Lecture 5- Hypertension and heart failure Flashcards
1
Q
What is BP?
A
- Driving force to perfuse organs with blood (force per. Unit area acting on vessels)
- Not uniform throughout body
- Reported as systolic (SBP) and diastolic (DBP)
- Cyclical with the cardiac cycle
- Physiologically regulated variable- it changes
2
Q
blood pressure equationa
A
Mean arterial pressure = CO x RPR
MAP= DBP + (SBP-DBP/3) (this is how we actually calculate)
3
Q
Blood pressure regulation
A
- Autonomic sympathetic activity
- RAAS
- Local action by autacoids e.g. bradykinin and NO- action of endothelium on vascular smooth muscle
4
Q
the higher the total peripheral resistance the higher the mean arterial pressure… what changes the resistance in blood vessels
A
radius of the blood vessel
Radius decreases and resistance increase
- Smooth muscle tone changes TPR
- Vasoconstriction increase peripheral resistance, requiring higher BP to drive blood through the systemic circulation
5
Q
hypertension (essential, primary, idiopathic) is still not
A
fully understoo
6
Q
hypertension causes vascular changes
A
- Remodelling
- Thickening
- Hypertrophy
7
Q
pathophysiology of vascular changes due to hypertension
A
- Increases vasoactive substances inc ET-1, NAd, angII
- Vascular remodelling also occurs as a direct result of local salt sensitivity
- Hyperinsulinemia and hyperglycaemia lead to endothelial dysfunction and increased reactive oxygen species- NO signalling reduced.
8
Q
vascular changes results in
A
- Permanent and maintained medial hypertrophy of vasculature increasing TPR and decreasing compliance of the vessel
- End organs specifically at risk
- Renal
- Peripheral vascular disease
- Aneurysm
- Vascular dementia
- Retinal disease
- Also causes hypertensive disease- left ventricular heart failure- dilated cardiac failure
- Increased morbidity and mortality
9
Q
Why treat hypertension if it is asymptomatic?
A
- Managing BP reduces risk of SBP and stroke etc
10
Q
NICE definition of hypertension
A
140/90 mmHg= hypertension
11
Q
types of hypertension
A
- 90% essential/primary/idiopathic hypertension
- Second hypertension (due to other pathology)
- Pre hypertension
- Isolated systolic/diastolic hypertension
- White coat/clinic
12
Q
white coat effect
A
13
Q
hypertension is a
A
silent killer- therefore increasing public awareness of risk factors is important
- screening those at risk is important
14
Q
clinical diagnosis (best practice)
A
- Sitting, relaxed and arm is supported
- Both arms, >15 mmHg difference repeat measurement and use arm with higher reading
- Measurements over period of visit +/- ABPM/HBPM
- Emergency treatment required? (>180 SBP or 120 DBP + clinical signs)
- CVD risk and end organ damage should be assessed whilst waiting for hypertension confirmation
15
Q
Aim of hypertension treatment
A
- Target BP (diff for diff populations)
- Reduced CVD risk
16
Q
Prehypertension
- Slippery slope (>120/60 <140/90 mmHg
- Aim (to reduce CVD risk)
- Promotion of regular exercise
- Modified diet
- Reduction in stress and increased relaxation
- Limit alcohol intake
- Discourage excessive caffeine consumption
- Smoking cessation
- Reduced dietary sodium
- These should be promoted in all patient groups
*
A
17
Q
desired bp
A
120/80 mmHG
18
Q
how many stages of hypertension
A
3
19
Q
stage 1 hypertension
A
- clinic BP raning from 140/90 mmHg to 159/99 mmHg
- ABPM (ambularotry blood pressure monitoring) or HBPM (home) daytime average raning from 135/85 mmHg to 149/94 mmHg
20
Q
stage 2 hypertension
A
- clinic BP raning from 160/100 mmHg to 180/120 mmHg
- ABPM (ambularotry blood pressure monitoring) or HBPM (home) daytime average raning from 150/85 mmHg or higher
21
Q
stage 3 or severe hypertension
A
clinic systolic BP of 180 mmHg or higher OR clinic diastolic BP 120mmHg or higher
22
Q
Primary hypertension therapeutic agents
A
- Angiotensin converting enzyme inhibitors (ACEi)
- Angiotensin (AT1) receptor blockers (ARBs)
- Calcium channel blockers (CCBs)
- Diuretics- thiazide and thiazide-like
- Other. Agents for resistant hypertension
23
Q
Lots of hypertension therapeutics target RAAS
A
- ACE is found on luminal surface of capillary endothelial cells- vascular tissue
- ACE catalyses conversion of angiotensin I–> angiotensin II(active vasoconstrictor)
- angiotensin II affords action through AT1 (and AT2 receptors)
- AT1 receptors subtype of classic angiotensin II action
- Vasoconstriction
- Stimulation of aldosterone which acts at distal renal tubule
- Cardiac and vascular muscle cell growth
- Vasopressin (ADH) release from posterior pituitary
- Angiotensin II and aldosterone increase BP through combination of vasoconstriction and increasing circulating blood volume
24
Q
outline the mechanism of action of ACEi
A
- Inhibits circulating tissue ACE
- Limit conversion of angiotensin I –> angiotensin II
-
Main action: Reduction in ATII:
- Vasodilation (decreased peripheral resistance à decreased afterload)
- Reduction in aldosterone release (increased sodium and H2O excretion)
- Reduced vasopressin (ADH) release (increased water excretion)
- Reduced cell growth and proliferation
- Remember: angiotensin II also produced from angiotensin I independently of ACE via chymases (see ARBs)
-
Secondary action: Bradykinin is also a substrate for ACE
- Use of ACEi potentiates bradykinin
- Vasodilation via NOS/NO and PGL2
- ACEi vasodilation in low-renin hypertensives
- Use of ACEi potentiates bradykinin
25
name some drugs that fall under the drug class: ACEi
Lisinopril
ramipril
26
**Adverse drug response: ACEi**
* Hypotension!
