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Pre-reg > High Risk Drugs > Flashcards

High Risk Drugs Flashcards

1
Q

Amiodarone

  • What is the half life?
  • What is the dosing regimen?
A

50 days - clinical effects and side effects may be present for a few months after discontinuation

200mg TDS 7 days
200mg BD 7 days
200mg OD thereafter

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2
Q

Amiodarone

What are the monitoring requirements?

A

Thyroid function test: before treatment then 6 monthly (T4, T3 and TSH)

Liver function tests: before treatment and then 6 monthly

Serum K+: before treatment

Chest x-ray: before treatment

Annual eye test

High risk of bradycardia with anti hepatitis meds - monitor, monitor ECG if given IV

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3
Q

Amiodarone

Contra-indications?

A

Severe hypotension

Heart block

Active thyroid disease

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4
Q

Amiodarone

Side effects?

A

Eyes:

  • Corneal micro-deposits - night time glares driving
  • Optic neuropathy - stop if vision impaired

Skin:

  • Phototoxicity - wear SPF during and for 2-3 months after
  • slate grey skin

Thyroid: hypo and hyper (withdraw if possible)

Lungs:

  • pneumonitis (dry cough)
  • pulmonary fibrosis (shortness of breath)

Hepatotoxicity:
- report jaundice, abdo pain, itching, bruising etc

also causes peripheral neuropathy (reversible), AV block/bradycardia, N+V and taste disturbance

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5
Q

Amiodarone

Common interactions outcomes?

A

Amiodarone is an enzyme INHIBITOR

QT prolongation risk increased

Risk of bradycardia, AV block and myocardial depression

Increased risk of myopathy with statins
(max simvastatin 20mg)

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6
Q

Amiodarone is an enzyme INHIBITOR

Which drugs have subsequent interactions?

A

Increases the effect of warfarin, phenytoin and digoxin (must HALVE digoxin dose) most notably

Also increases levels of dabigatran and flecainide

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7
Q

Amiodarone increases the risk of QT prolongation

Which drugs subsequently interact?

A

Antipsychotics - especially sulpiride (1), amisulpiride(2), pimozide(1) and haloperidol(1)

Quinolones (moxifloxacin)

Hydroxychloroquine, chloroquine, mefloquine, quinine

SSRIs (escitalopram/citalopram), TCAs, venlafaxine

Macrolides

Tolterodine (urinary frequency)

Lithium

Methadone, apomorphine

5HT-3 antagonists, domperidone

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8
Q

Amiodarone increases the risk of bradycardia, AV block and myocardial depression with which drugs?

A

Beta blockers

Rate limiting CCBs (diltiazem and verapamil)

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9
Q

ACEi and ARBs

Monitoring requirements?

A

Blood pressure

Renal function and serum electrolytes
1-2 weeks after starting and 1-2 weeks after dose increase

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10
Q

ACEi and ARBs

Side effects?

A

Dry cough - switch to ARB

Hyperkalaemia

Anaphylactoid reactions - angioedema

Renal impairment
- nephrotoxic (DAMN drug)
- abnormal renal function (renal artery stenosis - can give in unilateral but not bilateral)
- AKI (anuria, confusion, dehydration, N+V)
Note - renoprotective in CKD

Hypotension - give first dose at bedtime

Hepatotoxicity - cholestatic jaundice (ALT 3x ULN)

HypOglycaemia, mouth ulcers and taste disturbance

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11
Q

ACEi and ARBs

Interactions?

A

Increases plasma LITHIUM concentration

Hyperkalaemia - Aliskeren, K+ sparing diuretic and aldosterone antagonists

Nephrotoxicity - NSAIDs, aliskeren

Hypotension - diuretics

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12
Q

Digoxin

Therapeutic range and mechanism of action

A

0.7 mcg/L - 2 mcg/L

cardiac glycoside that increases the force of contraction (positive inotrope) and decreases conductivity in the AV node (negative chronotrope)

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13
Q

Digoxin

Monitoring?

