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Drug Formulary Y3 > Neurological Drugs > Flashcards

Neurological Drugs Flashcards

1
Q

Name 4 drugs dopaminergic drugs for Parkinson’s disease?

A
  1. Levodopa: as Co-Beneldopa
  2. Levodopa: as Co-Careldopa
  3. Ropinirole
  4. Pramipexol
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2
Q

Madopar is a combination drug used in the treatment of Parkinson’s disease (antiparkinsonian), what are the two active ingredients?

A
  1. Levodopa

2. Benserazide

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3
Q

Sinemet is another combination drug, as with madopar it is an antiparkinsonian agent, what are the two active ingredients?

A
  1. Levodopa
  2. Carbidopa
    - Co-careldopa
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4
Q

What is the important safety information to be aware of related to antiparkinsonian use? (madopar and sinemet).

A

Treatment with levodopa is associated with impulse control disorders, including pathological gambling, binge eating, and hypersexuality. Patients and their carers should be informed about the risk of impulse control disorders. If the patient develops an impulse control disorder, levodopa should be withdrawn or the dose reduced until the symptoms resolve.

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5
Q

What are the cautions associated with antiparkinsonian agents? (7)

A

People with:

  1. Cushing’s syndrome
  2. Diabetes
  3. Endocrine disorders
  4. History of convulsions
  5. History of MI with arrhythmias
  6. Osteomalacia
  7. Phaechromocytoma
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6
Q

What are the common side effects associated with antiparkinsoniam drugs? (21)

A
  1. Abnormal dreams
  2. Anorexia
  3. Anxiety
  4. Confusion/Dementia
  5. Depression
  6. Chorea
  7. Dizziness
  8. Drowsiness
  9. Dry mouth
  10. Dyskinesia
  11. Dystonia
  12. Euphoria
  13. Fatigue
  14. Insomnia
  15. Nausea
  16. Palpitations
  17. Postural hypotension
  18. Psychosis
  19. Syncope
  20. Taste disturbances
  21. Vomiting
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7
Q

What are the 3 specific indications for use of dopaminergic drugs for Parkinson’s disease?

A
  1. Early Parkinson’s disease
  2. Later Parkinson’s disease
  3. Secondary Parkinsonism
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8
Q

Which dopaminergic drugs are more commonly prescribed in early Parkinson’s disease? (2)

A
  1. Ropinirole

2. Pramipexol

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9
Q

Which drug is an integral part of management in later Parkinson’s disease?

A

Levodopa

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10
Q

What is secondary Parkinsonism?

A

Parkinsonian symptoms due to a cause other than idiopathic Parkinson’s disease

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11
Q

Briefly what is Parkinson’s disease and what is the mechanism of action of dopaminergic drugs?

A

In Parkinson’s disease, there is a deficiency of dopamine in the nigrostriatal pathway that links the substantia nigra in the midbrain to the corpus striatum in the basal ganglia. Via direct and indirect circuits, this causes the basal ganglia to exert greater inhibitory effects on the thalamus which, in turn, reduces excitatory input to the motor cortex. This generates the features of Parkinson’s disease, such as bradykinesia and rigidity.

Treatment seeks to increase dopaminergic stimulation to the striatum. It is not possible to give dopamine itself because it does not cross the blood-brain barrier. By contrast, levodopa (L-dopa) is a precursor of dopamine that can enter the brain via a membrane transporter. Ropinirole and pramipexol are relatively selective agonists for the D2-receptor, which predominates in the striatum.

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12
Q

What is the major problem with levodopa?

A

The ‘wearing off effect’, where the patient’s symptoms worsen towards the end of the dosage interval. This tends to get worse as duration of therapy increases. It can be partially overcome by increasing the dosage or frequency but this can generate the opposite effect: excessive and involuntary movements at the beginning of the dosage internal.

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13
Q

Why is levodopa always given in combination with another drug?

A

Levodopa is always given with a peripheral dopa-decarboxylase inhibitor (e.g. carbidopa) to reduce its conversion to dopamine outside the brain. This interaction reduces nausea and lowers the dose needed for therapeutic effect.

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14
Q

Which drugs should dopaminergic agents not be combined with?

