Endocrine & Analgesic Drugs Flashcards
(157 cards)
1
Q
Name 4 types of insulin?
A
- Insulin aspart
- Insulin glargine
- Biphasic insulin
- Soluble insulin
2
Q
What are the common indications for use of insulin? (4)
A
- Type 1 diabetes: for insulin replacement
- Type 2 diabetes: for control of blood glucose where oral hypoglycaemic treatment is inadequate or poorly tolerated
- Diabetic emergencies: DKA, hyperglycaemic hyperosmolar syndrome, perioperative glycaemic control.
- Hyperkalaemia: used in treatment, alongside glucose.
3
Q
What is the basic mechanism of action of insulin?
A
Exogenous insulin functions similarly to endogenous insulin. It stimulates glucose uptake from the circulation into tissues, including skeletal muscle and fat, and increases use of glucose as an energy source. Insulin stimulates glycogen, lipid and protein synthesis and inhibits gluconeogenesis and ketogenesis.
4
Q
What is the mechanism of action of insulin in treating hyperkalaemia?
A
Insulin drives K+ into cells, reducing serum K+ concentrations. However once insulin treatment is stopped, K+ leaks back out of the cells into the circulation, therefore this is a short-term measure while other treatment is commenced.
5
Q
Which type of insulin is used in medical emergencies, e.g. DKA and hyperkalaemia?
A
When IV insulin is required, soluble insulin e.g. Actrapid is usually used.
6
Q
Name a rapid acting form of insulin and its characteristics, e.g. duration?
A
Insulin aspart e.g. Novorapid - immediate onset, short duration
7
Q
Name a short acting form of insulin?
A
Soluble insulin e.g. Actrapid
8
Q
Name an intermediate acting form of insulin?
A
Isophane (NPH) insulin e.g. Humulin I
9
Q
Name two long acting forms of insulin?
A
- Insulin glargine e.g. Lantus
2. Insulin detemir e.g. Levemir
10
Q
Name a biphasic insulin and its characteristics?
A
Novomix 30 (insulin aspart/insulin aspart protamine). Preparations containing a mixture of rapid- and intermediate- acting insulins.
11
Q
What is the main adverse effect of insulin?
A
Hypoglycaemia
12
Q
What can occur when insulin is repeated injected subcutaneously in the same site?
A
Lipohypertrophy (fat overgrowth) - can be uncomfortable and unsightly
13
Q
What is the warning associated with insulin use in people with renal impairment?
A
The insulin clearance will be reduced, so there is an increased risk of hypoglycaemia
14
Q
Use of which type of drugs can increase insulin requirements?
A
Systemic corticosteroids
15
Q
Why should you avoid treating unexpected high blood glucose concentrations with subcutaneous Actrapid (short-acting insulin) ?
A
As the time to peak effect (2-3 hours) is longer than often appreciated, and trying to correct hyperglycaemia quickly is often unnecessary and can be dangerous. Understanding why the hyperglycaemia has occurred is more important, and making small alterations to the patient’s regular insulin regimen.
16
Q
What type of drug is gliclazide?
A
A sulphonylureas
17
Q
What is the indication for use of gliclazide?
A
Type 2 diabetes
18
Q
What is the mechanism of action of sulphonylureas?
A
The sulfonylureas act mainly by augmenting insulin secretion and consequently are effective only when some residual pancreatic beta-cell activity is present; during long-term administration they also have an extrapancreatic action.
19
Q
When are sulphonylureas contraindicated? (1)
A
Presence of ketoacidosis
20
Q
When/why should sulphonylureas be used with caution?
A
- Can encourage weight gain (should be prescribed only if poor control and symptoms persist despite adequate attempts at dieting)
- In the elderly
- In someone has a G6PD deficiency
21
Q
Which antibiotic has a known interaction with sulphonylureas?
A
Chloramphenicol - it is known to increase the exposure to gliclazide
22
Q
Why should sulphonylureas be avoided during pregnancy?
A
Can cause hypoglycaemia in neonates
23
Q
What are the side effects associated with sulphonylureas? (2)
A
Weight gain
Rarely: hypoglycaemia
24
Q
What is the risk when using sulphonylureas in patients wit hepatic/renal impairments?
