Breathlessness

Question 1

Loop Diuretics

Common indications

Answer 1

1. For relief of breathlessness in acute pulmonary oedema in conjunction with oxygen and nitrates
2. For symptomatic treatment of fluid overload in chronic heart failure
3. For symptomatic treatment of fluid overload in other oedematous states, e.g. due to renal disease or liver failure, where they may be given in combination with other diuretics

Question 2

Loop Diuretics

MOA

Answer 2

• As their name suggests, Loop Diuretics act principally on the ascending limb of the loop of Henle, where they inhibit the Na+/K+/2Cl- co-transporter
• This protein is responsible for transporting sodium, potassium and chloride ions from the tubular lumen into the epithelial cell
• Water then follows by osmosis. Inhibiting this process has a potent diuretic effect
• In addition, loop diuretics have a direct effect on blood vessels, causing dilation of capacitance veins
• In acute heart failure, this reduces pre-load and improves contractile function of the ‘overstretched’ heart muscle
• Indeed, this is probably the main benefit of loop diuretics in acute heart failure, as illustrated by the fact that the clinical response is usually evident before a diuresis is established

Question 3

Loop Diuretics

Adverse effects

Answer 3

• Water losses due to diuresis can lead to dehydration and hypotension
• Inhibiting the co-transporter increases urinary losses of sodium, potassium and chloride ions
• Indirectly, this also increases excretion of Mg, Ca and H ions
• You can, therefore, associate loop diuretics with almost any low electrolyte state (including metabolic alkalosis)
• A similar co-transporter is responsible for regulating endolymph composition in the inner ear
• At high doses, loop diuretics can affect this too, leading to hearing loss and tinnitus

Question 4

Loop Diuretics

Warnings

Answer 4

• Loop diuretics are contraindicated in patients with severe hypovolemia or dehydration
• They should be used with caution in patients at risk of hepatic encephalopathy (where hypokalaemia can cause or worsen coma)
• Those with severe hypokalaemia and/or hyponatraemia
• Taken chronically, loop diuretics inhibit uric acid excretion and this can worsen gout

Question 5

Loop Diuretics

Interactions

Answer 5

• Loop diuretics have the potential to affect drugs that are excreted by the kidneys
• For example, Li levels are increased due to reduce excretion
• The risk of digoxin toxicity may also be increased, due to the effects of diuretic-associated hypokalaemia
• Loop diuretics can increase the ototoxicity and nephrotoxicity of aminoglycosides

Question 6

Loop Diuretics

Communication

Answer 6

• Explain to your patient that their body is overloaded with water
• You are therefore offering a treatment to increase urine flow, which will hopefully improve this
• The medicine will inevitably cause them to need to pass water more often
• Provided they do not take doses late in the day it should not affect them at night

Question 7

Loop Diuretics

Monitoring

Answer 7

• For efficacy in the acute management of pulmonary oedema, evidence for a good response will include improvements in the patient’s symptoms, tachycardia, HTN, and O2 requirement
• Increased urine output typically occurs later and indicated the onset of the diuretic effect
• In longer-term therapy, you should monitor your patient’s symptoms, signs and body weight (aiming for losses of no more than 1kg/day
• For safety, periodic monitoring of serum sodium, potassium and renal function is also advisable, particularly in the first few weeks of therapy

Question 8

Strong opioid

Common indications

Answer 8

1. For rapid relief of acute severe pain, including post-operative pain and pain associated with acute myocardial infarction
2. For relief of chronic pain, when paracetamol, NSAID, weak opioids are insufficient
3. For relief of breathlessness in the context of end-of-life care
4. To relieve of breathlessness and anxiety in acute pulmonary oedema, alongside oxygen, furosemide and nitrates

Question 9

Strong opioid

MOA

Answer 9

• The term opioids encompass naturally-occurring opiates (e.g. morphine) plus synthetic analogues (e.g. oxycodone)
• Morphine and oxycodone are strong opioids, the therapeutic action of opioids arises from activation of opioid u receptors in the central nervous system
• Activation of the GPCR has several effects that, overall, reduce neuronal excitability and pain transmission
• In the medulla, they blunt the response to hypoxia and hypercapnia, reducing respiratory drive and breathlessness
• By relieving pain, breathlessness and associated anxiety, opioids reduce sympathetic nervous system (fight or flight) activity
• Thus, in myocardial infarction and acute pulmonary oedema, they may reduce cardiac work and oxygen demand, as well as relieving symptoms
• That said, although commonly used, the efficacy and safety of morphine in acute pulmonary oedema is not firmly established

Question 10

Strong opioid

Adverse effects

Answer 10

• Opioids cause respiratory depression by reducing respiratory drive
• They may cause euphoria and detachment, and in higher doses, neurological depression
• They can activate the CTZ, causing N&V, although this tends to settle with continued use
• Pupillary constriction occurs due to stimulation of the Edinger-Westphal nucleus
• In the large intestine, activation of u receptors increases smooth muscle tone and reduces motility leading to constipation
• In the skin opioids may cause histamine release, leading to itching, urticaria, vasodilation and sweating
• Continued use can lead to tolerance (a state in which the dose required to produce the same effect increases over time) and dependence
• Dependence becomes apparent on cessation of the opioid, when a withdrawal reaction occurs

Question 11

Strong opioid

Warnings

Answer 11

• Most opioids rely on the liver and the kidneys for elimination, so doses should be reduced in hepatic failure and renal impairment in the elderly
• Don’t give opioids in respiratory failure except under senior guidance
• Avoid opioids in billiary colic, as they may cause spasm of the sphincter of Oddi, which may worsen pain

Question 12

Strong opioid

Interactions

Answer 12

• Opioids should ideally not be used with other sedating drugs (e.g. antipsychotics, BZs, TCA)
• Where their combination is unavoidable, close monitoring is necessary

Question 13

Strong opioid

Communication

Answer 13

• Patients may be reluctant to accept morphine, due to the stigma associated with abuse and dependence
• Explain that it is a highly effective painkiller and that ‘addiction’ is not an issue when it is used for pain control
• That said, you should warn patients that the dose may need to be increased over time as they become tolerant to its effects; this is normal and should not cause alarm.
• Explain how the patient should take their morphine, e.g. CR v IR
• Explain N&V usually settle after a few days, but offer an antiemetic (e.g. metoclopramide)
• Constipation is a very common; pre-emptive use of laxative (e.g. senna), along with good hydration, is advisable
• Advise patients not to drive or operate heavy machinary if they feel drowsy or confused

Question 14

Strong opioid

Monitoring

Answer 14

• Acute pain, review your patients response to analgesia within an hour, as well as for adverse effects such as respiratory depression
• For chronic pain, schedule a review after a couple of weeks to assess the need to step up or down the analgesic ladder and/or specialist referral