hypertension Flashcards
hypertension :
-The association of — and — is continuous and thus the definition of hypertension is arbitrary and for convenience
-Hypertension is the – level where the benefits of — intervention or — out-weigh the –
-The definition depends on how – is measured:
-Office-based readings
-Unattended office-based readings
-24hr ambulatory readings
-Home-based readings
-App-based readings are not recommended
mortality and blood pressure
BP
lifestyle
pharmacotherapy
bp
hypertension
category: systolic:diastolic
optimal —- and —-
normal —- and/or —
high normal —- and/or —-
grade 1 hypertension —- and/or —
grade 2 hypertension — and/or —
grade 3 hypertension — and/or —
isolated systolic hypertension — and —
<120 , <80
120-129 , 80-84
130-139 , 85-89
140-159 , 90-99
160-179 , 100-109
>or equal 180 , >or equal 110
>or equal 140 , <90
-true or false:
Persistently elevated blood pressure and hypertension lead to hypertension-mediated organ damage and cardiovascular disease.
-blood pressure factors:
-Blood pressure depends on – , — , —
- — is important in regulating blood volume
- — disease causes hypertension
- Hypertension causes –
true
cardiac output , blood volume and vascular resistance
kidney
chronic kidney
kidney disease
hypertension and sodium:
-Sodium in plasma draws water into — . -Dietary sodium is excreted in the – to maintain —
-Inability to excrete excess sodium leads to:
Increase in —
Increase in —
Increase in —
Salt sensitive people are prone to developing — in response to dietary salt
-No test for – sensitivity
plasma
urine
plasma volume
plasma sodium
plasma volume
blood pressure
hypertension
salt
role of sodium:
Increase in —
–> Increase in —
Increase in –
-> – of small resistance vessels and large elastic arteries
— dysfunction
–> Reduction in — production
Increase in — tone
info:
so basically when we have high salt intake —> water retention –> expansion of circulatory volume —> increase cardiac output –> increase renal perfusion pressure –> increase glomerular filtration rate which can lead to either:
1- abnormal excretory ability of the kidney —> salt and water rentention –> increase ciculatory volume —> hypertension may develop
2- normal excretory ability of the kidney –> increase sodium excretion –> restoration of normal circulatory volume
plasma volume
osmotic pressure
reisstance
remodelling
endothelial
NO
sympathetic
-Reducing — recommended to reduce hypertension
- – ≠ —
->Sodium bicarbonate
->Monosodium glutamate
-European Society of Cardiology and WHO recommend that sodium intake should be limited to <– g per day (equivalent to <– g salt per day)
-Very low Na diet is equivalent to use of —
-Low sodium salt (addition of K to NaCl) helps reduce — consumption. However, — restricts its use
- – may have additional benefits on blood pressure
- lifestyle and hypertension:
- systolic bp reduction:
combination exercise,
isometric exercise,
aerobic exercise,
yoga,
normal exercise
- diastolic bp reduction:
acupuncture,
meditation,
combination exercise,
isometric exercise
yoga
dietary salt
sodium , salt
2
5
anti hypertensives
na
palatability
k+
- pre hypertensive systolic is — and diastolic is –
- weight loss and hypertension:
Meta-analysis
A reduction in weight of – kg reduced SBP by – mmHg and DBP by – mmHg
120-130 mmhg
90-98 mmHg
5
4.4
3.6
hypertension pharmacology:
1- Diuretics:
- —
- —
2-Angiotensin inhibitors
- —
- —
3- – blockers
4- — blockers
thiazide
thiazide like
ACE inhibitors
angiotensin
beta
calcium channel
diuretics:
- — filter ions from plasma which also brings –
-Some of the filtered ions are —
- Diuretics — urine production
- Thiazide diuretics act to inhibit – channel in kidney
–> Blocks resorption of –
—> Reduces —
- Used for hypertension :
-Hydrochlorothiazide
-Chlorthalidone
-Indapamide
kidnet
water
reabsorbed
increases
Na/Cl channels
Na
plasma volume
-Angiotensinogen is a – amino acid peptide synthesised in the –
-Angiotensin (Ang) I (Ang1-10) is the first – amino acids cleaved by –
- — is the inactive product of renin
-The removal of the terminal — amino acids by — produces —
–>Asp-Arg-Val-Tyr-Ile-His-Pro-Phe
-Ang II is further cleaved into —
-Ang II acts on —
-AT1 and AT2
-G-protein-coupled receptors
–> —- linked
-Ang II binding to — is primarily responsible for —- effects:
- —
- Increased – production
- Increased — reabsorption
452
liver
10 amino acids
renin
angiotensin I
2 amino acids
angiotensin converting enzyme (ACE)
Ang II (Ang1-8)
bioactive peptides
angiotensin ii receptors
Gaq-linked
AT1
vasopressors
vasoconstriction
noradrenaline
sodium
check slide 28
- aldesteron is a – hormone which promotes — and — bp
- ACE inhibitors:
- act to inhibit —
- reduces — levels
- decreases –
- important agent for hypertension as:
Captopril
Benazepril
Enalapril
Lisinopril
Ramipril - adverse effects include:
Cough
Angioedema
Hypotension
Hyperkalaemia
Birth defects - increased — levels implicated
steroid
Na reabsorption
increases
ACE
ang ii
bp
brandykinin
so basically:
angiotensionagen becomes — and then —- which can either be — and —
- kininogen becomes — which leads to – production and inactive —
angiotensin I
angiotensin ii
AT1 or AT2 receptors
brandykinin
nitric oxide
peptides
angiotensin receptor blockers:
These agents are selective for — receptors:
Losartan
Valsartan
Candesartan
Olmesartan
Similar effects as – inhibitors
As they do not affect – metabolism, they are generally free from – and –
