3 - Hypertension and Heart Failure Drugs Flashcards
What are the effects of hypertension and how is bp regulated?
- Increases arterial wall thickness by remodelling and hypertrophy. Stiffens the walls so they are less compliant
- Organ damage from lack of blood flow
- Regulated by RAAS, autonomic NS, bradykinin, NO and natriuretic peptides
What are the values that define hypertension and what are some of the causes?
>140/90
primary, secondary (conn’s, diabetes), isolated diastolic/systolic, white coat
What are target blood pressures (clinically and ambulatory) for different groups of people?
- <140/90 if less than 80 inc type II diabetes
- <150/90 if greater than 80
- <135/85 if type I diabetic
What is best practice when diagnosing hypertension?
- Sitting relaxed and arm supported
- Both arms should be within 15mm/Hg of each other, if not then repeat. Take highest reading
- Measure over a period of time including ambulatory and hoe machines
- CVD and organ damage should be assessed whilst waiting for hypertension confirmation
What are the stages of hypertension?
- Resistant hypertension at stage 3
- Emergency if >180/20 and clinical signs
What is prehypertension and how can progression of this be limited
>120/80 but less then 140/90
- Promote regular exercise
- Healthy balanced diet
- Reduce stress and increase relaxation
- Limit alcohol and caffiene intake
- Smoking cessation
- Reduce salt in diet
In general what are some classes of drugs that are used to treat primary hypertension?
- ACE inhibitors
- ARBs
- Calcium channel blockers
- Diuretics
- Alpha and Beta blockers
What is the mechanism of action of ACEi’s to treat hypertension?
Competitive inhibitors of Angiotensin Converting Enzyme:
- Reduce formation of angiotensin II
- Arteriole vasodilation
- Reduce circulating aldosterone so less ADH
- Build up of bradykinin which is a vasodilator as makes NO, good for low renin hypertensives
What are some examples of ACEi’s?
- Ramipril
- Lisinopril
What are some side effects of ACEi’s?
Side effects:
- Dry cough*
- Hypotension
- Hyperkalaemia* as loss of aldosterone
- Renal failure especially due to renal artery stenosis as efferent arteriole needs to constrict
- Angiooedema* due to BK, especially black population
What are some contraindications of using ACEi’s?
- Pregnancy (along with ARBs, can cause CVS and CNS defects and growth restriction and oligohydraminos)
- Hyperkalaemia
- NSAIDs, K+ raising drugs, antihypertensives
- AKD
- Breastfeeding
- Renal artery stenosis
What is the mechanism of action of ARBs?
- AngII mainly binds to AT1 receptor
- Inhibits vasoconstriction* better than ACEis as the AT1 receptor blocked so any AngII made from chymases can not work either
- Inhibits aldosterone stimulation*
- Less effective in low renin hypertensives as no effect on bradykinin
What are some examples of ARBs?
- Candesartan
- Losartan
What are some side effects and contraindications of ARBs as antihypertensives?
Side effects:
- No dry cough and angiooedema like ACEi
- Renal failure
- Hyperkalaemia
Contraindications:
- AKD
- Pregnancy and breast feeding
- Renal artery stenosis
- K+ raising drugs, NSAIDs, other antihypertensives
What is the mechanism of action of calcium channel blockers?
- Bind to alpha1 subunit of L-type calcium channel (VOCC), reducing cellular calcium entry causing vasodilation, reducing preload on the heart
- LTCC in vascuar smooth muscle, cardiomyocytes, SA and AV node. Different classes selective for different areas
If a patient had hypertension with low renin levels, what class of drug would be best to prescribe them first?
- CCB as doesn’t target RAAS
- ACEi as increases bradykinin
What are the three main classes of CCBs and give some examples for each?
- Dihydropyridines: amlodipine (long half life), nifedipine (selective for cerebral vasculature so used for subarachnoid haemorraghe), nimodipine
- Benzothiazapines: Diltiazem
- Phenylakylamines: Verapamil
Where do each of the classes of CCBs work in the body?
- Dihydropyridines: 1st line CCB most commonly used for hypertension. Selective for peripheral vasculature but little ino/chronotropic effect
- Phenylalkyamines: mainly act on myocardium, depress the SA node and slows AV conduction so negative inotropy. Used for SVTS. Can worsen heart failure so don’t give to a hypertensive with heart failure
- Benzothiazapines: Sit in the middle, act on myocardium and vascular smooth muscle, can worsen heart failure
What are the side effects and contraindications of the use of dihydropyridines (good oral absorption) for hypertension?
Side effects:
- Ankle swelling, flushing and headaches from vasodilation
- Palpitations as compensatory tachycardia
Contraindications:
- Unstable angina and severe aortic stenosis as the palpatations
- Amlodipine and simvastatin as increased effect of statin
- Other antihypertensives
What are the side effects and contraindications of the use of phenylalkylamines?
