💊Pharmacology💊 - Hypertension Flashcards
What are the therapeutic objectives with hypertension?
Set reasonable blood pressure reduction goals
Reduce cardiovascular risk associated with increased morbidity and mortality
What is the first threshold for blood pressure management?
Under 135/85mmHg - monitor at least every 5 years
What is the threshold for stage 1 hypertension, and what are the treatment options?
135/85 to 149/94
BP above 140/90, ABPM/HBPM offered
Start drug treatment if any of the following:
Target organ damage
CVD
Renal disease
Diabetes
10 year CVD risk >10%
What is the threshold for stage 2 hypertension?
150/95
Start drug treatment immediately
What are the NICE guideline first line hypertension treatments?
Calcium channel blockers
Amlodipine & felodipine common examples
What is the mechanism of action of calcium channel blockers?
What is drug clearance?
Clearance is the measure of the ability of the body to eliminate a drug
Clearance by means of various organs of elimination is additive
Elimination of drug may occur as a result of processes that occur in the liver, kidney, and other organs
What is the elimination half-life of a drug?
Elimination half-life is the length of time required for the concentration of a particular drug to decreasetohalf of itsstarting dose in the body
What is a drug’s time to peak plasma levels?
The time required for a drug to reach peak concentration in plasma
The faster the absorption rate, the lower is the time to peak plasma concentration
What does this information tell us about the difference between amlodipine and felodipine?
Felodipine is faster acting and shorter lasting - shorter half-life, possibly due to plasma clearance
Plasma clearance and elimination half-life always linked
What advantages does amlodipine have over felodipine?
Longest lasting
Less pronounced reflex tachychardia due to slower onset
What is reflex tachycardia?
Drop in systolic and diastolic blood pressure stimulates baroreceptors in the heart
Causes heart to increase rate of contraction to maintain blood flow and perfusion
What is the most common next line treatment after calcium channel blockers to manage hypertension?
ACE inhibitors
What is the mechanism of action of ACE inhibitors in the treatment of hypertension?
Prevents production of Angiotensin II
Prevents degradation of bradykinins
How does stopping the production of angiotensin 2 lower blood pressurs?
Angiotensin 2 causes:
Vasoconstriction
Salt (and therefore water) retention in the kidneys
Stimulates aldosterone secretion in the adrenals
When should ARB (andgiotensin 2 receptor blockers) be used instead of ACE inhibitors?
Patients over 65
Patients of African or Caribbean descent
Renin system is less sensitive making ARBs more effective
When are ACE inhibitors contraindicated?
Patients with renal artery stenosis need increased BP to maintain renal perfusion
What is the difference between a pro drug and an active drug?
Why might someone waiting for surgery not take ACE inhibitors?
Can raise serum potassium levels
Can lead to cancellation of surgery
What are the next treatment options for hypertension after calcium channel blockers?
Thiazide-like diuretics
What is the mechanism of action of Thiazide-like diuretics?
Inhibits Na+/Cl- co transporter it DCT
Increased Na+ and therefore H2O loss
Lowers blood volume, decreases BP
Why is it important that thiazide-like diuretics are excreted unchanged in urine?
Need to move from the blood, to basolateral transporter, to the apical transporter to reach the sodium chloride transporter (i.e. it is in the filtrate/urine when it has its effect, so must be present there unchanged)
Why do thiazide-like diuretics increase potassium excretion?
What is an important note about the length of time for which thiazides can be used?
The diuretic effect of thiazides only lasts for 1-2 weeks
The kidney becomes tolerant to the diuretics because there is a rebound activation of the renin angiotensin system which counteracts the diuretic effect due to increasing sodium reabsorption
Any continuing anti-hypertensive effect is due to a further (less well understood) vasodilating action
What is the primary mechanism of action of ACE inhibitors?
Inhibits angiotensin converting enzyme, and therefore production of angiotensin 2
What is the primary mechanism of action of calcium channel blockers
Blocks L-type calcium channels, predominantly on vascular smooth muscle
Prevents calcium influx, therefore stopping contraction and promoting vasodilation
What is the primary mechanism of action of thiazide/thiazide-like diuretics?
Block the Na+/Cl- co transporter
Na+ reabsorption limited
What is the primary mechanism of action of angiotensin receptor blockers?
Non-competitive antagonists of the AT1 receptor (found in kidneys and vasculature)
What is the target of ACE inhibitors?
Angiotensin converting enzyme
What is the target of calcium channel blockers?
L-type calcium channels
(Predominantly in vascular smooth muscle)
What is the target of thiazide/thiazide-like diuretcs?
Sodium/chloride cotransporter
What is the target of angiotensin receptor blockers?
Angiotensin receptors
What are the side effects of ACE inhibitors?
Cough
Hypotension
Hyperkalaemia
Foetal injury (AVOID IN PREGNANT WOMEN)
Renal failure (in cases of renal artery stenosis)
Urticaria/angioedema
What are the side effects of calcium channel blockers?
Ankle oedema
Constipation
Palpitations
Flushing/headaches
What are the side effects of thiazide/thiazide-like diuretics?
Hypokalaemia
Hyponatraemia
Metabolic alkalosis (due to increased H+ excretion)
Hypercalcaemia
Hyperglycaemia
Hyperuricaemia
What are the side effects of ARBs?
Hypotension
Hyperkalaemia
Foetal injury (AVOID IN PREGNANT WOMEN)
Renal failure (in cases of renal artery stenosis)
