Hypertension (Cardiovascular Disease I) Flashcards
What are 4 major causes of cardiovascular disease?
- Hypertension
- Angina pectoris
- Myocardial infarction
- Heart failure
What is hypertension?
Level of blood pressure associated with increased risk of cardiovascular disease
Why is blood pressure measured at home?
Less anxiety which means sympathetic nervous system activity is reduced so a more accurate reading is likely
Describe primary hypertension
- 90-95% of all cases
- Interaction of genes, environment and lifestyle
- Onset in mid 40s +
Describe secondary hypertension
- 5-10% of all cases
- Caused by underlying disease e.g. renal, endocrine etc
- Identify and treat cause
Name 5 benefits of treating hypertension
- Reduce incidence of stroke
- Reduce incidence of heart attack
- Reduce incidence of heart failure
- Reduce incidence of renal failure
- Reduce incidence of retinopathy
Name 2 main lifestyle interventions which can reduce cardiovascular disease
- Blood pressure reduction
2. Cardiovascular risk reduction
Name 3 methods of blood pressure reduction
- Weight reduction
- Reduced salt intake
- Physical exercise
Name 3 methods of cardiovascular risk reduction
- Reduced total and saturated fat
- Smoking elimination
- Diabetes management
Name 4 common anti-hypertensive agents used in clinical practice
- ACE inhibitors / ARBs
- β-adrenoceptor antagonists
- Calcium channel modulators
- Thiazide diuretics
Give 2 examples of an ACE inhibitor drug
- Enalapril
2. Ramipril
Give 2 examples of an ARB drug
- Valsartan
2. Candesartan
What does ARB stand for?
AT₁ receptor blocker
What system do ACE inhibitor and ARB drugs act on?
Renin Angiotensin Aldosterone System (RAAS)
What is the function of the RAAS?
Role in maintenance of circulatory volume and blood pressure
What is the function of angiotensin II?
Promotes vasoconstriction
What are 3 functions of aldosterone?
- Secretion
- Prompting sodium retention
- Prompting potassium loss
How does the RAAS function?
- Baroreceptors detect fall in BP
- RAAS activated
- Renin converts angiotensinogen to angiotensin I
- ACE converts angiotensin I to angiotensin II
- Aldosterone stimulation from adrenal gland
What does ACE stand for?
Angiotensin-converting enzyme
What is a secondary function of ACE inhibitors?
Inhibit metabolism of bradykinin
Why is the inhibition of bradykinin metabolism beneficial?
Bradykinin is a vasodilator so reduces vasoconstriction effects of angiotensin II
Name 4 general side effects of ACE inhibitors or ARBs?
- Hyperkalaemia
- Skin rash
- Teratogenicity
- First dose hypotension
Why may the accumulation of bradykinin be a negative side effect?
It can cause a dry cough and in rare cases, cause angioedema
What is a contraindication of using ACE inhibitors or ARBs?
Renovascular disease as vasoconstriction of the efferent arteriole in glomerulus cannot occur, causing filtration pressure to fall off in kidney
What is the major difference in the side effects of ACE inhibitors and ARBs?
ARBs do not cause accumulation of bradykinin so will not cause a dry cough
What is the distribution and function of β₁-adrenoceptors?
- Heart and kidney
- Increase heart rate, force of contraction and conduction velocity
- Increase renin secretion
What is the distribution and function of β₂-adrenoceptors?
- Nerve terminals and certain blood vessels
- Increase noradrenaline release
- Vasodilatation of vessels supplying skeletal muscles and skin
What is the distribution and function of β₃-adrenoceptors?
- Skeletal muscle and fat
- Lipolysis
- Thermogenesis
Describe 4 important pharmacodynamic properties of β-blockers
- Selectivity for β₁ adrenoceptors
- Partial agonist activity
- α₁ antagonism
- Increased NO release
Describe 4 important pharmacokinetic properties of β-blockers
- Solubility in water v lipid
- Ability to enter CNS
- Route of elimination
- Duration of action
Why do β-blockers cause an initial fall in blood pressure?
- Fall in cardiac output
- β₁-adrenoceptors in heart antagonised
- Soon compensated by rise in peripheral vascular resistance
How does rise in peripheral vascular resistance occur as a result of the initial fall in blood pressure caused by β-blockers?
