Case 1 SBA

Question 1

Indications for lisinopril

Answer 1

Take by mouth, initially 10mg once daily. Usual maintenance 20mg once daily, maximum 80mg daily.

Question 2

Contraindications for lisinopril

Answer 2

Patients with or family history of angioedema, patients with diabetes mellitus in combination with aliskiren

Question 3

Indications for losartan

Answer 3

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

Question 4

Contraindications for losartan

Answer 4

Patients with low GFR, patients with diabetes mellitus in combination with aliskiren

Question 5

Indications for amlodipine

Answer 5

take by mouth, initially 5mg once daily, increased to 10mg once daily if necessary

Question 6

Contraindications for amlodipine

Answer 6

Patients with unstable angina, significant aortic stenosis, or cardiogenic shock

Question 7

Indications for indapamide

Answer 7

take by mouth in the morning. 2.5mg daily for immediate release, 1.5mg for modified release

Question 8

Contraindications for indapamide

Answer 8

Patients with electrolyte imbalances

Question 9

Pharmacokinetics of lisinopril

Answer 9

oral, 25% bioavailability, 12hr half-life, water soluble, not metabolised in liver, undergoes renal excretion unchanged

Question 10

Pharmacokinetics of losartan

Answer 10

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

Question 11

Pharmacokinetics of amlodipine

Answer 11

oral, 60% bioavailability, 30-50hr half-life, reaches steady state after 7-8 days, slowly metabolised by liver CYP450

Question 12

Pharmacokinetics of indapamide

Answer 12

oral, virtually complete bioavailability, 76-79% protein bound, 16hr half-life, 93% metabolised by liver, excreted in urine and faeces

Question 13

Side effects of lisinopril

Answer 13

Dry cough, alopecia, vertigo, hypotension

Question 14

Side effects of losartan

Answer 14

Postural hypotension, vertigo, vomiting, hyperkalaemia

Question 15

Side effects of amlodipine

Answer 15

Headache, peripheral oedema, nausea, tachycardia

Question 16

Side effects of indapamide

Answer 16

Postural hypotension, electrolyte imbalance, constipation, diarrhoea

Question 17

Hypertension medication pathway if type II diabetes or <55 and not of black or Afro-Caribbean origin

Answer 17

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

Question 18

Hypertension medication pathway if >55, black or Afro-Caribbean family origin and no type II diabetes

Answer 18

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

Question 19

ACE inhibitor mechanism of action

Answer 19

Bind to and block the angiotensin converting enzyme which blocks the production of angiotensin II

Question 20

ARB mechanism of action

Answer 20

antagonists which block the angiotensin II receptors on the kidney

Question 21

Calcium channel blocker mechanism of action

Answer 21

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

Question 22

Thiazide-like diuretics mechanism of action

Answer 22

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

Question 23

Potential problems in measuring blood pressure accurately

Answer 23

Incorrect cuff size, cuff upside down, unable to identify Korotkoff sounds, caffeine or nicotine use by patients, incorrect patient positioning

Question 24

Define clearance

Answer 24

Volume of plasma cleared of drug per unit time

Question 25

What is clearance a significant factor in determining?

Answer 25

Limiting time course of drug

Question 26

Define half-life

Answer 26

time taken for plasma concentration of drug to halve

Question 27

What is drug half-life useful for?

Answer 27

Estimating frequency of dosing

Question 28

Define volume of distribution

Answer 28

Proportionality factor that relates the amount of drug in the body to the concentration of drug measured in the plasma

Question 29

What affects volume of distribution?

Answer 29

Drug permeability across tissue barriers, plasma protein binding, accumulation in tissues, pH partition

Question 30

What does volume of distribution define?

Answer 30

Dose as has an effect on plasma concentration which dictates the ability of a drug to reach its target organ

Question 31

Concentration/time graph for a drug with first order kinetics

Answer 31

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

Question 32

What is first order kinetics?

Answer 32

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.

Question 33

Describe drugs with short half-lives

Answer 33

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

Question 34

Describe drugs with long half-lives

Answer 34

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.