Week 9 Flashcards
Treating hypertension
Hypertension > 140/ and or 90 mmHg
Patients often asymptomatic
Compliance issues
Consequences of non-treatment
Lifestyle: diet, exercise, smoking, alcohol
Drugs?
ABP= CO x TPR
Decrease in CO or TPR decrease BP
Physiological BP maintenance
Homeostatic process
Baroreceptors reflex
Autonomic nervous system- fast
-heart (SNS and PNS)
-vessels (SNS)
Renin-angiotensin-aldosterone system
-kidneys -> alter blood volume -slow
-vessels- fast
Lots of potential drug targets
What determines drug choice
Newly diagnosed patients
-age
-genetics
-comorbidities/ health status
—pregnancy
Current guidelines drugs
<55– A (ACE inhibitors or ARBs)
>55 or A-C— C (calcium channel blockers)
- A+C or A+D (diuretics) or C+A or C+D
— A+C+D
—— + another diuretic, alpha blocker, beta blocker
Step 4 is alternative actions if BP not easily controlled
Angiotensin-converting enzyme (ACE) inhibitors
Eg lisinopril, enalapril
Mechanism:
-decrease angiotensin II
-decrease TPR/CO
-affects venous return
-decreases degradation for vasodilator kinins eg bradykinin, so vasodilatory action can continue
Side effects:
-dry cough
-severe sudden hypotension if taken with diuretics-> short lived
Clinically: first line treatment for uncomplicated, mild hypertension in younger patients
Angiotensin AT1 receptor antagonists
Eg Losartan, irbesartan
Mechanism:
-decrease vasoconstriction by angiotensin II
-decreases TPR/CO
No cough as it doesn’t interfere with bradykinin
No common major adverse effects reported yet
Clinically:used if ACEi aren’t tolerated
Affect arterial and venous vessels so affect TPR and venous return-> CO
Calcium channel blockers
Eg amlodipine
Decrease TPR
Action of arterial constriction
Side effects:
-heart
-decrease GIT activity
Clinically- first line treatment for uncomplicated, mild hypertension
Diuretics
Drugs act at various sites in the kidney
Biphasic mechanism
Initially
-increase water/Na+ excretion from kidneys
-decreasing blood volume decreasing CO and therefore BP
Compensation:
-thiazide/thiazide-like better than loop diuretics in context of hypertension best at decreasing blood volume so not primary action of antihypertensives
-longer term effects= arterial dilation
-decreasing TPR
-Na+ depletion -> decrease intracellular Ca2+ in smooth muscle blood vessels
Side effects:
-hypokalaemia
Clinically- first line treatment for uncomplicated, mild hypertension
Drugs acting on peripheral SNS Beta blockers
Beta adrenoreceptor antagonists:
-eg propranolol (B1 and 2), atenolol (B1)
Mechanism:
-decrease heart rate/contractility decrease CO
-decrease renin secretion decrease angiotensin II decrease TPR and CO
Side effects:
-B2-bronchospasm. Exercise intolerance, blockade B1 in heart
Clinically
-recent guidance is to avoid, long term use can result in increased chance type 2 diabetes
-but well controlled patient
Drugs acting on peripheral SNS alpha blocker
Alpha1 adrenoceptor antagonist
Eg Prazosin, doxazosin
Mechanism:
-target a1 receptors
-block vasoconstriction, indirect vasodilators
-decreases TPR and CO
Side effects:
-postural hypotension-> potential falls-> elderly
Clinically:
-severe hypertension not adequately controlled
-for patients with other cardiac/renal problems
Drugs summary
Drugs fall into 2 major catergories:
-directly reducing RAAS
—ACE inhibitors, ARBS, (beta blockers) A+B
-no effect on RAAS:
-Ca2+ channel blockers, diuretics C+D
Worsening hypertension
Increase dose , increases chance side effects
Combination therapy
-decrease toxic effects
-increase chances successful therapy
How are drugs combined
A+C work better
Or A+D
C+D
Hypotension
Hypotension may occur:
Eg haemorrhage/burns/shock
Shock eg anaphylactic shock
-sympathomimetics
—eg adrenaline
—increases CO increase BP
Chronic hypotension advised to increase salt intake or lifestyle changes, not drugs to not increase too much. Difficult to treat in reality not treated to same degree
