3.1 Hypertension Flashcards
how do we work out mean arterial pressure?
cardiac output x total peripheral resistance
or
DBP + (SBP-DBP/3)
what 2 mechanisms do we use to regulate blood pressure?
autonomic sympatheitc activity
renin-angiotensin-aldosterone system
what are autocoids and how do they affect the vascular smooth muscle?
molecules that act as local hormones such as bradykinin and nitric oxide
act as vasodilators
what is the main determinant of resistance to flow?
radius of vessel
how does hypertension affect blood vessels?
causes remodelling, thickening and hypertrophy
what can cause vascular remodelling?
hypertension
local salt sensitivity
what are some of the pathological consequences of hypertrophy?
end organ damage - renal, peripheral vascular disease, aneurysm, vascular dementia, retinal disease
hypertensive heart disease - LVH and dilated heart failure
increased morbidity and mortality
linear relationship with coronary artery disease and stroke
what is hypertension?
an elevation in blood pressure that is associated with an increase in risk of some harm
greater than 140/90mmHg
what is the most common cause of hypertension?
essential/primary/idiopathic hypertension
how do we increase diagnoses of hypertension?
- Screening those at risk - often hypertensive patients are asymptomatic
- Increasing public awareness of risk factors
- Appropriate lifestyle changes to limit risk – no immediate gain presents a challenge.
- Reliable measurements based on clinical guidelines
- Regular monitoring and refinement of medication
how do we measure blood pressure to diagnose hypertension?
- Sitting, relaxed and arm is supported. Cuff placed at the level of the heart
- Both arms, >15 mmHg difference repeat measurement and use arm with higher reading
- Measurements over period of visits +/- ABPM/HBPM
when is emergency treatment for hypertension advised?
> 180 SBP or 120 DBP + clinical signs (retinopathy/headaches/seizures)
what are the target blood pressures in hypertensives?
- 140/90 < 80 years old including type II diabetes
- 150/90 > 80 years old
- 135/85 type 1 diabetes
what is the desired BP?
120/80mmHg
what is stage 1 hypertension?
Clinic blood pressure ranging from 140/90 mmHg to 159/99 mmHg and subsequent ABPM daytime average or HBPM average blood pressure ranging from 135/85 mmHg to 149/94 mmHg.
what is stage 2 hypertension?
Clinic blood pressure of 160/100 mmHg or higher but less than 180/120 mmHg and subsequent ABPM daytime average or HBPM average blood pressure of 150/95 mmHg or higher.
what is stage 3 or severe hypertension?
Clinic systolic blood pressure of 180 mmHg or higher OR clinic diastolic blood pressure of 120 mmHg or higher.
what is the BP range of prehypertension?
> 120/80 <140/90 mmHg
what is the advice given to patients that are prehypertensive?
- Promotion of regular exercise
- Modified healthy/balanced diet
- Reduction in stress and increased relaxation
- Limited/reduced alcohol intake
- Discourage excessive caffeine consumption
- Smoking cessation
- Reduction in dietary sodium
name some primary hypertension therapeutic drugs?
• Angiotensin converting enzyme (ACE) inhibitors (ACEi)
Angiotensin (AT1) receptor blockers (ARBs)
• Calcium channel blockers (CCBs)
• Diuretics – thiazide and thiazide-like
where is ACE predominantly found?
on the luminal surface of capillary endothelium in the lungs
what are the main receptors of angiotensin-II?
AT1 (vasoconstriction)
AT2 (opposes action of AT1)
what are the main actions of AT-II?
vasoconstriction
stimulation of aldosterone
cardiac and vascular muscle cell growth
ADH release form posterior pituitary
what are the main actions of ACEi?
A reduction in Angiotensin-II activity, resulting in
vasodilation (↓ peripheral resistance →↓afterload)
reduction in aldosterone release (↑Na + H2O excretion)
reduced vasopressin (ADH) release (↑ H2O excretion)
reduced cell growth and proliferation
how can AT-II be produced from AT-I independently of ACE?
via chymases
how do ACEi cause vasodilation?
