Week 5 - Anti-hypertensive drugs Flashcards
What is hypertension
High blood pressure
It is sustained systolic (>140) and diastolic (>90) blood pressure
- normal BP = 120/80 (90-120/60-80)
3 Stages
- Stage 1 = on cusp of hypertension, may be thinking about treatment
- Stage 2 = more serious
- Stae 3 = emergency situation, treatment given immediately
How is hypertension causes
- Primary hypertension (cause is unknown)
- most diagnosed type of hypertension (90% of cases) - Secondary hypertension (have an identified cause e.g.)
- tumours in renal medulla (tumours may secrete aldosterone = Na+ retention and can excessively produce adrenaline which causes contraction)
- polycystic renal disease
- age (middle aged men more likely than women)
- ethnicity (black African / Caribbean more prone than Caucasian)
- diabetic
- obesity
- drugs (e.g. contraceptive pill, aspirin)
Why does hypertension need to be treated
Treatment depends on age, CV risk (QRISK), lifestyle + other diseases
- detected thrown blood pressure testing / checks
- It can ↑ risk of other CV diseases e.g. heart attack, stroke, ischaemic heart disease, peripheral vascular diseases
- Can lead to reduced blood flow to legs = pain in legs, amputation
- Can ↑ risk of death from heart disease / stroke
What are the NICE guidelines for hypertension
- Diagnosed with hypertension
- Given angiotensin-converting enzyme (ACE) inhibitor (1st line) OR calcium channel blocker (CCB)
- Thiazide-like diuretic may be added
- No improvement given triple therapy (combination of ACEi, CCB and thiazide diuretic)
What factors are involved in controlling blood pressure
- Baroreceptors
- Juxtaglomerulus apparatus
Baroreceptors:
1. Baroreceptors (in carotid sinus + aortic arch) detect changes in BP
2. Send signals to medulla, medulla sends signals to SAN
3. Vasomotor centre sends signals to arterioles causing contraction
4. Modifies blood flow until BP is return to normal
In hypertension baroreceptors reset leading to a higher BP becoming the normal BP = why body mechanism can’t combat high BP
baroreceptors cause reflex tachycardia when detect ↓ in BP
Juxtaglomerulus apparatus (RAAS):
1. Apparatus detects blood flow, if flow drops it secretes renin
2. Renin catalyses activation of angiotensinogen
3. Angiotensinogen is converted into in angiotensin I
4. Angiotensin I is converted into angiotensin II (potent vasoconstrictor) by ACE
5. Causes secretion of aldosterone (causes Na+/H2O retention)
List the treatments for hypertension
Antihypertensive drugs
AIM: ↓ BP, not cause hypotension, reduce incidence of complications e.g. stroke, not cause serious side effects
- ↓ BP by ↓ cardiac output (done by reducing ↓ blood vol.)
- ACE inhibitors
- Angiotensin I (AT I) receptor blockers
- Calcium channel blockers (CCB)
- Beta blockers (B-blockers)
- Selective a1 (alpha 1) adrenoreceptor blocker
- Diuretics
- Vasodilators
- Centrally acting drug & newer drugs
Explain how ACE (angiotensin converting enzyme) inhibitors work
1st line treatment
- MECHANISM: ↓ production of angiotensin II + ↓ breakdown of bradykinin
- dilates veins + arteries = ↓ vasoconstriction = ↓ cardiac workload
- ↓ angiotensin II = ↓ Na+/H2O retention
- ACE catalyses conversion of angiotensin I into II (potent vasoconstrictor)
- ACE catalysis breakdown of bradykinin (inflammatory mediator) = inactivating bradykinin = vasodilation
- also leads to spasmic action on baronial smooth muscle = dry cough
- EXAMPLES: Ramipril, Captopril
- SIDE EFFECTS: rash, swelling, persistent dry cough, hypotension, not safe in pregnancy
Explain how Angiotensin I (AT I) receptor blockers
- NOT 1st line
- MECHANISM: prevent conversion of angiotensin I into II
