ABSTRACT
Select the drug from the list above that is most likely to be the cause of the effect below:
1 Tremor 2 ‘Cerebellar’ ataxia 3 Vestibular toxicity causing loss of balance 4 Proximal myopathy 5 Tenosynovitis
For each clinical scenario below, suggest the most appropriate therapy:
1 Acute migraine in a 20-year-old woman, which is unresponsive to paracetamol, ibuprofen and metoclopramide
2 A 40-year-old man with troublesome myoclonic jerks 3 A 70-year-old man with schizophrenia, who has developed
incapacitating tardive dyskinesia on his maintenance therapy of oral chlorpromazine
4 A 40-year-old man with endogenous depression 5 Severe disabling insomnia
156 DRUG-INDUCED MOVEMENT DISORDERS
DISORDERS AND DEMENTIA
Select the drug from the above list which is licensed for the indication below:
1 Idiopathic Parkinson’s disease 2 Hemifacial spasm 3 Myasthenia 4 Fluphenazine-induced dystonia 5 Alzheimer’s disease
158 ANALGESICS/PAIN
Link each of 1 to 5 below with the most appropriate item from A to J:
1 Mild analgesic suitable for children 2 Suitable for acute gout 3 Used by injection for patient-controlled self-administration 4 Overdose causes tinnitus 5 Can be administered as transdermal patch
ANSWERS: see pages 66-68
82 a) True Benzodiazepines, whilst being much safer than the b) True barbiturates, still have the problems of dependence, c) True potentiation of alcohol, respiratory depression in overdose d) True and suppressing REM sleep e) True
83 a) False – Buspirone is a non-benzodiazepine anxiolytic drug. It does not have marked hypnotic, anticonvulsant or muscle relaxant properties. It does not alleviate benzodiazepine withdrawal symptoms
b) True c) False – The full withdrawal picture usually appears after an
interval of 3-8 days d) True e) False – It is common practice to substitute shorter-acting with
longer-acting benzodiazepines (e.g. temazepam to diazepam) to assist withdrawal
84 a) False – Up to 50 hours, the active desmethyl metabolite has a halflife of 36-200 hours
b) True c) True d) False – Usually in combination with alcohol or other drugs e) True
85 a) True – 5-6 hours in comparison with 20-50 hours b) True – This combination is a cause of fatal overdose as well as
disinhibited behaviour which may lead to crime or road traffic accidents
c) False – Patients must be warned not to drive or operate heavy machinery if affected
d) False – Temazepam is a controlled drug e) False
86 a) False – Absorption is rapid with peak plasma levels being obtained at 60 minutes. Clomethiazole undergoes extensive first-pass metabolism so oral bioavailability is only approximately 15 per cent
b) False – The half-life is 50 minutes. The short half-life reduces the risk of hangover, ataxia and confusion the next day
c) True – This results from decreased first-pass metabolism
intravenous infusions. Constant rate infusions lead to accumulation
e) False – It potentiates the effects of alcohol although it may be used to treat acute alcohol withdrawal
87 a) False – Promethazine is an H1 antihistamine b) True c) True – Antimuscarinic effects d) True – May cause coma e) True
88 a) False Zopiclone is a non-benzodiazepine hypnotic which enhances b) False GABA activity. In addition to sedation adverse effects include c) False bitter, metallic taste, anorexia, nausea and vomiting, visual d) True hallucinations, amnesia, aggression and agitation e) True
89 a) True Occasionally drug-induced hallucinations/psychosis may b) False be mistaken for schizophrenia. The hypothesis that chronic c) True cannabis use and LSD can cause schizophrenia is unproven d) False e) True
90 a) True Prolonged use of D2 receptor blockers is associated with b) True the onset of tardive dyskinesia which may involve c) False structural brain damage and is often irreversible d) True e) False
91 a) True – Anticholinergic b) True – Anticholinergic c) True – Peripheral alpha-adrenoceptor blockade d) True – Hypothermia in cold weather, hyperthermia in hot weather e) True – Jaundice occurs in 0.5 per cent of patients taking
chlorpromazine. It is due to intrahepatic cholestasis and is a hypersensitivity phenomenon associated with eosinophilia
