Flashcards in L17. Drugs Influencing the CVS Deck (35):
What is the clinical definition of hypertension?
Blood pressure > 140/90 mmHg
Hypertension is a risk factor for...
MI, Ischaemic heart disease, chronic heart failure
Aortic aneurysm, retinal haemorrhage
What are the risk factors for developing hypertension?
A multifactorial disease:
Smoking, diet, weight, stress, family Hx
What is the aim for hypertension therapies?
Reduce the blood pressure below 140/85
Or below 130/80 for diabetic for obese patients
Mainly achieved by reducing the risk factors
For Homeostatic control of blood pressure:
Regulated variable is ____
Controlled variables ______
Effector Signals _______
Regulated variable is __Blood Pressure__
Sensors __Baroreceptors and Osmoreceptors__
Controlled variables __HR and SV (CO) and TPR____
Effectors __Blood vessels, Heart and Kidney___
Effector Signals __Neuronal and Hormonal__
Which system (Para or symp) takes precedence in controlling BP?
Sympathetic is the major regulator for changing blood pressure (parasympathetic is for rest situations)
What receptors to noradrenaline and adrenaline act on to control blood pressure?
alpha 1 adrenoreceptors in the blood vessels
beta 1 adrenoreceptors in the heart and in the kidneys
What are the main results of adrenaline acting on these receptors in blood y
Increased Blood Volume
Describe the Renin-Angiotensin System
Noradrenaline binding to B1 receptors in the kidney
Stimulates secretion of renin by the kidney
Converts angiotensinogen into angiotensin I
ACE converts angiotensin I into angiotensin II
What are the main actions of Angiontensin II?
Acts on AT1 receptors: Vasoconstriction of blood vessels
Acts on AT1 receptors: Release of aldosterone leading to salt and water retention
Cell growth (hypertrophy of the heart)
Positive feedback to sympathetic nervous system (increase noradrenaline)
Why would we use Angiotensin Converting Enzyme Inhibitors (ACE inhibitors) in hypertension?
They prevent the conversion of AngI to AngII: reducing vascular tone, reducing aldosterone production (reduces water retention, reduces SV) and reduces cardiac hypertrophy
What is another mechanism of ACE inhibitors (involving bradykinin)?
ACE works like Kininase II: breaks down bradykinin
ACE inhibitors prevent bradykinin breakdown allowing it to have longer potent vasodilatory effects
What are the adverse effects of ACE inhibitors?
First dose hypotension
loss of taste
hyperkalaemia (often given in combination with diuretics)
Acute renal failure
Itching, rash, angio-oedema
What are some contraindicators of ACE inhibitors?
Bilateral renal stenosis
What are some examples of ACE inhibitors?
What are the antiotensin receptor antagonists?
What happens with you block the AT receptors?
AT1 and AT2
Reduce aldosterone formation
Reduce cardiac hypertrophy
Reduce sympathetic activity (inhibits the positive feedback)
What is the major difference between AT antagonists and ACE inhibitors (that it thought to make them safer)?
AT antagonists do not have an effect on bradykinin
What are the adverse effects of AT antagonists?
What are the contraindications for AT antagonists?
Contraindicators are the same for the ACE inhibitors:
Bilateral renal stenosis
What are the b1 adrenoreceptor antagonists?
metoprolol (b1 selective)
pindolol (partial agonist for b1 and b2)
What is the aim of using B1 adrenoreceptor antagonists in hypertension?
Reduce the Cardiac Output and reduce renin release (decreases blood volume) by preventing sympathetic innervation
How to the B blockers vary within the class? 
1. Vary with selectivity (for receptors)
2. With intrinsic sympathomimetic activity (eg. partial agonist activity)
3. Vary with lipid solubility (eg. ability to cross the blood brain barrier)
What are the adverse effects of b adrenergic receptor antagonists?
Cold extremities: occurs acutely when CO is dropped by the drug, a reflex alpha 1 constriction occurs
Fatigue: puts a limit on the sympathetic nervous system to increase HR and blood vessel supply
Dreams and insomnia (CNS lipid solubility)
Bronchoconstriction (B2 adrenoreceptor blockage)
What are some contraindications for b1 adrenergic receptor antagonists?
AV conduction block
Must take care with heart failure and metabolic syndrome
What are the Calcium Channel Blockers?
Dihydropyridines: felodipine and nifeipine
What is the mechanism of action of the Calcium channel blockers in hypertension?
Inhibit voltage gated L-type Calcium channels in the myocardium and the vasculature.
= reduced cardiac and vascular contractility
= Reduced vascular resistance
What are the 2 types of calcium channel blockers?
1. reduce cardiac and vascular contractility
2. Reduce vascular resistance
What are the adverse effects of calcium channel blockers?
Oedema, flushing, headache
Bradycardia (for reduced cardiac contractility)
Reflex tachycardia (for reduced vascular resistance)
What is the mechanism of action of thiazide diuretics in terms of hypertension?
Inhibit NaCl co-transporter in the distal convoluted tubule of the kidneys leading to decreased reabsorption: increases the Na and water excretion form the kidney
Also has a loss of K from the collecting duct
= lowers blood volume
What is an example of a thiazide diuretic used in hypertension?
What is an adverse effect of the thiazide diauretics?
Hypokalaemia: Loss of K leading to gout, hyperglycaemia and allergic reactions
What are some other drugs used in hypertension (when the main ones don't work)?
Alpha 1 adrenoreceptor antagonists
alpha 2 antagonists (CNS)
New renin inhibtors
What are the main drugs used to combat hypertension?
Angiotensin System Inhibitors
Calcium channel blockers