A
  1. Antipsychotics
  2. Metoclopramide
    Their effects on dopamine receptors are contradictory.
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15
Q

What is the indication for use of phenytoin?

A
  1. Status epilepticus - to control seizures, where benzodiazepines are ineffective
  2. Epilepsy - to reduce the frequency of generalised or focal seizures (although drugs with fewer side effects are usually preferred).
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16
Q

What is the mechanism of action of phenytoin?

A

The mechanism is incompletely understood. Phenytoin reduces neuronal excitability and electrical conductance among brain cells, which inhibits the spread of seizure activity. It appears to do this by binding to neuronal Na+ channels in their inactive state, prolonging inactivity and preventing Na+ influx into the neurone. This prevents a drift in membrane potential from the resting (-70mV) to the threshold (-55mV) value required to trigger an action potential. A similar effect in cardiac Purkinje fibres may account for both antiarrhythmic and cardiotoxic effects of phenytoin.

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17
Q

What are the side effects associated with appearance, when using phenytoin?

A

Long-term phenytoin treatment can cause a change in appearance: skin coarsening, acne, hirsutism and gum hypertrophy.

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18
Q

What are the neurological side effects associated with taking phenytoin?

A

Dose-related neurological effects include cerebellar toxicity (e.g. nystagmus, ataxia and discoordination) and impaired cognition or consciousness.

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19
Q

What other side effects are associated with phenytoin use?

A
  1. Haematological disorders & osteomalacia - by inducing folic acid and vitamin D metabolism
  2. Hypersensitivity reactions
  3. Phenytoin toxicity –> cardiovascular collapse and respiratory depression
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20
Q

What is the warning associated with phenytoin use, in relation to therapeutic window and toxicity?

A

Phenytoin is metabolised by the liver with zero-order kinetics (at a constant rate irrespective of plasma concentrations) for concentrations at or above the therapeutic range. Moreover, the therapeutic index is low, implying that the safety margin between therapeutic and toxic doses is narrow.

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21
Q

When should the dose of phenytoin be reduced?

A
  1. In people with hepatic impairment
22
Q

Which patients taking phenytoin also need to take high doses of folic acid?

A

In female patients planning pregnancy.

23
Q

Phenytoin is an inducer of which enzyme?

A

Cytochrome P450

24
Q

As phenytoin is a cytochrome P450 inducer, what will its effect be on other drugs metabolised by P450 enzymes?

A

It will reduce plasma concentrations and efficacy of the drugs metabolised by P450 enzymes, e.g. warfarin, and oestrogens/progesterones.

25
Q

What else needs to be taken into consideration as phenytoin as well as being an inducer, is also metabolised by P450 enzymes?

A

Certain drugs - P450 enzyme inhibitors, will increase its adverse effects and plasma concentrations. (e.g. amiodarone, diltiazem and fluconazole).

26
Q

Which type of drugs reduce the efficacy of anti-epileptic drugs? (2)

A
  1. SSRIs & Tricyclic antidepressants

2. Tramadol

27
Q

What are the 3 indications for use of carbamazepine?

A
  1. Epilepsy - as a first choice treatment for focal seizures with and without secondary generalisation and for primary generalised seizures.
  2. Trigeminal neuralgia - as a first choice treatment to control pain and reduce frequency and severity of attacks.
  3. Bipolar disorder - as an option for prophylaxis in patients resistant to or intolerant of other medication
28
Q

What is the mechanism of action of carbamazepine?

A

It appears to inhibit sodium channels, stabilising resting membrane potentials and reducing neuronal excitability.

29
Q

How is carbamazepines mechanism of action useful in epilepsy?

A

As it reduces neuronal excitability, this may inhibit spread of seizure activity.

30
Q

How do carbamazepines help trigeminal neuralgia?

A

It controls neuralgic pain by blocking synaptic transmission in the trigeminal nucleus

31
Q

How do carbamazepines treat bipolar disorder?

A

They stabilise mood in bipolar disorder by reducing electrical kindling in the temporal lobe and limbic system.

32
Q

What are the indications for use of sodium valproate/valproic acid? (2)

A
  1. Epilepsy - first-line choice drug for the control of generalised or absence seizures and as a treatment option for focal seizures.
  2. Bipolar disorder - acute treatment of manic episodes and prophylaxis against recurrence.
33
Q

What is the mechanism of action of valproate?

