L12+13- Hypertension Flashcards
What does 120 over 80 mean?
systolic pressure over diastolic pressure. pressure is 120 while the heart is contracting and 80 while the heart is relaxed and filling
What is hypertension?
Increased diastolic pressure
Increased systolic pressure
Increased pulse pressure
WHat are the 2 classes of hypertension by aetiology? (what it’s cause by)
- Primary (essential/idiopathic) hypertension- cause unknown
- Secondary hypertensin- identified cause e.g. kidney problems
Hypertension can cause damage to arteries leading to what?
Deposition of fats and blockage of the arteries and increases risk of thrombosis and thromboembolism
What is the formula for blood pressure?
BP= cardiac output x peripheral resistance
What are the 4 main drugs prescribed for hypertension?
- Ace inhibitors
- AII antagonists
- Ca2+ antagonists
- B-blockers
What are peripheral resistance vessels?
Arterioles that can relax and contract in response to sympathetic input
What does noradrenaline cause at resistance arterioles?
It binds to alpha 1 adrenoceptors, causing constriction- so blood pressure goes up
How does noradrenaline cause membrane depolarisation at the arterioles?
- noradrenaline binds to alpha 1 adrenoceptors
- this activates phospholipase C
- Phospholipase C causes IP3 release (inositol trisphosphate)
- This releases Ca2+ so [Ca] increases in the cell
- Ca- sensitive Cl- channels open and Cl floods out
- Membrane depolarisation
How does membrane depolarisation of the arteriole lead to contraction?
Depolarisation
Opening of L type Ca channels
Ca influx
Contraction
What are the 3 main classes of drugs that act on L type ca channels?
- Benzothiazepines- eg. dialtazem
- Dihydropyridine- eg. nifedipine
- Phenylalkylamine- eg. verapamil
What do calcium antagonists do?
Reduce the opening of L type calcium channels
WHat do diuretics do?
INcrease urine output, reducing blood pressure
What else can diuretics treat?
Oedema- the accumulation of fluid in the tissues eg lungs
What is an osmotic diuretic?
Diuretics that increase the osmolarity of the urine in the nephron and prevents water from being reabsorbed, so pulls water out of the kidneys into urine
What’s the main expample of an osmotic diuretic?
Mannitol. It’s a metabolically inert sugar given by IV injection. It passes through the glomerus into the nephron but cant be reabsorbed
What is special about mannitol?
It’s the only diuretic that exerts effects outside the kidneys. When it’s in the bloodstream it can draw water out of the tissues. This can help reduce intracranial pressure. If mannitol is given orally, causes MEGA DIARRHOEA
What are loop diuretics? How do they act?
Act in the loop of henle. Act by inhibiting a cotransporter that moves Na, K and 2 Cl into the cells, out of the lumen of the loop. Loop diuretics decrease the amount of NaCl and KCl reabsorbed.
Main example of loop diuretic?
Frusemide (aka furosemide)
Why can water not be absorbed from the descending loop when loop diuretics are used?
The descending loop has no active transport mechanisms. But it is water permeable. The loss of water in descending is normally driven by movement of NaCl from ascending henle. If this process is blocked then less water is reabsorbed from descending henle.
WHat’s the best example of a thiazide diuretic?
Bendroflumethiazide
What do thiazide diuretics do?
Inhibit a different kind of transporter to the loop diuretics- a Na/Cl cotransporter in the lumenal membrane. Inhibiting this transporter again causes less salt to be reabsorbed. In collecting duct?
When are thiazide diuretics used?
Oedema due to heart failure. Hypertension
What;s the main problem with loop and thiazide diuretics?
Loss of potassium-> hypokalaemia
How can you stop hypokalaemia?
Use potassium sparing diuretics. Decrease Na movement across principal cells, stop negative potential of lumen from increasing
Give 3 examples of potassium sparing diuretics?
- spironolactone- also an aldosterone antagonist
- Amiloride
- Triamterene
WHat are the effects of aldosterone?
INcrease sodium absorption by increasing the number of sodium channels and stimulating sodium channels (via protein mediators)
How is the active angiotensin 2 octamer made?
Renin cleaves angiotensin
Angiotensin 1. (ACE activates)
Angiotensin 2
What is Renin?
A protease that cleaves angiotensin to produce angiotensin 1
Angiotensin 2 binds to 2 receptorsm which si the most important one?
AT receptor type 1 (AT1R). This receptora stimulates aldosterone release from the adrenal cortex and causes vasoconstriction
Where is renin secreted from?
A distinct set of cells in the juxta glomerular apparatus
What are 2 examples of ACE inhibitors?
Captopril
Enalapril
What else does ACE do?
Breaks down a peptide hormone called bradykinin,
Beneficial beause bradykinin causes vasodilation. However bradykinin causes cough
What is the sympathetic fight or flight response mediated by?
Noradrenaline released from sympathetic neurones and adrenaline released as a hormone from adrenal medulla
What does beta 3 adrenergic receptors control?
Present fo fat cells and stimulate breakdown of fat. Metabolic not really concerned with it
What are the five adrenergic receptor types?
alpha1, alpha2, beta 1, beta 2, beta 3
What G proteins are linked to each adrenergic receptors?
alpha 1- Gq
alpha2- Gi
beta 1-Gs
beta 2- Gs
What are the main effects of the four adrenoceptors?
alpha 1- Vasoconstriction
alpha 2- transmitter release ( eg insulin)
beta 1- heart rate and force
beta 2- Bronchodilation
What are the unwanted effects of beta blockers?
Bronchoconstiction
Hypoglycaemia
Cold extremities
Vivid dreams
Where are the most important B1 adrenoceptors?
The heart and the kidneys
What do beta blockers do in the heart?
Reduce heart rate and stroke volume, decreasing cardiac output
What do beta blockers do in the kidneys?
Regulate renin release, decrease renin
Give three examples of beta blockers?
propranolol- non selective
atenolol, metaprolol- more selective
What does prozasin do?
Dilates arterioles and veins by blocking alpha 1 adrenoceptors. Used when other therapies haven’t worked.
Has notable side effects- incontinence, retragrade ejaculation. not good at the bladder lads
Name two alpha adrenoceptor antagonists
Phentolamine- NOT useful for hypertension treatment
Prozasin- alpha 1 selective- USEFUL