A
Hypoglycaemia
25
What is the only type of biguanide licensed for use?
Metformin
26
What is the indication for use of metformin?
Type 2 diabetes: first choice medication for control of blood glucose, used alone or in combination with other oral hypoglycaemic drugs (e.g. sulphonylureas) or insulin
27
What is the mechanism of action of metformin?
Metformin (a biguanide) lowers blood glucose by increasing the response (sensitivity) to insulin. It suppresses hepatic glucose production (glycogenolysis and gluconeogenesis), increases glucose uptake and utilisation by skeletal muscle and suppresses intestinal glucose absorption. It achieves this by diverse intracellular mechanisms, which are incompletely understood.
28
Why does metformin not cause hypoglycaemia?
It does not stimulate pancreatic insulin secretion and therefore does not cause hypoglycaemia.
29
How is metformin helpful in preventing worsening of insulin resistance and progression of type 2 diabetes?
It reduces weight gain and can induce weight loss, which helps to slow deterioration of diabetes.
30
What common adverse effects are caused by metformin? (3)
1. GI upset - including nausea, vomiting and diarrhoea
2. Taste disturbance
3. Anorexia
(these adverse effects may contribute to weight loss)
31
What rare adverse effect is associated with metformin use?
Lactic acidosis - this doesn't occur in stable patients, but can be precipitated by intercurrent illness, including renal impairment, illness that results in increased lactate production (e.g. sepsis, hypoxia, cardiac failure) or reduced lactate metabolism (e.g. liver failure).
32
What are the contraindications for metformin use? (3)
1. Severe renal impairment
2. AKI
3. Severe tissue hypoxia
33
What are the warnings for using metformin, often including advise on dose reduction? (4)
1. Moderate renal impairment
2. Hepatic impairment
3. Acute alcohol intoxication
4. Chronic alcohol overuse
34
What are the important drug interactions associated with metformin? (3)
1. IV contract media - metformin must be withheld before and for 48 hours after injection
2. Any drugs with potential to impair renal function e.g. NSAIDs, ACE inhibitors, diuretics, should be used with caution
3. Prednisolone, thiazide and loop diuretics all elevate blood glucose, therefore reduce the efficacy of metformin
35
Why is metformin the first-choice treatment for type 2 diabetes, as opposed to sulphonylureas or insulin?
Metformin does not cause weight gain
36
Name 2 thyroxine drugs?
1. Levothyroxine
| 2. Liothyronine
37
What are the indications for use of thyroxine drugs? (3)
1. Primary hypothyroidism
2. Hypothyroidism secondary to hypopituitarism
3. Thyroid excision secondary to hyperthyroidism
38
What is the mechanism of action of thyroxine drugs?
Thyroid hormones regulate metabolism and growth. Deficiency of these hormones cause hypothyroidism, with clinical features including lethargy, weight gain, constipation and slowing of mental progression. Levothyroxine (synthetic T4) is a long-term replacement of the hormones. Liothyronine (synthetic T3) has a shorter half-life and quicker onset (a few hours) and offset (24-48 hours) of action than levothyroxine.
39
When is liothyronine used?
For emergency treatment of severe or acute hypothyroidism.
40
What are the adverse effects associated with levothyroxine use?
They are related to excessive doses, so similar to that of hyperthyroidism.
1. GI disturbances: diarrhoea, weight loss, vomiting
2. Cardiac manifestations: palpitations, arrhythmias, angina
3. Neurological manifestations: tremor, restlessness, insomnia
41
What are the warnings/cautions associated with taking thyroxine?
1. Coronary artery disease: as thyroid hormones increase heart rate and metabolism, they can precipitate cardiac ischaemia in people with coronary artery disease therefore a low dose will be required with careful monitoring.
2. Hypopituitarism: corticosteroid therapy must be initiated before thyroid hormone replacement to avoid precipitating Addisonian crisis
42
Which drugs need to be taken at different times to levothyroxine due to their effect in reducing absorption of levothyroxine? (2)
1. Antacids
| 2. Calcium or iron salts
43
In whom would an increased dose of levothyroxine be required due to the process of metabolism of the drug?