- ↓ production of angiotensin II = ↓ vasoconstriction and ↓ Na+/H2O retention - SIDE EFFECTS: same as ACE inhibitor except NO cough (drug is better tollerated)
Explain how calcium channel blockers (CCB) work
MECHANISM:
- inhibit / ↓ opening of L-type calcium channels = ↓ smooth muscle contraction
- ↓ AV node conduction = ↓ myocardial contractility
- ↓ heart rate (by binding to SAN)
- causes vasodilation in vessels by ↓ vascular resistance
- ↓ MAP
Ca2+ causes smooth muscle contraction
- PIP2 is converted into IP3 by phospholipase C, IP3 causes release of Ca2+ from sarcoplasmic reticulum
- Ca2+ binds to calcium sensitive chloride channels causing Cl- to enter + depolarise cell
- depolarisation causes L-type calcium channels to open = more Ca2+ released = contraction
EXAMPLES: Amlodipine, verapamil
SIDE EFFECTS: peripheral oedema, headache
Explain how Beta blockers (B-blockers) work
MECHANISM:
- ↓ heart rate + ↓ myocardial contractility
- inhibit release of renin = ↓ vasoconstriction
- less aldosterone produced = less Na+ absorbed + retained
- block sympathetic tone = ↓ vasoconstriction
- B1 receptors on SAN + myocardium
- B1 receptors stimulate juxtaglomerulus apparatus = renin released = cascade leading to constriction
- renin-angiotensin system also produces aldosterone (which retains Na+ / H2O) - Vasomotor centre sends d=signals to vessels to constrict
EXAMPLES: propranolol (B1 and B2 antagonist) non-selective, atenolol (B1 antagonist) more selective
SIDE EFFECTS:
- bronchocosntriction (avoid in patients with respiratory issues as it blocks B2 receptor)
- hypoglycaemia (masks symptoms diabetic patients experience before going into hypoglycaemia coma)
- cardiac failure
- reduced blood flow to poorly perfused areas
Explain how ‘selective a1 (alpha 1) adrenoreceptor’ blocker work
- Dilate arterioles + veins (vasodilation) = ↓ BP
- as noradrenaline is prevented from binding to a1 receptor
- noradrenaline causes vasoconstriction - ↓ LDL to HDL ratio = ↓ atherosclerosis formation
EXAMPLE: prazosin
SIDE EFFECTS: feeling faint, urinary incontinenece
- If block a2 receptor at cardiac synapse = noradrenaline accumulates in synapse = repeated stimulation of B1 receptor - unacceptable reflex tachycardia
Explain how diuretics work
Thiazide:
- ↓ Na+ uptake = ↑ excretion of water
- has vasodilator effects
- SIDE EFFECTS: hyopkalemia, reduced insulin release
Loop:
- most powerful diuretic
- ↓ BP + has vasodilator effects
- causes excretion of large amounts of fluid (treats oedema)
- SIDE EFFECTS: hypokalaemia, gout
Potassium sparing:
- inhibits sodium/potassium pump in collecting duct
- SIDE EFFECTS: hyperkalemia (combat by co-administering with other diuretics)
Explain how vasodilators work
- Open Katp channels
- ↓ BP (detected by baroreceptors) stimulates reflex tachycardia - Acts on arteries/aterioles
- given if have very high BP
EXAMPLES:
- hydralazine; side effects = palpitations, GI disturbance
- minoxidil; side effects = peripheral oedema, Gi disturbance
- causes fluid retention
Explain how centrally acting drug & newer drugs works
Methyldopa:
- Treats hypertension during pregnancy
- Blocks DOPA decarboxylase = ↓ dopamine production
- dopamine is precursor for noradrenaline = less sympathetic response
- Side-effects: GI disturbance, dry mouth, ↓ HR
Clonidine:
- Alpha-2 agonist =↓ sympathetic outflow from brain
- ↓ CO and TPR (the peripheral resistance)
- Side-effects: sedation, fatigue, sleep disturbance
Aliskiren:
- New drug
- Highly potent + selective renin inhibitor
- blocks renin-angiotensin system
- Used alone or combined with other antihypertensives (should NOT be used with ACE-I or ARB)
- Side-effects: Arthralgia (joint pain), dizziness, hyperkalaemia, diarrhoea
- NOT USED IN WOMEN OF CHILDBEARING AGE
