Pharmacological Management of Hypertension Flashcards
What is the difference between primary and secondary hypertension?
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Primary hypertension
- Idiopathic; unknown origin; >90% of cases.
-
Secondary hypertension
- Known cause; <10% of cases.
- Examples: renal disease, phaeochromocytoma, diabetes, Cushing’s, some drugs.
Differentiate between ‘low’ BP, normal BP, stage 1 and stage 2 hypertension.
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What are the chances of harm due to hypertension?
- Depends on:
- How high the BP is
- How long the person has had high BP
- Whether any relevant concurrent health problems (such as high cholesterol or diabetes)
- Concordance with medication / lifestyle changes
What is hypertension a major risk factor for?
- Stroke
- MI
- Heart failure
- CKD
- Cognitive decline
- Premature death
- Untreated hypertension can cause cascular and renal damage leading to a treatment-resistance state.
What are the goals of hypertension treatment?
- Reduce arterial BP to recommended targets.
- Reduce risk of end organ damage (CV, renal, cerebrovascular).
- Reduce risk of mortality due to CV disease.
Describe the care pathway for hypertension.
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What are the indications to prescribe for management of hypertension?
- Patients of any age with stage 2 or 3 hypertension.
- Patients with stage 1 hypertension who have one or more of the following:
- Target organ damage
- Established CV disease (CHD, CVA)
- Renal disease
- Diabetes
- 10-year CV risk equivalent to 20% or greater
What are the risk score calculators for estimating CV risk?
- ASSIGN
- Qrisk
- JBS3
- Based on:
- BP
- Age
- Weight/height
- Gender
- Smoking
- Cholestrol
- Ethnicity
- Social class
- Family history
- Diabetes, rheumatoid arthritis, renal function
What are the BP treatment targets?
- Standard patients
- <140/90mmHg
- Over 80 years of age
- <150/90mmHg
- More important than controlling BP is preventing falls. Do not drop BP too fast or too low.
- Cardiac / renal disease or diabetes
- <130/80mmHg
- BUT, make it patient centres:
- Individualised targets based on appropriateness, tolerability and frailty.
Before prescribing anti-hypertensive medication, you must review the patient’s drugs.
Which drugs cause a possible increase in BP?
- NSAIDs (e.g. ibuprofen, diclofenac)
- Oral steroids (e.g. Prednisolone)
- Venlafaxine (anti-depressant)
- Oral sympathomimetic decongestants (e.g. Pseudoephedrine - “Sudafed”)
- Soluble or dispersible drugs - contains SALT
- Illicit drug use.
What are the factors which regulate arterial BP?
- Cardiac output (CO) - HR, SV
- Total peripheral resistance (TPR) - or systemic vascular resistance.
- TPR x CO = MAP
Give a summary of the stepwise anti-hypertensive drug treatment.
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What are the major classes of anti-hypertensive drugs?
- Renin-Angiotensin system inhibitors
- Calcium channel blockers
- Diuretics
Give examples of the Renin-Angiotensin system inhibitors.
- Angiotensin converting enzyme inhibitors (ACE inhibitors)
- Ramipril, lisinopril, captopril
- Angiotensin AT1 receptor antagonists (ARBs)
- Losartan, candesartan, irbesartan
Give examples of calcium channel blockers.
- Amlodipine
- Felodipine
- Lercanidipine
Give examples of the diuretics used in management of hypertension.
- Thiazide-like diuretics - often essential at step 2 or 3, but not effective in moderate-severe renal impairment.
- Indapamide, bendroflumethiazide
- High dose loop diuretics (e.g. Furosemide) may be used for raised BP in renal failure.
What are the additional treatments for resistant hypertension?
- Sympathetic nervous system antagonists
- β-blockers
- E.g. atenolol
- α1 adrenoceptor blockers
- E.g. doxazosin
- β-blockers
- Kidney function modifiers
- Potassium sparing diuretics and aldosterone antagonists
- E.g. amiloride, spironolactone
- Potassium sparing diuretics and aldosterone antagonists
Describe the parts of the pathway which ACE-Inhibitors and ARBs act upon to produce their anti-hypertensive effects.
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What are the contraindications for prescribing ACE-I or ARBs?
- Allergy, hypersensitivity.
- History of angioneurotic oedema (hereditary, idiopathic or due to previous angioedema with ACE-I or ARBs).
- Significant bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney.
- Pregnancy.
What are the common side effects of ACE Inhibitors?
- Persistent dry cough (15%) which is untreatable (patients need to switch to ARB); dizziness; tiredness; headaches.
- Slight increased risk of angioedema in African/Carribean ethnicity.
- Risk of hyperkalaemia (care with drug interactions).
- Renal impairment.
What are the common side-effects of ARBs?
- Dizziess; headaches; back / leg pain.
- Risk of hyperkalaemia, renal impairment.
Describe the mechanism of action of calcium channel blockers.
- Block entry of calcium through slow channels in cardiac and smooth muscle.
- Reduce cardiac output (class 4 anti-arrhythmics - verapamil, diltiazem).