- reduce angiotensin-II activity that would have caused vasoconstriction
- Bradykinin is a substrate for ACE. ACEi increase the effects of bradykinin causing vasodilation via NOS/NO and PGI2
give some examples of ACEi
lisinopril
ramipril
what are the ADRs of ramipril?
hypotension dry cough hyperkalaemia cause or worsen renal failure angioedema
what are the contraindications of ACEis?
Renal artery stenosis, AKD, pregnancy, (CKD - caution), idiopathic angioedema
what are the important drug reactions of ACEis?
increasing K+ drugs, NSAIDs, other antihypertensive agents
give some examples of ARBSs/ AT1 receptor blockers?
candesartan
lasartan
what are some of the ADRs of ARBs?
Hypotension!
hyperkalaemia (low aldosterone ↑K+) cause or worsen renal failure
why are ARBs more effective at inhibiting Ang-II mediated vasoconstriction than ACEi?
as angiotensin1 receptor blockers work further down the pathway than ACEi. As chymases can act to still produce AngII in the presence of ACEi, they are less effective.
why are ACEi more effective in treating hypertension than ARBs in patients with low-renin?
as still have effects of vasodilation mediated by bradykinin. As ARBs do not effect bradykinin they are less effective in low renin patients?
what are some of the contraindications of ARBs?
renal artery stenosis, pregnancy, AKD caution in CKD
what is the function of L-type calcium channels
to allow the influx of calcium into cells when stimulated to open by an electric current. allows contraction. also known as voltage gated.
where are L-type calcium channels expressed?
in vascular smooth muscle, cardiac myocytes and the Sa and AV node
what are the 3 different types of calcium channel blockers and how do they vary?
dihydropyridines, non-dihydropyridines (phenylalkylamines and benxothiazapines) each class interact with different sites on (α1) subunit of VOCC - they have different selectivity for vascular smooth muscle or myocardium
what is the function of dihydropyridines?
to treat hypertension without heart involvement (little chronotropic or inotropic effect). only work by acting on peripheral vasculature
what is the function of phenylalkylamines?
act to depress the SA node and slow AV conduction. have a negative inotropic and chronotropic affect
what is the function of benzothiazapines?
used to treat hypertension as have some vasodilatory effect on peripheral vasculature aswell as some SA/AV node effects
what is the primary choice antihypertensive in low renin patients?
CCBs
give some examples of dihydropyridine drugs
amlodipine
nifedipine
nimodipine
when in nimodipine indicated?
nimodipine is a dihydropyridine with cerebral vasculature selectivity. Is useful for ischaemic effects of subarachnoid haemorrhage
what are some of the ADRs of amlodipine?
Ankle swelling, flushing, headaches (vasodilation)
Palpitations (compensatory tachycardia)
what is the contraindications of dihydropyridines?
unstable angina
severe aortic stenosis
what are the important drug interactions of amlodipine?
simvastatin. increases the effect of the statin.
give an example of a phenylalkylamine
verapamil
what is the mechanism of action of verapamil?
Class IV anti-arrhythmic agent/prolongs the action potential/effective refractory
period
Less peripheral vasodilatation, negative chronotropic and inotropic effects
what is verapamil used for?
arrhythmia
angina
hypertension
what are some of the ADRs if verapamil?
constipation
bradycardia
heart block
cardiac failure
what are the drug interactions of verapamil?
beta blockers
other antihypertensives
antiarrhythmic agents
give an example of a benzothiazapine?
diltiazem
give an example of a thiazide diuretic
bendroflumethiazide
give an example of a thiazide like diuretic
indapamide
what is the mechanism of action of thiazide diuretics?
Inhibit N+/Cl- co-transporter in distal convoluted tubule (RAAS compensates with time)
Long term effects mediated by sensitivity of vascular smooth muscle to vasoconstrictors Ca2+/NAd
when are diuretics indicated in the treatment of hypertension?
in oedema
what are the adverse drug reactions of bendroflumethiazide?
