High-Risk Drugs

Question 1

Each assessment is likely to include at least one question on each of the following drugs or drug groups:

antibiotics
anticoagulants
antihypertensives
chemotherapy
insulins
antidiabetic drugs
drugs with a narrow therapeutic index
non-steroidal anti-inflammatory drugs
methotrexate
opiates
parenteral drugs
valproate

Question 2

Sodium Valproate Contraindications

-Acute liver disease
-Personal or family history of severe, drug-related, hepatic dysfunction
-Acute porphyria
-Mitochondrial disorders
-Females- must be enrolled in a pregnancy prevention plan

Answer 2

.

Question 3

Sodium Valproate Drug Interactions

-Valproate is highly protein bound- other drugs that are highly protein bound, such as aspirin, may displace valproate and cause valproate toxicity.
-Less strongly protein bound drugs such as _ can be displaced by valproate= toxic levels of that drug
-Drugs that inhibit CYP450 enzymes can cause valproate toxicity (fluoxetine, erythromycin)
-TCAs- increased concentration of them
-Lamotrigine- increased exposure
-Carbapenem antibiotics
-Quetiapine

Answer 3

Warfarin

Question 4

Valproate Monitoring

-FBC, LFTs and BMI should be measured prior to starting treatment; re-measure _ months after starting treatment, and then every _ months after that.

-Valproate levels not routinely measured unless signs of toxicity or ineffectiveness.

-Advise patient how to know the signs of blood disorders, liver disorders and pancreatitis- rare issues caused by valproate use.

Answer 4

6
12

Question 5

What are some drugs that valproate can interact with?

Answer 5

-Valproate is highly protein bound- other drugs that are highly protein bound, such as aspirin, may displace valproate and cause valproate toxicity.
-Less strongly protein bound drugs such as warfarin can be displaced by valproate= toxic levels of that drug
-Drugs that inhibit CYP450 enzymes can cause valproate toxicity (fluoxetine, erythromycin)
-TCAs- increased concentration of them
-Lamotrigine- increased exposure
-Carbapenem antibiotics
-Quetiapine

Question 6

What can methotrexate be used to treat?

Answer 6

-Severe crohn’s disease
-Maintenance of remission of severe crohn’s
-Moderate-severe active rheumatoid arthritis
-Neoplastic diseases
-Severe psoriasis unresponsive to conventional therapy

Question 7

Methotrexate Monitoring

• FBC, renal tests, LFTs repeated every 1-2 weeks until stabilised on therapy, then every 2-3 months after.
  -Report all signs of infection, especially a sore throat

Answer 7

.

Question 8

Methotrexate Key Interactions

-Amoxicillin/Flucloxacillin
-Aspirin
-Benzydamine
-NSAIDs
-Ciprofloxacin
-PPIs

Answer 8

.

Question 9

Methotrexate Doses

-Severe Crohn’s: Injection of _mg weekly until remission induced, then maintain on 15mg weekly. Maintenance can also be orally of 10-25mg weekly.

-Rheumatoid arthritis: _mg orally weekly, adjusted according to response to a maximum of 20mg weekly. For injections, initially 7.5mg weekly, increased by 2.5mg each week according to response to a maximum of 25mg.

Answer 9

25
7.5

Question 10

What is the dosing instructions for methotrexate for severe crohn’s disease?

Answer 10

25mg weekly via injection to achieve remission, then maintenance of 15mg weekly. For oral maintenance, 10-25mg weekly.

Question 11

Opiates

-Usually should see a laxative prescribed alongside it, as well as something for nausea.
-Patients will usually experience withdrawal when it comes to these medications, especially if they have been on them for a while.
-Withdrawing the medication should involve tapering the dose down gradually.
-Interact with anti-epileptic medications such as carbamazepine, certain antibiotics such as clarithromycin, certain antidepressants.

Question 12

NSAIDs

Ibuprofen, Naproxen, Diclofenac, Celecoxib, Ketoprofen, Indometacin, Meloxicam, Mefanamic acid, Piroxicam, Aspirin.

-Work by inhibiting the enzyme cyclo-oxygenase; selective COX-2 inhibitors (celecoxib) are associated with less GI intolerance.

