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pre reg > Chapter 4: Nervous System > Flashcards

Chapter 4: Nervous System Flashcards

1
Q

What is dementia?

A

Dementia is caused when the brain is damaged by diseases such as Alzheimer’s, strokes or parkinson’s

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2
Q

Dementia cognitive symptoms ?

A
  • memory loss e.g. difficulty recalling
  • difficulties thinking e.g. concentration or problem solving
  • language e.g. cant find the right word
  • orientation e.g. losing track of the date
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3
Q

Dementia non-cognitive symptoms?

A
  • psychiatric and behavioural problems e.g. delusions or aggression
  • difficulties with daily activities
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4
Q

Management of mild-moderate alzheimers disease?

A

ACETYLCHOLINESTERASE INHIBITORS

  • donepezil (neuroleptic malignant syndrome; risk increased with concomitant antipsychotics)
  • galantamine (stop at first appearance of skin rash; serious skin reactions can occur e.g. SJS)
  • rivastigmine (use in parkinsons disease. GI disturbances: withold until resolved. Transdermal patches - less GI side effects)
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5
Q

Management of moderate-severe alzheimer’s disease?

A

NMDA GLUTAMATE RECEPTOR ANTAGONIST

- memantine (anticholinesterases are c/i in moderate/severe)

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6
Q

Cholingeric side effects: (parasympathomimetic)

A 
DUMB BELS
Diarrhoea
Urination
Muscle weakness, muscle cramps, miosis
Bronchospasm

Bradycardia
Emesis (vomiting)
Lacrimation (teary eyes)
Salivation/sweating

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7
Q

Management of non-cognitive dementia symptoms?

A

ANTIPSYCHOTIC DRUGS
- for severe non-cognitive symptoms causing significant distress or immediate risk of harm to self or others
MHRA ADVICE: clear increased risk of stroke and death when antipsychotics are used in elderly patients with dementia.
- carefully assess benefits and risk including any history of:
- stroke/TIA
- cerebrovascular disease risk factors: HT, diabetes, AF, smoking

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8
Q

Management of extreme violence, agression and extreme agitation?

A
  • Oral benzodiazepines or antipsychotic

If IM needed for behaviour control: haloperidol, olanzapine, lorazepam

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9
Q

Management of dementia with lewy body (parkinsons disease)?

A
  • acetylcholinesterase inhibitors i.e. rivastimine
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10
Q

What is epilepsy?

A

A sudden surge of electrical activity of neurons in the brain.

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11
Q

What are non-epileptic seizures?

A

Unrelated to abnormal electrical activity in the brain and are of 2 types:

  • organic: e.g. hypoglycaemia, fever
  • psychogenic (mental/emotional processes) e.g distressing thoughts
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12
Q

5 types of seizures ?

A
  • focal (partial) seizures with/without secondary generalisation
  • tonic-clonic seizures
  • absence seizures
  • myoclonic seizures
  • atonic/tonic seizures
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13
Q

Treatment for focal (partial) seizures with/without secondary generalisation?

A

FIRST LINE = lamotrigine or carbamazepine

Alternative = levetiracetam, valproate, oxcarbazepine

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14
Q

Treatment of tonic-clonic seizures?

A

FIRST LINE = Valproate or lamotrigine alternative

Also first line option = Carbamazepine

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15
Q

Absence seizures treatment?

A

FIRST LINE = ethosuximide or valproate (high risk of generalised tonic-clonic seizure)
Alternative = lamotrigine

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16
Q

Myoclonic seizures treatment?

A

FIRST LINE = Valproate

Alternative = topiramate, levetiracetam

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17
Q

Atonic/tonic seizures treatment?

A

FIRST LINE = valproate

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18
Q

Antiepileptic drug brands warning?

A

MHRA ADVICE: antiepileptic drugs: potential harm when switching between different manufacturer products for a particular drug in the treatment of epilepsy

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19
Q

Which antiepileptic drugs is it advised to maintain on same brand?

A

CATEGORY 1: carbamazepine, phenytoin, phenobarbital, primidone. Rx should include brand name OR generic name + manufacturer

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20
Q

Which antiepileptic drugs brand maintaining is based on clinical judgement and patient consultation?

A

CATEGORY 2: valproate, lamotrigine, clonazepam, topiramate

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21
Q

Which antiepileptic drugs do not need to maintain on same product?

A

CATEGORY 3: levetiracetam, gabapentin, pregabalin, ethosuximide

  • for category 2+3 also consider:
  • patient perceptions of differences in supply e.g taste or confusion
  • difficulties for co-morbid autism, mental health issues, or learning diability
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22
Q

Withdrawal of antiepileptics?

A
  • gradually reduce the dose under specialist supervision
  • avoid abrupt withdrawal; can precipitate severe rebound seizures
  • withdraw one antiepileptic drug at a time if on combination therapy
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23
Q

Epilepsy and the DVLA?

A

INFORM DVLA
- can drive car, NOT large goods or passenger carrying vehicle

1 year:

  • seizure free
  • established seizure pattern where no influence on consciousness
  • no history of unprovoked seizures
  • seizure due to prescribed change or withdrawal (earlier if treatment reinstated for 6 months and no further seizures)

Sleep seizures:

  • after each sleep seizure. Can drive IF:
    • history of no awake seizures for 1 year from first sleep seizure
    • established pattern of sleep seizures fro 3 years
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24
Q

When are you banned from driving with epilepsy?

A
  • during medication changes or withdrawal
  • 6 months after last dose
  • 6 months for first unprovoked epileptic seizure or single isolated seizure
    (5 year ban for large goods or passenger carrying)
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25
Q

Antiepileptics and pregnancy, which drugs increase risk of teratogenicity ?

A

HIGHEST RISK - valproate/valproic acid: minor and major congenital malformations & long term developmental disorders

INCREASED RISK - carbamazepine, phenytoin (antifolate), phenobarbital, primidone, lamotrigine

CLEFT PALATE: topiramate in first semester

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26
Q

What antiepileptic drug increases cleft palate risk in pregnancy?

A

Topiramate in first semester

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27
Q

Which antiepileptic drug reduces the efficacy of hormonal contraception?

A

ENZYME-INDUCING ANTI-EPILEPTICS e.g. carbamazepine

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28
Q

What drugs need dose adjustments based on plasma drug concentration in pregnancy?

A

Phenytoin, carbamazepine, lamotrigine

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29
Q

With which drugs do you need to monitor foetal growth in pregnancy?

A

Topiramate/levetiracetam

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30
Q

What to do when planning a pregnancy on antiepileptics?

A

options: withdrawal and resume after the 1st trimester OR monotherapy

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31
Q

What can be taken in pregnancy to reduce the risk of neural tube defect?

A

5mg folic acid daily, taken before conception until week 12 of the pregnancy

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32
Q

What minimises the risk of neonatal haemorrhage?

A

Vitamin K injection in newborn

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33
Q

Which drugs can cause withdrawal effects in newborns?

A

Especially benzodiazepines and phenobarbital

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34
Q

What needs to be monitored when breastfeeding on antiepileptics?

A
  • drowsiness
  • weight gain
  • feeding difficulty
  • adverse effect
  • developmental milestones
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35
Q

Which antiepileptic drugs are present in high amounts in breast milk?

A
  • zonisamide
  • ethosuximide
  • lamotrigine
  • primidone
    (ZELP)
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36
Q

Which antiepileptic drugs accumulate due to slower metabolism in infant?

A
  • phenobarbital

- lamotrigine

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37
Q

Which antiepileptic drugs inhibit infant’s sucking reflex in breastfeeding?

A
  • phenobarbital and primidone (largely converted to phenobarbital)
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38
Q

Which antiepileptic drugs have an established risk of drowsiness in babies breastfeeding?

A
  • benzodiazepines
  • phenobarbital
  • primidone
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39
Q

Which antiepileptic drugs should you avoid abrupt withdrawal of breastfeeding ?

A

Risk of withdrawal symptoms especially with phenobarbital/primidone

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40
Q

Antiepileptic drugs side effects?

A
  • anti-epileptic hypersensitivity syndrome
  • risk of suicidal behaviour and thoughts (can occur within 1 week report any mood changes/distressing thoughts)
  • skin rashes
  • blood dyscrasias
  • eye problems
  • encephalopathic symptoms
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41
Q

What is anti-epileptic hypersensitivity syndrome and what drugs are associated with it?

A
  • Rash, fever, lymphadenopathy and systemic involvement in first 1-8 weeks of starting; discontinue immediately.
  • Associated with certain antiepileptics drugs e.g. carbamazepine, phenytoin, phenobarbital, primidone and lamotrigine (CP3L)
  • Risk of cross-sensitivity between antiepileptic drugs: e.g. carbamazepine and phenytoin
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42
Q

Which antiepileptic drugs are associated with skin rash side effects?

A
  • lamotrigine; steven-johnson syndrome, toxic epidermal necrolysis
  • higher risk: high initial dose, rapid dose increase, with valproate
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43
Q

Which antiepileptic drugs are associated with blood dyscasias side effect?

A
  • carbamazepine, valproate, ethosuximide, topiramate, phenytoin, lamotrigine, zonisamide: C Vet Plz
  • counselling: report signs of infection, bruising or bleeding
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44
Q

Which antiepileptic drugs are associated with eye problems ?

A
  • vigabatrin: visual field defects
  • counselling: report new visual symptoms
  • topiramate: acute myopia with secondary angle-closure glaucoma. Also choroidal effusions and anterior displacement of lens and iris.
  • counselling: report signs of raised intra-ocular pressure
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45
Q

Which antiepileptic drugs are associated with encephalopathic symptoms ?

A
  • vigabatrin; marked sedation, stupor and confusion with non-specific slow wave EEG. withdraw or reduce dose
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46
Q

MHRA/CHM advice for gabapentin and resp depression?

A

gabapentin is associated with rare risk of severe respiratory depression even without concomitant opioid medications.

Patients at higher risk:

  • compromised resp function
  • respiratory disease or neurological disease
  • elderly
  • renal impairment (gabapentin is renally cleared)
  • concomitant use of CNS depressants e.g. benzodiazepines, opioids, hypnotics, barbiturates, antipsychotics, lithium, antidepressants, alcohol, antiepileptics
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47
Q

What antiepileptic drug is an enzyme inhibitor which leads to increased plasma concentrations?

A

Sodium valproate

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48
Q

Which antiepileptic drugs are enzyme inducers and result in decreased plasma concentrations?

A
  • carbamazepine
  • phenytoin
  • phenobarbital

Interacts with oral contraceptives and warfarin

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49
Q

Phenytoin MOA?

A

Binds to neuronal sodium channels in their inactive state; prolongs inactivity

HIGH RISK DRUG (NARROW THERAPEUTIC INDEX)

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50
Q

Phenytoin use (indication)?

A

Focal seizures and generalised tonic-clonic seizures. Exacerbates absence and myoclonic seizures - AVOID

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51
Q

What is the therapeutic range for phenytoin?

A

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

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52
Q

What is the relationship between phenytoin dose and plasma concentration?

A

Non-linear

- small changes in dose/missed doses/change in drug absorption = large changes in plasma concentration

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53
Q

Is phenytoin protein bound or not?