A

It appears to be a weak inhibitor of neuronal sodium channels, stabilising resting membrane potentials and reducing neuronal excitability. It also increases the brain content of GABA, the principal inhibitory neurotransmitter, which regulates neuronal excitability.

34
Q

What side effects can valproate cause? (4)

A
  1. GI upset (nausea, gastric irritation and diarrhoea)
  2. Neurological and psychiatric effects (tremor, ataxia and behavioural disturbances)
  3. Thrombocytopenia
  4. Hypersensitivity reactions - hair loss…with subsequent regrowth being curly hair
35
Q

What are the rare but dangerous side effect that valproate can cause? (4)

A

Life-threatening idiosyncratic effects include:

  1. Severe liver injury
  2. Pancreatitis
  3. Bone marrow failure
  4. Antiepileptic hypersensitivity syndrome
36
Q

When should use of sodium valproate be avoided where possible? (1)

A

In women of child-bearing age, particularly around time of conception and in the first trimester of pregnancy.

37
Q

Why should sodium valproate be avoided in pregnancy?

A

It is the anti epileptic drug associated with greatest risk of fetal abnormalities, including neural tube defects, craniofacial, cardiac and limb abnormalities and developmental delay.

38
Q

When should sodium valproate be prescribed with caution or avoided? (2)

A

In patients with:

  1. Hepatic impairment
  2. Severe renal impairment.
39
Q

What are the important drug interactions to be aware of with valproate?

A

Valproate inhibits hepatic cytochrome P450 enzymes, increasing plasma concentration and toxicity of drugs metabolised by P450 enzymes, including for example warfarin and other anti epileptic drugs.

40
Q

What type of drug is lamotrigine?

A

Anti-convulsant

41
Q

What are the indications for use of lamotrigine? (2)

A
  1. Focal seizures

2. Bipolar disorder

42
Q

Which other drug is lamotrigine often used in combination with or as an adjunct therapy, for both bipolar disorder and focal seizures?

A

Valproate

43
Q

What common side effects are associated with lamotrigine use? (15)

A
  1. Blurred vision
  2. Aggression
  3. Agitation
  4. Arthralgia
  5. Ataxia
  6. Back pain
  7. Diarrhoea
  8. Diplopia/Nystagmus
  9. Dizziness/drowsiness
  10. Dry mouth
  11. Headache
  12. Insomnia
  13. Nausea/Vomiting
  14. Rash
  15. Tremor
44
Q

What are the two cautions/contraindications for using lamotrigine?

A
  1. Myoclonic seizures
  2. Parkinson’s disease
    It may exacerbate both of these
45
Q

There are many important drug interactions associated with lamotrigine use, they all have the same effect on the body, which is what?

A

CNS depressant effects

46
Q

Which drug has a severe interaction with lamotrigine, and what is the effect?

A

Desmopressin - increased risk of hyponatraemia

47
Q

What type of drug is levetiracetam?

A

An anti-convulsant (anti-epileptic)

48
Q

What are the 3 types of seizures that levetiracetam is indicated for use in treated?

A
  1. Focal seizures
  2. Myoclonic seizures
  3. Tonic-clonic seizures
49
Q

What are the common side effects associated with levetiracetam use? (…according to the BNF there’s fecking 21 of them).

A
  1. Abdominal pain
  2. Aggression
  3. Anorexia
  4. Anxiety
  5. Ataxia
  6. Convulsion
  7. Cough
  8. Depression
  9. Diarrhoea
  10. Dizziness
  11. Drowsiness
  12. Dyspepsia
  13. Headache
  14. Insomnia
  15. Irritability
  16. Malaise
  17. Nasopharyngitis
  18. Nausea/Vomiting
  19. Rash
  20. Tremor
  21. Vertigo
50
Q

Levetiracetam interacts with one drug in particular, what is it, and what is its effect?

A

Methotrexate - decreases the clearance of methotrexate from the body

51
Q

What are the cautions for use of levetiracetam? (3)

A
  1. Hepatic impairment
  2. History of psychosis/suicidal thoughts
  3. Women who are breastfeeding

Drug Formulary Y3 (9 decks)

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