Hypertension, Heart Failure & Diuretics Flashcards by Emily Wilson

What is the clinical definition of hypertension?

BP taken in the clinic is over 140/90mmHg

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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

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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

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What is the main side effect of ACE inhibitors?

List some other important side effects.

Main: dry cough

Others: angio-oedema, renal failure, hyperkalaemia

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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)

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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)

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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

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Give some examples of calcium channel blockers

Amlodipine

Verapamil

Diltiazem

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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

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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)

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Give an example of an angiotensin II receptor blocker

Azilsartan (Edarbi)

Candesartan (Atacand)

Eprosartan.

Irbesartan (Avapro)

Losartan (Cozaar)

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Give an example of a K+ sparing diuretic

Amiloride

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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

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Would alpha-blockers be safe to use in a patient with renal disease?

Yes

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Give some adverse effects of alpha blockers

Postural hypotension

Headache, fatigue

Oedema

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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)

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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

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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

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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

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Give an example of. combo hypertension rx

Hydrochlorthiazide + amiloride

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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 :(

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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

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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

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Give some examples of conditions that cause hypertension (i.e. secondary causes)

Conn’s syndrome

Bilateral adrenal hyperplasia

Adrenal catecholamine-secreting tumour

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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)

**R**egulatory- fluid, pH, electrolyte balance **E**xcretory- waste, drug elimination **E**ndocrine- renin, erythropoetin, prostaglandins, 1alphs calcidol **M**etabolism- 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

1. Protect the heart - Calcium glyconate 2. Lower serum K+ - insulin/ dextrose (high dose salbutamol if don't have these) 3. Remove K+ from body - Calcium resonium

Hypertension, Heart Failure & Diuretics Flashcards

(67 cards)