A
  • Highly protien-bound
    When protein-binding is reduced, monitor the plasma free-drug concentration: pregnancy, children (neonates < 3 months), elderly and liver failure. These pt groups can show early signs of toxicity.

Neonates <3 month have therapeutic range: 6-15mg/L or 25-60micromol/L

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54
Q

Signs and symptoms of phenytoin toxicity?(SNAtCHeD)

A

Slurred speech
Nystagmus (uncontrolled repetitive eye movements e.g eye rolling)
Ataxia (lack of voluntary co-ordination of muscle movement
Confusion
Hyperglycaemia
Diplopia (double vision), Blurred vision

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55
Q

Do you have to maintain on the same brand of phenytoin?

A

Yes - phenytoin is a risk category 1 antiepileptic drug, different oral formulations vary in bioavailability: phenytoin sodium is NOT bioaequivalent to phenytoin base

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56
Q

What is the dose conversion for phenytoin sodium to phenytoin base?

A

100mg phenytoin sodium = 92mg phenytoin base

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57
Q

Phenytoin side effects?

A
  • change in appearance: acne, hirsutism, gingival hypertrophy (maintain good oral hygeine)
  • blood dyscasias (phenytoin is also an antifolate): report signs of infection e.g. fever, sore throat, mouth ulcers, or unexplained bruising or bleeding. monitor FBC
  • hypersensitivity reaction: antiepileptic hypersensitivity syndrome. report fever, rash, swollen lymph nodes
  • rashes (skin disorders): report rashes, discontinue. If mild reintroduce cautiously but discontinue if recurrence
  • low vitamin D = ostomalacia and rickets (phenytoin induces vitamin D metabolism.
  • hepatotoxicity: discontinue stat and do not re-administer
  • suicidal ideation
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58
Q

Pre treatment screening for phenytoin: what patients have an increased risk of Steven-Johnson syndrome?

A

Han chinese and thai patients with HLA-B*1502 allele

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59
Q

Signs of liver toxicity?

A

Dark urine, nausea and vomiting, abdominal pain, itching, jaundice

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60
Q

Side effects of IV phenytoin?

A
  • bradycardia, hypotension
  • other common side effects: arrhythmias, cardiovascular collapse. respiratory arrest. If too rapid = CVS/CNS depression (monitoring ECG/BP) If bradycardia or hypotension occurs reduce administration rate
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61
Q

Side effects of IV infusion of fosphenytoin?

A

Severe cardiovascular reactions
- asystole, ventricular fibrillation, cardiac arrest, heart block, hypotension and bradycardia (monitoring: heart rate, BP, resp function during infusion and observe patient for 30 mins after infusion)
If hypotension occurs reduce infusion rate or discontinue

Fosphenytoin 1.5mg = phenytoin sodium 1mg
Fosphenytoin (prodrug of phenytoin) given IV and IM only, has less injection site reactions and can be given more rapidly with IV

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62
Q

Which drugs interact with phenytoin to increase phenytoin concentration (toxicity)?

A
  • amiodarone
  • cimetidine
  • miconazole
  • fluconazole
  • chloramphenicol
  • metronidazole
  • clarithromycin
  • fluoxetine
  • sertaline
  • diltiazem
  • valproate (enzyme inhibitors)
  • trimethoprim (also increased antifolate effect)
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63
Q

Which drugs interact with phenytoin to reduce phenytoin conc (therapeutic failure)?

A
  • St johns wort

- rifampicin (enzyme inducers)

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64
Q

Which drugs interact with phenytoin to antagonise anticonvulsant effects?

A
  • quinolones
  • tramadol
  • mefloquine
  • SSRIs
  • antipsychotics
  • TCA and related antidepressants (lowers seizure threshold)
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65
Q

What drugs interact with phenytoin to increase antifolate effect = increased risk of blood dyscasias ?

A
  • methotrexate

- trimethoprim

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66
Q

Phenytoin is an enzyme inducer, which drugs does it reduce the drug concentrations of ?

A
  • hormonal contraceptive/HRT (reduced efficacy)
  • warfarin (reduces anticoagulant effect)
  • corticosteroids
  • levothyroxine, liothyronine (increased risk of hypothyroidism)
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67
Q

Carbamazepine MOA?

A
  • inhibits neuronal sodium channels, stabilises membrane potential and reduces neuronal excitability

HIGH RISK NARROW THERAPEUTIC INDEX

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68
Q

Carbamazepine use (indication)?

A
  • First line in focal seizures, generalised tonic-clonic seizures
  • Exacerbates atonic, clonic and myoclonic seizures
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69
Q

Carbamazepine therapeutic range?

A

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

Plasma carbamazepine monitoring: measured after 1-2 weeks

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70
Q

Signs and symptoms of carbamazepine toxicity? iHANDBAG

A

ico-cordination

Hyponatraemia
Ataxia (lack of volutary co-ordination of muscle movement)
Nystagmus (uncontrolled repetitive eye movements e.g. eye rolling
Drowsiness
Blurred vision and diplopia (double vision)
Arrythmias
Gastro-intestinal disturbance (nausea, vomiting and diarrhoea)

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71
Q

Carbamazepine side effects?

A
  • blood dyscrasias e.g. leucopoenia, thrombocytopenia pt counselling: report signs of infection e.g. fever etc monitor FBC
  • hepatotoxicity, monitoring LFTS
  • hypersensitivity reactions: antiepileptic hypersensivitiy syndrome
  • rashes (avoid in HLAB*1502 as well as phenytoin)
  • hyponatraemia (in rare cases can lead to water intoxication)

MR Preparations can reduce risk of side effects

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72
Q

What carbamazepine side efects are dose-related and dose-limiting?

A
  • headache
  • ataxia
  • drowsiness
  • nausea
  • vomiting
  • blurred vision
  • unsteadiness
  • allergic skin reactions

more common at the start of treatment and in elderly patients

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73
Q

What drugs interact with carbamazepine to increase concentration (toxicity)?

A
  • cimetidine
  • macrolides
  • fluoxetine
  • miconazole
    (enzyme inhibitors)
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74
Q

Which drugs decrease carbamazepine concentration?

A
  • st johns wort
  • phenytoin
    (enzyme inducers)
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75
Q

Which drugs antagonise anticonvulsant effect when given with carbamazepine?

A
  • quinolones
  • mefloquine
  • SSRIs
  • antipsychotics
  • TCA and related antidepressants
    (lowers seizer threshold)
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76
Q

Which drugs increase the risk of hyponatraemia when given with carbamazepine?

A
  • aldosterone antagonists
  • SSRIs
  • TCAs
  • diuretics
  • NSAIDs e.g. naproxen
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77
Q

Which drugs increase the risk of hepatotoxicity when given with carbamazepine?

A
  • tetracyclines
  • sulfasalazine
  • sodium valproate
  • methotrexate
  • isoniazid
  • statins
  • fluconazole
  • alcohol
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78
Q

Carbamazpine is an enzyme inducer, reduces concentration of what drugs ?

A
  • warfarin (possible reduces anticoagulant effect)

- hormonal contraceptives/HRT (reduced efficacy)

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79
Q

Sodium valproate MOA?

A

Weak inhibitor of neuronal sodium channels, stabilises resting membrane potential and reduces neuronal excitability

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80
Q

Sodium valproate use?

A

First line in all types of generalised seizures

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81
Q

MHRA alert for sodium valproate in women and girls?

A

(most teratogenic antiepileptic)
: c/i in women and girls of childbearing potential unless in pregnancy prevention programme and only if not alternatives. c/i in pregnant women for bipolar disorder and only considered in epilepsy if no other alternative

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82
Q

What can be done to support patients on the PPP?

A
  • patient info card
  • annual specialist review
  • dispense as whole pack - warning labels and stickers
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83
Q

Sodium valproate side effects ?

A
  • hepatotoxicity (potentially fatal)
  • report signs of liver toxicity e.g. vomiting, abdominal pain, jaundice, malaise, drowsiness
  • LFTS - discontinue if abnormally prolonged prothrombin time
  • blood dyscasias e.g. leucopeonia, thrombocytopenia
  • report sign of infection e.g. fever, sore throat, mouth ulcers, or bruising/bleeding
  • pancreatitis
  • report abdominal pain, N+V
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84
Q

Which drugs cause an antagonised anticonvulsant effect when given with sodium valproate?

A
  • quinolones
  • mefloquine
  • SSRIs
  • antipsychotics
  • TCA and related antidepressants
    (lowers seizure threshold)
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85
Q

Which drugs increase the risk of hepatotoxicity when given with sodium valproate?

A
  • statins
  • carbamazepine
  • tetracyclines
  • fluconazole
  • isoniazid
  • itraconazole
  • methotrexate
  • sulfasalazine
    (hepatotoxic drugs)
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86
Q

Is valproate an enzyme inducer or inhibitor?

A

INHIBITOR; increases drug concentration

- e.g. of lamotrigine, phenobarbital

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87
Q

What is status epilepticus ?

A

Epileptic fits follow one after the other without regaining consciousness

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88
Q

What treatment is given for convulsive status epilepticus?

A

IV lorazepam

Avoid IV diazepam; causes thrombophlebitis

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89
Q

What treatment is given for non-convulsive status epilepticus?

A

If incomplete loss of awareness:
- continue or restart usual oral antiepileptic drug

If complete loss of awareness or failure to respond to oral antiepileptic drug:
- treat same as convulsive

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90
Q

What are febrile convulsions and what is used to treat?

A

Seizures that occur when a child has a high fever

- paracetamol (antipyretic) if >5 mins treat the same as status epilepticus

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91
Q

What is done if convulsive seizures or febrile seizures have been going on for longer than 5 mins?

A
  • diazepam rectal solution OR
  • midazolam oromucosal solution

repeated once after 10-15 mins if necessary

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92
Q

Anxiety psycohological symptoms?

A
  • restlessness
  • worry
  • fear
  • difficulty concentrating
  • irratbility
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93
Q

Anxiety physical symptoms?

A
  • palpitations
  • muscles aches and tension
  • trembling or shaking
  • excessive sweating
  • SOB
  • insomnia
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94
Q

Drugs used to treat anxiety ?

A

BENZODIAZEPINES (CD 4 part 1)

  • alprazolam (LA)
  • clobazam (LA, also adjunct in epilepsy)
  • chlordiazepoxide (LA, also adjunct in acute alcohol withdrawal)
  • diazepam (LA)
  • lorazepam (SA)
  • oxazepam (SA)
  • use SA in elderly, liver impairment but carries greater risk withdrawal symptoms

BETA-BLOCKERS

BUSPIRONE (5HT1a agonist)
low potential for abuse and dependence, takes 2 weeks to work

ANTIDEPRESSANTS

ANTIPSYCHOTICS

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95
Q

Benzodiazepines MOA?

A

Facilitates and enhances the binding of GABA to the GABAa receptor to cause widespread depressant effect on synaptic neurortransmission

  • clinical manifestations include anxiolysis, sedation, muscle relaxation and anticonvulsant effects
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96
Q

Benzodiazepine use?

A

Short term (2-4 weeks) relief of anxiety that is severe, disabling or causing patient unacceptable distress

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97
Q

Long acting benzodiazepines?

A
  • alprazolam
  • clobazam
  • chlordiazepoxide
  • diazepam
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98
Q

Short acting benzodiazepines?

A
  • lorazepam

- oxazepam

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99
Q

Benzodiazepine side effects?

