Hypertension Flashcards
Hypertension
High blood pressure
<140/90mmHg
Determinants of blood pressure
- Cardiac output = increased cardiac output causes an increase in blood pressure
- Vascular tone = increased peripheral resistance increased blood pressure
- Blood volume = increased blood volume increases blood pressure
Sympathetic nervous system
The sympathetic nervous system works to increase blood pressure
- Increases contraction force
- Increases heart rate
- Reduces cardiac efficiency
Occurs via activation of B1-adrenoceptors by catecholamines
Parasympathetic nervous system
Works to decrease blood pressure
- Cardiac slowing
- Inhibition of AV conduction
Occurs via activation of muscarinic (M2) receptors by acetylcholine
Adrenergic receptors
Ligand is catecholamines
Key cardiac adrenergic receptor is the B1-adrenoceptor
A GPCR (Gs)- stimulation increases the probability that calcium channels will open, increasing inward calcium ion flow and the force of cardiac contraction
Nicotinic receptors
Ligand is acetylcholine
Less important in cardiac pharmacology because they are non-specific and have CNS effects
Muscarinic receptors
Ligand is acetylcholine
Key cardiac muscarinic receptor is M2
A GPCR (Gi) - stimulation inhibits the opening of L-type calcium channels, slowing the flow of calcium Also opens potassium channels, hyperpolarising the cell
RAAS
- Angiotensinogen is released from the liver
- Renin is released from the kidney and converts angiotensinogen to angiotensin I
- ACE is released from the pulmonary and renal endothelium and converts angiotensin I to angiotensin II
Angiotensin II
Angiotensin II has several effects which raise blood pressure
- Stimulates release of noradrenaline from the sympathetic nervous system
- Stimulates release of aldosterone which increases salt reabsorption
- Causes arterial vasoconstriction
- Stimulates release of anti-diuretic hormone
Beta blockers
B-adrenoceptor antagonists
Decrease output from the sympathetic nervous system to reduce cardiac output
Atenolol is specific for B1-adrenoceptors only
Propanolol targets B1 & B2 adrenoceptors
Propanolol tends to be more effective but has more side effects
Beta blockers side effects
- Heart failure
- Bradycardia
- Fatigue
- Cold extremities
- Hypoglycaemia
- Sleep disturbances
ACE inhibitors
Inhibitors of the ACE
Prevents conversion of angiotensin I to angiotensin II
Angiotensin I is biologically inactive, so the RAAS is prevented from increasing blood pressure
ACE inhibitors side effects
-Dry cough
Due to the inhibition of the breakdown of bradykinin
Angiotensin II receptor antagonists
AT1 receptor antagonists
AT1 is a GPCR (Gq)
Inhibits the action of angiotensin II, although without inhibiting the breakdown of bradykinin
Angiotensin II receptor antagonists side effects
- Hypotension
- Dizziness
Renin inhibitors
Used to treat hypertensin by inhibiting plasma renin activity
Side effects = diarrhoea, rash
Diuretics
Diuretics encourage the excretion of water to reduce blood volume
There are several types of diuretic
Loop diuretics
The most powerful
Act upon the ascending limb of the loop of Henle to inhibit water reabsorption by inhibiting the Na/K/Cl carrier
Side effects = gastric irritation, hypotension, hyperglycaemia
Thiazide diuretics
Act upon distal convoluted tubules to inhibit sodium reabsorption
Achieved by inhibiting the action of the Na/Cl co-transport system
Side effects = postural hypotension, gastric irritation, hyperglycaemia
K+ sparing diuretics
Act upon distal convoluted tubules to prevent sodium reabsorption only
Less effective, mostly used as an add-on therapy
Side effects = gastric irritation, dry mouth, rash
Aldosterone antagonists
Act upon distal Na/K exchange
Have limited diuretic effects when used alone but can prolong survival in heart failure patients
Side effects = hyperkalaemia, gastric irritation
Vasodilators
Vasodilators decrease peripheral resistance to decrease blood pressure
There are several types of vasodilator
Nitrates
Cause acute, short-lived vasodilation by causing nitric oxide release
Nitric oxide activates guanylate cyclase, which produces cGMP
cGMP activates protein kinase C which leads to muscle relaxation
Not suitable to treat chronic hypertension
Calcium channel blockers
Prevent influx of calcium, therefore inhibiting smooth muscle contraction
Side effects - abdominal pain, nausea, palpitations, oedema
