Cardiac pharmacology and hypertension Flashcards
What is high BP a major risk factor for?
Stroke – ischaemic and haemorrhagic
Myocardial infarction
Heart failure
Chronic renal disease
Cognitive decline
Premature death
Increases the risk of: Atrial fibrillation (independent stroke risk)
Each 2 mmHg rise in systolic BP is associated with:
7% increased mortality from ischaemic heart disease
10% increased mortality from stroke
Continuous risk with increases in BP
When do you have suspected hypertension?
Clinic BP 140/90 mmHg or higher
How are people with suspected hypertension confirmed to have hypertension?
ambulatory blood pressure monitoring (ABPM)
Stage 1 hypertension features?
140/90 Clinic BP
135/85 Ambulatory/Home readings
Stage 2 hypertension features?
160/100 Clinic BP
150/95 Ambulatory/Home readings
Severe hypertension features
Systolic BP 180/120
Diastolic PB 110
What are the treatments for primary hypertension?
Lifestyle modification
Antihypertensive drug therapy
Who do we offer antihypertensive drug treatment too?
people aged under 80 years with stage 1 hypertension who have one or more of the following:
- Target organ damage
- Established cardiovascular disease
- Renal disease
- Diabetes
- A 10-year cardiovascular risk of 20% or greater.
Offer antihypertensive drug treatment to people of any age with stage 2 hypertension.
What do we target for therapy in BP control?
Cardiac output and Peripheral Resistance
Interplay between:
a. Renin-Angiotensin-Aldosterone system
b. Sympathetic nervous system (noradrenaline)
Local vascular vasoconstrictor and vasodilator mediators
What is the most potent vasoconstrictor and main reason for increase in BP?
Angiotensin 2
What does angiotensin 2 do?
1.Vascular Growth:
Hyperplasia
Hypertrophy
Salt retention
1. Aldosterone release
2. Tubular sodium reabsorption- kidney
3. Increase peripheral resistance and Cardiac output
4. act on sympathetic nerve ends to cause noradrenaline release
What does noradrenaline do?
Part of symapthetic ns
Increased renin production
Increases peripheral resistance and CO
What do ACE inhibitors do?
Block ACE, conversion from angiotensin 1 to angiotensin 2
Decrease BP
What do ARB’s do? (Angiotensin receptor blockers)
Block angiotensin 2 on their receptors decreasing CO and PR
Block angiotensin 2 at receptor level
End in sartan
All very similar drugs
Widely used
What do calcium channel blockers do?
Act on PR receptors
What do beta blockers do?
block beta adrenoreceptors – have effect on cardiac output
When are ACE inhibitors used?
Hypertension
Heart failure
Diabetic nephropathy
Examples of ACE inhibitors?
RAMIPRIL
PERINDOPRIL
ENALAPRIL
TRANDOLAPRIL
Side effects of Ace inhibitors?
- Related to reduced angiotensin II formation
a. Hypotension
b. Acute renal failure
c. Hyperkalaemia
d. Teratogenic effects in pregnancy - Related to increased kinin production
a. Cough
b. Rash
c. Anaphylactoid reactions
Main clinical indications for ARBs?
Hypertension
Diabetic nephropathy
Heart failure (when ACE-I contraindicated)
Examples of ARBs?
CANDESARTAN
VALSARTAN
TELMISARTAN
LOSARTAN
IRBESARTAN
Main side effects of ARBs?
Symptomatic hypotension (especially volume deplete patients)
Hyperkalaemia
Potential for renal dysfunction
Rash
Angio-oedema
Contraindicated in pregnancy
Generally very well tolerated
Main clinical indications of calcium channel blockers?
Hypertension
Ischaemic heart disease (IHD) – angina
Arrhythmia (tachycardia)
Examples of calcium channel blockers?
AMLODIPINE
NIFEDIPINE
DILTIAZEM
FELODIPINE
LACIDIPINE
VERAPAMIL
CCB: Dihydropyridines
nifedipine, amlodipine, felodipine, lacidipine
affect vascular smooth muscle
Peripheral arterial vasodilators
CCB: Phenylalkylamines
verapamil
Main effects on the heart
Negatively chronotropic, negatively inotropic
CCB: Benzothiazepines
diltiazem
peripheral vascular effects
Side effects of CCB: Dihydropyridines
Due to peripheral vasodilatation (mainly dihydropyridines)
Flushing
Headache
Oedema
Palpitations
Side effects of verapamil
Due to negatively chronotropic effects (mainly verapamil/diltiazem)
Bradycardia
Atrioventricular block
Due to negatively inotropic effects (mainly verapamil)
Worsening of cardiac failure
Verapamil causes constipation
Main clinical indications of beta adrenoreceptor blockers?