A
  • paradoxical increase in hostility aggression: range from talkativeness and excitement to aggression and antisocial acts, increased anxiety and perceptual disorders also occur
  • sedation: careful driving/operating machinery, avoid alcohol
  • dependence: avoid long term use and avoid abrupt withdrawal
  • overdose: ataxia, drowsiness, dysarthria, nystagmus, resp depp/coma
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100
Q

What is benzodiazepine withdrawal syndrome?

A

Increased anxiety, insomnia, weight loss, tremors, sweating, loss of appetite, perceptual disorders, tinnitus

Occurs within a day of stopping a short acting benzo
Occurs within 3 weeks of stopping a long acting benzo

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101
Q

Steps for benzodiazepine withdrawal?

A
  1. gradually convert (over 1 week) to equivalent diazepam done ON
  2. reduce diazepam dose by 1-2mg increments every 2-4 weeks (up to 1/10th every 1-2 weeks for high doses)
  3. reduce diazepam dose further, can reduce in smaller steps of 500mcg towards the end
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102
Q

Which drugs cause increased sedation and CNS depressant effects when given with benzodiazepines?

A
  • alcohol
  • opioids
  • antihistamins
  • antidepressants
  • barbiturates
  • antipsychotics
    -z-drugs
    (sedating drugs)
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103
Q

Which drugs increase plasma concentrations of benzodiazepines?

A
  • amiodarone
  • diltiazem
  • macrolides
  • fluconazole
    (enzyme inhibitors)
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104
Q

ADHD symptoms?

A
  • hyperactivity
  • impulsivity
  • inattention
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105
Q

ADHD treatment in chidren 5+?

A

FIRST LINE: methylphenidate (concerta, medikinet, equasym)

SECOND LINE: Lisdexamfetamine (elvanse)

Alternative: atomoxetine guanfacine

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106
Q

ADHD adult treatment ?

A

FIRST LINE: Methylphenidate/lisdexamfetamine

Alternative: atomoxetine

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107
Q

Methylphenidate MOA?

A

Potent CNS stimulant; increases dopamine and noradrenaline levels in the brain

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108
Q

Methylphenidate side effects?

A
  • appetite loss, insomnia, weight loss
  • increased heart rate and BP
  • tics and tourettes
  • growth restriction in children (monitor height and weight)
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109
Q

Methylphenidate monitoring?

A
  • pulse, BP, appetite, weight and height on starting, dose change and every 6 months
  • psychiatric symptoms: e.g depression, psychosis and suicidal ideation
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110
Q

Methylphenidate contraindications?

A
  • CVD, hyperthyroidism, severe hypertension, uncontrolled bipolar disorder, severe depression
  • prescribe by brand for MR preparations
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111
Q

Dexamfetamine and lisdexamfetamine MOA?

A

Potent CNS stimulant; increases dopamine and noradrenaline levels in brain

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112
Q

Lisdexamfetamine side effects?

A
  • appetite loss, anorexia
  • increased heart rate and blood pressure
  • tics and tourettes
  • growth restriction in children
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113
Q

Signs of lisdexamfetamine overdose?

A
  • wakefulness
    -hyperactivity
  • paranoia
  • hallucinations
  • hypertension
    followed by
  • exhaustion
  • convulsions
  • hyperthermia and coma
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114
Q

Lisdexamfetamine monitoring?

A
  • pulse, BP, appetite, weight and height on starting, after dose change and every 6 months
  • psychiatric symptoms
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115
Q

Lisdexamfetamine c/is?

A
  • CVD, hyperthyroidism, moderate/severe hypertension, agitated states
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116
Q

Atomoxetine MOA?

A

Noradrenaline reuptake inhibitor causes increased levels of noradrenaline at synaptic cleft

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117
Q

Atomoxetine side effects?

A
  • suicidal ideation (report suicidal thoughts etc)
  • hepatotoxicity (report signs of liver toxicity)
  • QT prolongation (avoid concomitant drugs that also prolong QT interval
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118
Q

Atomoxetine monitoring?

A
  • pulse, BP, psychiatric symptoms, appetite, weight and height at start/dose change/every 6 months
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119
Q

How is Bipolar disorder characterised?

A

2 types of episodes:
1. Mania - feeling very high and overactive (less severe is called hypomania)

  1. Depression - very low and lethargic
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120
Q

What is used to treat acute episodes of mania and hypomania?

A
  • benzodiazepines - short term use (risk of dependence)
  • antipsychotics = Quetiapine, Olanzapine or Risperidone
  • lithium or valproic acid is added to antipsychotic if inadequate response.
  • asenapine (2nd gen) in moderate/severe manic episodes
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121
Q

What is used for the prophylaxis of bipolar disorder - 2 years?

A
  • lithium salts
  • valproate (valproic acid or sodium valproate)
  • olanzapine (if response in manic episode)
  • carbamazepine (rapid-cycling bipolar disorder unresponsive to other drugs
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122
Q

Contraindications in bipolar disorder?

A

Do not give antidepressants:

- rapid-cycling bipolar disorder, recent history of hypomania, manic episode, rapid mood fluctuations

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123
Q

Lithium salts MOA?

A

(high risk, narrow therapeutic window)

- MOA not fully understood

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124
Q

Lithium use?

A

Prophylaxis and treatment of mania, hypomania, and depression in bipolar disorder, resistant depression and aggressive or self-harming behaviour

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125
Q

Lithium therapeutic range ?

A
  • 0.4mmol/L to 1mmol/L (lower end of prophylactic treatment/elderly)
  • 0.8mmol/L to 1mmol/L for acute manic episodes, patients who have previously relapsed or have subsyndromal symptoms
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126
Q

Plasma lithium monitoring?

A
  • blood sampes taken 12 hours post dose
  • monitored every 3 months
  • additional monitoring if significant intercurrent illness or significant changes to diet or water intake

Avoid abrupt withdrawal

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127
Q

Signs and symptoms of lithium toxicity? (REVeNGe)

A
  • Renal disturbances: polyuria, hypernatraemia
  • Extrapyramidal symptoms: fine tremor increasing to coarse tremor, ataxia, dysarthria, myoclonus, nystagmus and muscle weakness
  • Visual disturbances e.g. blurred vision
  • Nervous system disturbances: confusion, drowsiness increasing to incoordination, restlessness and stupor
  • GI effects e.g. diarrhoea and vomiting

> 2mmol/L = renal failure, arrythmias, seizures, blood pressure changes, circulatory failure, coma and sudden death

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128
Q

Lithium side effects?

A

Mild cognitive/memory impairment, thyroid disorders with long term use

  • thyroid disorders (TFTs) hyper or hypo
  • renal impairment (monitor renal function) report polyuria/polydipsia
  • benign intracranial hypertension (report persistent headaches, visual disturbance)
  • QT prolongation (monitor cardiac function)
  • lowers seizure threshold
  • hyponatraemia predisposes to lithium toxicity
  • prescribe by brand
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129
Q

Lithium counselling points ?

A
  • report signs and symptoms of lithium toxicity
  • maintant constant adequate salt and water intake especially in intercurrent infection, diarrhoea or vomiting = dehydration
  • lithium treatment pack: alert card
  • driving and skilled tasks: lithium can cause drowsiness, avoid alcohol
  • OTC interactions e.g. ibuprofen, soluble analgesics, antacids
  • teratogenic: effective contraception - toxicity can occur in breastfeeding
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130
Q

Which drugs can cause an increased risk of seizures when given with lithium>?

A
  • ciprofloxacin (quinolones)
  • SSRIs
  • epilepsy
    (lowers seizure threshold)
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131
Q

Which drugs can cause QT prolongation (increased risk of arrhythmias) when given with lithium?

A 
(drugs that prolong QT interval)
- quinolones 
- citalopram (SSRI)
- clarithromycin (macrolides)
- amiodarone
- antipsychotics 
- imipramine (TCAs)
(drugs that cause hypokalaemia)
- theophylline
- corticosteroids
- B2 agonists
- loop/thiazide
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132
Q

Which drugs cause hyponatraemia (which predisposes to lithium toxicity)?

A
  • diuretics (loop thiazides, K+ sparing, aldosterone antagonists)
  • antidepressants (SSRI, TCAs)
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133
Q

Which drugs increase the risk of extrapyramidal symptoms when given with lithium?

A
  • haloperidol
  • clozapine
  • phenothiazines
    (antipsychotic drugs)
  • parkinsons
  • metoclopramide
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134
Q

Which drugs affect salt balance when given concomittantly with lithium?

A

OTC interactions: soluble/effervescent analgesics (high salt), sodium containing antacids

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135
Q

Which drugs increase the risk of neurotoxicity when given with lithium?

A
  • phenytoin
  • carbamazepine (antiepileptics)
  • antipsychotics
  • amitriptyline
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136
Q

Which drugs increase the risk of serotonin syndrome when given with lithium?

A
  • sumatriptan (5HT1a agonists)
  • citalopram (SSRIs)
  • granisetron
  • MAOIs
  • amfetamines
  • st johns wort
  • tramadol
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137
Q

Depression psychological/physical symptoms ?

A

PSYCHOLOGICAL

  • low self esteem
  • worry and anxiety
  • suicidal thoughts

PHYSICAL SYMPTOMS

  • lack of energy
  • changes in weight/appetite
  • insomnia: early morning wakeness
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138
Q

Antideppressant general MOA?

A

Depression is said to be caused by the underactivity of monoamine neurotransmitters. Antidepressants increase monoamine levels at synapse

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139
Q

Tricyclic antidepressants ?

A

(Raises 5-HT, NA)

  • amitriptylline (also used in neuropathic pain)
  • clomipramine
  • doselupin (dangerous in overdose - specialist use)
  • doxepin
  • imipramine (most antimuscarinic TCA)
  • lofepramine (hepatotoxicity)
  • nortriptylline (also used in neuropathic pain)
  • trimipramine

TCA related

  • mianserin
  • trazodone
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140
Q

SSRIs? (selective serotonin reuptake inhibitors)

A

(raises 5-HT)

  • citalopram (QT prolongation)
  • escitalopram (QT prolongation)
  • fluoxetine (only antidepressant given in children)
  • fluvoxamine
  • paroxetine (greater risk of withdrawal reactions)
  • sertraline (safe to use after MI/unstable angina)
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141
Q

Irreversible monoamine oxidase inhibitors?

A

(Raises 5-HT, NA, DA)

  • phenelzine (hepatotoxicity more likely)
  • isocarboxazid (hepatotoxicity more likely)
  • tranylcypromine (hypertensive crises more likely)
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142
Q

Reversible monoamine oxidase inhibitors ?

A
  • moclobemide ( no washout period needed; short acting)
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143
Q

Other antidepressant drugs?

A
  • agomelatine (hepatoxicity; give treatment booklet)
  • duloxetine (SNRI also used in diabetic neuropathy)
  • flupentixol (antipsychotic)
  • mirtazepine (blood dyscrasias)
  • reboxetine (NRI)
  • tryptophan
  • venlafaxine (SNRI; higher risk of withdrawal reaction)
  • vortioxetine
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144
Q

First line antidepressants?

A

SSRIs

  • better tolerated and safer in overdose than other classes
  • less sedating, antimuscarinic, epileptogenic, cardiotoxic than TCAs

MAOIs are rarely used; dangerous food and drug interactions.