Hypokalaemia, hyponatraemia, hyperuricemia (gout), arrhythmia
↑glucose (especially with beta-blockers)
small ↑cholesterol and triglyceride
what are some of the drug interactions of bendroflumethiazide?
NSAIDs
K+ decreasing drugs such as loop diuretics
when are ACEi or ARBs considered first line in treating hypertension?
in patients with type 2 diabetes
in non-black patients under 55 years
when is CCB considered the first line in treatment of hypertension?
in patients over 55 years
in black African and black-caribbean patients
what is the two pronged effect of treating hypertension with ACEi or ARBs?
decrease peripheral vascular resistance to decrease BP
dilation of the efferent glomerular arteriole to reduce intraglomerular pressure
if the patient is still hypertensive after taking a ARB/ACEi + thiazide diuretic + CCB, what is the next step in treatment?
spironolactone - an aldosterone receptor antagonist
or
alpha or betablockers if high K+
what is the adverse drug reactions of spironolactone?
hyperkalaemia
gynaecomastia
how does spironolactone cause gynaecomastia?
Spironolactone is a mineralcorticoid antagonist but is not highly selective. Can therefore bind to other steroid receptors such as the testosterone receptor. this down regulates the testosterone production, and increases the conversion of testosterone to oestrogen hence causing breast enlargement
give some examples of beta adrenoceptor blockers
labetalol
bisoprolol
metoprolol
what is the mechanism of action of beta adrenoceptor blockers?
decrease sympathetic tone by blocking noradrenaline and reducing the myocardial contraction. reduced CO
decreases renin secretion
what are the adverse drug reactions of beta adrenoceptor blockers?
Bronchospasm, heart block, Raynaud’s (cold hands), lethargy, impotence
Mask tachycardia – sign of insulin induced hypoglycaemia
what are the drug interactions of beta blockers?
the non-dihydropyridine CCbs - verapamil and diltiazem = asystole
what are the contraindications of beta blockers?
asthma
copd
haemodynamic instability
hepatic failure
give an example of an alpha adrenoceptor blocker
doxazosin
what are the indications of alpha 1 adrenoreceptor blockers?
hypertension - reduced peripheral vascular resistance (doxazosin)
benign prostatic hyperplasia (tamsulosin)
what are the adverse effects of alpha1 adrenoceptor blockers?
Postural hypotension
dizziness, syncope, headache and fatigue
what is CO in a healthy adult?
5L/min
what variables affect cardiac output?
preload – filling pressure
afterload – “load” that ventricle must eject blood against
contractility
heart rate
what are the common symptoms of heart failure?
exercise intolerance
dyspnoea
fatigue
how does cardiac failure cause remodelling?
- decreased Bp is detected by the baroceptors causing a neurohormonal response - there is proliferative signalling of ANG-II, NAd, Aldosterone which increase RAAS and sympathetic drive. this damages the cardiac tissue over time causing remodelling
- sympathetic NS and RAAS increase vasocontriction and blood volume. This increases the preload and afterload and therefore the work of the heart resulting in remodelling
what are the 3 main steps in the management of heart failure?
- correct underlying cause - angioplasty/ valve replacement
- non pharmacological management - decrease salt intake and liquid reduction
- addition of diuretic plus other therapeutic agents
what are the aims of treatment of heart failure?
heart failure cannot be sured so current treatments are supportive and focus on:
• reduction in symptoms (dyspnoea, fatigue, oedema)
• managed increase in exercise tolerance
• address arrhythmias, hyperlipidaemia, diabetes
• increase quality of life and slow morbidity
what are the steps of drugs given in heart failure?
- loop diuretic (furosemide) to reduce signs of volume overload - dyspnoea and peripheral oedema
- offer ACEi (lisinoprila and ramipril) to reduce sympathetic output, vasodilation and water retention and add BB ( bisoprolol) to reduce remodelling and improve systolic function
- mineralcorticoid agonist (spironolactone) - decrease preload and afterload to improve CO
- consider ARB if intolerant to ACEi