A

Monitor serum electrolytes (K+, Mg2+, Ca2+) - hypOkalaemia, hypOmagnesaemia and hypERcalcaemia can potentiate toxicity (hypoxia also increases risk)

Renal function - toxicity risk increases when eGFR falls

Routine plasma monitoring is not required unless toxicity is suspected or there is renal impairment

Plasma level should be taken 6 hours post dose

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14
Q

Digoxin

Doses in atrial flutter and non-paroxysmal AF?
Doses in severe heart failure?

A

Atrial flutter/AF = 125 - 250mcg

Heart failure = 62.5 - 125mcg

Loading doses required due to long t1/2

Note: elixer (75%), tablet (90%), IV (100%)

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15
Q

Digoxin

Signs of toxicity?

A

SLOW AND SICK

  • Bradycardia/heart block
  • GI effects: N+V, abdominal pain, diarrhoea
  • Visual disturbances: blurred or yellow vision
  • Confusion or delirium
  • Rash

Risk of toxicity in hypoK, hypoMg, hyperCa, hypoxia and renal impairment

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16
Q

Digoxin

Management of toxicity?

A

Withdraw digoxin

Give digoxin specific antibody for life-threatening arrhythmias unresponsive to atropine

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17
Q

Digoxin

Interactions?

A

Drugs that cause hypokalaemia (predisposes to toxicity)
Diuretics (loop/thiazide), B2 agonist, steroids, theophylline (give K+ or K+ sparing diuretics)

Enzyme inhibitors (toxicity)
Amiodarone (HALVE digoxin dose), rate limiting CCBs, macrolides, ciclosporin 
Enzyme inducers (subtherapeutic treatement)
St Johns wort, rifampicin

Drugs that reduce renal clearance (toxicity)
NSAIDS, ACEi/ARBs

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18
Q

Digoxin

Interaction acronym?

Hint: CRASED

A

CRASED

C - calcium channel blockers (verapamil)
R - rifampicin 
A - amiodarone (half dose)
S - st johns wort 
E - erythromycin 
D - diuretics
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19
Q

Phenytoin

Mechanism of action and therapeutic range?

A

Binds to neuronal Na channels in inactive state to prolong inactivity

10 - 20 mg/L or 40 -80 micromol/L

Note: non-linear relationship between dose and plasma drug concentration (small changes in dose, a missed dose or changes in drug absorption can cause a big change in plasma concentration)
May be more appropriate to measure free drug concentration when protein binding is reduced (neonates, elderly, pregnancy and liver disease)

20
Q

Phenytoin

Monitoring?

A

Serum concentration

Liver function (hepatotoxic)

FBC (can cause blood disorders) and serum folate (anti-folate drug)

Vitamin D

Phenytoin is highly protein bound so take extra precaution in patients whom may have reduced protein binding as they may show early signs of toxicity (elderly, liver impairment, gravely ill)

21
Q

Phenytoin

Toxicity signs and symptoms?

Hint: SNAtCHeD (CHANDS)

A

SNAtCHeD

S - slurred speech 
N - nystagmus 
A - ataxia 
C - confusion 
H- hyperglycaemia 
D - diplopia or blurred vision
22
Q

Phenytoin

Side effects?

A

Antiepileptic hypersensitivity syndrome - fever, rash, swollen lymph nodes

Blood dyscrasias - severe leucopenia requires withdrawal, report sore throat, fever, bleeding/bruising, mouth ulcers

Skin disorders - rashes (pre-screen Han Chinese and Thai patients for HLA-B*1502) as it leads to an increased risk of SJS

Changes in appearance - acne, hirsutism, gingival hypertrophy

Low vitamin D - phenytoin increases vit D metabolism which can lead to osteomalacia and rickets; consider vit D supplements (if dietary deficiency of calcium or reduced sun exposure)

Hepatotoxicity - Discontinue immediately

Suicidal ideation

23
Q

Phenytoin

Phenytoin sodium vs phenytoin base

A

100mg phenytoin sodium = 92mg phenytoin base

1.5mg Fosphenytoin = 1mg Phenytoin sodium

24
Q

Phenytoin

IV specific side effects?