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145
Q

How long to antidepressants take to work?

A

MINIMUM 2 weeks

  • initially feel worse; increased agitation, anxiety, and suicidal ideation
  • review every 1-2 weeks at start of treatment
  • wait at least 4 weeks (6 weeks in elderly) before deeming it ineffective
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146
Q

How long should you take antidepressants for?

A
  • continue for at least 6 months (12 in elderly) after remission
  • 12 months in generalised anxiety disorder (high risk of relapse)
  • 2 years in recurrent depression
147
Q

Next steps if first line antidepressant therapy is not responsive/not tolerated?

A

SECOND LINE

  • increase SSRI dose OR
  • different SSRI OR
  • mirtazepine

OTHER CHOICES:

  • lofepramine (TCA)
  • reboxetine
  • moclobemide (reversible MAOI)
  • Other TCAs/venlafaxine = more severe depression
  • irreversible MOAIs = specialist supervision
148
Q

Third line antidepressant therapy?

A
  • add another antidepressant class
  • OR augmenting agent e.g. lithium or antipsychotic
  • OR electroconvulsive therapy in severe refractory depression
149
Q

Antidepressant side effects?

A
  • hyponatraemia: drowsiness, confusion, convulsion (especially SSRIs and usually elderly)
  • suicidal ideation and behaviour: children/adults/history of suicidal behaviour at risk –> monitor especially at start
  • serotonin syndrome
    1. neuromuscular hyperactivity: tremors, myoclonus, muscle rigidity
    2. altered mental state: agitation, confusion and mania
    3. autonomic dysfunction: labile blood pressure, urination, diarrheoa, hyperthermia, tachycardia, pallor, sweating, shivering
150
Q

Switching between antidepressants ?

A

Washout period required when antidepressant is stopped before switching to different antidepressant class; avoid serotonin syndrome

151
Q

MAOIs washout period?

A

Wait 2 weeks before switching.

moclobemide (short acting/reversible) does not require washout period

152
Q

SSRI washout period?

A

Wait 1 week before switching

2 weeks if sertraline, 5 weeks if fluoxetine

153
Q

TCAs washout period?

A

Wait 1-2 weeks before switching

3 weeks if imipramine or clomipramine

154
Q

When can antidepressant withdrawal reactions occur?

A
  • within 5 days of stopping
  • risk of withrawal reactions is increased if: antidepressant stopped suddenly after taking for 8 weeks or more
  • reduce dose gradually over 4 weeks, or longer if withdrawal symptoms (6 months in patients on long-term maintanence treatment)
155
Q

Which antidepressants have a higher risk of withdrawal?

A

Paroxetine

Venlafaxine

156
Q

SSRI MOA?

A

Selectively inhibit the reuptake of 5-HT from synaptic cleft

157
Q

Which SSRI is safe in MI an unstable angina?

A

Sertraline

158
Q

Which SSRI is the only antidepressant licensed for children?

A

Fluoxetine

159
Q

Which SSRIs cause QT prolongation?

A

Citalopram/Escitalopram

160
Q

SSRI side effects?

A

SSRIs are less SEDATING, less ANTI-MUSCARINIC and less CARDIOTOXIC than TCAs

  • GI disturbances = nausea, vomiting, diarrhoea
  • Appetite or weight disturbance = gain or loss
  • Serotonin syndrome = triad of symptoms
  • Hypersensitivity reactions = stop if rashes occur
  • bleeding risk increased
  • QT prolongation (citalopram/escitalopram)
  • seizure threshold lowered
  • movement disorders and dyskinesia
161
Q

SSRI overdose symptoms?

A

Nausea, vomiting agitation, tremor, nystagmus, drowsiness, sinus tachycardia and convulsions

162
Q

What increases plasma concentrations of SSRIs?

A

grapefruit juice (enzyme inhibitor)

163
Q

Which drugs increase the risk of bleeding when given with SSRIs?

A
  • NSAIDs/Aspirin (GI bleeding)
  • Anticoagulants
  • Anti-platelets
164
Q

Which drugs increase the risk of QT prolongation when given with citalopram/escitalopram?

A
  • erythromicin (macrolides)
  • TCAs
  • sotalol
  • amiodarone (anti-arrhythmics)
  • chloroquine
  • mefloquine (anti-malarials)
  • lithium
  • quinine
  • antipsychotics
  • thophylline*
  • beta 2 agonists*
  • loop/thiazide diuretics*
  • corticosteroids*

*hypokalaemia increases risk of torsade de pointes

165
Q

Which drugs increase the risk of hyponatraemia when given with SSRIs?

A
  • diuretics e,g, loop/thiazide
  • desmopressin
  • carbamazepine
  • NSAIDs
  • PPIs e.g. omeprazole
166
Q

Which drugs increase the risk of serotonergic effects/ serotonin syndrome when given with SSRIs?

A
  • st johns wort (serotonergic herbal antidepressant)
  • amfetamines
  • sumatriptan (5-HT1a agonist)
  • selegiline (MAO-B inhibitor)
  • tramadol (opioid that also inhibits reuptake of 5-HT + NA)
  • TCAs/MAOI (serotonergic drugs)
  • ondasetron (5-HT3 antagonists)
167
Q

TCA and related antidepressant MOA?

A

Inhibits the reuptake of 5-HT and NA. Also blocks a wide array of receptors M, H1, alpha1/2 and D2

168
Q

TCA doses?

A

Once daily at night

169
Q

Sedating TCAs?

A

(give in anxious, agitated patients)

  • amitriptyline (also in neuropathic pain)
  • clomipramine
  • dosulepin (dangerous in overdose - specialist use)
  • doxepin
  • trimipramine
170
Q

Less sedating TCAs?

A

(give in withdrawn apathic patients)

  • imipramine (most antimuscarinic effects)
  • lofepramine (rarely causes hepatotoxicity)
  • nortriptylline (also used in neuropathic pain)
171
Q

Tetracyclic antidepressants?

A
  • trazodone
  • mianserin

(sedating, give in anxious agitated patients)

172
Q

TCA side effects?

A

More sedating, more epileptogenic, more cardiotoxic, more antimuscarinic
TCAS
More Toxic in overdose than SSRIs
Cardiac side effects = QT prolongation and arrhythmias, heart block, hypertensino
Antimuscarinic side effects = dry mouth, blurred vision, constipation, tachycardia, urinary retention, pupil dilation raised intra-ocular pressure, angle closure glaucoma
Seizures

Other: hallucinations, mania (increased 5-HT/NA), hypotension (alpha blockade), sexual dysfunction, breast changes, EPS (D blockade)

173
Q

Which drug reduces plasma concentrations when given with TCAs?

A

Carbamazepine (enzyme inducer)

174
Q

Which drug increases plasma concentrations of TCAs?

A

Cimetidine (enzyme inhibitors)

175
Q

Which drugs increase hyponatraemia risk when given with TCAs?

A
  • diuretics e.g. loop/thiazide
  • desmopressin
  • carbamazepine
176
Q

Which drugs increase the risk of QT prolongation when given with TCA (clomipramine)?

A
  • amiodarone
  • sotalol
  • antipsychotics
  • citalopram/escitalopram
  • loop/thiazide diuretics
  • b2 agonists
  • corticosteroids
  • theophylline
177
Q

Which drugs increase the risk of hypotension when given with TCAs?

A
  • Anti-hyperrtenisves
  • antipsychotics
  • levodopa/dopaminergics
  • NSAIDs
  • SGLT2 inhibitor (glifozin)
  • diuretic e.g. loop/thiazide
  • phosphodiesterase type 5 inhibitor e.g. sildenafil
178
Q

Which drugs increase antimuscaric effects when given with TCAs?

A
  • antimuscarinic drugs
  • antihistamines
  • atropine
  • antipsychotics
179
Q

Which drugs increase the risk of serotonin syndrome when given with TCAs?

A
  • MAOIs/selegiline (MAO-B inhibitor) (increase 5-HT/NA)
  • tramadol (works on adrenergic and serotonin pathway)
  • amfetamines, 5-HT1a agonists e.g. sumatriptan, SSRIs
  • 5-HT3 receptor antagonists e.g. ondansetron (increase 5-HT)
  • lithium (also neurotoxicity)
180
Q

Monoamine oxidase inhibitors MOA?

A

Blocks monoamine oxidase enzymes which leads to acculumation of monoamines: DA, NA, 5-HT

181
Q

MAOI use ?

A

Rarely used due to significant food/drug interactions

182
Q

Irreversible MOA-A and MAO-B inhibitors?

A
  • Phenelzine (hepatotoxicity more likely)
  • Isocarboxazid (hepatotoxicity more likely)
  • Tranylcypromine (greatest stimulant action)
183
Q

Reversible MOA-A inhibitors?

A
  • moclobemide (no washout period - short acting)
184
Q

MOA side effects?

A
  • hepatotoxicity (more likely with phenelzine and isocaboxazid)
  • postural hypotension/hypertensive responses (discontinue if palpitations or frequent headaches occur)
  • hypertensive crises (tranylcypromine; most stimulant action - discontinue if hypertensive crises with throbbing headaches occur)
185
Q

MOA interactions?

A

Hypertensive crises:

  • pseudoephedrine, adrenaline, noradrenaline (sympathomimetics)
  • levodopa, DRAs, MAO-B inhibitors (dopaminergic drugs)
  • TCAs (potentially lethal especially tranylcypromine and clomipramine)
186
Q

MOAi patient counselling points?

A
  • avoid food containing tyramine: mature cheese, wine, pickled herring, game, broad bean pods, meat stocks (bovril/oxo), marmite or similar, fermented soy bean products (miso)
  • eat only fresh food, avoid stale/going off
  • avoid alcohol, low alcohol drinks

*The dangers of food and drug interactions exist 2 weeks after stopping an irreversible MAOI

187
Q

What drug is used for the control of inappropriate sexual behaviour?

A

Benperidol

188
Q

What are the four dopamine pathways?

A
  1. Overactivity in mesolimbic pathway: POSITIVE SYMPTOMS
  2. Underactivity in mesocorticol pathway: NEGATIVE SYMPTOMS
  3. D2 antagonism in nigrostriatal pathway: EXTRAPYRAMIDAL SYMPTOMS
  4. D2 antagonism in tuberofundibular pathway: HYPERPROLACTINAEMIA
189
Q

Describe the 1st dopamine pathway

A

Overactivity in mesolimbic pathway: POSITIVE SYMPTOMS

  • hallucinations
  • delusions
  • disorganised speech/thoughts
190
Q

Describe the 2nd dopamine pathway?

A

Underactivity in mesocorticol pathway: NEGATIVE SYMPTOMS

  • social withdrawal
  • poor hygeine
  • apathy
  • calatonia
191
Q

Describe the 3rd dopamine pathway?

A

D2 antagonism in nigrostriatal pathway: EXTRAPYRAMIDAL SYMPTOMS

  • parkinsonism
  • tardive dyskinesia
  • akathisia
  • dystonia
  • dyskinesia
192
Q

Describe the 4th dopamine pathway?

A

D2 antagonism in tuberofundibular pathway: HYPERPROLACTINAEMIA

  • menstrual disturbances
  • galactorrhoea
  • breast enlargement
  • sexual dysfunction
193
Q

Advice of royal college of psychiatrists on doses of antipsychotic drugs above bnf upper limit ?