AT1
ace
brandykinin
free cough and angiodema
calicum channels:
1- voltage gated as :
2- ligand gated as — receptor , — receptor , — channels
- L type calcium channel:
Found in –,— and – muscle
Mediates —
Triggers — release
Plays an important role in regulating –
1-
L type
n type
p type
t type
IP3 receptor
ryanodine receptor
2 pore chanel
skeletal smooth and cardiac muscle
muscle contraction
aldosterone
blood pressure
calicium chanel blockers:
Three types
1-Phenylalkylamines :
Verapamil
2-Benzothiazepines:
Diltiazem
3-Dihydropyridines:
Amlodipine
Nifedipine
- Bind to three distinct but overlapping — sites
- Second and third generation agents have— half lives
1- dihydropyridine causes — with minimal impact on —-
- adverse effects include :
headache,
Light headedness,
flushing,
peripheral oedema
2- non- dihydropyridne are – potent – but reduce —
- adverse effects are – and —
- shouldn’t be used on patients w — or — with — ejection fraction
allosteric sites
longer
vasodilation
cardiac contractility
less
vasodilators
cardiac contraciltiy
constipation and bradycardia
beta blockers or heart failure w reduced ejection fraction
beta blockers and blood pressure:
Adrenaline and noradrenaline bind to—
-b1 receptors on the heart — heart rate and induce – secretion, causing an — in BP
-b2 receptors are found in the – where they cause —
- —- block both b1 and b2 receptors:
Propranolol,
Carvedilol
-Cardioselective agents have – affinity for b1-receptors:
Atenolol
Bisoprolol
b adrenergic receptors
increase
renin
increase
lungs
smooth muscle relaxation
non selective b blockers
higher
Beta blockers — heart rate and cause –
Adverse effects are due to the – distribution of beta-receptors
Non-specific agents should not be used in –
— and — are typical adverse effects
reduced
vasodilation
wide
asthmatics
bradycardia and hypotension
hypertension pharmacotherapy:
-Treat to target BP (typically — mmHg) is the basic principle of hypertension pharmacotherapy
-Recent trials (SPRINT, ACCORD BP, RESPECT, and ESPRIT) suggest that 120 mmHg is better than 140 mmHg
ESC 2024 guidelines recommend a target for SBP 120-129 mmHg
-Start at a – dose of drug and titrate up
-Monitor BP and if target is not achieved add additional agents
-Continue to monitor BP to ensure target is achieved and maintained
-As multiple drugs are often used, — interactions are a concern
-Don’t use two agents that target the – together
- — also impact choice of drug
- Multiple treatment algorithms exist from different societies
140/90
low
drug drug
heart
co morbidities
acute hypertension:
-Hospitalised patients may have hypertension
-Can be due to cardiovascular disease or identified during assessment for another disease
-Hypertension crisis is blood pressure in excess of 180/120 mm Hg associated with — damage
-This needs a rapid reduction in BP but no more than – over – hour
-Asymptomatic hypertension is blood pressure in excess of > — mm Hg in the absence of – damage
-A more – approach is used
end organ
25%
1 hour
180/120
end organ
conservative
anti hypertensive - the future :
1- Zilebesiran - a —
Double stranded RNA that separates into 2 strands in the cell
Guide strand binds to the angiotensinogen mRNA chains, which is then degraded
2- IONIS-AGT-LRx is an —
Binds to angiotensinogen mRNA leading to –
-Both are covalently linked to an N-acetylgalactosamine [GalNAc] ligand
->Binds with high affinity to the hepatic asialoglycoprotein receptor
–Both lead to reduced angiotensin levels
-KARDIA-1 (PII study) showed that a single injection of zilebesiran reduced BP for 6-months
small interfering RNA [siRNA]
anti sense RNA
degradation
hypotension:
-Typically defined as — mmHg
-Not a problem if — :
Confusion
Dizziness/lightheaded
Fainting (syncope)
- Reduced — e.g haemorrhage
-Bradycardia ,heat failure or cardiac valve problems
-Septic shock
-Orthostatic (postural) hypotension
->Hypotension upon standing
- Multiple causes:
-> neurogenic:
— neuropathy
—- disease
–> Non-neurogenic
— depletion
- Medication
90/60
asymptomatic
blood volume
peripheral
neurodegenrative disease
volume
orthrastatic hypotension pharmacotherapy:
1- Midodrine
— receptor agonist
2- Droxidopa
— that is converted into –
3- Fludrocortisone
— agonist
4- Pyridostigmine
— inhibitor
alpha 1 adrenergic
pro drug
noradrenaline
aldosterone
acetylcholinesterase
shock :
-Shock arises when there is significant tissue – due to –
-Treat underlying –
- — support may be necessary:
- Intravenous fluids to – blood volume
- —
- — adrenergic agonists:
Adrenaline
Noradrealine
Phenylephrine
Dopamine
— adrenergic agonists:
Dobutamine
— inhibitor :
Milrinone
— antagonist:
Atropine
hypoxia
hypperfusion
cause
haemodynamic
increase
vassopressors
alpha 1
b1
phosphodeterase 3
cholinergic
the challenge of hyper and hypotension :
Aggressive treatment of hypertension prevents heart disease but increases the risk of adverse effects such as hypotension and renal failure
Cardiologist: “Save the heart and screw the kidney”
GP: More concerned with adverse effects and overall health
Studies suggest that 10% relative risk reduction for 5 point decrease in BP
Based on quartiles of CV risk the absolute reductions in CV events when treating 1000 patients for 5-years were
13, 20, 24 and 38
Thus more aggressive treatment is more important in high risk patients
Pushing for a 5 point drop in BP in a low risk patient may be not worth it while important in a high risk patient