- Mainly used to treat arrhythmias (SVTs) and angina not HTN
Side effects:
- Constipation, bradycardia, heart block, cardiac failure
Contraindications:
- Poor LV function
- AV nodal conduction delay
- B-blockers, other antihypertensives, other antiarrhytmic agents
What are the properties and adverse effects of Benzothiazepines e.g. diltiazem?
- Properties (same as phenylalkylamines): impedes calcium transport across the myocardial and vascular smooth muscle cell membrane, peripheral vasodilation, ↓ myocardial contractility
- Adverse effects: bradycardia, can worsen heart failure
What thiazide/thiazide-like diuretics are used to treat hypertension and what is their mechanism of action?
Reduce distal tubular sodium reabsorption by blocking NaCl channel
- Initial blood volume decrease
- Later, total peripheral resistance falls
- RAAS compensates
- Useful over CCBs in oedema
What are some examples of thiazides?
- Bendroflumethiazide
- Indapamide (thiazide like)
What are some side effects and contraindications associated with the use of thiazides in treating hypertension?
Side effects:
- HypoK, hypoNa, hyperuricemia
- Arrhythmia
- Increased glucose
- Increased cholesterol and triglycerides
Contraindications:
- HypoK, HypoNa
- Gout
- NSAIDs, K+ lowering drugs
What are the steps recommended by NICE in treating primary hypertension?
- ACD rule with step 4 considering:
- alpha/beta blocker/other diuretics
- adherance of patient
- referral to expert advice
Why are hypertensive type II diabetics treating with an ACEi first regardless of age?
- Two pronged approach as ACEi decreases PVR so drop in B.P and also dilates efferent glomerular arteriole so reduced intraglomerular pressure
- ACEi are antiproteinuric! Stops progression of diabetic nephropathy
What diuretics, other than thiazides, are added in step 4 of treating hypertension and what are the contraindications of this drug?
- Spironolactone: aldosterone receptor antagonist
- Contraindications:
- Hyper K
- Addisons
- K+ raising drugs, ACEis, ARBs
If a patient is at step 4 of treating hypertension but has hyperkaelamia, what other drug can be added to their regimen?
- NOT spironolactone as hyperkalaemic
- Add alpha or beta blocker
What is a centrally acting drug?
- Lowers heart rate and reduces blood pressure by blocking sympathetic nervous system
- e.g Labetalol in pregnancy or hypertensive emergency
What are the actions of betablockers and some examples?
- Reduce HR and CO
- Inhibit renin release
- Initially TPR increases later falls to normal
- Labetalol, bisoprolol, metoprolol
What are some side-effects and contraindicaitons of the use of beta blockers?
Side effects:
- Heart block
- Lethargy
- Impotence
- Bronchospasms
- Bradycardia
- Impaired glucose tolerance
Contraindications:
- Asthma
- Hepatic failure
- Non-dihydropyridine CCBs as asystole
What are the mechanisms of actions of alpha receptor blockers? e.g doxazosin
- Selective antagonism of a-1 adrenoreceptors can be used for BPH and HTN
- Antagonise contractile effects of NA on vascular smooth muscle
- Reduce peripheral vascular resistance
- Benign effect on plasma lipids / glucose
What are some side effects and contraindications of the use of alpha blockers?
Side effects: postural hypotension so dizziness, syncope, headche and fatigue, oedema
Contraindications: postural hypertension or taking dihydropyridine CCBs
What are the causes of heart failure and how can non-pharmacological treatment help to alleviate symptoms like oedems, dyspnoea?
- Ischaemic heart disease
- Hypertension
- Valve disease
- Reduce salt intake, exercise and stop smoking and drinking alcohol
In four steps, describe the clinical management of heart failure
- Diuretics
- ACE inhibitor
- ARB
- β-blocker
- Spironolactone
Drugs are given to help sympoms, delay progression and reduce mortality
What drugs are given to a patient diagnosed with heart failure?
- Furosemide loop diuretic to relieve symptoms
- ACEi (ramipril) and Beta blocker (bisoprolol) to reduce heart rate, b.p and therefore the work load and oxygen demand of the heart
- Spironolactone if needed as refractory hyperaldosteronism may occur
- Statins if heart failure due to MI
Why are older and black patients treated with CCBs rather than ACEi’s for hypertension initially?
These populations have lower renin levels
What drug treatment would you consider at this stage?
Post MI bundle:
- Beta blocker (be careful as asthmatic)
- ACEi
- High dose statin
- Antiplatelet
What should your plan of action be for the following clinic blood pressures:
- <140/90
- 140/90 to 179/110
- 180/20 or more
What are some actions of ACEi’s that lower blood pressure?
- Less vasoconstriction
- Less sympathetic activity
- Less aldosterone so less salt and water retention
Which diureic is an add on therapy in resistant hypertension?
Spironolactone if patient has normal K+ levels. Thiazide already added in three step approach
What are some drugs added in resistant hypertension, apart from a diuretic?
Beta Blocker (e.g bisoprolol): lowers renin levels, -ve chronotrope, decreases cardiac output
Alpha Blocker (doxazosin): causes vasodilation reducing PVR