A
  1. Consider alternative e.g. adjuncts, newer or 2nd gen - clozapine
  2. Be aware of risk factors e.g. obesity, elderly
  3. Consider potential drug interactions
  4. ECG to exclude QT prolongation and other abnormalities, repeat periodically and reduce dose if QT interval prolonged/cardiac abnormality
  5. Increase the dose slowly and once weekly
  6. Regular pulse, BP and temperature checks; adequate fluid intake
  7. Consider high-dose therapy for limited period only and review regularly. Stop if there is no improvement after 3 months
194
Q

Important administration of antipsychotic drugs in psychotic episode ? - how to administer

A
  • IM route, IM dose lower than oral dose (avoids first pass effect in oral route), This is espcially in very active patients (increased blood flow)
  • Prescription should specify dose for each route
  • Review dose of antipsychotic at least daily
195
Q

Prescribing antipsychotics in the elderly ?

A
  • In elderly patients with dementia = small increased risk of death and increased risk of stroke/TIA
  • Susceptible to postural hypotension and hyper/hypothermia
  • Do not treat mild-moderate psychotic symptoms
  • Initial dose should be half adult dose; account for patient factors e.g. weight, concomitant meds and co-morbidites
  • review treatment regularly
196
Q

1st generation antipsychotics MOA?

A

Blocks post-synaptic dopamine d2 receptors in the brain

197
Q

Characteristics of the 1st generation antipsychotics?

A
  • More Extrapyramidal side effets (EPS)
  • more hyperprolactinaemia
  • Sedating
198
Q

Most sedating 1st gen antipsychotics ? (group 1)

A 
Phenothiazines (hepatotoxic and acute dystonic reactions)
GROUP 1
- chlorpromazine (contact sensitisation)
- levomepromazine 
- promazine (used as sedative OTC)
199
Q

Least EPS 1st gen antipsychotics (group 2)?

A
  • pericyazine
200
Q

Group 3 1st gen antipsychotics ? (most EPS)

A
  • fluphenazine
  • perphenazine
  • prochlorperazine
  • trifluoperazine
    (MOST EPS)
201
Q

What antipsychotics are butyrophenones?

A

Haloperidol (QT interval prolongation) (Most EPS)

202
Q

Which antipsychotics are the thioxanthenes ?

A
  • flupentol (alerting effect; should NOT take in the evening)
  • zuclopenthixol (depot prep used in agitated/aggressive patients and more effective in preventing relapse)
203
Q

Other antipsychotics?

A
  • pimozide (QT interval prolongation)
  • sulipride
  • loxapine (bronchospasms)
204
Q

Which antipsychotics have the most EPS?

A
  • fluphenazine
  • perphenazine
  • prochlorperazine
  • trifluoperazine
  • haloperidol
205
Q

Which antipsychotics prolong the QT interval?

A
  • haloperidol

- pimozide

206
Q

Which antopsychotic has an alerting effect and therefore should not be taken in the evening?

A

Flupentixol

207
Q

What antipsychotic causes contact sensitisation?

A

Chlorpromazine; avoid direct contact

208
Q

What antipsychotic is used as a sedative OTC?

A

Promazine

209
Q

2nd generation antipsychotics MOA?

A

Blocks post-synaptic Dopamine D1-D4 receptors and act on wide range of other receptors = distinct clinical side effects

210
Q

What characteristics are associated with 2nd gen antipsychotics?

A
  • reduced EPS
  • more metabolic side effects
  • may be more effective at treating negative symptoms
211
Q

List of 2nd gen antipsychotics? (8)

A
  • amisulpride
  • aripiprazole
  • clozapine
  • lurasidone
  • olanzapine
  • paliperidone
  • quetiapine
  • risperidone
212
Q

2nd gen antipsychotics that cause most hyperprolactinaemia?

A
  • amisulpride
  • risperidone
  • Also 1st gen cause hyperprolactinaemia e.g. haloperidol, phenothiazines, butyrophenones, thioxanthenes)
213
Q

Which 2nd gen antipsychotic causes the most weight gain and diabetes?

A
  • Olanzapine (most)

- Also clozapine

214
Q

Which 2nd gen antipsychotic is the most effective?

A
  • Clozapine
215
Q

Clozapine use?

A
  • licensed for resistant schizophrenia

: tried 2 or more drugs (including a 2nd gen) for at least 6-8 weeks each

216
Q

How long should you try clozapine for?

A
  • At least 8-10 weeks to assess effectiveness. If symptoms do not respond to an optimized dose, measure plasma clozapine levels before augmenting with 2nd antipsychotic drug
217
Q

What is a missed clozapine dose?

A

> 2 missed doses = re-initiate by specialist

218
Q

Clozapine drug interactions?

A
  • increased risk of agranulocytosis (blood dyscrasias)
    • aminosalicylates
    • immunosuppressants e.g. methotrexate, cytotoxic drugs
219
Q

Clozapine side effects?

A
  • myocarditis and cardiomyopathy
  • granulocytosis and neutropenia
  • GI obstruction (MHRA: reminder of potentially fatal risk of intestinal obstruction. faecal impaction and paralytic ilues.) Report constipation before taking next dose
220
Q

Monitoring for myocarditis and cardiomyopathy with clozapine?

A
  • Persistent tachycardia, especially in first 2 months = prompt observation
  • physical examination and full medical history before starting
  • stop permanently if myocarditis and cardiomyopathy occur
221
Q

Monitoring for granulocytosis and neutropenia with clozapine?

A
  • clozapine patient monitoring = leucocute and differential blood count every week for 18 weeks, then every 2 weeks for a year, then monhtly afterwards.
  • avoid drugs that depress leucopoiesis (chemotherpy drugs, azathioprine, sometimes NSAIDs)
  • counselling: report influenza-like illness
222
Q

Monitoring for GI obstruction in clozapine therapy?

A
  • intestinal peristalsis impaired = constipation, faecal impaction, paralytic ileus
  • take caution with constipating medication e.g hyoscine used to treat hypersalivation with clozapine.
  • actively recognise and treat constipation
223
Q

Antipsychotic depot preparations ?

A
  • Long acting administered every 1-4 weeks by IM injection
  • For maintenance therapy to aid compliance
  • give a test dose as undesirable effects are prolonged with depots
  • give oral antipsychotic whilst stabilising on depot
  • depot preparations typically end in “decanoate”
224
Q

Important safety information for IM haloperidol?

A

IM haloperidol decanoate is used for maintenance treatment

IM haloperidol is used for rapid control in acute episodes

225
Q

Schizophrenia monitoring ?

A

Physical health monitoing every year (including cardiovascular assessment

226
Q

Extrapyramidal side effects?

A
  • parkinsonism (tremors) - more common in adults and elderly
  • dystonia (abnormal face and body movement) and dyskinesia = more common in children and young adults. appears after a few doses
  • akathisia (inner restlessness) characteristically after large initial doses
  • tardive dyskinesia (rhythmic involuntary movements of tongue, face, jaw) most serioud manifestation; can be irreversible. most common in elderly. usually appears after long term treatment or high doses
  • stop at first sign: fine vermicular movements of tongue

OCCURS MOST FREQUENTLY WITH GROUP 3 PHENOTHIAZINES, BUTYROPHENONES AND 1ST GEN DEPOT PREP

227
Q

What is hyperprolactinaemia and what drugs cause it?

A
  • drugs that block d2 receptors STOPS the inhibition of prolactin, so prolactin release INCREASES (dopamine d2 antagonist drugs)
  • most likely with risperidone, amisulpride and 1st gen antipsychotics
  • breast symptoms = enlargement, pain, galactorrheoa
  • reduced bone mineral density
  • menstrual irregularities
  • sexual dysfunction = reduced libido
228
Q

Hyperprolactinaemia monitoring?

A
  • monitor prolactin levels at start, 6 months and then yearly
  • endocrine function in children: weight, height, sexual maturation, menstrual function
229
Q

Which is the only antipsychotic drug that does NOT cause hyperprolactinaemia?

A

Aripiprazole: partial dopamine agonist

230
Q

What are the metabolic side effects associated with antipsychotics ?

A
  • hyperglycaemia and sometimes diabetes: most with CiROQ = clozapine, risperidone, olanzapine, quetiapine
  • weight gain (olanzapine and clozapine)
  • lipid changes (dyslipidaemia)

More common with 2nd gen antipsychotics

231
Q

Which antipsychotics is sexual dysfunction most common with and why does it occur?

A

Haloperidol and risperidone

  • multiple mechanisms:
  • block D receptors = hyperprolactinaemia; low libido
  • block M receptors = arousal disorders
  • block alpha 1 receptors = erectile dysfunction and ejaculatory problems
232
Q

Which antipsychotics are more associated with caridovascular side effects and what are they?

A
  • tachycardia, arrhythmias, hypotension
  • QT interval prolongation: most risk: pimozide, haloperidol. Higher risk: IV antipsychotic and doses above maximum limit. Annual CVD risk assessment in patients
233
Q

Which antipsychotic drugs are associated with hypotension and interference with temperature regulation ?

A
  • postural hypotension = clozapine, chlorpromazine, lurasidone, quetiapine
  • elderly especially at risk of falls, hypothermia/hyperthermia (do not treat in elderly with mild/moderate symptoms and initial dose should be half the adult dose )
234
Q

What is neuroleptic malignant syndrome?

A
  • FATAL
  • antipsychotic side effects
  • muscle ridigity, fluctuating consciousness, hyperthermia and autonomic dysfunction with pallor, tachycardia, sweating, urinary incontinence, and labile blood pressure)
  • discontinue antipsychotic drug immediately
  • can treat with bromocriptine or dantrolene; dopamine receptor agonists
  • lasts 5-7 days after stopping but longer with depot
235
Q

Other antipsychotic side effects?

A
  • Antimuscarinic side effects: dry mouth, constipation, urinary retention, blurred vision. angle-closure glaucoma etc
  • blood dyscrasias: perform blood counts if unexplained infection or fever develops
  • photosensitivity (high doses): avoid direct sunlight
  • jaundice (including cholestatic)
  • sedation: driving can be impaired; effects of alcohol enhanced
236
Q

Other antipsychotic side effects?

A
  • Antimuscarinic side effects: dry mouth, constipation, urinary retention, blurred vision. angle-closure glaucoma etc
  • blood dyscrasias: perform blood counts if unexplained infection or fever develops
  • photosensitivity (high doses): avoid direct sunlight
  • jaundice (including cholestatic)
  • sedation: driving can be impaired; effects of alcohol enhanced
237
Q

Pimozide monitoring?

A
  • prolongs QT interval; cases of sudden death
  • ECG monitoring is recommended before treatment and yearly
  • if QT interval prolonged: stop or reduce dose
  • do not give concomitant drugs that prolong QT interval e.g. TCAs, antipsychotics, antiarrythmics
  • do not give concomitant drugs that cause electrolyte imbalance e.g. hypokalaemia with diuretics
238
Q

Phenothiazine antipsychotics side effects?

A
  • hepatotoxicity
  • acute dystonic reactions: facial and skeletal muscle spasms and oculogyric crises. At risk: children (especially girls and young women)
239
Q

Antipsychotic drug monitoring?

