilatation, negative chronotropic and inotropic effects
• Used for: Arrhythmia, angina, (hypertension)
• # Constipation, bradycardia (i .v. ), heart block and cardiac failure, gums become thick
• X Poor LV function (caution), AV nodal conduction delay
• Δ β-blockers (cardiologist use only), caution with other antihypertensive and antiarrhythmic agents
Amiodarone
Class - K+ channel blockers
Uses - arrhythmias eg SVT and ventricular tachycardia
Mechanism -prolong repolarisation (qt interval prolonged)
Side-effects - can be arrythmogenic, Lung fibrosis ◦ Hepatotoxic ◦ Optic neuritis ◦ Thyroid toxicity ◦ Peripheral neuropathy
Contraindications -
Interactions - digoxin, warfarin
semaglutide
• ↑glucose dependant synthesis of insulin secretion from β-cells
by activating GLP-1 receptor.
It is resistant to degradation by DPP-4
Subcutaneous injection as peptide hormones are degraded in the stomach
Promote satiety and weight loss
• NICE suggest swap with one of the drugs in triple therapy if triple therapy is ineffective (triple therapy is metformin and 2 other oral drugs).
• # GI upset, decreased appetite with weight loss
• X Renal impairment - cannot give with end stage renal failure
• Δ other hypoglycaemic agents
Clopidogrel
Anti-platelet
ADP receptor antagonist:
Irreversible inhibitors of P2Y12 so ADP cannot bind. No activation of GPIIIb/GPIIIa receptors so no platelet aggregation.
Oral
Stop 7 days before surgery
Slow onset of action without loading dose
Side effects - GI bleeding, dyspepsia, diarrhoea
Warnings- high bleeding risk patients with renal/hepatic impairment
Drug interactions - needs to be activated by CYP in liver so do not give with CYP inhibitors eg omeprazole, PPIs, SSRIs, ciprofloxacin, erythromycin
Careful with other NSAIDs and anti-coagulants and anti-platelets
Uses
Given with aspirin
Ischaemic Stroke
TIA
STEMI or NSTEMI
Dapagliflozin
competitive reversible inhibition of SGLT-2 in PCT
↓glucose absorption from tubular filtrate, ↑urinary glucose excretion
• Modest weight loss, hypoglycaemic risk is low
• TIIDM as add on therapy
New guidelines suggest offering to CVD risk patients as early add on to metformin
• # UTI and genital infection, thirst and polyuria, pancreatitis?, , fornius gangrene
• X hypovolaemia - possible hypotension
• Δ antihypertensive and other hypoglycaemic agents
Aspirin
NSAIDs and anti-platelet
Mechanism- thromboxane A2 (TXA2) formed from arachidonic acid by COX-1 • Aspirin - inhibits COX-1 mediated production of TXA2 and reduces platelet aggregation –
irreversible
Higher doses inhibit endothelial prostacyclin (PGI2) which contributes to maintenance of blood flow and mucosal repair
Metabolism - Absorbed by passive diffusion – hepatic hydrolysis to salicylic acid
Uses - 75mg -non-analgesic. 300mg in acute coronary syndrome.
Some atrial fibrillation (AF) patients post stroke
• Secondary prevention of stroke and TIA (acute ischaemic stroke initial 300 mg daily 2 weeks)
• Secondary prevention of acute coronary syndromes (ACS) - 75mg aspirin + ADP receptor antagonist
• Post primary percutaneous coronary intervention (PCI) and stent to reduce ischaemic
complications
• NSTEMI/STEMI - initial once only 300 mg loading dose
• # Gastrointestinal irritation, GI bleeding (peptic ulcer), haemorrhage (stroke)
hypersensitivity
• X Reye’s syndrome – avoid <16 years
Hypersensitivity
3rd trimester – premature closure of ductus arteriosus
• Δ caution - other antiplatelet and anticoagulants (additive/synergistic action)
• COX-1 polymorphisms result in lack of efficacy in some
tranexamic acid
Menorrhagia, nose bleeds
Inhibits plasminogen to plasmin
Celecoxib
COX-2 inhibitor
• Less inhibitory action on COX-1
• Less GI ADRs, renal ADRs similar to non-selective
Do not share antiplatelet action but inhibit PGI2
• Can be useful when monitored in severe osteo and rheumatoid arthritis for longer term treatment
# Dyspepsia, nausea, peptic ulceration, bleeding and perforation
• ↓mucus and bicarbonate secretion, ↑acid secretion • ↓mucosal blood flow → enhanced cytotoxicity and hypoxia
• # Exacerbation of inflammatory bowel disease
X elderly, prolonged use, smoking, alcohol, history of peptic ulceration, helicobacter pylori, X ALL NSAIDs (not low dose aspirin) increase risk of MI including in low risk people
• Δ aspirin, glucocorticoid steroids, anticoagulants (PPI should be considered)
Renal considerations
• # NSAIDs produce some reversible ↓GFR ↓renal blood flow
• X More likely in underlying CKD, heart failure where there is greater reliance on prostaglandins for vasodilatation and renal perfusion
azathioprine
fentanyl
