3.1) Hypertension Flashcards
- What is blood pressure? Is this uniform throughout the body?
BP is the driving force to perfuse organs with blood (force per unit area acting on vessels)
It is NOT uniform— differs based on position, time and activities
What is the equation for mean arterial pressure?
Mean arterial pressure= cardiac output x total peripheral resistance
Which systems are responsible for blood pressure regulation?
Autonomic sympathetic activity and Renin-angiotensin-aldosterone system
Which endogenous chemicals can be released to modify BP?
Autacoids— bradykinin and nitric oxide—- act on vascular smooth muscle to cause vasodilation.
What is the relationship between radius, smooth muscle tone and peripheral resistance?
Radius decreases cause resistance increase.
Smooth muscle tone changes total peripheral resistance.
How does an increased peripheral resistance impact on BP?
Increased peripheral resistance increases BP
What is hypertension?
High blood pressure
Above 135 ambulatory
Above 140 in clinic
What is the importance of reducing BP?
A reduction in both SBP and DBP reduces cardiovascular disease risk.
What are some of the different types of hypertension?
Essential/primary/idiopathic- no known cause
Secondary- as a result of other pathology
Pre-hypertension- state preceding hypertension (where prophylaxis is helpful)
Isolated diastolic/systolic hypertension
White coat/clinical hypertension- anxiety of attending practice increases BP
How is hypertension staged?
Desired= 120/80mmHg
Stage 1= ranging clinic pressure 140/90- 159/99mmHg
Stage 2= clinic pressure of 160/100 mmHg or higher but less than 180/120mmHg
Stage 3 (severe)= clinical systolic BP of 180 or higher
What is prehypertension?
How is this treated?
Between 120/80 and 140/90 mmHg
Treated with promotion of regular exercise, modifications to diet, reduction of stress, reduced alcohol intake, discouraging excessive caffeine, reduction of dietary sodium
Which agents can be used to treat primary hypertension?
Angiotensin converting enzyme inhibitors (ACEi)
Angiotensin receptor (AT1) blockers (ARBs)
Calcium channel blockers (CCBs)
Diuretics- thiazide and thiazide-like
How does the RAAS system increase BP?
- decrease in renal perfusion detected by macula densa cells of DCT, stimulates release of renin from granular cells.
- renin cleaves angiotensinogen to angiotensin I
- angiotensin I to lungs acted on by ACE to form angiotensin II
-angiotensin II has actions on: increases sympathetic activity, increases tubular reabsorption of sodium and electrolytes in nephron (absorbs water also- increasing plasma volume), stimulates adrenal cortex to increase aldosterone release (increases expression eNac to reabsorb more), arteriolar vasoconstriction.
How do ACEi have an anti-hypertensive effect?
Limit the conversion of angiotensin I to angiotensin II. Therefore, reduced amounts of angiotensin II to have hypertensive effects.
Why might ARBs be more effective at controlling hypertension than ACEi?
Angiotensin II can also be produced from angiotensin I independently of ACE via action of chymases. Thus this form of angiotensin II will not be prevented from acting in the case of ACEi.
Give examples of ACEi
Lisinopril
Ramipril
What are some of the side effects of ACEi agents?
Hypotension
Dry cough— due to potential ion of bradykinin
Hyperkalaemia— lower aldosterone, increases K+
Cause or worsen renal failure
Angioedema
Contraindications of ACEi?
Renal artery stenosis
Acute kidney injury
Pregnancy
Chronic kidney disease
Idiopathic angioedema
Interactions with ACEi may include?
Hyperkalaemia causing drugs (potentiates)
NSAIDs- disruption to renal function
Other antihypertensive agents— hypotension
ARBs target which receptor?
AT1 receptor
What are examples of ARBs?
Candesartan
Losartan
Do ARBs have an effect on bradykinin?
No—- less likely to have a dry cough or angioedema
What are the possible side effects of ARBs?
Hypotension
Hyperkalaemia- low aldosterone, increases K+
Cause or worsen renal failure
What are some of the contraindications of ARBs?
Renal artery stenosis
AKD
Pregnancy
CKD
Interactions between ARBs and other drugs?
Hyperkalaemia causing drugs
NSAIDs- affect renal function
Other antihypertensive agents
What are the 3 classes of CCBs?
What do they all interact with?
Dihydropyridines
Non-dihydropyridines- phenylalkylamines and benzothiazepines
All interact with different sites on alpha 1 subunits of voltage gated calcium channels.