Patients who take cytochrome P450 inducers (phenytoin, carbamazepine).
44
Name two anti-thyroid drugs?
1. Carbimazole
| 2. Propylthiouracil
45
What is the indication for use of carbimazole and propylthiouracil?
Hyperthyroidism.
| Carbimazole is first-line treatment, whereas propylthiouracil is reserved for when patients cannot tolerate carbimazole.
46
When is the use of carbimazole contraindicated? (1)
In people with severe blood disorders
47
What are the common side effects associated with carbimazole? (8)
1. Arthralgia
2. Fever
3. Headache
4. Jaundice
5. Malaise
6. Mild gastro-intestinal disturbances/nausea
7. Pruritus/rash
8. Taste disturbance
48
What is the mechanism of action of carbimazole?
Carbimazole is a carbethoxy derivative of methimazole. Once converted to its active form of methimazole, it prevents the thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T3 and T4.
49
What can rashes and pruritus be treated with to allow continuation of carbimazole therapy?
Antihistamines
50
What important adverse effect can carbimazole induce, and what symptoms are patients advised to inform their doctors of?
Bone marrow suppression --> patients need to report any symptoms that suggest an infection, especially a sore throat and mouth ulcers.
51
When carbimazole is used in the hyperthyroidism blocking-replacement regime, which other drug is it used in combination with?
Levothyroxine
52
Propylthiouracil has very similar side effects to carbimazole, however there is one side effect it can cause that carbimazole doesn't, what is it?
Hepatotoxicity - Severe hepatic reactions have been reported, including fatal cases and cases requiring liver transplant—discontinue if significant liver-enzyme abnormalities develop.
53
There is a big difference in the dosing between carbimazole and propylthiouracil, what is the dose conversion between the two?
Carbimazole 1mg is considered the equivalent of 10mg of propylthiouracil
54
Name 3 examples of Bisphosphonates?
1. Alendronic acid
2. Disodium pamidronate
3. Zoledronic acid
55
What are the common indications for use of bisphosphonates? (4)
1. Osteoporosis/Osteoporotic fragility fractures - alendronic acid is the first-line drug treatment options for at risk patients.
2. Severe hypercalcaemia of malignancy - pamidronate and zoledronic acid are used, after appropriate IV rehydration.
3. Myeloma/Breast cancer with bone metastases.
4. Paget's disease - first-line treatment of metabolically-active Paget's disease,
56
Which bisphosphonates are indicated for use in myeloma or breast cancer with mets? (2)
1. Pamidronate
| 2. Zoledronic acid
57
How do pamidronate/zoledronic acid help in patients with myeloma/breast cancer mets?
They reduce the risk of pathological features, cord compression and the need for radiotherapy or surgery
58
How do bisphosphonates help in Paget's disease?
The aim is to reduce bone turnover and pain
59
What is the mechanism of action of bisphosphonates?
They reduce bone turnover by inhibiting the action of oestoclasts, the cells responsible for bone resorption. Bisphosphonates have a similar structure to naturally occurring pyrophosphate, hence are readily incorporated into bone. As bone is resorbed, bisphosphonates accumulate in osteoclasts, where they inhibit activity and promote apoptosis. The net effect is reduction in bone loss and improvement in bone mass.
60
What are the side effects that bisphosphonates can cause? (4)
1. Oesophagitis
2. Hypophosphataemia
3. Osteonecrosis of the jaw (rare but serious - more likely in high dose IV therapy)
4. Atypical femoral fracture
61
Due to the possible side effect of osteonecrosis of the law, when taking bisphosphonates, what is important for patients to be aware of?
Good dental hygiene, and to visit their dentist on a regular/recommended basis
62
What are the contraindications for using bisphosphonates? (3)
1. Severe renal impairment
2. Hypocalcaemia
3. Upper GI disorders (oral administration contraindicated)
63
When should bisphosphonates be prescribed with caution? (2)
Due to the risk of jaw osteonecrosis;
1. Smokers
2. Dental disease
64
If a patient with osteoporosis has hypocalcaemia, but needs to be taking bisphosphonates, what is the option for treatment?