• Analgesic effect should normally be obtained within a week, anti-inflammatory effect may not be achieved for up to _ weeks. If not effect after this time, try a different NSAID.

Answer 12

3

Question 13

Which two NSAIDs are the preferred option for managing mild-moderate dental pain?

Answer 13

Ibuprofen
Diclofenac

Question 14

NSAID use in the Elderly- Contraindications

-Warfarin use
-Alongside antiplatelet agent without a PPI
-History of peptic ulcer disease or GI bleeding, unless alongside PPI
-eGFR less than _ mL/minute/1.73m2
-Concurrent corticosteroid use without PPI
-Severe _ or severe heart failure

Answer 14

50
Hypotension

Question 15

When would NSAID use be contraindicated in the elderly?

Answer 15

-Warfarin use
-Alongside antiplatelet agent without a PPI
-History of peptic ulcer disease or GI bleeding, unless alongside PPI
-eGFR less than 50 mL/minute/1.73m2
-Concurrent corticosteroid use without PPI
-Severe hypotension or severe heart failure

Question 16

NSAIDs and Cardiovascular Events

-Small increase in risk of MI and stroke, especially in those on high doses long-term.
-COX-2 selective inhibitors, diclofenac and ibuprofen= highest risk
-Prescribe lowest effective NSAID dose for the shortest period of time, and review the need for long-term treatment periodically.

Answer 16

.

Question 17

NSAIDs and GI Events

-All NSAIDs are associated with severe GI toxicity, especially in the elderly.

-Ibuprofen tends to carry the lowest risk (besides selective COX-2 inhibitors), with naproxen, diclofenac and indometacin being the next best afterwards.

-DO NOT use more than one NSAID at a time

-NSAID + low-dose aspirin can increase GI issue risk= only use if absolutely necessary.

-Long-term use of an NSAID should be prescribed alongside a PPI

Answer 17

.

Question 18

REMEMBER: NSAIDs can worsen asthma

Question 19

Drugs with a Narrow Therapeutic Index

-Aminoglycosides (Gentamicin, Amikacin, Streptomycin, Neomycin etc)
-Ciclosporin
-Carbamazepine
-Digoxin
-Digitoxin
-Flecainide
-Lithium
-Phenytoin
-Phenobarbital
-Rifampicin
-Theophylline
-Warfarin

Answer 19

.

Question 20

Lithium

-Treatment and prophylaxis of mania/bipolar disorder/recurrent depression/aggressive or self-harming behaviour.

-Dosing is initiated as divided doses, but once stabilised once daily dosing is the preferred maintenance.

-Narrow therapeutic index- overdose symptoms include visual disturbances, muscle weakness, increased GI disturbances, tremor, BP changes… eventually can progress to renal failure, circulatory failure, coma and death.

Answer 20

.

Question 21

Lithium Use Contraindications

-Addison’s disease
-Dehydration
-Untreated hypothyroidism
-Cardiac insufficiency

Cautions:
-Mild to moderate Renal impairment- avoid in severe
-Elderly (reduce dose)
-Epilepsy (can lower seizure threshold)
-Psoriasis (risk of exacerbation)
-Diuretic treatment (toxicity risk)
-Myasthenia gravis
-QT interval prolongation

Answer 21

.

Question 22

When would the use of lithium be cautioned?

Answer 22

-Elderly (reduce dose)
-Epilepsy (can lower seizure threshold)
-Psoriasis (risk of exacerbation)
-Diuretic treatment (toxicity risk)
-Myasthenia gravis
-QT interval prolongation

Question 23

Long-Term Use of Lithium

-Associated with _ disorders and mild cognitive and memory impairment.
-Monitor thyroid function every 6 months, or more if there are signs of deterioration.
-Regularly assess need for continued therapy and only maintain on lithium after 3-5 years if there is a clear need and benefit.

Answer 23

Thyroid

Question 24

Lithium Use and Pregnancy

-Need effective contraception whilst on lithium
-Avoid pregnancy if possible, risk of teratogenicity and cardiac abnormalities in _ trimester.
-May require dose increase during second and third trimester, return abruptly to normal after delivery.
-Need to closely monitor serum-lithium concentrations during pregnancy to avoid toxicity to neonate.
-Lithium is present in breast milk- AVOID breastfeeding

Answer 24

First

Question 25

You can breastfeed whilst taking lithium. True or False?

