T3 L11: Treatment for hypertension Flashcards
What are the 6 types of drugs used to treat hypertension?
ACE inhibitors, Angiotensin receptor blockers, Ca2+ channel antagonists, diuretics, beta blockers, and vasodilators
What is the 1st stage hypertension prescription for a white person aged <55?
ACE inhibitors
What is the 1st stage hypertension prescription for someone >55 or of black origin?
Ca2+ blockers
What is the 2nd stage prescription for hypertension?
ACE inhibitors and Ca2+ blockers
What is the 3rd stage prescription for hypertension?
A combination of ACE inhibitors, Ca2+ blockers and a thiazide-like diuretic
What is the 4th stage prescription for hypertension?
A combination of ACE inhibitors, Ca2+ blockers, thiazide-like diuretic plus a further diuretic or alpha/beta blocker. At this point you would seek expert advise
What is resistant hypertension?
When treatment for hypertension has failed even after the all the stages. It requires expert advice
What is the biggest side effect of ACE inhibitors and what is the mechanism behind it?
A dry cough. It develops because ACE inhibitors stop the action of Kinase 2 so substance P and bradykinin can’t be turned into inactive peptides so they build up and cause irritation
What is meant by 1st dose hypotension and how is this minimised?
A drug will act on different areas of the body causing sudden hypotension while the body gets used to the hypertension drugs. This is minimised by getting the patient to take the first dose at night
How are renal impairments prevented when someone is taking ACE inhibitors?
Renal function is taken before the prescription begins to measure creatine levels because it should be getting cleared by the kidneys
How do ACE inhibitors affect renal function?
They cause dilation of the efferent arteriole which causes decreased pressure and therefore impaired renal function
Why are ACE inhibitors good for diabetics?
Ace inhibitors have no effect on serum glucose or lipids so they protect from diabetic nephropathy
What are -pril drugs?
ACE inhibitors
When are ACE inhibitors used?
For people aged <55 and at any age when a patients is at risk of diabetes or cardiovascular disease
How do ACE inhibitors cause hyperalkalaemia?
They cause increased K+ uptake in the kidneys because of the decreased angiotensin II activity. This can lead to seizures
How do ABR’s (Angiotensin receptor antagonists (blockers)) work?
They block the action of angiotensin II by working on the AT1-R (receptor)
What is the main side effect of ABR’s?
Hypokalaemia so it requires monitoring
What type of drug is Spironolactone and when is it used?
It’s an ARB (Angiotensin receptor blocker) used as an add on for resistant hypertension and frontline for patients with primary aldosteronism
What is aldosteronism?
When the adrenal glands produce too much aldosterone leading to high blood pressure
What is the function of aldosterone?
It’s a steroid hormone that regulates salt and water in the body and therefore has an effect on blood pressure
When are Ca2+ blockers used?
For those >55 or of black descent
How do Ca2+ blockers of class dihydropyridines work?
They block L-type Ca2+ channels on smooth muscle of arterioles. This causes decrease in peripheral resistance
Give an example of a dihydropyridine Ca2+ blocker
Amlodipine
How do Ca2+ blockers of class phenylalkylamine and benzothiazepines work?
They target L-type Ca2+ channels in the heart and decrease the frequency and force of contraction
When are Ca2+ blockers of phenylalkylamines and benzothiazepines used?
Not common, but are used when the hypertension is caused by tachycardia
Does cAMP cause relaxation or constriction in smooth muscle?
Relaxation
Does Ca2+ cause relaxation or constriction of smooth mmuscle?
Constriction
How do Ca2+ blockers cause peripheral oedema?
They impair the function of the pre-capillary sphincter muscles which increases hydrostatic pressure across the capillary and this prevents fluid reabsorption
What are pre-capillary sphincter muscles?
A ring of muscle that can constrict and relax to regulate blood flow in capillaries
How do Ca2+ blockers cause flushing?
They cause more blood to flow to the surface
How do Ca2+ blockers cause headaches?
They cause the blood vessels supplying the meninges to become dilated
What is CYP3A4 (cytochrome P450 3A4)?
A protein in the liver and intestine responsible for oxidising toxins and drugs and helping them to be removed from the body
Why must grapefruit not be eaten with Ca2+ blockers?
Because the proteins in grapefruit decrease the action of the protein Cytochrome P450 so the drug isn’t metabolised and therefore builds up in the body and that can cause an overdose
When are Thiazide-like diuretics given?
As step 3 (when the combination of Ca2+ and ACE inhibitors doesn’t work
What do thiazide-like diuretics do (2 things to reduce hypertension)?
Increase the production of urine but also activate K-ATP in smooth muscle of blood vessels to dilate arterioles and decrease BP
What does indapamide work on smooth muscle cells?
It hyperpolarises smooth muscle cells causing relaxation/dilation by acting on K-ATP. It causes K+ to leave the cells so less Ca2+ enters cells
What is hyperpolarisation?
Become more negative. If this happens in neurones, they won’t fire as often
How do thiazide-like diuretics cause hypokalaemia and what are the consequences if this?
More ions are removed from the body because there is increased urination. The consequence is that excitable tissues won’t function properly
Why are thiazide-like diuretics not given to patients with gout?
Because thiazide-like diuretics cause an increase in uric acid and gout patients already have very high concentration of this
Why are thiazide-like diuretics not given to diabetics or those with cardiovascular disease?
Because they increase blood glucose and lipids
Why is Bendroflumethiazide commonly taken by the elderly?
Because they were prescribed this in the past but now the main thiazide-like diuretic is indapamide
What class of drug is indapamide?
A thiazide-like diuretic
How do thiazide-like diuretics increase blood glucose?
They close K-ATP channels and this prevents an influx of Ca2+ in the pancreas. Without the Ca2+, less insulin is released
How do beta-blockers cause fatigue?
They cause a decrease in cardiac output so when someone wants to be active, their cells can’t keep up because they aren’t getting enough nutrients and O2 so the person feel tired
How can beta-blockers cause vaso/broncho constriction?
Beta receptors are found in the airways and blood vessels too and even though most beta-blockers are selective, some beta-1 selective beta blockers can still act on beta-2 receptors causing constriction
Which class of drug used to treat hypertension is not prescribed to those with asthma or with Raynauds disease?
Beta-blockers
What are the 3 symptoms of hypoglycaemia that diabetics learn to recognise?
Tremor, palpitations and sweats
Why are beta-blockers not prescribes to diabetics?
Beta-blockers block the symptoms that tell someone they have hypoglycaemia so the patients are no longer to recognise hypoglycaemia and this can be life threatening
Give an example of a non-selective beta-blocker
Propanolol
Give an example of a selective beta-1 blocker
Bisoprolol
Why are beta-blockers not prescribed to those with cardiovascular disease?
Beta-blockers increase blood lipids
How do vasodilators work?
They block alpha-1 receptors (noradrenaline - alpa-1 receptor - IP3 - Ca2+ - constriction)
What drug is used to treat hypertension when someone has benign prostatic hypertrophy and why?
Vasodilators because the prostate has a muscular sheath with alpha-1 receptors so giving vasodilators to someone helps to relax the muscular sheath and this helps them to urinate
Why do those with benign prostatic hypertrophy have trouble urinating?
Because the enlarged prostate pushes against the urethra
What is doxazosin and when is it used?
It’s a vasodilator used when someone has hypertension and benign prostatic hypertrophy
What does Monoxidil act on?
K+ channels. It hyperpolarises a cell so that muscles can’t contract which decreases peripheral resistance and therefore BP