Calcichew 6 days a week, alendronic acid to be taken on the one day when calcichew isn't taken.
65
What is the important drug interaction to be aware of with bisphosphonates?
Bisphosphonates bind to calcium, their absorption is therefore reducing if taken with claim salts (including milk), as well as antacids and iron salts.
66
What are the different types of calcium and vitamin D in terms of drug prescriptions?
1. Calcium carbonate
2. Calcium gluconate
3. Colecalciferol
4. Alfacalcidol
67
What are the indications for use of calcium and vitamin D?
1. Osteoporosis (used to ensure positive calcium balance)
2. CKD
3. Severe hyperkalaemia
4. Hypocalcaemia
5. Vitamin D deficiency (prevention and treatment of - including for rickets (in children) and osteomalacia (in adults)
68
Why are calcium and vitamin D prescribed in patients with CKD?
They are used to treat and prevent secondary hyperparathyroidism and renal osteodystrophy
69
Why is calcium (as calcium gluconate) used in patients with severe hyperkalaemia?
It prevents life-threatening arrhythmias, other treatments e.g. insulin, are given to lower the potassium concentration
70
What are the symptoms of hypocalcaemia?
1. Paraesthesia
2. Tetany
3. Seizures
71
At what level is hypocalcaemia classified as severe? (in terms of mmol/L)
<1.9mmol/L
72
What is the mechanism of action of calcium and vitamin D?
Calcium is essential for normal function of muscles, nerves, bone and clotting. Calcium homeostasis is controlled by parathyroid hormone and vitamin D, which increase serum calcium levels and bone mineralisation, and calcitonin which reduces serum calcium levels.
73
In osteoporosis, what is the mechanism of action of calcium and vitamin D?
In osteoporosis there is a loss of bone mass, which increases the risk of fracture. Restoring calcium balance (either by dietary means or by administering calcium and vitamin D) may reduce the rate of bone loss (though whether this prevents fractures is less clear).
74
How do calcium and vitamin D help in patients with CKD?
In CKD, impaired phosphate excretion and reduced activation of vitamin D cause hyperphosphataemia and hypocalcaemia. This stimulates secondary hyperparathyroidism, which leads to a range of bone changes called renal osteodystrophy. Treatment may include oral calcium supplements to bind phosphate in the gut, and alfacalcidol to provide vitamin D that does not depend on renal activation.
75
How do calcium and vitamin D help in hyperkalaemia?
Calcium raises the myocardial threshold potential, reducing excitability and the risk of arrhythmias. It has no effect on the serum potassium level.
76
What are the possible side effects caused by oral calcium? (2)
Oral calcium may cause:
1. Dyspepsia
2. Constipation
77
What can calcium gluconate cause, if administered IV for the treatment of hyperkalaemia?
Cardiovascular collapse (if administered too fast) and/or local tissue damage if accidentally given into subcutaneous tissue
78
When should calcium and vitamin D use be avoided? (1)
In patients with hypercalcaemia
79
Oral calcium reduces the absorption of which drugs? (4)
1. Iron
2. Bisphosphonates
3. Tetracyclines
4. Levothyroxine
...and many others
80
What is the dose for IV calcium gluconate in patients with life-threatening hyperkalaemia?
10mL of calcium gluconate 10% IV over 5-10 minutes
81
What is the mineralocorticoid drug?
Fludrocortisone acetate
82
What is the indication for use of fludrocortisone?
1. Neuropathic postural hypotension
2. Mineralocorticoid replacement in adrenocortical insufficiency
3. Adrenocortical insufficiency resulting from septic shock (in combination with hydrocortisone)
83
What is the mechanism of action of fludrocortisone?
Fludrocortisone binds the mineralocorticoid receptor (aldosterone receptor). This binding (or activation of the mineralocorticoid receptor by fludrocortisone) in turn causes an increase in ion and water transport and thus raises extracellular fluid volume and blood pressure and lowers potassium levels.
