Nervous System Flashcards
What are 3 examples of anxiolytics?
Diazepam
Lorezepam
Midazolam
How do anxiolytics work?
Increase GABA activity - inhibit neurotransmission
When can anxiolytics be used?
- Epilepsy
* Anxiety
What drug classes can be used for nausea and vomiting?
- H1 antagonists
- D2 antagonists
- 5HT3 antagonists
- Neurokinin-1 antagonists
Give an example of a H1 antagonist.
Cyclizine
Give an example of two D2 antagonists.
Domperidone
Metoclopramide
What is an example of a 5HT3 antagonist?
Ondansetron
What is the mechanism of action of ondansetron peripherally and centrally?
Peripherally - reduces GI motility and GI secretions
Centrally - inhibits the chemoreceptor trigger zone (CTZ)
Who is ondansetron good for?
Almost everyone - often 1st line treatment
What are some side effects of ondansetron?
Uncommon - constipation, headache, increased liver enzymes, prolonged QT interval, extra-pyramidal effects e.g. dystonia and parkinsonism
What is an example of a muscarinic antagonist used to treat nausea and vomiting?
Hyoscine hydrobromide
What is the mechanism of action of hyoscine hydrobromide?
Competitively block EACh receptors in the vestibular nuclei and at the CTZ
What are some side effects of the muscarinic antagonist hyoscine hydrobromide?
- Sedation
- Memory problems
- Glaucoma
- Dry mouth
- Constipation
(ACh receptors all over body, part of parasympathetic nervous system)
What are the common indications for hyoscine hydrobromide?
- Motion sickness
- Bowel obstruction
Good for those who can’t take tablets - available as patches
What is an example of a neurokinin-1 antagonist?
Aprepitant
What is the mechanism of action of aprepitant?
- Prevents substance P action at CTZ and in peripheral nerves
- Boosts effects of 5HT3 receptors antagonists
- Anxiolytic and antidepressant properties
What is aprepitant often used for?
- Chemotherapy (especially delayed emesis)
What are some side effects of aprepitant?
- Headache
- Diarrhoea/constipation
- Stevens-Johnson syndrome - rash
Give two examples of antipsychotic drugs.
- Chlorpromazine
* Haloperidol
What can chlorpromazine and haloperidol be used for aside being antipsychotics?
Can be used as anti-emetics
What is the mechanism of action of chlorpromazine and haloperidol?
D2 receptor antagonists (post synaptic D2 receptors)
Act on CTZ
What circumstances is haloperidol good and not good for?
Chemo and palliation (esp due to sedative action)
Not good if someone has Parkinson’s (Parkinsonism side effects)
What is chlorpromazine good for?
Motion sickness and vertigo
Give 9 examples of analgesics.
- Aspirin
- Paracetamol
- Buprenorphine
- Codeine
- Diamorphine
- Fentanyl
- Methadone
- Morphine
- Tramadol
What is the mechanism of aspirin as an analgesic?
Inhibits prostaglandin synthesis
What is the mechanism of action of paracetamol?
COX-2 inhibition in the spinal cord?
What do you give in paracetamol overdose?
N-acetylcysteine
What metabolite is it that builds up when you take paracetamol, that causes the overdose?
NAPQI - at normal doses, conjugates with glutathione, but hepatic glutathione is limited
What dose of paracetamol is sufficient to cause irreversible damage?
150mg/kg
What class of drugs are buprenorphine, codeine, diamorphine, fentanyl, methadone and tramadol?
Opioid receptor agonists
By which two mechanisms can people develop tolerance to opioids?
- Phosphorylation and uncoupling - phosphorylation modulates the neuroreceptors
- cAMP production - if you remove the opioid, there’s a rebound effect, increased cAMP production, increased excitability so withdrawal symptoms
Which three opioids are the strong agonists?
- Methadone
- Morphine
- Fentanyl
Which opioid is a moderate agonist?
Codeine
Which opioid is a mixed agonist/antagonist or partial agonist?
Buprenorphine
Which opioid is “other”?