Ischaemic heart disease (IHD) – angina
Heart failure
Arrhythmia
Hypertension
Examples of beta-adrenoreceptor blockers?
BISOPROLOL
CARVEDILOL
PROPRANOLOL
METOPROLOL
ATENOLOL
NADOLOL
What drugs are B1 receptive?
Metoprolol
Bisoprolol
What drugs are B1/B2 receptive?
Propanolol
Nadolol
Carvedilol
Half of receptors in heart are…
B2
What are the main side effects of of beta adrenoreceptor blockers?
Fatigue
Headache
Sleep disturbance/nightmares
Bradycardia Hypotension Cold peripheries Erectile dysfunction
What do beta blockers worsen?
Asthma (may be severe) or COPD
PVD – Claudication or Raynaud’s
Heart failure – if given in standard dose or acutely
Main clinical indications of diuretics?
Hypertension
Heart failure
What are the classes of diuretics?
Thiazides and related drugs (distal tubule)
Loop diuretics (loop of Henle)
Potassium-sparing diuretics
Aldosterone antagonists
Examples of thiazide and related diuretics?
BENDROFLUMETHIAZIDE
HYDROCHLOROTHIAZIDE
CHLORTHALIDONE
Examples of loop diuretics?
FUROSEMIDE
BUMETANIDE
Examples of potassium-sparing diuretics?
SPIRONOLACTONE
EPLERENONE
AMILORIDE
TRIAMTERINE
Main adverse effects of diuretics
Hypovolaemia (mainly loop diuretics)
Hypotension
hypokalaemia
hyponatraemia
hypomagnesaemia
hypocalcaemia
Raised uric acid (hyperuricaemia – gout)
Erectile dysfunction (mainly thiazides)
Impaired glucose tolerance
A1 adrenoreceptor blockers?
Doxazosin
Centrally acting hypertenisves
MOXONIDINE
METHYLDOPA
Direct renin inhibitor
ALISKIREN
Treatment steps for hypertension
(Under 55 years)
- ACE-inhibitor or
Angiotensin II receptor Blocker - ACE-I / ARB + CCB
- ACE-I / ARB + CCB
+ Thiazide-like diuretic - Resistant Hypertension
Consider addition of
Spironolactone, high dose thiazide-like diuretic,
Alpha blocker, beta blocker, (others
Treatment steps for hypertension
(Over 55 years or any AFRO-Carribbean age)
- Calcium channel blocker
- ACE-I / ARB + CCB
- ACE-I / ARB + CCB
+ Thiazide-like diuretic - Resistant Hypertension
Consider addition of
Spironolactone, high dose thiazide-like diuretic,
Alpha blocker, beta blocker, (others
What is LVSD?
Heart failure due to left ventricular systolic dysfunction
What is HFPEF?
Heart failure with preserved ejection fraction (diastolic failure)
What is heart failure?
Heart failure is a complex clinical syndrome of symptoms and signs that suggest the efficiency of the heart as a pump is impaired.
What is heart failure caused by?
It is caused by structural or functional abnormalities of the heart.
What is the most common cause of heart failure?
Coronary artery disease
What are the effects of heart failure?
Causes morbidity, mortality, hospital admissions and substantial cost
What is chronic heart failure due to?
Most of the evidence for pharmacology is in chronic heart failure due to LVSD
How can we help with chronic heart failure?
Main benefit is with vasodilator therapy via neurohumoral blockade (RAAS - SNS) and not from LV stimulants
Heart is impaired therefore it affects circulation – response to that is sympathetic nervous system response – the RAAS system
What does aldosterone release do?
Increase sodium and water retention increasing BP
Aldosterone antagonist stops this
Symptomatic treatment of congestion:
First line: ACE inhibitors and beta blocker therapy
Low dose and slow uptitration
Diuretic
2nd: Aldosterone antagonists – diuretics – stops sodium and water retention
3. Consider ARNI – Aldosterone receptor antagonist and Neprilysin inhibtitor
4. Consider SGLT2 inhibitor
What do you give if your ACE-I intolerant in congestion?
Angiotensin receptor blocker
What do you give if your ACE- I intolerant and ARB intolerant?
Hydralazine/nitrate combination
What can you also consider?