Mineralocorticoids act on the distal tubules of the kidney to enhance the reabsorption of sodium ions from the tubular fluid into the plasma; they increase the urinary excretion of both potassium and hydrogen ions.
84
What are the effects of fludrocortisone toxicity?
Effects of overexposure include:
1. Irritation
2. Cardiac oedema
3. Increased blood volume
4. Hypertension
5. Cardiac arrhythmias
6. Enlargement of the heart
7. Headaches
8. Weakness of the extremities.
85
What side effects can fludrocortisone cause? (59?!?!......59 side effects!)
As with all corticosteroids:
1. Abdominal distension
2. Acute pancreatitis
3. Aggravation of epilepsy
4. Aggravation of schizophrenia
5. Amenorrhoea
6. Anaphylaxis (in children)
7. Bruising
8. Candidiasis
9. Congestive heart failure
10. Corneal thinning
11. Cushing's syndrome (with moon face, striae and acne) 12. Dyspepsia
13. Ecchymoses
14. Exacerbation of ophthalmic fungal disease
15. Exacerbation of ophthalmic viral disease
16. Exophthalmos
17. Facial erythema
18. Glaucoma
19. Headache
20. Hiccups
21. Hirsutism
22. Hypercholesterolaemia
23. Hyperglycaemia
24. Hyperhidrosis
25. Hyperlipidaemia
26. Hypersensitivity reactions (in children)
27. Impaired healing
28. Increased appetite
29. Increased intra-ocular pressure
30. Increased intracranial pressure with papilloedema (usually after withdrawal) (in children)
31. Increased susceptibility to and severity of infection
32. Insomnia
33. Leucocytosis
34. Long bone fractures
35. Malaise
36. Menstrual irregularities
37. Muscle weakness
38. Myocardial rupture following recent myocardial infarction
39. Nausea
40. Negative calcium/nitrogen balance
41. Oesophageal ulceration
42. Papilloedema (in adults)
43. Petechiae
44. Posterior subcapsular cataracts
45. Potassium loss
46. Psychological dependence
47. Reactivation of dormant tuberculosis
48. Scleral thinning
49. Skin atrophy
50. Sodium retention
51. Suppression of growth (in children)
52. Telangiectasia
53. Tendon rupture
54. Thromboembolism
55. Urticaria
56. Vertebral fractures
57. Vertigo
58. Water retention
59. Weight gain
86
Name some commonly prescribed NSAIDs? (3)
1. Naproxen
2. Ibuprofen
3. Etoricoxib
4. Diclofenac
5. High dose aspirin
87
What are the common indications for use of NSAIDs?
1. Mild-to-moderate pain
| 2. Pain related to inflammation, particularly MSK.
88
Which drug is preferred to NSAIDs when used as an analgesic?
Paracetamol - a single dose of each has similar analgesic effects, so paracetamol is preferred as there are less side effects. Obviously often they are used in combination together.
89
Give some examples of MSK conditions that NSAIDs are indicated for use in? (3)
1. Rheumatoid arthritis
2. Severe osteoarthritis
3. Acute gout
90
What is the mechanism of action of NSAIDs?
NSAIDs inhibit synthesis of prostaglandins from arachidonic acid by inhibiting cyclooxygenase (COX). COX exists as two main isoforms. COX-1 is the constitutive form. It stimulates prostaglandin synthesis that is essential to preserve integrity of the gastric mucosa; maintain renal perfusion (by dilating afferent glomerular arterioles); and inhibit thrombus formation at the vascular endothelium. COX-2 is the inducible form, expressed in response to inflammatory stimuli. It stimulates production of prostaglandins that cause inflammation and pain. The therapeutic benefits of NSAIDs are principally mediated by COX-2 inhibition and adverse effects by COX-1 inhibition, although there is some overlap between the two. Selective COX-2 inhibitors (e.g. etoricoxib) were developed in an attempt to reduce the adverse effects of NSAIDs.
91
What are the main adverse effects associated with NSAID use? (3)
1. GI toxicity
2. Renal impairment
3. CV events (e.g. increased risk of MI and stroke)
92
Of all the non-selective NSAIDs, which one is associated with lowest risk of GI effects?