Have different selectivity for vascular smooth muscle or myocardium
Which agents fall into the dihydropyridine class?
What tissue are these selective for?
Amlodipine
Nifedipine
Nimodipine
Selective for peripheral vasculature
What is special about amlodipine in relation to other dihydropyridines?
Has a longer half life
Which of the dihydropyridines is selective for cerebral vasculature?
Nimodipine
Useful in ischaemic effects of subarachnoid haemorrhage
Side effects of dihydropyridines include?
Ankle swelling
Flushing
Headaches (vasodilation in the cerebral vasculature)
Palpitations (compensatory tachycardia)
Contraindications of D-CCBs?
Unstable angina
Severe aortic stenosis
What is a possible DDI of D-CCBs?
Amlodipine and simvastatin
—-causes increased effect of statin
Phenylalkylamines have what mechanism of action?
Class IV anti-arrhythmic agents- prolongs the action potential to have a negative inotropic and chronotropic effect
Which drug is an example of a phenylalkylamine?
Verapamil
Side effects of Non-dihydropyridine calcium channel blockers include?
Constipation
Bradycardia
Heart block
Cardiac failure
Contraindications of ND-CCBs include?
Poor left ventricular function (caution)
AV nodal conduction delay
Interactions with ND-CCBs may include?
Beta blockers
Other anti hypertensive and anti-arrhythmic agents
Diltiazem is an example of which class of agent?
Benzothiazepine
Non-dihydropyridine calcium channel blocker
What is the mechanism of action of the azide and thiazide- like diuretics?
Inhibit the Na+/Cl- co-transporter in the distal convoluted tubule, reduces sodium and water reabsorption
Give examples of thiazide agents
Bendroflumethiazide
Indapamide
What are some of the side effects of diuretic use?
Hypokalaemia
Hyponatraemia
Hyperuricaemia (gout)
Arrhythmia
Increased plasma glucose
Increases cholesterol and triglyceride plasma levels
What are some of the contraindications to thiazide diuretics?
Patients already experiencing hypokalaemia, hyponatraemia and gout
What are some of the DDIs associated with thiazide diuretics?
NSAIDs
Hypokalaemia causing drugs ie loop diuretics (electrolyte monitoring required)
Which treatments are firstline for individuals aged 55 or less no Afro-Caribbean heritage?
Which other demographic also?
ACEi/ARBs
Type 2 diabetes mellitus
What if firstline for patients aged 55 or over or with an Afro-Caribbean heritage?
CCBs
Second line management?
T2DM/under 55= add CCB or thiazide like diuretic
Without T2DM/Afro-Caribbean= add ACEi/ARB or thiazide like diuretic
Third line management?
ACEi or ARB + CCB + thiazide like diuretic
What is resistant hypertension?
Hypertension that persists after step 3 of management.
Need to consider patient adherence or secondary cause for hypertension that could control BP once managed
What does Step 4 of management involve?
Spironolactone (if patients K+ normal)
- could cause hyperkalaemia, gynaecomastia
Contraindicated in situations potassium is high or Addisons
Instead use alpha and beta blockers or centrally acting drugs ie labetalol to reduce sympathetic outflow
Give examples of beta blockers
Labetalol
Bisoprolol
Metoprolol
How do beta blockers work?
Decease sympathetic tone by blocking noradrenaline binding and reducing myocardial contraction (reducing CO)
What are some of the side effects of beta blockers?
Brconshospasm
Heart block
Raynaud’s
Lethargy
Impotence
In what circumstances may beta blockers be contraindicated?
Asthma (beta 2 antagonists), haemodynamic instability, hepatic failure
What are some of the DDI that may occur with beta blockers?
ND-CCBs- verapamil and diltiazem can cause asystole
Doxasozin is a drug within which class?
Alpha adrenoceptor blocker (antagonist)
Which receptors are specifically targeted by alpha blockers?
How does this achieve changes to BP?
Alpha 1 receptors
Reduce peripheral vascular resistance- act on alpha 1 receptors in smooth vascular muscle.
What are some of the side effects of alpha blockers?
Postural hypotension
Dizziness
Syncope
Headache
Fatigue
In which circumstances are alpha blockers contraindicated?
Postural hypotension
Indicate some of the DDIs associated with alpha blockers
D-CCBs- increased risk of oedema