Noradrenaline action on vasoconstrictor α₁ adrenoceptors
Why do β-blockers cause a delayed fall in blood pressure?
- Continued reduction in cardiac output due to decrease in renin secretion
- Decrease in central sympathetic outflow by blockade of facilitator pre-synaptic β₂ receptors on sympathetic nerve terminals
- Indirect fall in peripheral vascular resistance
Name 5 side effects of β-blockers
- Bradycardia / acute heart failure
- Nightmares / insomnia
- Exacerbation of peripheral vascular disease
- Weight gain
- Fatigue
How can nightmares / insomnia be influenced when a patient takes β-blockers?
- Nightmares / insomnia are caused due to central effects
- Less lipid soluble β-blockers are less likely to cross the blood brain barrier
- Therefore, less lipid soluble β-blockers less likely to cause central side effects
What can occur on sudden withdrawal of β-blockers?
Rebound sympathetic drive
Why can β-blockers be dangerous for asthmatics?
Causes bronchospasms by blocking β₂ receptors in trachea and lungs
Name an indication for using labetalol
Labetalol has added α₁-adrenoceptor blocking or NO releasing action in blood vessels
What 2 reasons are β-blockers not used for uncomplicated hypertension?
- Less protective against stroke in elderly
2. Increased risk of impaired glucose tolerance
What is the function of calcium channel modulators?
Reduce opening probability of voltage-gated L-type calcium channels in vascular smooth muscle, resulting in less calcium influx, vasodilatation and reduced peripheral vascular resistance
Where do calcium channel modulators work most effectively?
Arteriole circulation
Name 2 types of calcium channel modulators
- Non rate-limiting (dihydropyridines)
2. Rate-limiting
Name 2 examples of dihydropyridine drugs
- Amlodipine
2. Nifedipine
Name 2 types of rate-limiting calcium channel modulators
- Verapamil
2. Diltiazem
Describe the effects of dihydropyridines
- Vascular-selective
- Decreases blood pressure by lowering peripheral vascular resistance
- Drop in blood pressure cause increased sympathetic drive so can indirectly cause increase in heart rate
Describe the effects of non-rate limiting calcium channel modulators
- Less effective than dihydropyridines on blood vessels but more effective on the heart
- Reduced cardiac output by:
- Reduces heart rate
- Reduces heart contractibility
- Reduces AV node conduction
Name 5 adverse effects of calcium channel modulators
- Throbbing headache
- Postural hypotension
- Flushing
- Ankle oedema (mainly dihydropyridines)
- Heart block / failure
What is a side effect which tends to be unique to verapamil?
Constipation
How do most diuretics function?
- Inhibit renal tubule transporter proteins to increase secretion of sodium
- Reduction in plasma volume reduces pre-load and cardiac output
Describe the ADME of thiazide-like diuretics
- Good oral bioavailability
- Plasma half-life approx. 12 hours
Name a thiazide diuretic
Bendroflumethiazide
Name 2 thiazide-like diuretics
- Chlorthalidone
2. Indapamide
How do thiazide and thiazide-like diuretics function?
- Inhibit NaCl transporter in DCT
- Attracts water into tubule
- More water composition in the urine
Name 5 side effects of thiazide and thiazide-like diuretics
- Hypokalaemia
- Hypercalcaemia
- Hyperuricaemia
- Hyperlipidaemia
- Impaired glucose tolerance
How do loop diuretics function?
Inhibit NaKCl cotransporter in the Loop of Henle
Give an example of a loop diuretic drug
Furosemide
Why are loop diuretic drugs not used as first-line treatments?
- Lack good 24 hour control
- Relatively ineffective due to massive counter-regulation
How do potassium-sparing diuretics function?
- Reduce sodium absorption and potassium excretion in late DCT and collecting duct
Name 2 reasons potassium-sparing diuretics would be prescribed in hypertension
- Counter thiazide-induced hypokalaemia
2. Treat specific secondary cause (aldosterone excess)
Name 2 examples of potassium-sparing diuretics
- Amiloride
2. Spironolactone
Name 4 effects of hypertension treatment therapies on oral health
- Gingival overgrowth with calcium channel modulators
- Taste disturbances with ACE inhibitors or ARBs
- Diuretics can cause xerostomia
- Diuretics and propranolol associated with Stevens Johnson syndrome (rarely)