Ibuprofen
93
Which two NSAIDs are associated with lowest risk of CV events?
1. Ibuprofen
| 2. Naproxen
94
What are COX-2 inhibitor NSAIDs associated with in terms of side effects?
They cause fewer GI side effects compared to non-selective NSAIDs, but are associated with an increased risk of CV events.
95
Are any NSAIDs not associated with impaired renal function?
No, all NSAIDs including COX-2 inhibitors can cause renal impairment.
96
What are adverse effects can NSAIDs cause? (2)
1. Hypersensitivity reactions e.g. bronchospasm and angioedema
2. Fluid retention (which can worsen heart failure and hypertension).
97
When is NSAID use contraindicated?
1. Severe renal impairment
2. Heart failure
3. Liver failure
4. NSAID hypersensitivity
98
When should NSAIDs be avoided/used with caution (4), and what is the advice given if they have to be used?
1. Peptic ulcer disease
2. GI bleeding
3. Cardiovascular disease
4. Renal impairment
Use the safest NSAID at the lowest effective dose, for the shortest period of time
99
Name some commonly prescribed compound-preparation opioids?
1. Co-codamol
| 2. Co-dydramol
100
What is the indication for use of co-codamol/co-dydramol?
Mild-to-moderate pain; as second-line agents when simple paracetamol/ibuprofen is insufficient.
101
On the WHO 'pain ladder', which rung are co-codamol/co-dydramol on?
The second rung
102
What is the mechanism of action of co-codamol?
Has two mechanisms of action - paracetamol and codeine. The mechanism of action of paracetamol is poorly understood, but it is a weak inhibitor of COX. In the CNS, COX inhibition appears to increase the pain threshold.
Codine and dihydrocodeine are weak opioids. They are metabolised by cytochrome P450 enzymes to morphine and morphine-related metabolites. These metabolites, which are agonists of opioid u-receptors, probably account for most of their analgesic effect.
103
Why is it effective combining paracetamol and codeine?
As the two analgesics have different mechanisms of action, they may offer better pain control than can be achieved with either drug alone.
104
What are the adverse effects associated with co-codamol/co-dydramol?
1. Nausea
2. Constipation
3. Drowsiness
105
What would be the clinical signs of a co-codamol overdose?
1. Paracetamol overdose causes hepatotoxicity
| 2. Opioid toxicity causes neurological and respiratory depression
106
What are the warnings associated with taking weak opioids/compound preparation opioids? (4)
Dose reduction/caution when prescribing to patients with:
1. Significant respiratory disease
2. Renal impairment
3. Hepatic impairment
4. Elderly
107
What are the important drug interactions to note with co-compound preparations of opioids?
Opioids should not ideally be used with other sedating drugs:
1. Antipsychotics
2. Benzodiazepines
3. Tricyclic antidepressants
108
Name some weak prescription opioids?
1. Codeine
2. Tramadol
3. Dihydrocodeine
109
What is the indication for use of weak opioids?
Mild-to-moderate pain, including post-operative pain. It is one the same second 'rung' of the WHO pain ladder, as with compound preparation opioids.
110
What is the key enzyme that metabolises opioids, that 10% of caucasians have a less active form of?
Cytochrome P450 2D6
111
Where are weak opioids metabolised?
In the liver, to form small amounts of morphine
112
What is tramadol?
It is a synthetic analogue of codeine, and is better classified as a moderate strength opioid.
113
How is tramadols mechanism of action different to that of codines/dihydrocodeines?
Tramadol and its active metabolite are also u-receptor agonists (just like codeine) but in addition to this, tramadol also affects serotonergic and adrenergic pathways, where it is thought to act as a serotonin and noradrenaline re-uptake inhibitor. This is thought to contribute to its analgesic effects.
114
What are the side effects associated with weak opioid use? (4)
1. Nausea
2. Constipation
3. Dizziness
4. Drowsiness
115
What are the effects of an opioid overdose?
Neurological and respiratory depression
116
Does tramadol cause more or less side effects than other opioids?
