Hypertension, Heart Failure & Diuretics Flashcards
What is the clinical definition of hypertension?
BP taken in the clinic is over 140/90mmHg
What is the current NICE guidance of pharmacological therapy for hypertension?
ACE inhibitors/ ARBs
Calcium channel blockers
Diuretics
<55 years: A –> A + C–> A+C+D–> A+C+D+D or alpha blocker
>55 years, Afrocaribbean origin: C–> A+C–>A+C+D–> A+C+D+D or alpha blocker
What is the mechanism of action of ACE inhibitors in the treatment of hypertension?
Give some examples of such drugs
Reduction in AngII formation
Reduced vasoconstriction
Reduced salt/water retention
Reduced sympathetic activity
e.g. Lisinopril, Ramipril
What is the main side effect of ACE inhibitors?
List some other important side effects.
Main: dry cough
Others: angio-oedema, renal failure, hyperkalaemia
What is the mechanism of action of Angiotensin Receptor Blockers (ARBs)?
Why might this be used over ACE inhibitors?
Bind to the angiotensin AT1 receptor
Inhibit vasoconstriction and aldosterone stimulation caused by AngII
Less side effects that ACE inhibitors (no dry cough)
How do calcium channel blockers work to reduce hypertension?
Bind to specific alopha subunit of L-type calcium channel, reducing cellular calcium entry
Vasodilate peripheral, coronary and pulmonary arteries
Prolongs AP/ ERP
Reduction in cardiac preload and myocardial contractility (NOT good to HF patients)
What are the three main groups of calcium channel blocker?
What are they each most commonly used to treat?
Dihydropyridines - hypertension
Benzothiazepines- angina
Phenylalkylamines - rhythm disturbance
Give some examples of calcium channel blockers
Amlodipine
Verapamil
Diltiazem
How are thiazide/thiazide like diuretics helpful in the treatment of hypertension?
They reduce tubular sodium reabsorption
Reducing H20 reabsorption as a result
Blood volume decreases and then total peripheral resistance falls
Give some adverse effects of thiazide diuretics
Hypokalaemia
Increased urea and uric acid levels
Impaired glucose tolderance
Cholesterol and triglyceride levels increased
RAAS activatation (give with RAAS inhibitor)
Give an example of an angiotensin II receptor blocker
Azilsartan (Edarbi)
Candesartan (Atacand)
Eprosartan.
Irbesartan (Avapro)
Losartan (Cozaar)
Give an example of a K+ sparing diuretic
Amiloride
Give an example of an alpha-adrenoceptor blocker and briefly explain how it works to reduce BP
Doxazosin
Block alpha receptors and therefore antagonise the contractile effects of NA on vascular smooth muscle
Reduce peripheral resistance
Would alpha-blockers be safe to use in a patient with renal disease?
Yes
Give some adverse effects of alpha blockers
Postural hypotension
Headache, fatigue
Oedema
Give some exmples of drugs that block beta-adrenergic receptors and describe how they work to lower BP
Atenolol, bisoprolol, nebivolol
Block the effects of NA on beta-adrenergic receptors
Lower HR and cardiac output = Reduced myocardial oxygen demand
Inhibit renin release
Total peripheral resistance is reduced (rises initially)
Describe some of the adverse effects that may be experienced by a patients on beta-blockers
Lethargy, imparied concentration
Reduced exercise tolerance
Bradycardia
Raynaud’s
Imparied glucose tolerance
Aliskiren is an example of what kind of drug?
How does this work to reduce BP?
Direct renin inhibitor
Binds to renin blocking the cleavage of AngI to AngII
AngII unable to produce its effects
Vasodilation occurs—> BP reduced
Give some examples of centrally acting agents that may be used to treat hypertension, how do they lower BP?
These are rarely used in clinical practice. In which clinical situations might these be specifically used?