Answer 25

False
Present in breast milk- toxic to neonate

Question 26

Lithium- Therapeutic Drug Monitoring of Serum-Lithium Concentrations

-Narrow therapeutic index
-Take blood sample 12 hours after the dose to achieve a concentration of 0.4-1.0 mmol/litre (lower end of the range ideally for maintenance and elderly).
-Target concentration of 0.8-1.0 mmol/litre in acute episodes of _, or patients who have previously relapsed. Need to determine optimum range for each individual patient.

-Routine serum-lithium monitoring weekly after initiation, and after each dose change until stable. Then every _ months for the first year, then every 6 months thereafter.
-Patients 65+, taking drugs that interact with lithium, renal impairment/thyroid impairment risk, raised calcium levels, poor adherence or those whose last concentration was 0.8mmol/litre or higher = monitoring every 3 months.

Answer 26

Mania
3

Question 27

What is the typical target serum-lithium concentration?

Answer 27

0.4-1mmol/litre

Question 28

What is the typical recommended serum-concentration monitoring guidance when initiating lithium therapy?

Answer 28

Routine serum-lithium monitoring should be performed weekly after initiation and after each dose change until concentrations are stable, then every 3 months for the first year, and every 6 months thereafter.

Question 29

Monitoring of Patient Parameters on Lithium

-Assess renal, cardiac and _ function prior to starting treatment.
-BMI, serum electrolytes and FBC should also be measured prior to initiation.
-ECG recommended in patients with CVD or risk factors for it.

-Measure BMI, electrolytes, eGFR and thyroid function every _ months during treatment, or more if evidence of impaired renal or thyroid function, or raised _ levels. Also monitor cardiac function regularly.

Patients need to report signs of lithium toxicity, hypothyroidism, renal dysfunction and benign intracranial hypertension (headaches and visual disturbances). Need to maintain fluid intake and keep a consistent sodium intake.

Answer 29

Thyroid
6
Calcium

Question 30

What should be assessed prior to starting lithium treatment?

Answer 30

-Renal, cardiac and thyroid function
-BMI, serum electrolytes and FBC
-ECG if patient has CVD or risk factors for it

Question 31

Lithium Treatment Cessation

-DO NOT abruptly withdraw, high risk of relapse.
-Reduce dose gradually over a period of at least _ weeks (preferably up to 3 months).
-If there is a need to stop lithium abruptly, consider changing therapy to an atypical anti-psychotic or valproate.

Answer 31

4

Question 32

What are the three insulin regimen options for type 1 diabetics?

Answer 32

-Multiple daily injection basal-bolus insulin regimens.
-Mixed (biphasic) regimen (the person has one, two, or three insulin injections per day).
-Continuous insulin infusion (insulin pump) therapy.

Question 33

What is the general definition of hypoglycaemia?

Answer 33

Blood glucose levels less than 3.5mmol/L

Question 34

What are the symptoms of hypoglycaemia?

Answer 34

-Hunger
-Anxiety
-Irritability
-Palpitations
-Sweating or tingling lips

Question 35

What is the treatment for severe hypoglycaemia?

Answer 35

Intramuscular glucagon injection

Question 36

What are the examples of rapid-acting insulin?

Answer 36

Insulin aspart (Fiasp, Novorapid)
Insulin glulisine
Insulin lispro

Question 37

What are biphasic insulins?

Answer 37

Biphasic insulins (biphasic isophane insulin, biphasic insulin aspart, biphasic insulin lispro) are pre-mixed insulin preparations containing various combinations of short-acting insulin (soluble insulin or rapid-acting analogue insulin) and an intermediate-acting insulin.

Question 38

What are some examples of long-acting insulins?

Answer 38

Insulin detemir (once or twice daily)
Insulin glargine (once daily)
Insluin degludec (once daily)

Question 39

Denosumba is associated with hypocalcaemia

Question 40

Which antidote can reverse rivaroxaban and apixaban overdose?

Answer 40

Andexanet alfa

Question 41

Which antidote reverses LMWH and unfractionated heparin overdose?