Less side effects
117
Which opioids must never be given intravenously, due to a severe reaction similar to anaphylaxis? (2)
Codine and dihydrocodeine
118
Is the severe reaction to IV codeine/dihydrocodeine an allergic response?
No, although it is mediated by histamine release
119
What is the contraindication for tramadol use?
Tramadol lowers the seizure threshold so is best avoided in patients with epilepsy and contraindicated in people with uncontrolled epilepsy
120
Which drugs should tramadol not be prescribed alongside?
Other drugs that lower seizure threshold; SSRIs and tricyclic antidepressants
121
Why might patients have a red patch on their thigh after an operation in which the anaesthetist administered post-operative analgesia?
Anaesthetists may give an IM infection of codeine towards the end of an operation, to provide post-operative analgesia. A red patch can form at the site of injection.
122
Name two strong opioids?
1. Morphine
| 2. Oxycodone
123
What are the common indications for use of strong opioids?
1. Acute severe pain; for rapid relief, including post-operative pain, and pain associated with acute MI
2. Chronic pain; 'rung' 3 of the WHO pain ladder, where all other analgesics beforehand were insufficient
3. Breathlessness - in the context of end of life care
4. Acute pulmonary oedema - to relieve breathlessness and anxiety
124
What are drugs are prescribed alongside strong opioids when treating acute pulmonary oedema? (3)
1. Oxygen
2. Furosemide
3. Nitrates
125
What is the mechanism of action of strong opioids?
Opioids encompasses naturally-occurring opiates e.g. morphine, and synthetic analogues e.g. oxycodone. The therapeutic action of opioids arises from activation of opioid (mu) receptors in the CNS. Activation of these G protein-coupled receptors has several effects that, overall, reduce neuronal excitability and pain transmission. In the medulla, they blunt the response to hypoxia and hypercapnoea, reducing respiratory drive and breathlessness.
126
By relieving pain and breathlessness, what overall effect do opioids have on the sympathetic nervous system?
Opioids reduce the sympathetic nervous system (fight or flight) activity.
127
As opioids reduce sympathetic nervous systemic activity, what is their contribution to helping people with an acute MI or pulmonary oedema?
Opioids reduce cardiac work and oxygen demands, as well as relieving symptoms. Although the efficacy of morphine in acute pulmonary oedema is not fully understood/firmly established.
128
What side effect do strong opioids have on the respiratory system?
They cause respiratory depression by reducing respiratory drive.
129
What side effects can strong opioids cause, other than respiratory depression? (5)
1. Euphoria and detachment, which can lead to neurological depression
2. Nausea and vomiting
3. Pupillary constriction
4. Constipation
5. Itching, urticaria, vasodilation and sweating
130
Why do strong opioids cause nausea and vomiting?
They can activate the chemoreceptor trigger zone
131
Why do strong opioids cause pupillary constriction?
They stimulate the Edinger-Whestphal nucleus.
132
What effect do strong opioids have on the colon, leading to constipation?
They activate u (mu)-receptors, which increases muscle tone and reduces motility, leading to constipation.
133
Why can opioids cause itching, urticaria etc.?
They mediate the release of histamine
134
What are the symptoms/clinical signs of opioid withdrawal (particularly when patient has become dependent)? (5)
The opposite of the clinical effects of opioids:
1. Anxiety
2. Pain
3. Breathlessness
4. Pupils dilate
5. Skin is cool and dry
135
What are the warnings associated with strong opioid use? (4)
Same as with any other opioids:
1. Hepatic failure
2. Renal impairment
3. Respiratory failure
4. Biliary colic (can worsen pain as cause spasm of the sphincter of Oddi)
136
What is the drug interaction associated with strong opioid use? (same as with other opioids)
Opioids should not be used with other sedating drugs: e.g. antipsychotics, benzodiazepines and tricyclic antidepressants.
137
What are the common indications for use of paracetamol?
1. Acute and chronic pain : first-line analgesic
| 2. Antipyretic : can reduce fever and its associated symptoms e.g. shivering
138
What is the mechanism of action of paracetamol?