- Peripheral vasodilation, reduced TPR.
Which kind of calcium channel blockers should be used as anti-hypertensives and why?
- In hypertension, use dihydropyridine-like CCBs:
- E.g. amlodipine, felodipine, lercanidipine.
- Used because they have less effect on cardiac muscle cells, greater impact on vascular smooth muscle, reduces PR.
What are the contraindications of dihydropyridine-like calcium channel blockers?
- Uncontrolled heart failure
- Cardiogenic shock (MI) (recent)
- Significant aortic stenosis
- Unstable angina
- Pregnancy (but consider risk / benefit)
What are the common side-effects of dihydropyridine-like calcium channel blockers?
- Flushes
- Headaches
- Ankle oedema
- Dizziness
Which classes of drugs are kidney function modifiers?
Where in the kidney do they act?
- Thiazide-like diuretics
- Aldosterone antagonists
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Give examples of thiazide-like diuretics.
- Indapamide
- Bendroflumethiazide
Give an example of an aldosterone antagonist.
- Spironolactone
What is the mechanism of action of thiazide diuretics?
- Inhibits the NaCl co-transporter in the distal tubule
- so less NaCl is reabsorbed
- so causing moderate diuresis, reducing oedema and BP.
- Direct relaxant effect on vascular smooth muscle (reduces BP).
What are the indications for prescribing thiazide?
- Hypertension (not if also have moderate-severe renal impairment).
- Mild heart failure.
- Severe resistant oedema (plus loop diuretic).
- Nephrogenic diabetes insipidus.
Give examples of the contraindications for prescribing thiazides.
- Hypercalcaemia
- Hyponatraemia
- Hypokalaemia
- Symptomatic hyperuricaemia
- Addison’s disease
What are the common side-effects of thiazides?
- Low K, Na, Mg
- Promotion of calcium retention / hypocalciuria
- Metabolic alkalosis
- Gout
- Erectile dysfunction
- Hyperglycaemia, hyperlipidaemia
What are the indications for aldosterone antagonists?
- Hypertension
- Oedema (heart, liver, nephrotic syndrome)
- Conn’s syndrome (primary hyperaldosteronism)
From which class of drugs are aldosterone antagonists?
Mineralocorticoid receptor antagonists (MRAs).
What are the contraindications for prescribing mineralocorticoid receptor antagonists?
- Addison’s disease
- Anuria / kidney failure +++
- Hyperkalaemia
What are the side-effects of mineralocorticoid receptor antagonists?
- Hypotension
- Renal impairment
- High potassium (care if renal impairment!)
- Hyponatraemia
- GI upset
- Metabolic acidosis
- Gynaecomastia with spironolactone
What is amiloride?
Describe its mechanism of action.
- Potassium-sparing weak diuretic.
- Acts by directly blocking epithelial sodium channels in the collecting tubule so less sodium is reabsorbed, causing diuresis.
- Usually synergistically combined with thiazide or loop diuretics.
What are the indications for amiloride?
- Hypertension
- Oedema including ascites
What are the contraindications for amiloride?
- Addison’s disease
- Anuria
- Hyperkalaemia
What are the side-effects of amiloride?
- High potassium (care if renal impairment)
- GI upset
- Metabolic acidosis
- Renal impairment
What are β-blockers?
Give examples.
- Sympathetic nervous system antagonist
-
Atenolol, Bisoprolol, Carvedilol
- β1 receptor blockers (cardioselective)
- Act centrally, reducing sympathetic activity, reduce CO, and also reduces renin release.
- No longer first choice
- Less effective at reducing cardiac events and stroke than ACE-I / ARB, CCB and thiazides.
What are the contraindications for β-blockers?
- Asthma
- Cardiogenic shock / uncompensated heart failure
- Hypotension
- Marked bradycardia
- Severe peripheral arterial disease
What are the β1-blocker side effects?
- Fatigue
- Cold extremities
- Peripheral vascular disease
- Bradycardia
- Bronchospasm
- GI upset
- Erectile dysfunction
- Heart failure
- Sleep disorders
Describe the mechanism of action of α1 antagonists.
Give an example.
- Example: doxazosin
- Sympathetic NS antagonist, blocking alpha 1 receptors.
- Block vasoconstriction, resulting in vasodilation.
What are the side-effects of α1 antagonists?
- Postural hypotension
- Dizziness
- Lethargy
- GI upset
- Headache
- Peripheral oedema
What are the contraindications for α1 antagonists?
- History of micturition syncope (in patients with benign prostatic hypertrophy)
Summarise antihypertensive drug treatment.
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What are the pros of multi-drug treatment of hypertension?
- Reduced mortality / morbidity.
- Each drug class working at different sites on the body - can achieve BP targets more quickly.
- Reduces dose burden of individual drugs, thereby minimising side-effects.
What are the cons of multi-drug treatment of hypertension?
- Concordance a problem:
- “I felt fine before I started these drugs!”
- “I keep forgetting to take all these drugs!”
- Side-effects may be more frequent
- Increased drug costs to the NHS