Answer 41

Protamine

Question 42

All cytotoxic drugs can cause bone marrow suppression except which two?

Answer 42

Vincristine
Bleomycin

Question 43

Warfarin is potentially teratogenic and should not be given in the first trimester of pregnancy, as well as the third.
True or False?

Answer 43

True

Question 44

Monitoring of Warfarin

-Hepatic impairment: cautioned in mild-moderate, avoid in severe.
-Renal impairment: Monitor INR more frequently in severe renal impairment
-Acute illness may necessitate a dose reduction, as the effects of warfarin may be exaggerated.

-Base-line prothrombin time should be determined, but an initial dose should not be delayed whilst awaiting a result.
-INR must be measured daily or on alternate days in early days of treatment, then at longer intervals and then up to every _ weeks.

Answer 44

12

Question 45

Key Warfarin Interactions

-Amiodarone- increases warfarin concentration, monitor INR more.

-Amoxicillin/penicillins- alters anticoagulant effect of warfarin. Monitor INR and adjust dose.

Azathioprine/’Thioprines’- decreases anticoagulant effect of warfarin

Antifungals (especially miconazole)- increases anticoagulant effect of warfarin

Cranberry juice- increases effects of warfarin

Doxycycline/Tetracyclines: increases effects of warfarin

Enzyme Inducers: decrease anticoagulant effect of warfarin

Metronidazole- increases anticoagulant effect of warfarin

Steroids- increase the anticoagulant effect of warfarin

St John’s Wort- decreases anticoagulant effect

Tamoxifen: increases anticoagulant effect

Trimethoprim- increases anticoagulant effect

Answer 45

.

Question 46

What is the interaction if you combine warfarin with tetracyclines?

Answer 46

Increased anticoagulant effect of warfarin

Question 47

What is the interaction if you combine ‘thioprine’ drugs with warfarin?

Answer 47

Decreases the effects of warfarin

Question 48

What is the interaction if you combine enzyme-inducing drugs with warfarin?

Answer 48

Decreases the effects of warfarin

Question 49

What is the interaction if you combine steroids with warfarin?

Answer 49

Increases the effects of warfarin

Question 50

Cautions with Lithium

-Use alongside diuretics increases toxicity risk
-Lowers _ threshold, so cautioned in epilepsy
-Can exacerbate psoriasis
-Can prolong QT interval- cautioned when used alongside other drugs that can do this
-Long-term use associated with _ disorders and mild cognitive and memory impairment- thyroid function should be monitored every _ months.

Answer 50

Seizure
Thyroid
6

Question 51

What are the requirements/recommendations in regards to lithium during pregnancy?

Answer 51

Avoid in first trimester- teratogenic
Dose requirements increased during second and third trimesters, abruptly returns to normal after delivery- need to closely monitor serum concentrations throughout pregnancy

Question 52

Monitoring Lithium Concentrations

-Take samples _ hours after the dose to aim for a concentration of 0.4-1.0 mmol/litre (lower end for maintenance therapy and elderly).
-Target: 0.8-1.0 mmol/litre for acute mania.

-Perform serum-lithium monitoring weekly after initiation, and after each dose change until stable. Then every _ months for the first year, and every 6 months after that.
-Patients with risk factors, e.g. over 65, taking drugs that interact etc: monitor every 3 months.

Answer 52

12
3

Question 53

Monitoring Lithium Patient Parameters

-Assess renal, cardiac and thyroid function before starting treatment
-ECG recommended in patients with CVD or risk factors
-BW/BMI, serum electrolytes and FBC should also be measured prior to initiation- monitor this every 6 months during treatment, and more often if needed. Should also monitor _ function regularly.
-Patients should report signs of lithium toxicity, hypothyroidism, renal dysfunction and benign intracranial hypertension (persistent headaches and visual disturbances).

-Withdrawing treatment should be done gradually over a period of _ weeks (preferably up to 3 months). If treatment is to be stopped abruptly, consider switching to an _ antipsychotic or _.

Answer 53

Cardiac
4
Atypical
Valproate

Question 54

What is the therapeutic range of phenytoin?

Answer 54

10-20 mg/L