Methydopa
Clonidine
Moxonidine
Lower BP by reducing sympathetic outflow
During pregnancy
Give an example of. combo hypertension rx
Hydrochlorthiazide + amiloride
Briefly explain some of the pathophysiological events that occur following an MI that may lead to heart failure
1) Ischaemic injury (MI)
2) Scar tissue formation
3) Remodelling of tissue
4) Dilation
5) Reduced contractility
6) HF :(
Give some of the different methods that may be used currently to treat a patient with heart failure
Pharmacological methods: diuretics, ACEi, ß-blockers
Intervention: Valve surgery, transplantation, pacemaker
Lifestyle modification: Reduce salt, alcohol intake, lower BP, ++ exercise
Why must we initially be careful when prescribing beta-blockers in HF?
How can we overcome this?
Failing myocardium is dependent on the HR of the individual
Need to initiate at a LOW DOSE and titrate slowly
Give some examples of conditions that cause hypertension (i.e. secondary causes)
Conn’s syndrome
Bilateral adrenal hyperplasia
Adrenal catecholamine-secreting tumour
BP over what figure would be classed as a hypertensive emergency?
220/120 mmHg
Hypertensive emergency is associated with which acute conditions?
Pulmonary oedema
Renal failure
Aortic dissection
What drug could we use to treat a patient with potential fatally high BP?
Describe its mechanism of action
Sodium Nitroprusside
Mimics endogenous NO on vascular smooth muscle= potent vasodilator
IV
What precautions should be taken when using Sodium Nitroprusside to treat very high BP?
Avoid prolonged use (>72 hours)
Caution when using in liver disease as is broken down into cyanide
Describe the 4 physiological roles of the kidneys
(+ mnemonic to remember them)
Regulatory- fluid, pH, electrolyte balance
Excretory- waste, drug elimination
Endocrine- renin, erythropoetin, prostaglandins, 1alphs calcidol
Metabolism- vitamin D, polypeptides (insulin), drugs
“REEM” : |
Where is the majority of Na+ absorbed in the kidney?
PCT of the nephron
Which type of drug acts on the PCT of the nephron?
Carbonic anhydrase inhibitors
(1) on the diagram
What are some of the side effects of carbonic anhydase inhibitors
Metabolic acidosis (due to blockage of HCO3- reabsorption)
Hypokalaemia (due to excretion of K+)
Which part of the kidney do osmotic agents act on?
Give an example of such
PCT and descending limb of LoH
Mannitol
(2) on diagram
How do osmotic agents such as mannitol help to increase water loss through their actions on the kidney?
Increase the osmotic gradient throughout the nephron
Retaining water in the kidney tubule rather than reabsorbing it
What conditions might mannitol be useful in treating and which conditions might it not be as helpful?
Useful in brain swelling
Not as useful in oedema
Give an example of a side effect of mannitol
Hypernatraemia
Where in the kidney nephron do loop diuretics work?
How do they achieve water loss?
The thick ascending lumb of the loop of henle
Block Na+ and Cl- channels- stopping them from being reabsorbed and therefore stopping water reabsorption
(3) on diagram
Besides increasing water loss, loop diuretics can be used to treat patients with high levels of _____ in their blood
Ca2+
Loop diuretics can cause _____kalaemia as a side effect
hypo
Where in the kidney nephron do thiazide diuretics work?
How do they increase water excretion from the kidneys?
Distal convoluted tubule
Block NaCl reabsorption
(4) on diagram
Apart from NaCl channels, which other channels are blocked by thiazide diuretics?
What may be the clinical consequence of this?
ENaK
Hypokalaemia
Thiazide diuretics can be helpful in the treatment of _____calcaemia
Hypo
What is an unwanted side effect of thiazide diuretics?
Hyperuricaemia as they help to reabsorb urate
Where in the kidney nephron do aldosterone antagonists act?
Give an example of such
Cortical collecting duct
(4) on diagram
Sprionolactone
How to aldosterone antagonists increase water excretion from the kidneys?
Inhibit Na retention by inhibiting ENaK and NaKATPase
Where in the kidney nephron do ADH antagonists elicit their effect?
What do these drugs do?
Medullary collecting duct
Effects free water absorption- loss of pure water rather than water + salt
Give three examples of ADH antagonists
What are they each used to treat?