92 a) False – Antipsychotic drugs may cause maligant neuroleptic syndrome. This rare syndrome (hyperthermia, varying conscious level, rigidity and autonomic dysfunction) may be treated with dantrolene or bromocriptine
b) False – Volume of distribution is large, approximately 22 L/kg c) False – Metabolism predominantly by hepatic microsomes. Over
70 metabolites have been identified d) True e) True
b) decanoate are valuable in the management of c) True schizophrenia for maintenance therapy to ensure d) True compliance which is often poor in such patients e) True
94 a) True Clozapine is an ‘atypical antipsychotic’. The term is used b) True imprecisely but generally covers those antipsychotic drugs c) True whose principal pharmacological effect is not D2 blockade d) True and are rarely associated with extrapyramidal side-effects e) True – Neutropenia or agranulocytosis develops in up to 3 per
cent of patients taking clozapine for 1 year. Although dystonias and tardive dyskinesias are rare, clozapine is associated with fits in 3-4 per cent of patients and postural hypotension (particularly after the first dose)
95 a) False In comparison to the conventional antipsychotics where b) False potency is closely related to D2 receptor blockade, atypical c) False antipsychotics bind less tightly to D2 receptors and have d) True additional pharmacological activity which varies with the e) True drug. Efficacy against negative symptoms as well as fewer
extrapyramidal side-effects are characteristic. These may be the result of the transient (‘hit and run’) binding to D2 receptors. May also block D4 and 5HT2 receptors
96 a) True Tricyclic drugs of the amitriptyline type raise synaptic b) True stores of NA and 5HT and are antidepressant. MAO c) True inhibitors which increase total brain NA and 5HT are also d) True antidepressant. Amphetamine and cocaine raise synaptic e) True NA and alter mood but are not antidepressant
97 a) True See Textbook of Clinical Pharmacology and Therapeutics, b) True Chapter 20. Although clinical experience is most c) True extensive with the tricyclic antidepressants, the side-effect d) True profile of selective serotonin reuptake inhibitors (SSRIs) is e) True usually less troublesome and these drugs are safer in
overdose
98 a) True The less sedative tricyclic and related antidepressants b) True include desipramine, imipramine, lofepramine and c) False nortriptyline. Protriptyline is a stimulant. The more d) False sedative drugs are preferred for agitated and anxious e) False patients, whilst the less sedative are preferred in
withdrawn patients. Citalopram, paroxetine and sertraline are SSRIs. SSRIs are less sedating than most tricyclic antidepressants. Insomnia occurs in some patients on SSRIs
b) Patients may die from cardiac dysrhythmias, convulsions or c) True direct CNS depression leading to respiratory arrest/ d) True asphyxia. See Textbook of Clinical Pharmacology and e) True Therapeutics, Chapter 54
100 a) True Amitriptyline is a sedative tricyclic antidepressant which is b) True usually administered as a single nocte dose c) False d) True e) True
101 a) False – Fluvoxamine is an SSRI b) False c) True d) True – Fluvoxamine inhibits CYP1A2 and therefore decreases the
metabolism of theophylline and warfarin. Both these drugs have a narrow therapeutic index hence their concomitant administration with fluvoxamine should be avoided if possible
e) False
102 a) False Fluoxetine is an SSRI. It is safer in overdose and causes b) False fewer antimuscarinic side-effects than the tricyclic c) True antidepressants. The most common adverse effects related d) True to SSRIs are nausea, dyspepsia, diarrhoea, dry mouth, e) False headache, insomnia and dizziness. Sweating, erectile
dysfunction and delayed orgasm are well-recognized associations
103 a) False Phenelzine (and isocarboxazid and tranylcypromine) are b) False irreversible non-selective MAO inhibitors c) False d) True e) True – Adrenaline is metabolized by catechol-O-methyltransferase
104 a) True – Moclobemide is a reversible, competitive, selective MAO-A inhibitor
b) False – Selegiline, an MAO-B inhibitor, is used in Parkinson’s disease c) False d) False – No anticholinergic action (cf. tricyclic antidepressants) e) True