A
  • FBC (blood dyscrasias), urea/electrolytes, LFT (jaundice, hepatotoxicity with phenothiazines) at start and then annually
  • Blood lipids (dyslipidaemia), weight (gain) at baseline , 3 months then yearly
  • Fasting bloog glucose (insulin resistance, diabetes) at base line, 4-6 months and then yearly
  • ECG at start (QT/CVD side effects), particularly if patient has risk factors
  • Blood pressure (hypotension) before starting and frequently during dose titration of antipsychotic drugs
240
Q

Which drugs increase the risk of QT interval prolongation when given with antipsychotics?

A
  • amiodarone (anti-arrhythmics)
  • cirpofloxacin (quinolones)
  • macrolides
  • quinine
  • SSRIs
241
Q

Which drugs increase the risk of EPS with antipsychotics ?

A
  • metoclopramide (dopamine antagonist)

- parkinsons disease (levodopa)

242
Q

Which drugs increase the risk of sedation and CNS depressant effects when given with antipsychotics?

A
  • hypnotics (e.g. zopiclone)
  • benzodiazepines
  • opioids
  • antiepileptics
243
Q

Which drugs increase the risk of hypotension when given with antipsychotics ?

A
  • anti-hypertensives (e.g. beta-blockers/CCBs etc)
  • diuretics
  • nitrates
244
Q

Which drugs increase risk of antimuscarinic effects with antipsychotics?

A
  • TCAs
  • antihistamines
  • antimuscarinics (e.g. hyoscine)
245
Q

What drugs can be used for 4.1 dystonias and other involuntary movements?

A
  • promazine 25mg and 50mg licensed for short term adjunctive management of psychomotor agitation and agitation/restlessness in elderly (antipsychotic)
  • tetrbenazine 25mg for management of tardive dyskinesia (monoamine depleting drugs)
  • antimuscarinic drugs e.g. procyclidine hydrochloride, orphenadrine hydrochloride, trihexyphenidyl hydrochloride
246
Q

Describe parkinsons disease?

A

Progressive loss of dopaminergic neurones = dopamine deficiency in nigrostriatal pathway; regulated body movement

247
Q

Parkinsons symptoms ?

A
  1. Motor symptoms: hypokinesia, bradykinesia, rigidity, rest, tremor, postural instability
  2. Non-motor symptoms: dementia, depression, sleep disturbances, speech and language change, swallowing problems and weight loss

NOTIFY DVLA AND CAR INSURANCE

248
Q

Why shouldnt you abruptly withdraw Parkinsons treatment ?

A

actue akinesia and neuroleptic malignant syndrome

249
Q

What is used to treat nasuea and vomiting in parkinsons?

A

Domperidone (doesnt cross BBB, less likely to cause central nervous system side-effects)
NOT metoclopramide as this crosses the BBB

250
Q

Dopaminergic drugs?

A
  • levodopa
  • dopamine receptor agonists (mimics action of dopamine)
  • MAO-B inhibitors (prevents degradation of dopamine)
  • COMT inhibitors (prevents degradation of dopamine)
251
Q

What is first line in parkinsons with motor symptoms that decrease quality of life?

A
  • LEVODOPA (with carbidopa/benserazide)
252
Q

What is first line in parkinsons with motor symptoms that DO NOT affect quality of life?

A

Choices:

  • levodopa
  • non-ergot derived dopamine-receptor agonists
  • MAO-B inhibitors
253
Q

What is used as adjuvant therapy in dykinesia and motor fluctuations with levodopa ?

A

Choices:

  • non-ergot derived dopamine-receptor agonists
  • MAO-B inhibitors
  • COMT inhibitors
  • ergot-dervied dopmaine receptor agonists if inadequate response with non-ergot
  • amantadine (if dyskinesia not adequately managed by modifying therapy)
254
Q

What is used in advanced parkinsons disease ?

A

Apomorphine (SC intermittent injections/continuous infusion)

  • USE; refractory motor fluctuations “OFF” episodes
  • side effects:
  • nausea and vomiting: start domperidone 2 days before apomorphine treatment and disconinue ASAP
  • QT interval prolongation: domperidone and apomorphine both cause prolongation = serious risk of arrhythmias, asses cardiac risk factors

Levodopa-carbidopa intestinal gel (severe motor fluctuations)

Deep brain stimulation (only if symptoms not adequately controlled with the best drug treatment)

255
Q

Levodopa MOA?

A

Levodopa is the amino acid precursoe of dopamine and acts by replenishing depleted dopamine levels in the brain

  • overall improvement in motor performance is more noticeable with levodopa than with dopamine-receptors agonists (
256
Q

Levodopa drugs and characteristics?

A
  • co-careldopa (levodopa + carbidopa)
  • co-beneldopa (levodopa + benserazide)

Peripheral dopa-decarboxylase inhibitiors:
= less side effects: N+V, cardiovascular side effects
= lower dose required for therapeutic effect

  • take at specific times of day to avoid “OFF” periods
257
Q

Levodopa side effects?

A
  1. impulse control disorders (compulsive gambling, hypersexuality, binge eating, obsessive shopping)
  2. excessive sleepiness and sudden onset of sleep (warning: driving or operatine machinery)
  3. motor complications;
    dyskinesia = involuntary muscle movements
    response fluctuation = large variations in motor performance
    “ON” period = normal function
    “OFF” period = weakness and restricted mobility
  4. End-of-dose deterioration with shorter length of benefit: MR preps may help
258
Q

Dopamine receptor agonists MOA and characteristics?

A

Direct action on dopamine D2 receptors in striatum

- associated with more hallucinations, excessive sleepiness and impulse control disorders than with levodopa

259
Q

Which parkinsons drug is a first line option in patients with motor symptos that do not affect QOL OR as an adjunct to levodopa?

A

non-ergot derived dopamine receptor agonists

260
Q

Dopamine receptor agonists list?

A

Non-ergot derived:

  • pramipexole
  • ropinirole
  • rotigotine

Ergot-derived

  • bromocriptine
  • carbergoline
  • pergolide

Apomorphine (advanced)

Amantadine (weak dopamine receptor agonist)

261
Q

Ergot derived dopmaine receptor agonist side effect?

A

FIBROTIC REACTIONS

  • pulmonary (dysponea, persistent cough)
  • retroperitoneal (abdominal pain and tenderness)
  • pericardial (cardiac failure)
262
Q

Dopamine receptor agonist side effects?

A
  1. Impulse control disorders: compulsive gambling, hypersexuality, binge eating, obsessive shopping
  2. Excessive sleepiness and sudden onset of sleep: warning driving etc
  3. Psychotic symtpoms: e.g. hallucinations, delusions
  4. Hypotensive reaction in first few days: warning driving etc
263
Q

MAO-B inhibitors MOA?

A

Inhibits monoamine oxidase B enzymes which are responsible for the breakdown of monoamines; dopamine

  • used alone in parkinsons in patients with motor symptoms not effecting QOL OR as an adjunct to levodopa
264
Q

What is used alone in parkinsons in patients with motor symptoms not effecting QOL OR as an adjunct to levodopa?

A

MAO-B inhibitor

265
Q

MAO-B inhibitors?

A
  • rasagiline

- selegiline (metabolises to amfetamine; driving offence)

266
Q

MAO-B inhibitors interactions?

A

Hypertensive crises

  • psuedoephedrine, phenylephrine, xylometazoline, oxymetazoline (otc interations decongestants)
  • adrenaline, noradrenaline, methylphenidate, amphetamines, b2 agonists (drugs that increase blood pressure; sympathomimetics)
267
Q

COMT inhibitors MOA?

A

Prevents the peripheral breakdown of levodopa, by inhibiting catechol-O-methyltransferase, allowing more levodopa to reach brain.

  • catechol-O-methyltransferase is one of the enzymes that degrade catecholamines; domaine, adrenaline and noradrenaline.

Used as an adjunct to levodopa in “end-of-dose” motor fluctuations

268
Q

COMT inhibitors?

A
  • entacapone (colours urine reddish-brown)

- tolacapone (hepatotoxicity - report signs of liver toxicity)

269
Q

COMT inhibitors interactions?

A

Increased cardiovascular effects (sympathomimetics effects)

- adrenaline, noradrenaline, MOAIs e,g, trancylpromine (catecholamines)

270
Q

Nausea and labyrinth disorder causes?

A
  • drugs and toxic substances
  • labyrinthitis (inner ear infection)
  • vestibular disorders
  • motion sickness
  • gut irritation
  • higher stimuli (sights, smells, emotions)
271
Q

Why does nausea and vomiting occur?

A
  • N+V occurs when the vomiting centre inside the brain is activated by input from the chemoreceptor trigger zone (CTZ)
  • The chemoreceptor trigger zone is located in medulla oblongata of the brainstem and contains dopamine, serotonin, histamine and muscarinic receptors
272
Q

Nausea and labyrinth disorder treatment?

A
  • antiemetics work by antagonising the receptors in the CTZ

- antiemetics chosen according to the aetiology of vomiting

273
Q

Drugs used as antiemetics?

A

Dopamine antagonists: metoclopramide, domperiode Atipsychotics (+dopamine antagonists):
- prochlorperazine: buccal in migraine
- perphenazine, trifluoperazine, chlorpromazine (post op)
- haloperidol, levomepromazine (palliative)
- droperidol (post op)
Antihistamines:
- cinnarizine, cyclizine, promethazine (vertigo/motion sickness)
5-HT3 antagonists:
- granisetron, ondansetron, palonosetron (chemo or post op)
OTHERS:
- dexamethasone (cancer./chemo/post op)
- nabilone (synthetic cannabinoid; used in chemo)
- aprepitant fosaprepitant rolapitant (chemo)

274
Q

Vomiting during pregnancy?

A

Nausea in first trimester: mild; no drug treatment required

SEVERE VOMITING:

  • short term antihistamine e.g. promethazine
  • alternatives: prochloperazine or metoclopramide
  • if symptoms do not settle after 24-48 hours seek specialist
275
Q

Post-Op nausea and vomiting risk factors?

A

RISK FACTORS: anaesthetic used, type and duration of surgery, females, non-smokers, previous history, motion sickness, opioids use

276
Q

Post op antiemetic prevention?

A
  • 5-HT3 receptor antagonists. droperidol, dexamethasone, phenothiazine, antipsychotics e.g. prochlorperazine and antihistamine e,g, cyclizine
277
Q

What to do if high risk of post operative N+V?

A

combination of 2 or more antiemetics from different classes

278
Q

Metoclopramide MOA?

A

Antagonises d2 receptors in chemoreceptor trigger zone. Also acts directly on gut to promote gastric emptying; prokinetic effect

Useful in gastroduodenal, hepatic and biliary disease

279
Q

MHRA warning advice for metoclopramide?

A

Metoclopramide: risk of neurological adverse effects (crosses BBB) - restricted dose and duration of use

280
Q

Metoclopramide MAX use?

A

18+yrs: 5 days, 10mg TDS (max 500mcg/kg)

  • prevention of n+v: post op, radiotherapy induced, delayed chemotherapy induced
  • symptomatic treatment of n+v: e.g. acute migraine; also used to improve absorption or oral analgesics
281
Q

Metoclopramide side effects?