Consider digoxin or ivabradine
Nitrates
Arterial and venous dilators
Reduction of preload and afterload
Lower BP
Main uses of nitrates
Ischaemic heart disease (angina)
Heart failure
Examples of nitrates?
ISOSORBIDE MONONITRATE
GTN SPRAY
GTN INFUSION
Coronary artery diseases
1.Chronic stable angina
Anginal chest pain
Predictable
Exertional
Infrequent
Stable
****
2. Unstable angina / acute coronary syndrome (NSTEMI)
Unpredictable
May be at rest
Frequent
Unstable
******
- ST elevation Myocardial Infarction (STEMI)
Unpredictable
Rest pain
Persistent
Unstable
Treatment for chronic stable angina
Immediate: GTN spray
First line treatment: Beta blocker or Calcium channel blocker
If intolerant: Switch
If not controlled: Combine
Secondary treatment for chronic stable angina?
- Antiplatelet therapy
Aspirin
Clopidogrel if aspirin intolerant - Lipid-lowering therapy
Statins (simvastatin, atorvastatin, rosuvastatin, pravastatin)
If intolerant or uncontrolled what do you do?
Long acting nitrate
Ivabradine
Nicorandil
Ranolazine
Treatment for Acute coronary syndromes (NSTEMI and STEMI)
- Pain relief: GTN spray
Opiates – diamorphine – heroin - Dual antiplatelet therapy: Aspirin plus ticagrelor or prasugrel or clopidogrel
- Antithrombin therapy: Fondaparinux
- Consider Glycoprotein IIb IIIa inhibitor (high risk cases): tirofiban, eptifibatide, abciximab
- Background angina therapy: beta blocker, long acting nitrate, calcium channel blocker
- Lipid lowering therapy: Statins
- Therapy for LVSD/heart failure as required: ACE-I, beta blocker, aldosterone antagonist
Essential/primary hypertension:
accounts for 95% of hypertension.
essentially means that the hypertension has developed on its own and does not have a secondary cause.
Secondary causes of hypertension:
ROPE
Renal disease. This is the most common cause of secondary hypertension. If the blood pressure is very high or does not respond to treatment consider renal artery stenosis.
O – Obesity
P – Pregnancy induced hypertension / pre-eclampsia
E – Endocrine. Most endocrine conditions can cause hypertension but primarily consider hyperaldosteronism (“Conns syndrome”) as this may represent 2.5% of new hypertension. A simple test for this is a renin:aldosterone ratio blood test.
Complications of hypertension:
Ischaemic heart disease
Cerebrovascular accident (i.e. stroke or haemorrhage)
Hypertensive retinopathy
Hypertensive nephropathy
Heart failure
What should patients with clinic BP between 140/90 mmHg and 180/120 mmHg have?
24 hour ambulatory blood pressure or home readings to confirm the diagnosis.
Having your BP taken by a doctor or nurse causes :
“white coat syndrome”. The white coat effect is defined as more than a 20/10 mmHg difference in blood pressure between clinic and ambulatory or home readings.
What should all patients with a new hypertension be tested for?
Urine: albumin:creatinine ratio for proteinuria and dipstick for microscopic haematuria to assess for kidney damage
Bloods: for HbA1c, renal function and lipids
Fundus examination: for hypertensive retinopathy
ECG: for cardiac abnormalities
Medications for hypertension:
A – ACE inhibitor (e.g. ramipril 1.25mg up to 10mg once daily)
B – Beta blocker (e.g. bisoprolol 5mg up to 20mg once daily)
C – Calcium channel blocker (e.g. amlodipine 5mg up to 10mg once daily)
D – Thiazide-like diuretic (e.g. indapamide 2.5mg once daily)
ARB – Angiotensin II receptor blocker (e.g. candesartan 8mg to up 32mg once daily)
When are ARB’s used in place of ACE inhibitors?
if the person does not tolerate ACE inhibitors (commonly due to a dry cough) or the patient is black of African or African-Caribbean descent. ACE inhibitors and ARBs are not used together.
Spironolactone
potassium-sparing diuretic” that works by blocking the action of aldosterone in the kidneys, resulting in sodium excretion and potassium reabsorption.
can be helpful when thiazide diuretics are causing hypokalaemia.
What does using spironolactone do?
Using spironolactone increases the risk of hyperkalaemia.
ACE inhibitors can also cause hyperkalaemia.
Thiazide like diuretics can cause also electrolyte disturbances. For this reason it is important to monitor U+Es regularly when using ACE inhibitors and all diuretics.