105 a) True Patients on MAO inhibitors should be given a treatment b) True card which lists necessary precautions. Interactions with c) True foodstuffs, many proprietary preparations and prescribed d) True drugs may cause a hypertensive crisis. Phenotolamine e) True and/or labetalol are effective treatment for such a reaction
b) concentrations may rise insidiously and once adverse c) True effects such as tremor, ataxia, dysarthria and nystagmus d) True develop treatment must be stopped whilst the serum e) False lithium (avoid lithium heparin tubes to collect plasma) is
measured urgently
107 a) False – Selective serotonin reuptake inhibitor b) True – Irreversible non-selective MAO inhibitor c) True – Irreversible non-selective MAO inhibitor d) False – Reversible selective MAO inhibitor e) False – St John’s wort is a herbal remedy which is popular for self-
treatment of depression. It is a potent CYP450 enzyme inducer
108 a) True Muscarinic antagonists are effective in the treatment of b) False parkinsonian tremor and to a lesser extent rigidity. They c) False have minimal effects on bradykinesia. Although more d) False commonly prescribed to counteract antipsychotic druge) True induced parkinsonism they may be used alone in
idiopathic parkinsonism and postencephalitic parkinsonism if tremor is the predominant symptom
109 a) True Parkinsonism arises because of deficient dopaminergic b) True transmission. Bromocriptine and apomorphine are c) True dopamine receptor agonists. Acetylcholine is antagonistic d) False to dopamine within the striatum e) False
110 a) True Levodopa (unlike dopamine) can enter nerve terminals in b) False the basal ganglia where it undergoes decarboxylation to c) False form dopamine d) True – Entacapone is a catechol-O-methyltransferase inhibitor e) True
111 a) True The dose of levodopa is titrated upwards, balancing b) True efficacy against adverse effects. Nausea and vomiting are c) False reduced by the addition of a dopa decarboxylase inhibitor d) False and taking the drug after food e) True
112 a) False Bromocriptine may be used as an initial treatment in b) True Parkinson’s disease, particularly in younger patients c) False (70 years) or as an adjunct with levodopa-dopa d) False decarboxylase combinations in patients with severe motor e) True fluctuations. There is great inter-individual variation in its
efficacy. Ropinirole is another dopamine D2 receptor agonist
b) progression in idiopathic Parkinson’s disease. It usually c) False allows dose reduction and prolongs the duration of action of d) False levodopa. Oral selegiline is well absorbed (100 per cent) and e) False extensively metabolized in the liver. Rarely hypertension has
been reported. Amantadine (which stimulates release of endogenous dopamine) potentiates its anti-Parkinson effects
114 a) False Donepezil is used for Alzheimer’s disease. Riluzole is used b) False in motor neuron disease. Treatment of spasticity is seldom c) True very effective, but physiotherapy or limited surgical release d) True procedures have some place. The drugs used to reduce e) True spasticity have considerable limitations. Diazepam is
sedative, baclofen is less sedative at equi-effective doses but can cause vertigo, nausea and hypotension. Intrathecal baclofen is currently being evaluated. Dantrolene is less useful for spasticity as it markedly reduces muscle power. It is used in the management of neuroleptic malignant syndrome and malignant hyperthermia
115 a) True Tardive dyskinesia is thought to result from the b) True development of ‘denervation hypersensitivity’ in c) True dopaminergic postsynaptic receptors of the nigrostriatal d) False pathway following chronic receptor blockade by e) False neuroleptics. It is therefore due to a relative preponderance of
dopaminergic effects. Botulinum toxin A is one of the neurotoxins produced by Clostridium botulinum and is used to treat blepharospasm, certain other dystonias and dynamic equinus foot deformities due to spasticity in ambulant paediatric cerebral palsy patients. It blocks the release of acetylcholine at the neuromuscular junction and is given by local intramuscular injection. This is a specialist field!