A

Acute dystonic reactions:

  • facial and skeletal muscle spasms and oculogyric crises
  • more common in young, especially girl and young women and in very old
  • procyclidine (anti-parkinsonian drug) aborts dystonic attacks
282
Q

Metoclopramide interactions?

A
  • Antipsychotics: increased EPS

- Parkinsons disease: exacerbates condition

283
Q

Domperidone MOA?

A

Antagonises d2 receptora in chemoreceptor trigger zone. Also acts directly on gut to promote gastric emptying; prokinetic effect

284
Q

MHRA warning for domperidone?

A

MHRA: risk of cardiac side effects: restricted indication, new contra-indications, reduced dose and duration

285
Q

Max use for domperidone?

A

1 week 10mg TDS (adult/12+ and over 35kg) - children under 35kg: 250mcg/kg TDS)

  • symptomatic relief of n+v
  • choice antiemetic in parkinsons (does not cause eps)
286
Q

Domperidone cardiac side effects?

A
  • QT prolongation, ventricular arrhythmias, sudden death

- counselling; report signs of arrthymias: syncope, palpitations

287
Q

Domperidone c/i’s?

A
  • impaired cardiac conduction
  • cardiac disease
  • severe liver impairment
288
Q

Domperidone interactions?

A
  • potent CYP3A4 inhibitor e,g, amiodarone, ketoconazole, erythromycin
  • drugs causing QT prolongation: e.g. amiodarone, SSRIs, quinolone
289
Q

5-HT3 receptors antagonists MOA?

A

Blocks 5-HT3 receptors in the chemoreceptor trigger zone and GI tract. 5-HT is a key neurotransmitter released by the gut in response to emetogenic stimuli

290
Q

5-HT3 receptor antagonists examples and use?

A
  • granisetron
  • ondansetron
  • palonosetron (prevention of n+v associated with moderate or highly emetogenc cytotoxic chemo)

USE:
- granisetron and ondansetron for symptomatic relief of post op n+v and chemo induced n+v

291
Q

5-HT3 receptor antagonist side effects?

A

QT interval prolongation

292
Q

5-HT3 receptor antagonist interactions?

A
  • Increased risk of torsade de pointes with hypokalaemia: loop/thiazide diuretics, corticosteroids, beta-agonist e.g. salbutamol, theophylline, stimulant laxatives abulse, amphoteracin B
  • Increased risk of QT interval prolongation: amiodarone, clarithromycin, quinine, sumatriptan, lithium, antipsychotic
  • Serotonin syndrome: 5-HT1a agonists e.g. sumatriptan, MAOIs, SSRIs
293
Q

What is Merniere’s disease and what is used to treat it?

A

Meniere’s disease is a disorder of the inner ear that can lead to dizzy spells (vertigo) and hearing loss. In most cases, Meniere’s disease affects only one ear. Meniere’s disease can occur at any age, but it usually starts between young and middle-aged adulthood.

BETAHISTINE

294
Q

Types of pain?

A
  1. Noiciceptive pain
    - musculoskeletal pain: non-opioids, especially NSAIDs
    - dental pain: find route cause. NSAIDs
    - moderate to severe visceral pain: OPIOIDS
    - period pain: oral contraceptives, antispasmodics, or non-opioids
    - pain in palliative care
  2. Neuropathic pain
    - tricyclic antidepressants: amitriptylline, nortriptylline
    - antiepileptics: gabapentin, pregabalin
    - nerve compression by tumour: dexamethasone
295
Q

WHO analgesic ladder?

A

STEP UP IF PAIN PERSISTS OR INCREASES

  1. MILD PAIN: non-opioids (paracetamol, aspirin, NSAIDs) +/- adjuvant
  2. MILD-MODERATE PAIN: weak opioids (codeine, dihydrocodeine, tramadol (moderate)) +/- non-opioid/adjuvant
  3. MODERATE-SEVERE PAIN: strong opioids (morphine, diamorphine, oxycodone, hydrpmorphine, methadone, transdermal buprenorphine/fentanyl) +/-non-opioid/adjuvant

ADJUVANTS:

  • neuropathic pain: amitriptylline, nortriptylline, gabapentin, pregabalin
  • bone metastases: bisphosphonates, strontium ranelate
  • nerve compression by tumour: dexamethasone
296
Q

Non-opioid analgesics ?

A
  • paracetamol
  • NSAIDs
  • aspirin
  • nefopam
297
Q

Paracetamol uses and dose?

A
  • mild-moderate pain and fever. does not have anti-inflammatory action
  • preferred in elderly (does not cause gastric irritation like aspirin/NSAIDs)
  • Adult dose: 0.5g-1g every 4-6 hours as required, max 4g a day
298
Q

What is used to treat paracetamol overdose?

A

Overdose = liver damage (higher risk of hepatotoxicity <50kg)
Symptoms: nausea, vomiting, right subcostal pain/tenderness

Treatment: acetylcysteine IV

299
Q

Aspirin (NSAID and antiplatelet) uses and doses?

A

As antiplatelet:

  • medical emergencies: ACS, stroke/TIA 300mg dispersible
  • 2nd prevention of thrombotic arterial events: 75mg daily for life

As NSAID:
- fever and pain e.g. headache, musculoskeletal pain, dysmenorrhea 300-900mg every 4-6 hours as required. Max 4g per day

*take with or after food

300
Q

Aspirin side effects?

A
  • gastric irritation: use e/c formulations - take with food (avoid e/c in medical emergencies for rapid relief)
  • tinnitus (high doses)
301
Q

Aspirin c/i’s?

A
  • under 16yrs; reyes syndrome. exceptions: use in kawasaki disease ot as an antiplatelet
  • salicylate or NSAID hypersensitivity e.g. bronchospasms, asthma attacks, rhinitis, uticaria, angioedema
302
Q

Aspirin interactions?

A
  • increased risk of bleeding: antiplatelet or antocoagulants e.g. warfarin (special hazard)
303
Q

NSAIDS

A

refer to chapter 10 muscoloskeletal system

304
Q

Opioid analgesics (high risk drug) MOA?

A

Acts on various opioid receptors located in the brain, spinal cord and other nervous tissue to relieve pain.

305
Q

What opioid is given during labour?

A

pethidine (CD2), if accumulates causes convulsions

306
Q

Breakthrough pain?

A

Rescue doses: 1/10th or 1/6th of total daily dose of strong opioid, every 2-4 hours as required. Immediate-release preparations e.g. oral morphine solution, oxycodone oral solution

307
Q

Opioid overdose symptoms and antidote?

A
  • coma, pinpoint pupils, resp depression
  • antidote = naloxone (opioid recepter antagonist), reverses respiratory depression; main life threatning effect of opioids (effects of buprenorphine only partially reversed)
  • can be prescribed without a prescription e.g to a friend/family member by drug treatment services for the purpose of saving a life or in emergency e.g. heroin overdose
308
Q

Opioid side effects?

A
  • dry mouth
  • n+v (frequently with morphine) - antiemetic at start of treatment; prokinetic drug e.g. metoclopramide
  • contstipation: faecal softener and peristaltic stimulant e.g. senna + lactulose
  • sedation; warn patients driving may be impaired
  • reduced concentration and confusion
  • euphoria, hallucinatinos (common with morphine)
  • physical dependence and tolerance: avoid abrupt withdrawals
  • respiratory depression
  • hypotension, pupil contstriction, muscle rigidity (larger doses)
  • long term use: hypogonadism e.g. reduced fertility, amenorrhea, erectile dysfuncton,, adrenal insufficiency and hyperalgesia *reduce dose or switch to different treatmemt
309
Q

What is associated with long term use of opioids?

A
  • hypogonadism e.g. reduced fertility, amenorrhea, erectile dysfunction
  • adrenal insufficiency
  • hyperalgesia - reduce dose or switch to different treatment; specialist
310
Q

Opioid c/is?

A
  • comatose patients: opioids cause neurological depression and sedation
  • risk of paralytic ileus: opioids reduce GI motility, caution: IBD
  • resp depression caution: respiratory diseases: avoid in asthma attacks and COPD
  • head injury or raised intracranial pressure: opiods intefere with pupillary responses vital for neurological assessment
311
Q

Opioid interactions?

A
  • Increased sedation: antidepressants, antihistamines, alcohol Z drugs, antipsychotics, antiepileptics, benzodiazepines (also cause resp depression)
  • Possible CNS excitation or depression (hypertension or hypotension) MAOIs (antidepressants)
312
Q

ORAL ROUTE MORPHINE

A
  • choice oral opioid for severe pain in palliative care
  • causes the most euphoria, n+v
  • dose: every 4 hours immediate release preps/ 12hrly or 24hrly for MR
  • max dose increments: 1/3 or 1/2 of TDD per 24hrs
  • equivalent parenteral dose (SC,IM,IV) half oral dose
  • morphine oral solutions: CD5; if over 13mg/5ml = CD2
313
Q

PARENTERAL ROUTE DIAMORPHINE (HEROIN)

A
  • preferred over morphine when administering parenterally; diamorphine is more soluble and smaller volumes can be injected in emaciated patients in palliative care
  • equivalent dose of diamorpgine: 1/3rd or oral morphine dose
  • less nausea and hypotension than morphine
314
Q

Oral morhine maximum dose increments?

A

1/3 or 1/2 of total daily dose per 24hr

315
Q

Oral morphine equivalent parenteral dose ?

A

HALF ORAL DOSE

316
Q

What makes an oral morphine solution a cd2?

A

if over 13mg/5ml cd2, under is cd5

317
Q

Equivalent oral morphine dosr to parenteral diamorphine?

A

diamorphine = 1/3rd of oral morphine dose

318
Q

Opioid transdermal route: buprenorphine

A

Buprenorphine (72hr, 96hr, 7 day patch): LONG ACTING

  • partial agonist ( has antagonistic properties) = precipitates withdrawal symptoms e.g. pain in opioid-dependent patients and those who have taken another opioid
  • its effects are only partially reversed by naloxone in opioid toxicity
  • available sublingually for opioid dependence
319
Q

Opioid Transdermal route: fentanyl

A

Fentanyl (72hr patch)

  • risk of fatal respiratory depression in opioid-naive patients not previously treated with strong opioid; only use if opioid tolerant
  • counseling: immediately remove patch in case of breathing difficulties, marked drowsiness, confusion, dizziness or impaired speech. Seek prompt medical attention (opioid overdode)
320
Q

When switching opioid dose due to hyperalgesia what do you reduce dose to?

A

reduce dose of new opioid by 1/4 to 1/2

321
Q

When is transdermal opoid route unsuitable?

A

In acute pain or rapidly changing pain

  • long time to steady state prevents rapid titration of dose
  • given when dose is stable
  • avoid exposure to external heat = increased absorption, more side effects and possible toxicity
  • avoid sauna/hot baths
322
Q

Transdermal patch general application?

A
  • apply to dru, non-irritated and non-hairy skin on upper torso or upper arm
  • rotate patch site after each use
323
Q

Weak opioid analgesics: codeine

A
  • Activates opioid receptors
  • use in mild-moderate pain: 30-60mg every 4 hours
  • codeine linctus in dry or painful cough
  • acute diarrhoea
324
Q

MHRA advice: codeine for analgesia: restricted use in children due to reports of morphine toxicity?