* Dry cough (bradykinin association)
* Hyperkalaemia (low aldosterone)
* Cause or worsen renal failure (esp renal artery stenosis where constriction of efferent artery needed)
* Angioedema (more common in afro-caribbean pts)
27
**Contraindications: ACEi**
* Renal artery stenosis
* AKD
* Pregnancy
* Idiopathic angioedema
* CKD - caution
28
Drug-drug interaction: ACEi
* Other drugs which causes hyperkalaemia (low aldosterone associated with hyperkalaemia)
* NSAIDS (action in efferent arteriole)
* Other antihypertensive agents
29
Mechanism of action of Angiotensin II (AT2) receptor antagonists
* Work at AT1 and AT2
* AT1 – important relation to cardiovascular regulation
* Bit confusing known as – Ang-II blocker, AT1-receptor blockers or ARBs
* **No effect on bradykinin**- less effective in low-renin hypertensive pts
* More effective at inhibiting Ang-II mediated vasoconstrciton than ACEi --\> Ang- II is blocked further downstream in the pathway- conversion by chymase wont make a difference)
* Dry cough and angioedema less likely than ACEi
30
name some drugs that fall under the drug class: Angiotensin 2 receptor agonists
Cande**sartan,** lo**sartan**
31
**Adverse drug response: Angiotensin II receptor antagonist**
* Hypotension
* Hyperkalaemia
* Cause or worsen renal failure
32
**Contraindications:** Angiotensin II receptor antagonists
* Renal artery stenosis
* AKD
* Pregnancy
* CKD- caution
33
**Drug-drug interaction:** Angiotensin II receptor antagonists
* Other drugs which causes hyperkalaemia
* NSAIDS (action in efferent arteriole)
34
2 main branches of Calcium channel blockers (CCB)
* Dihydropyridines
* Non- dihydropyridine
* phenylalkylamines
* benzothiazepines
35
mechanism of action of calcium channel blockers (CCB)
* CCBs target L-type calcium channels (LTCC) which allow inward calcium flux into cells (voltage operated calcium channel (VOCCs))
* Expressed throughout the body
* Vascular smooth muscle cells
* Cardiac myocytes
* SA and AV nodes
* **Main action:** CCBs target calcium initiated smooth muscle contraction (in hypertension)
* 3 classes of CCB interact with different sites on (alpha1) subunit of VOCCà different selectivity for vascular smooth muscle or myocardium
36
MOA of different classes of CCBs: Dihydropyridine
**(most important for hypertension)**
* Selective for **peripheral vasculature**
* Little chronotropic or inotropic effects
* Cerebral and peripheral selectivity dictates which are use for hypertension
37
MOA of different classes of CCBs: Non-dihydropyridine
* **Phenylalkylamines**
* Depresses SA node and slows AV conduction
* Negative inotropy
* **Benzothiazepines**- sit in the middle (some action on vasculature and some on SA/AV node)
38
when are CCB used
* Primary choice antihypertensive in low renin pts
39
name some drugs that fall under the drug class: CCB- dihydropyridine class
* Amlo**dipine**
* Long half life
* Nife**dipine**
* Selectivity for cerebral vasculature (useful for ischaemic effects of subarachnoid haemorrhage)
* Nimo**dipine**
40
41
adverse drug response: Dihydropyridine
* Ankle swelling
* Flushing
* Headaches- vasodilation
* Palpitations (compensatory tachycardia)
42
**Contraindications:** Dihydropyridine class
* Unstable angina
* Severe aortic stenosis
43
**Drug-drug interaction:** Dihydropyridine class
Simvastatin should be given at a lower dose when given with Amlodipine should not be given with (increased effect of statin)
44
name some drugs that fall under the drug class: non-hhydropyridines- phenylalkylamines
verapamil
45
46
phenylaklylamines used for
* Arrhythmia, angina, (hypertension)