Tramadol
Does fentanyl have more or less side effects than morphine? Why?
Less, due to less histamine release and less sedation and constipation
What should you prescribe alongside codeine?
A laxative
How is buprenorphine eliminated?
Mostly in the biliary system (over renally)
When is buprenorphine used?
- Moderate to severe pain
* Opioid addiction treatment
What are some of the side effects of buprenorphine?
- Respiratory depression
- Low BP
- Nausea
- Dizziness
How does buprenorphine work?
It’s a partial agonist, so has a low Kd and a high affinity for mu receptors
Not easily displaced, so harder to reverse an overdose with buprenorphine, but this isn’t as likely
How does N-aceytlcysteine work?
Glutathione donation (glutathione precursor), so glutathione can then bind to NAPQI
What is used to treat opioid overdose?
Naloxone
How does naloxone work?
It’s a opioid receptor antagonist (binds competitively)
Infusion rather than quick delivery, otherwise wears off quickly as has a short-half life
Name 3 antiepileptic drugs that work by blocking sodium channels.
- Carbamazepine
- Lamotrigine
- Phenytoin
What is an AED that increases GABA synthesis?
Sodium valproate
What is levetiracetam?
An AED, that possibly blocks presynaptic calcium activity
When is phenytoin used?
- Status epilepticus
* Adjunct in generalised seizures
What’s unique about phenytoin?
Zero order kinetics
What are specific side effects if phenytoin?
- Myelosuppression
- Hypotension
- Arrhythmias if given by IV
What drug is good for focal epilepsy?
Lamotrigine
Which AED is most safe in pregnancy?
Levetiracetam
Which 3 AEDs are CYP inducers?
- Phenytoin
- Carbamazepine
- Barbituates
Which AED is a CYP inhibitor?
Sodium valproate
What is the initial management of a seizure?
ABCDE, get help, start a clock
What is the pharmacological staging in status epilepticus?
- 0-5 mins - benzodiazepine
- 0-15 mins - second benzodiazepine dose
- 15-45 mins - Phenytoin or levetiracetam
- 45+ mins - Thiopentone/anaesthesia and support
(consider IV thiamine if with alcohol use)
What classes of drugs are used to treat Parkinson’s disease?
- Dopamine receptor agonists
- Monoamine oxidase (MAO) type B inhibitors
- Catechol-O-methyl transferase (COMT) inhibitors
- Anticholinergics
Give 6 examples dopamine receptor agonists.
- Amantadine
- Apomorphine
- Ropinirole
- Rotigotine
Pre-cursors of dopamine - Levodopa (L-DOPA)
- Co-careldopa
- Co-beneldopa
Give two examples of MAO type B inhibitors.
- Rasagiline
* Selegiline
Give an example of a COMT inhibitor.
Entacapone
Give two examples of anticholinergics used to treat Parkinson’s.
- Orphenadrine
* Procyclidine
Only when is apomorphine used?
In patients with severe motor fluctuations
What are the advantages and disadvantages of dopamine receptor agonists?
- direct acting
- less dyskinesia/motor complications
- some neuroprotection
- less efficient than L-DOPA
- lead to impulse control disorders
- more psychiatric side effects
- expensive
What are the ADRs of dopamine receptor agonists?
- Sedation
- Hallucinations
- Confusion
- Nausea
- Hypotension
What is the mechanism of action of MAO B inhibitors?
Prevent breakdown of dopamine
Why don’t you give COMT inhibitors alone?
No therapeutic effect alone - only act to increase the amount of dopamine present, by reducing it’s peripheral breakdown
Why can you use anticholinergics to treat Parkinson’s?
ACh may have antagonistic effects to dopamine
What are the ADRs of anticholinergics?
- Confusion
- Drowsiness
- Anticholinergic side effects - dry mouth, constipation, blurry visions, problems urinating (esp. an issue in the elderly)
What are two advantages of using anticholinergics to treat Parkinson’s? What is a disadvantage?
Doesn’t act on dopamine systems and treats the tremor
No effect on the bradykinesia