A
  • for acute moderate pain in children above 12yrs only if it cannot be relieved by other painkillers such as paracetamol or ibuprofen alone
  • children aged 12-18 years: Max 240mg daily for 3 days. Dosage: up to 4 times a day with no less than 6 hour intervals
  • not recommended in children with compromised breathing: severe cardiac or respiratory conditions, respiratory infections, multiple trauma or extensive procedures
325
Q

Codeine c/is?

A
  • ultra rapid metabolisers (CYP2D6) (morphine toxicity)
  • children under 18yrs who undergo removeal of tonsils or adenoids for treatment of obstructive sleep apnoea
  • breastfeeding: do not give codeine to breastfeeding mothers; passes to baby through milk
  • not recommended in 12-18yrs children with breathing problems
326
Q

Should you give codeine/dihydrocodeine IV?

A

NEVER - severe reaction similar to anaphylaxis

327
Q

Tramadol (moderate opiod) drug action and side effects?

A
  • also affects serotonergic and noradrenergic pathways; acting as a NA and 5-HT reuptake inhibitor

Side effects

  • increased risk of bleeding
  • lowers seizure threshold
  • psychiatric reactions
328
Q

Tramadol interactions?

A
  • lowers seizure threshold: SSRIs, TCAs, antiepileptics (effect antagonised)
  • increased serotenergic effect; risk of serotonin syndrome: SSRIs, TCAs, 5-HT1 agonists, MAOIs (seroternergic drugs)
  • Increased risk of bleeding: warfarin (enhances anticoagulant effect of coumarins)
329
Q

Migraine and its symptoms?

A

Moderate/severe headache felt as a throbbing pain on one side of the head

Symtpoms:

  • intense throbbing headache on one side
  • n+v
  • sensitivity to light or sound
  • AURA (temporary warning symptoms before migraine)
  • visual disturbances
  • numbness/pins and needles starting in one hand, moves up arm before effecting face
  • dizzy/off balance
  • difficulty speaking
329
Q

Migraine and its symptoms?

A

Moderate/severe headache felt as a throbbing pain on one side of the head

Symtpoms:

  • intense throbbing headache on one side
  • n+v
  • sensitivity to light or sound
  • AURA (temporary warning symptoms before migraine)
  • visual disturbances
  • numbness/pins and needles starting in one hand, moves up arm before effecting face
  • dizzy/off balance
  • difficulty speaking
330
Q

Migraine treatment?

A

5-HT1 receptor agonists (“triptan”)

  • almortriptan
  • eletriptan
  • frovatriptan
  • naratriptan
  • rizatriptan
  • sumatriptan (can also treat cluster headache)
  • zolmitriptan (can also treat cluster headache)
Ergot alkaolids (rarely used)
- ergotamine (do not repeat in less than 4 days, limited to twice a month)

NSAID
- tolfenamic acid (specifically licensed for acute migraine attack)

331
Q

Prophylaxis of migraine attack?

A
  • propranolol, atenolol, metoprolol, nadolol, timolol
  • antiepileptics (topiramate, sodium valproate, gabapentin)
  • TCAs, valproic acid
  • pizotifen (antihistamine serotonin receptor antagonist; limited value, causes weight gain)
  • used if suffer at least 2 attacks a month
  • increasing frequency of headaches
  • significant disability despite treatment for mirgaine attacks
  • cannot take suitable treatment for attacks
332
Q

Acute migraine attacks first line and steps?

A

FIRST LINE: simple analgesic (soluble/dispersible/effervescent)
SECOND LINE: 5-HT1 agonist e.g. sumatriptan, freuqent, prolonged attacks despite treatment: combine with NSAID

  • ergotamine = peripheral vaspspasm, rarely used, stop if numbness or tingling of extremeties occur
  • antiemetics: metoclopramide/domperidone - prokinetics
  • antihistamines e,g, buclizine, phenothiazines e.g. prochloperazine
333
Q

5-HT1 receptor agonist (triptans) MOA?

A

Acts on 5-HT1D and 5-HT1B present on cranial arteries and veins to cause vasoconstriction

334
Q

5-HT1 receptor agonist use/dose?

A

Treatment of acute migrain
- take one asap after onset, followed by a second dose at least 2 hours later (4 hours if naratriptan) if migraine recurs. Do not take a second dose for same attack

335
Q

5-HT1 receptor agonist side effects and c/is?

A

Side effects:
- coronary vasoconstriction or anaphylaxis

C/is:
- ischaemic heart disease, previous MI, coronary vasospasm, prinzmetals angina, uncontrolled or moderate-severe hypertension, peripheral vascular disease, previous stroke/TIA

Counselling: stop if intense tingling, heat, heaviness, pressure or tightness in any part of the body

336
Q

Cluster headaches?

A

Acute attacks: SC sumatriptan treatment of choice

- alternative: zolmitriptan nasal spray, 100% oxygen

337
Q

Porphylaxis for frequent cluser headache attacks lasting more than 3 weeks?

A
  • verapamil, lithium, prednisolone, ergotamine

* refer to BNF

338
Q

Drugs used for neuropathic pain?

A

TCAs

  • amitriptylline
  • nortriptylline

Antiepileptics

  • gabapentin
  • pregabalin

Opioid analgesics

  • if there is inadequate response to other drugs, opioids can be given
  • morphine and oxycodone prescribed by specialist only
  • tramadol prescribed in the meanwhile
339
Q

What can be used in compression neuropathy?

A

Corticosteroids

340
Q

What is trigeminal neuralgia and what is used to treat?

A
  • sudden and severe facial pain described as electric shocks in the jaw, teeth or gums. Occurs in short unpredictable attacks
  • treated with carbamazepine or phenytoin
341
Q

What is used in chronic oral and facial pain?

A

specialist referral

342
Q

What is used for localised pain?

A

Topical local anaesthetic or capsaicin cream

343
Q

Insomnia symptoms?

A
  • difficulty initiating/maintaining sleep

- early morning awaking, poor sleep quality

344
Q

Types of insomnia?

A
  1. transient insomnia:
    - causes: environmental factors such as noise, shift work, jet lag
    - choose short acting (raidly eliminated)
    - give only one or two doses
  2. Short term insomnia:
    - related to emotional problem or serious medical illness
    - insomnia may last a few weeks and may recur
    - take intermittently and omit some doses
    - give for no more than 3 weeks

3, Chronic insomnia:

  • common causes: psychiatric disorders e.g. anxiety and depression, alcohol/drug abuse, pain, dysponea and prutitus
  • treat underlying cause
345
Q

Drugs used in insomnia?

A

Z drugs (cd4 part 1): short acing hypnotics: short term use: hangover effects

  • zopiclone (taste disturbance)
  • zolpiem (GI disturbance, leave 8 hours before driving)
  • zaleplon

Benzodiazepines sedatives (cd4 part 1): short term use:

  • nitrazepam, flurazepam, diazepam (long acting hypnotics)
  • temazepam (cd3), lorazepam, loprazolam, lormetazepam, oxazepam (shorter acting hypnotics)

Avoid z drugs/benzodiazepines in elderly; ataxia and confusion = falls/injury

Other hypnotics

  • melatonin (pineal hormone in over 55yrs)
  • clomethiazole
  • chloral hydrate
  • antihistamines: promethazine
346
Q

Z drugs (cd4 part 1) MOA?

A

Act on benzodiazepine site of GABAa receptors to facilitate and enhance binding or GABA to GABAa receptors

347
Q

Z drugs use ?

A
  • short term use up to 4 weeks (2 weeks if zaleplon) for severe insomnia that interferes with daily life
348
Q

Z drugs side effects?

A
  • Paradoxical effects; paradoxical increase and hostility and aggression; talkitivensss, and excitement to aggression and antisocial acts. Also increased anxiety and perceptual disorders. Adjust dose up ot down can sometimes attenutate the impulses
  • daytime sleepiness: avoid alcohol, CNS depression enhanced
  • avoid long term use: dependence and withdrawal, also rebound insomnia, broken sleep with vivid dreams, avoid abrupt withdrawal.
  • tolerance develops in 3 - 14 days of continuous use: only take when needed
349
Q

Which z drug causes taste disturbances?

A

Zopiclone

350
Q

Which z drug causes GI disturbance and hangover effect?

A

zolpidem - leave 8 hours before driving

351
Q

What is narcolepsy ?

A

Rare long-term brain disorder that causes a person to suddenly fall asleep at inappropriate times

352
Q

How is narcolepsy treated?

A

CNS stimulants

  • modafinil (CD4)
  • methyphenidate (cd2)
  • dexamfetamine (cd2)
  • sodium oxybate (cd2)
  • pitolisant
353
Q

What is used to assist alcohol withdrawal?

A
  • chlordiazepoxide or diazepam
    primary care: fixed dose reducing regimen
    inpatient or residential setting: fixed dose or symptom triggered regimen

Alteranatives:

  • carbamazepine
  • clomethiazole (with alcohol = fatal resp dep)
354
Q

What is used for alcohol withdrawal seizures?

A

Lorazepam (fast acting benzodiazepines)

355
Q

What is used for delirum tremens?

A

First line: oral lorazepam

- persistent or if patient declines oral treatment: parenteral lorazepam or haloperidol

356
Q

What is used to treat alcohol dependence?

A
  • acamprosate or naltrexone

Alternative: disulfram (unpleasant systemic reaction to small amounts of alcohol = flushing, throbbing headache, palpitation, tachycardia, nausea, vomiting

357
Q

What is used in the reduction of alcohol consumption in patients without physical withrawal symptoms ?

A

Nalmefene: for patients with a high drinking risk level, who do not require immediate detoxification

358
Q

What is used for wernickes encephalopathy?

A

Wernicke encephalopathy (WE), also Wernicke’s encephalopathy, is the presence of neurological symptoms caused by biochemical lesions of the central nervous system after exhaustion of B-vitamin reserves, in particular thiamine (vitamin B1).
GIVE
- thiamine (vitamin b1)
- patients with alcohol dependence are at risk
- high risk: malnourished or decompensated liver disease

359
Q

What is used for nicotine dependence?

A

NRT

  • prolonged release preps: 16hr/24hr patches
  • used 24hr if strong craving for cigarettes on waking
  • immediate release prep: urge to smoke: gum/lozenge, nasal spray stc
  • Bupropion
  • Varenicline (selective nicotine receptor partial agonist)
    for patients with an expressed desire to stop smoking, given in conjunction with behavioural therapy
    MHRA: stop and see GP for agitation, depression and suicidal thoughts
360
Q

NRT side effects?

A
  • mild local reactions due to urritant effects of nicotine

- GI disturbances; nausea, vomiting, dyspepsia hiccup

361
Q

Opioid dependence?

A

Methaone/buprenorphine

362
Q

Methadone dose and side effects?

A
  • once daily
  • more sedating: long history of opioid misuse, increased anxiety during withdrawal, abuses sedative drugs/alcohol
  • long half life, accumulates = toxicity
  • increased risk of toxicity in non-dependent adults
  • side effects: QT interval prolongation
363
Q

Buprenorphine dose and side effects?`

A
  • dose once daily
  • less sedating: patient has a job or drives
  • safer when used with other sedating drugs amd less interactions
  • milder withdrawal reaction
  • lower risk of overdose
  • side effects (partial agonist): precipiptate withdrawal reaction: take first dose on withdrawal signs, take first dose 6-12 hours after heroin (24-48 hours after methadone

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