* Class IV anti-arrhythmic agent/prolongs AP/effective refractory period
* Less peripheral vasodilatation, negative chronotropic and inotropic effect
47
**Adverse drug response:** Phenylalkylamines
* Constipation
* Bradycardia (IV)
* Heart block
* Cardiac failure
48
**Contraindications:** Phenylalkylamines
* Poor LV function- caution
* AV nodal conduction delay
49
50
**Drug-drug interaction:** Phenylalkylamines
* B-blockers – high risk
* Other hypertensive and antiarrhythmic agents
51
name some drugs that fall under the drug class: non-hydropyridines- benzothiazepines
diltiazem
52
benzothiazepines
* Sit between other CCB classes
* Some action of vasculature and SA/AV node
53
diuretics used to treat hypertension
* Thiazide- Bendroflumethiazide
* Thiazide- like- Indapamide
54
**Mode of action of thiazide diuretics**
* Inhibit Na+/Cl- co-transporter in the DCT
* Decrease sodium and water reabsorption in the short term (RAAS compensates with time)
* **Main action**:
* Long term effects mediated by modulating sensitivity of vascular smooth muscle to vasoconstrictors Calcium/ Noradrenaline
* Useful over CCB in oedema
55
**Adverse drug response: thiazide diuretics**
* Hypokalaemia
* Hyponatraemia
* Hyperuricemia (gout)
* Arrhythmia
* Increased glucose (esp with BB)
* Small increase in cholesterol and triglyceride
56
**Contraindications: thiazide diuretics**
* Hypokalaemia
* Hyponatraemia
* gout
57
**Drug-drug interaction: thiazide diuretics**
* NSAIDs
* Potassium decreasing drugs such as loop diuretics
58
treating hypertension pathway
**If patients are hypotensive and type 2 diabetics, regardless of their race, they will follow the ACEi or ARB pathway straight away**
* ACEi/ARB decrease diabetic nephropathy and CKD with proteinuria by dilation of efferent glomerular arteriole
* Two pronged approach
* Decrease PVR à decrease BP and dilation of efferent glomerular arterioleà reduced intraglomerular **pressure- good for T2DM**
**Step 4- Resistant hypertension therapeutics**
* If BP not controlled after step 3
* May need to consider acting extra drugs if pt not taking drugs properly
59
Resistant hypertension therapeutics
ACE inhibitor or an angiotensin II receptor blocker (A), a calcium channel antagonist (C), and a thiazide or thiazide-like
60
name some drugs that fall under the drug class: aldosterone antagonist
spironolactone
61
**Adverse drug response:** Aldosterone receptor antagonist
* Hyperkalaemia
* Gynaecomastia
62
**Contraindications:** Aldosterone receptor antagonist
* Hyperkalaemia
* Addison’s
63
**Drug-drug interaction:** Aldosterone receptor antagonist
* Drugs which increase potassium
* pregnancy
64
Resistance hypertension therapeutics if potassium too high
**Alpha and B blockers**
65
name some drugs that fall under the drug class: B blocker
* Labet**alol**
* Bisopr**olol**
* Metopr**olol**
66
**MOA of B blockers**
* Decrease sympathetic tone by blocking adrenaline/ noradrenaline from, binding to B-adrenergic receptors
* B1- blockers selective to B1 used to treat hypertension
* B2
* B3
* Therefore reducing myocardial contraction resulting in reduced CO
* Reduction in renin secretion (B1)
67
**Adverse drug response: B blockers**
* Bronchospasm (B2- B1 blockers can have effect on B2)
* Heart block (B1)
* Raynaud’s
* Lethargy
* Impotence
* Mask tachycardia- sign of insulin induce hypoglycaemia
68
69
**Contraindications: B blockers**
* Asthma (bronchoconstriction)
* COPD
* Haemodynamic instability
* Hepatic failure
70
**Drug-drug interaction: B blockers**
Non-dihydropyridine CCBs (verapamil and diltiazem- asystole!!)