Fosphenytoin side effects?

A

Bradycardia and hypotension - Monitor ECG and BP
(+arrhythmias, CV collapse, respiratory arrest)
MHRA: risk of death and severe harm with injectable phenytoin

IV Fosphenytoin - severe CV reactions
Observe during and 30 mins post infusion

25
Q

Phenytoin

Interactions?

A

Enzyme inhibitors (toxicity)

Other drugs that increase level - fluoxetine, sertraline, disulfiram, diltiazem,

Enzyme inducers (subtherapeutic) - SJW and rifampicin

Increased anti-folate effect - trimethoprim, methotrexate

Phenytoin is an enzyme inducer
Reduces levels of ciclosporin, hormonal contraceptives, warfarin, corticosteroids, levothyroxine

26
Q

Carbamazepine

MOA and therapeutic range

A

Inhibits neuronal sodium channels, stabilises membrane potential and reduces neuronal excitability

4 - 12 mg/L or 20 - 50 micromol/L

27
Q

Carbamazepine

Monitoring?

A

Measure plasma level after 1-2 weeks to ensure in range

FBC, LFTs and renal function

Pre-treatment screening for HLA-B*1502 in patients of Han Chinese or Thai origin owing to risk of Stevens-Johnson syndrome

28
Q

Carbamazepine

Signs and symptoms of toxicity?

Hint: I HANDBAG

A

I HANDBAG

I - incoordination
H - hypOnatraemia 
A - ataxia 
N - nystagmus 
D - drowsiness 
B - blurred vision and diplopia 
A - arrhythmias
G - GI disturbance (N+V+D)
29
Q

Carbamazepine

Side effects?

A

Blood dyscrasias - leucopenia, thrombocytopenia
report signs of infection

Hepatotoxicity

Hypersensitivity - antiepileptic hypersensitivity syndrome
(report rash, fever, lymphadenopathy)

Rashes - SJS

HypOnatraemia

30
Q

Carbamazepine

Interactions?

A 
Enzyme inhibitors (toxicity)
Levels also increased by fluoxetine

Enzyme inducers (subtherapeutic)

Antagonism of anticonvulsant effect
Antipsychotics, ‘quines’, TCAs, SSRIs

Increased risk of hyponatraemia
Aldosterone antagonists, SSRIs, TCAs, diuretics, NSAIDs

Hepatotoxicity
Tetracyclines, sulfasalazine, SV, methotrexate, isoniazid, statins, fluconazole, alcohol

Carbamazepine is also an enzyme inducer
Warfarin, antipsychotics, steroids, contraceptives

31
Q

Sodium valproate

MOA and use?

A

Weakly inhibits neuronal sodium channels, stabilises membrane potential and reduces neuronal excitability

First line in all generalised seizures

32
Q

Sodium valproate

Monitoring?

A

LFTs before treatment and during first 6 months

FBC before starting and before surgery (to ensure no increased risk fo bleeding)

33
Q

Sodium valproate

Side effects?

A

Hepatotoxicity - discontinue if PT abnormally long

Blood dyscrasias - leucopenia, thrombocytopenia

Pancreatitis - vomiting, abdominal pain and anorexia

34
Q

Sodium valproate

PPP requirements?

A

7 day prescription validity, max 30 day supply

Must see specialist and sign risk assessment form annually to confirm risk understood

Must use highly effective contraception - user independent or two complementary user dependent forms (e.g. pill and barrier)

Dispensing - must give warning card EVERY TIME, dispense full packs where possible, give IPL and do not obscure labels, ensure they have received a patient guide

35
Q

Sodium valproate

Interactions?