Lithium - treat mania
Deneclocycline - treat infection
Tolvaptan- Autosomal dominant Polycystic CKD (APCKD)
How does aldosterone usually effect the kidney nephron?
Increases the expression of ENaC and Na/K/ATPase in the prinicple cells of the collecting duct
How do aldosterone antagonists act as K+ sparing diuretics?
They inhibit the expression of ENaC and Na/K/ATPase
Don’t secrete as much K+ into tubule and therefore don’t excrete K+
Are amiloride and triamterene alosterone antagonists?
NO!
They are potassium sparing, but they act by blocking ENaC channels - still K+ sparing but are weaker in their effects
Name two substances that we may comsume in everyday life that have diuretic action
How do they work?
Alcohol - inhibit ADH
Caffeine - increase GFR, decrease tubular reabsorption of Na+
Give some generic adverse drug reactions of diuretics
Anaphylaxis
Photosensitivity
Hypovolaemia & hypotension (activation of RAAS)
Electrolyte disturbance
Give some specific side effects of thiazide diuretics
Hyperuricemia- Gout
Hyperglycaemia- DM
Erectile dysfunction
Hyperlipidaemia
Hypercalcaemia
Give some speific ADRs of loop diuretics
Ototoxicity- toxic to ear!
Alkalosis
Hyperlipidaemia
Gout
Give some examples of conditions where diuretics may be used
Give the type of diuretic used for each
Hypertension- Thiazide, spironolactone, loop(if kidney dysfunction)
Heart failure- Loop, spironolactone (protective to heart)
Compensated liver diease (not making albumin)- Spironolactone, loop
NephrOtic syndrome (losing albumin in urine)- Loop +/- thiazide, +/- K+ sparing
Chronic kidney disease - Loop +/- thiazide-like, AVOID K+ sparing
How are diuretics delivered to the renal tubule?
(start in the gut, end in the tubule lumen)
Absorbed through the gut
Blood flows to proximal tubule
OAT transporters take across PCT basolateral membrane of epithelial cells
OAT transporters take across luminal side into the lumen of the tubule
What is refractory oedema?
Peripheral oedema that does not respond to dietary sodium restriction and combined diuretic treatment including a loop diuretic
Often caused by an evident underlying cardiac or pulmonary condition
Which diuretic type is best for the treatment of oedema?
Loop diuretic
Which conditions are carbonic anhydrase inhibitors used to treat?
Glaucoma
Altitude sickness
Give some examples of potentially nephrotoxic drugs
Aminoglycosides
Vancomycin
Aciclovir
NSAIDs
Give some examples of drugs that are not necessarily nephrotoxic but that can make renal disease worse or cause AKI
How might each of these cause renal damage?
ACE inhibitors - overrides intrinsic autoregulatory mechanisms
Diuretics
Metformin- propensity to make you acidotic then + acidosis = BAD
What do we need to take into account when prescribing in patients with CKD?
Avoid nephrotoxins
Gentamicin/vancomycin DOSED very carefully
Check with pharmacist whether allopurinol, digoxin, cyclosporin, LMW heparins need altering
Morphine, nitrofurantoin, statins might all cause problems
Give some causes of hyperkalaemia
Movement of K+ out of cells: acidosis, hypertoncicity, muscle damage
Reduced urine loss: reduced GFR, reduced distal Na+ delivery, reduction secretion in CD
Drugs: RAAS inhibitors, NSAIDs, ENaC blockers
What is the main concern in patients with hyperkalaemia?
Might lead to life-threatening cardiac arrhythmias
What progressive ECG changes might you see on an ECG of a patient with hyperkalaemia?
Tall T waves
Small/absent P waves
Increased P-R interval
Wide QRS complex
“Sine wave” :(
Asystole very soon after sine wave :((((
Give the three steps that should be taken in the management of hyperkalaemia
Give the drugs used for each step
- Protect the heart - Calcium glyconate
- Lower serum K+ - insulin/ dextrose (high dose salbutamol if don’t have these)
- Remove K+ from body - Calcium resonium