71
72
name some drugs that fall under the drug class: A blocker
Doxazosin
73
**Mode of action** Alpha blockers
* Selective antagonism of alpha-1 adrenoreceptors
* Reduce peripheral vascular resistance
* Urinary tract inc bladder neck and prostate- benign prostatic hyperplasia (tamsulosin)
* Relatively safe in renal disease
74
**Adverse drug response: Alpha blockers**
* Postural hypotension
* Dizziness
* Syncope
* Headache
* fatigue
75
**Contraindications: Alpha blockers**
postural hypotension
76
**Drug-drug interaction**: Alpha blockers
dihydropyridine CCBs- oedema
77
**Heart failure**- the broken pump
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* Cardiac output = 5L/min in a typical healthy adult
* CO varies in response to both physiological and pathological factors
* Preload- filling pressure
* Afterload- load that ventricles must eject blood against
* Contractility
* Heart rate
78
heart failure symptoms (may present/ often in later stages)
* Exercise intolerance
* Dyspnoea
* Fatigue
79
heart failure is caused by a
**Self perpetuating spiral**
Physiological neurohormonal response attempts ot compensates but will eventually lead to further pathology
80
**Management of heart failure**
Usually dealing with LV systolic dysfunction associated with reduced LV ejection fraction (\<45%)
* Correcting underlying cause (replace valve, angioplasty)
* Non-pharmacological management
* Reduction in salt intake
* Liquid reduction (1.4L a day)
* Addition of diuretic plus other therapeutic agents
**Aims of treatment**
* Reduce symptoms
* Managed increase in exercise tolerance
* Address arrhythmias, hyperlipidaemia, diabetes
* Increase quality of life and slow morbidity
81
Managment of heart failure
82
name some drugs that fall under the drug class: A blocker**Drug class:** Aldosterone receptor antagonist
Spironolactone
83
Mode of action:Aldosterone receptor antagonist
* Diuretic- Inhibits aldosterone receptor
* Some individuals with HF develop refractory hyperaldosteronism
* Excessive RAAS activity (aldosterone scape) in spite of ACEi/ARB
* Given adjunct to ACEi/ARB + diuretic
84
name some drugs that fall under the drug class: B blocker used to treat heart failure
Canedilol
85
86
A 60 year old man is found to have a persistently raised blood pressure of around 180/115. He also has signs and symptoms of mild congestive heart failure.
PMH: Type II diabetes controlled by diet alone. Osteoarthritis of both knees. Medication: Naproxen 500 mg twice daily.
What drug might be most suitable for first line treatment? What advice would you give the patient about the prescription?
he has type 2 diabetes so go go down ACEi or ARB pathway
- beware of NSAIDs for both
87
what is the first line treatment for someone with hypertension without diabetes
Calcium channel blockers
88
if first line treatment doesnt suffieciently decrease BP
ACEi or ARB +CCB + thiazide
(for both those with and without diabetes)
89
which drug is contraticted in diabetes
thiazide like diuretics
90
e there any medications that you are able to offer to reverse the progression of the chronic heart failure?
no you cannoy reverse CHF
91
n echocardiogram confirms significant left ventricular dysfunction. You decide to initiate ACE inhibitor therapy.
9) How does an ACEi help in the management of CHF in this patient? Think about their mechanisms of action and the trial data we have discussed.
reduced BP therefore decreased after load and decreased LV hypertrophy
92
A 35 year old lady presents at an antenatal appointment where her blood pressure is recorded as 155/105 mmHg. This is her first pregnancy and she reports that there is no familial history of pre-eclampsia. Prior to becoming pregnant her blood pressure was 123/84 and she was fit and healthy with a BMI of 26 kg/m2.
13) What test should be carried out prior to initiating any treatment? (
- test for protein in urine (Pre-eclampsia)
- glucosuria (gestational diabtes)
93
a 35 year old lady presents at an antenatal appointment where her blood pressure is recorded as 155/105 mmHg. This is her first pregnancy and she reports that there is no familial history of pre-eclampsia. Prior to becoming pregnant her blood pressure was 123/84 and she was fit and healthy with a BMI of 26 kg/m2.
A diagnosis of gestational hypertension is confirmed. What is the recommended treatment for this patient and what is the mechanism of action of this therapeutic class?
first line: Labetalol (B blocker) - reduce sympathetic acitvity
second line: Nifedipine (dihydropyridine CCB)
ACEi and ARB not safe in pregnancy
94
A 46 year black man is having a routine health check for by occupational health at his employer after 6 months in a new job. His BMI is 29 kg/m2 and his total cholesterol is 7.0 mmol/litre. His blood pressure is recorded as 145/125. The new role is particularly sedentary requiring very little physical activity.
If blood pressure hasn’t been significantly lowered after a further 12 weeks what would the course of action be
afro-caribean thereofore liekly to be low renin
- thiazide
- could also give ACEi or ARB
95
if renin is high what class of drug will be prescribed
ACEi
(black people tend to have a less active RAAS i.e. ACEi will be is less effective CBB
96
An 84 year old lady presents to her GP for her annual flu vaccination. On the advice of her daughter she requests an “MOT”. She reports that she feels very well and that she is appeasing her daughter by having the check-up. The GP measures the ladies blood pressure whilst she sits in the consulting room. A reading of 150/92 is recorded.
what is the recommended next step
BP not too high for such an old person
- antihypertensives could cause syncope and cause more damage than benefit