Paracetamol is weak inhibitor of COX, the enzyme involved in prostaglandin metabolism. In the CNS, COX inhibition appears to increase the pain threshold and reduce prostaglandin (PGE2) concentrations in the thermoregulatory region of the hypothalamus, controlling fever. Paracetamol has specificity for COX-2 (the isoform induced in inflammation) rather than COX-1 (the isoform involved in protecting the gastric mucosa and regulating renal blood flow and clotting).
139
Why is paracetamol a weak anti-inflammatory drug, if it has COX-2 specificity?
Paracetamol is a weak anti-inflammatory, as its actions are inhibited in inflammatory lesions by the presence of peroxides.
140
What are the side effects associated with paracetamol use?
Paracetamol is a very safe drug, with few side effects.
141
What are the effects of paracetamol overdose?
In overdose, paracetamol causes liver failure.
142
Why does paracetamol overdose cause liver failure?
Paracetamol is metabolised by cytochrome P450 enzymes to a toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), which is conjugated with glutathione before elimination. After overdose, this elimination pathway is saturated and NAPQI accumulation causes hepatocellular necrosis.
143
How can hepatotoxicity be avoided with a paracetamol overdose?
Treatment with the glutathione precursor - acetylcysteine.
144
What are the warnings associated with paracetamol use?
Paracetamol dose should be reduced in people at increased risk of liver toxicity:
1. Either because of increased NAPQI production: chronic excessive alcohol use ...or...
2. Due to reduced glutathione stores: malnutrition, low body weight and severe hepatic impairment.
145
What are the important drug interactions with paracetamol use?
There are few clinically significant interactions. However cytochrome P450 induces, e.g. phenytoin and carbamazepine, increase the rate of NAPQI production and risk of liver toxicity after paracetamol overdose
146
Name some xanthine oxidase inhibitors?
1. Allopurinol (commonly prescribed)
2. Aloprim
3. Febuxostat
4. Uloric
147
What are the common indications for use of allopurinol? (3)
1. To prevent acute attack of gout
2. To prevent uric acid and calcium oxalate renal stones
3. To prevent hyperuricaemia and tumour lysis syndrome associated with chemotherapy
148
What is the mechanism of action of allopurinol?
Allopurinol is a xanthine oxidase inhibitor. Xanthine oxidase metabolises xanthine (produced from purines) to uric acid. Inhibition of xanthine oxidase lowers plasma uric acid concentrations and reduces precipitation of uric acid in the joints or kidneys.
149
What are the side effects caused by allopurinol? (1)
The most common side effect is a skin rash, which may be mild or may indicate a more serious hypersensitivity reaction such as Stevens-Johnson syndrome or toxic epidermal necrolysis.
150
As well as severe skin reactions leading to Stevens-Johnson syndrome, what are syndrome can allopurinol cause?
Drug hypersensitivity syndrome (aka drug rash with eosinophilia and systemic symptoms - DRESS). This is a rare, life-threatening reaction to allopurinol that can include fever, eosinophilia, lymphadenopathy and involvement of other organs, such as the liver and skin.
151
What can allopurinol do if started during an acute gout attack?
Worsen the attack.
152
What are the contraindications for use of allopurinol? (3)
1. Acute attacks of gout
2. Recurrent skin rash
3. Severe hypersensitivity
153
Where is allopurinol metabolised and where is it excreted, and what does this mean in terms of dosage?
Allopurinol is metabolised by the liver and excreted by the kidneys, therefore the dose should be reduced in patents with severe renal or hepatic impairment.
154
In which drugs does allopurinol inhibit their metabolism, and therefore increase the risk of toxicity? (2)
The cytotoxic drug mercaptopurine and its pro-drug azathioprine, require xanthine oxidase for metabolism. When allopurinol is prescribed with these drugs, it inhibits their metabolism and increase the risk of toxicity.
155
Co-prescription of allopurinol and which antibiotic, leads to a skin rash (or increases the chances of)?
Amoxicillin
156
Co-prescription of allopurinol and which drugs, increase the risk of hypersensitivity reactions? (2)
1. ACE inhibitors
| 2. Thiazides
157
Which drugs can induce gout? (2)
1. Thiazide or loop-diuretics
| 2. Aspirin