A

Anticonvulsant effect antagonised
Antipsychotics, ‘quines’, TCAs, SSRIs

Hepatotoxicity
Tetracyclines, sulfasalazine, carbamazepine, methotrexate, isoniazid, statins, fluconazole, alcohol

SV is an enzyme inhibitor
Increases concentration of - lamotrigine

36
Q

Lithium

Therapeutic range?

A
  1. 4 - 1 mmol/L (maintenance therapy, elderly)

0. 8 -1 mmol/L (acute mania, maintenance)

37
Q

Lithium

Monitoring?

A

Serum lithium - weekly and after each dose change until concentrations are stable, then every 3 months for the first yearly, then every 6 months
Take level 12 hours post dose

Monitor BMI, renal function (electrolytes and eGFR), and thyroid function every 6 months (or more often if concerned or raised calcium)

Assess renal , cardiac (ECG) and thyroid function before starting as well as BMI electrolytes and FBC

Additional monitoring should be carrie doubt in intercurrent illness or if there is a significant chance to diet or water consumption

38
Q

Lithium

Signs and symptoms of toxicity?

Hint: REVeNGe

A

REVeNGe

R - renal disturbances (polyuria, hypernatraemia)
E - extra pyramidal symptoms 
V - visual disturbances 
N - nervous system disturbances 
G - GI effects (D+V)

Serum concentration >2 mmol/L = serious overdose
Seizures, coma, renal failure, arrhythmia, BP changes, circulatory failure, death

39
Q

Lithium

Side effects?

A

Thyroid disorders - mainly hypothyroidism

Renal impairment - polyuria and polydipsia (lithium is nephrotoxic and renally cleared)

Benign intracranial hypertension - report headaches and visual disturbances

QT prolongation

Lowers seizure threshold

40
Q

Lithium

Counselling?

A

Always carry an alert card

Maintain a constant and adequate salt and water intake

OTC interactions - ibuprofen (decreases clearance), soluble analgesics (contain salt), antacids

Driving and skilled tasks - causes drowsiness, avoid alcohol

41
Q

Lithium

Interactions?

A

Increased risk of seizures (lowers seizure threshold)
Quinolones, SSRIs, epilepsy

QT prolongation (increases risk of arrhythmia)
Drugs that prolong QT
Drugs that cause hypokalaemia

Reduced renal excretion (increase risk of toxicity)
ACEi/ARBs, NSAIDs

HypOnatraemia (predisposes to toxicity)
Diuretics, antidepressants

Increased risk of EPS
Antipsychotics, metoclopramide (more at risk if pt has PD)

Drugs that affect salt balance (effervescent, antacids)

Increased risk of neurotoxicity
Antiepileptics (phenytoin and carbamazepine), antipsychotics, amitriptyline

Serotonin syndrome
5-HT1 agonists, SSRIs, 5-HT3 antagonists, MAOis, amfetamines, SJW, tramadol

42
Q

Theophylline

Therapeutic range?

A

10 - 20mg/L or 55 - 110micromol/L

Take level 4-6 hours post dose

Measure 5 days after starting and at least 3 days after a dose change

43
Q

Theophylline

Monitoring?

A

Must stay on the same brand

Plasma theophylline levels

44
Q

Theophylline

Signs and symptoms of toxicity?

A

FAST AND SICK

GI effects - vomiting, diarrhoea, gastric irritation
Tachycardia
CNS stimulation (restlessness, agitation, dilated pupils)
Hyperglycaemia

Serious side effects: convulsions, arrhythmias, hypOKalaemia

45
Q

Theophylline

Interactions (drug and disease)?

A

Increased risk of hypOKalaemia
Loop/thiazide diuretics, B2 agonists, steroids

Increased risk of convulsions
ciprofloxacin

Increased plasma conc
Enzyme inhibitors, HF, hepatic impairment, viral infection, elderly

Decreased plasma conc
Enzyme inducers, SMOKING and alcohol

Pre-reg (1 decks)

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