Case 1 SBA Flashcards
Indications for lisinopril
Take by mouth, initially 10mg once daily. Usual maintenance 20mg once daily, maximum 80mg daily.
Contraindications for lisinopril
Patients with or family history of angioedema, patients with diabetes mellitus in combination with aliskiren
Indications for losartan
take by mouth
Under 75: initially 50mg once daily for several weeks then increased to 100mg once daily if necessary.
Over 75: start at 25mg then increase to 100mg if necessary
Contraindications for losartan
Patients with low GFR, patients with diabetes mellitus in combination with aliskiren
Indications for amlodipine
take by mouth, initially 5mg once daily, increased to 10mg once daily if necessary
Contraindications for amlodipine
Patients with unstable angina, significant aortic stenosis, or cardiogenic shock
Indications for indapamide
take by mouth in the morning. 2.5mg daily for immediate release, 1.5mg for modified release
Contraindications for indapamide
Patients with electrolyte imbalances
Pharmacokinetics of lisinopril
oral, 25% bioavailability, 12hr half-life, water soluble, not metabolised in liver, undergoes renal excretion unchanged
Pharmacokinetics of losartan
oral, 32% bioavailability, 14% converted in first pass metabolism, undergoes CYP450 metabolism, 2hr half-life or 3-9hr half-life for active metabolite, undergoes extensive plasma protein binding, excreted in urine and bile
Pharmacokinetics of amlodipine
oral, 60% bioavailability, 30-50hr half-life, reaches steady state after 7-8 days, slowly metabolised by liver CYP450
Pharmacokinetics of indapamide
oral, virtually complete bioavailability, 76-79% protein bound, 16hr half-life, 93% metabolised by liver, excreted in urine and faeces
Side effects of lisinopril
Dry cough, alopecia, vertigo, hypotension
Side effects of losartan
Postural hypotension, vertigo, vomiting, hyperkalaemia
Side effects of amlodipine
Headache, peripheral oedema, nausea, tachycardia
Side effects of indapamide
Postural hypotension, electrolyte imbalance, constipation, diarrhoea
Hypertension medication pathway if type II diabetes or <55 and not of black or Afro-Caribbean origin
ACE or ARB → add CCB or thiazide-like diuretic → combination treatment with ACE/ARB, CCB, and thiazide-like diuretic → if potassium <4.5 mmol/L consider adding spironolactone or if potassium >4.5 mmol/L consider adding alpha or beta blocker
Hypertension medication pathway if >55, black or Afro-Caribbean family origin and no type II diabetes
CCB → if CCB not tolerated switch to thiazide-like diuretic → add ACE, ARB, or thiazide-like diuretic → combination treatment with ACE/ARB, CCB, and thiazide-like diuretic → if potassium <4.5 mmol/L consider adding spironolactone or if potassium >4.5 mmol/L consider adding alpha or beta blocker
ACE inhibitor mechanism of action
Bind to and block the angiotensin converting enzyme which blocks the production of angiotensin II
ARB mechanism of action
antagonists which block the angiotensin II receptors on the kidney
Calcium channel blocker mechanism of action
Inhibits influx of Ca+ into vascular smooth muscle cells in arteries → reduced levels of Ca+ in muscle cytosol. Level of constriction in arterioles reduced causing vasodilation, reduced total peripheral resistance, and BP
Thiazide-like diuretics mechanism of action
blocks Na and Cl reabsorption from DCT by blocking Na/Cl symporter. More Na in urine means increased urine volume excreted → reduction in circulating blood volume → reduced BP
Potential problems in measuring blood pressure accurately
Incorrect cuff size, cuff upside down, unable to identify Korotkoff sounds, caffeine or nicotine use by patients, incorrect patient positioning
Define clearance
Volume of plasma cleared of drug per unit time
What is clearance a significant factor in determining?
Limiting time course of drug
Define half-life
time taken for plasma concentration of drug to halve
What is drug half-life useful for?
Estimating frequency of dosing
Define volume of distribution
Proportionality factor that relates the amount of drug in the body to the concentration of drug measured in the plasma
What affects volume of distribution?
Drug permeability across tissue barriers, plasma protein binding, accumulation in tissues, pH partition
What does volume of distribution define?
Dose as has an effect on plasma concentration which dictates the ability of a drug to reach its target organ
Concentration/time graph for a drug with first order kinetics
as time increases, plasma concentration decreases. Shaped like a downwards curve. The fraction eliminated (Kel – the elimination constant) per each unit time is the same. Using a log scale for the plasma concentration results in a straight line with a negative gradient
What is first order kinetics?
increasing the drug plasma concentration increases the rate of metabolism – metabolic rate is proportional to drug concentration and half-life is constant. Rate of drug elimination increases as the plasma drug concentration increases. This is the case for most drugs at most doses.
Describe drugs with short half-lives
tend to reach steady state quite rapidly. In general, those with very short half-lives require intravenous infusion to maintain the continued presence of the drug as their effects wear off quickly
Describe drugs with long half-lives
may take longer to start working but their effects persist for longer, so they may only need to be dosed once a day, once a week, or even less frequently. Chronic dosing (long interval over long time period) used to achieve therapeutic range at steady state.
