Drugs to control blood pressure Flashcards
Main groups of drugs used to lower blood pressure
- Diuretics
- Beta-adrenoceptor blockers
- Calcium channel blockers
- Angiotensin converting enzyme (ACE) inhibitors
- Angiotensin receptor blockers
- Alpha-adrenoceptor blockers
- Direct renin inhibitors
Why should digoxin not be given with loop diuretics?
Digoxin is a competitive inhibitor of K+, act on the same site at the Na+/K+ pump. If extracellular K+ is high, digoxin will be less effective, low K+ enhances effects. Loop diuretics cause a reduction in plasma K+ levels and therefore potentiates it’s effects (lack of competition). Leads to loss of K+ and arrhythmias.
Function of natriuretic hormones
ANP: released from atrial myocytes in response to stretch
BNP: released from ventricular myocytes in response to hypertrophy
CNP: endothelial factor released in atheroma
All bind to guanylate cyclase coupled receptors. Result in increased GFR and reduced Na+ reabsorption. Decreases RAAS and therefore lowers blood volume to reduce bp.
Name three endothelium-derived vasoactive factors
Prostacyclin
Nitric oxide
Carbon monoxide
C-type natriuretic peptide
Endothelin-1
Angiotensin II
Conn’s syndrome
Primary hyperaldosteronism caused by adrenal adenoma or adrenal hyperplasia. Aldosterone promotes increased Na+ reabsorption in principal cells (increasing water retention) and also promotes secretion of K+ and H+. Patients present with hypertension and hypokalaemia.
Non-pharmacological treatment of bp
Weight
Exercise
Salt reduction
More potassium
Moderate alcohol intake
Quit smoking
Why are smoking and obesity major CV risk factors?
Fat produces its own angiotensin, which increases blood pressure
Smoking impairs production and bioavailability of NO
Difference between primary and secondary hypertension
Primary hypertension (95%) has no known cause but is associated with age, obesity, physical inactivity, smoking, alcohol, genetics
Secondary hypertension (5%) is caused by renal disease (activates RAAS) or endocrine disease
Diuretics used in hypertension
Thiazides, loop diuretics, K+-sparing diuretics
Use of thiazides in hypertension
Thiazides are the most powerful anti-hypertensives (e.g. bendroflumethiazide). Preferred as they are weak and long acting. They act at the DCT and inhibit the Na/Cl co-transporer in the luminal membrane. Increased Na+ and water is excreted and K+ secretion is increased. Reduced blood volume reduces filling of the heart
Adverse effects: hypokalemia (muscle weakness), hyponatremia (causes confusion) hyperuricaemia (gout), raised glucose and cholesterol
K+-sparing diuretics in hypertension
Produce mild diuresis and cause excretion of 2-3% sodium. Used in combination with other drugs, useful in excess aldosterone. Contraindicated in renal patients
- Spironolactone: aldosterone antagonist. Competitive antagonist of receptor and reduces Na+ absorption and therefore K+ and H+ secretion
- Triamterene and Amiloride: Ep Na+ channel blocker. Block Na+ reabsorption by principal cells, reducing membrane potential and reducing K+ secretion. Decreased H+ secretion.
Side effects: High K+ and low Na+ Interact with ACEi to increase hyperkalemia. Aldosterone similar to oestrogen, causes gynaecomastia.
Use of beta blockers in hypertension
Atenolol: cardioselective (b1)
Propanolol: non-selective (b1,b2)
Decrease cardiac output and prevent fatal arrhythmias, heart attack and stroke. Also blocks adrenal system (sympathetic innervation direct to adrenal gland)
CV effects of calcium channel blockers
vascular smooth muscle relaxation
decreased myocardial force generation
decreased heart rate
natriuresis & diuresis
Chemical classes of calcium channel blockers
Dihydropyridines: nifedipine, amlodipine (arterioselective - vascular effects, relaxes arteries and increases excretion of Na+ and water but increases HR)
Benzothiazepine: diltiazem (cardioselective, relaxes arteries, decreases HR and SV)
Phenylalkalamine: verapamil (cardioselective, relaxes arteries, decreases HR and SV)
Cardioselective calcium channel blockers
Verapamil and diltiazem
Side effects:
Heart failure
Heart block
Peripheral oedema
Constipation
Facial flushing, headaches
Side effects of dihydropyridines
Marked facial flushing
Headaches
Peripheral oedema
Polyuria (exacerbate prostatism)
Adverse effects of angiotensin II
Excess Ang II stimulates NADPH oxidase to produce superoxide
Superoxide is a potent oxygen free radical
Oxidation by superoxide impairs protein & DNA function
Superoxide also inactivates nitric oxide:
Action of ACEi
Inhibit the formation of angiotensin II, also inhibit the breakdown of bradykinin (vasodilator)
Side effects:
Dry cough Angioedema Hyperkalemia
Contraindicated in asthmatics
Why are ACEi and ARBs contraindicated in renal artery stenosis?
Patients with bilateral renal artery stenosis may experience renal failure if ARBs are administered.
The reason is that the elevated circulating and intrarenal angiotensin II in this condition constricts the efferent arteriole more than the afferent arteriole within the kidney, which helps to maintain glomerular capillary pressure and filtration.
Removing this constriction by blocking angiotensin II receptors on the efferent arteriole can cause an abrupt fall in glomerular filtration rate.
Action of ARBs
Receptor antagonists that block type 1 angiotensin II (AT1) receptors on blood vessels and other tissues such as the heart. These receptors are coupled to the Gq-protein and IP3 signal transduction pathway that stimulates vascular smooth muscle contraction
Effect of NorA on arterial pressure
Acts via alpha1 to cause constriction of the arteries and beta1 receptors to produce mroe forceful contractions. This causes an increase in HR, systolic and diastolic pressure.
This is detected by baroreceptor reflexes which lower the hear rate in reponse.
Overall effect: raised systolic & diastolic pressure, lower HR
Alpha-adrenoreceptor blockers
α1-adrenoceptor antagonists cause vasodilation by blocking the binding of norepinephrine to the smooth muscle receptors.
Non-selective α1 and α2-adrenoceptor antagonists block postjunctional α1 and α2-adrenoceptors, which causes vasodilation.
Alpha-blockers dilate both arteries and veins because both vessel types are innervated by sympathetic adrenergic nerves; however, the vasodilator effect is more pronounced in the arterial resistance vessels.
Phaeochromocytoma
Neuroendocrine tumour of the adrenal medulla. Results in excess production of catecholamines, particularly NorA
Patients suffer with elevated HR and bp, palpitations, anxiety, headaches and elevated blood glucose.
Classification of blood pressure in adults
Normal: 120-140 systolic, 80-90 diastolic
Mild: 140-150 systolic, 90-100 diastolic
Moderate: 160-180 systolic, 100-110 diastolic
Severe: >180 systolic, >120 diastolic
