Nervous System Flashcards
Paracetamol - Indications
1) Acute and Chronic pain
2) Antipyretic
Paracetamol - MOA
- Poorly understood
- Weak inhibitor of cyclo-oxygenase (COX) : enzyme involved in prostaglandin metabolism
- COX inhibition, increase pain threshold and reduce prostaglandin concentration s in thermoregulation pathway –> controlling fever
Paracetamol - Side Effects
Few SE
Overdose : causes liver failure
Paracetamol - Contraindication
None
Paracetamol - Caution
- Chronic excessive alcohol use
- Liver toxicity, Hepatic impairment
Paracetamol - Interactions
CYP inducers - increase risk of liver toxicity after overdose
Paracetamol - Max dose
4g / day
Weak/ Moderate Opioids - Examples
Tramadol
Codeine
Dihydrocodeine
Weak/ Moderate Opioids - Indication
1) Mild - to - Moderate pain
- -> 2nd line
Weak/ Moderate Opioids - MOA
They are metabolised by the liver to produce small amounts of morphine.
- These are agonists of opioid µ (mu) receptors. Thus have an analgesic effect
Weak/ Moderate Opioids - Side Effects
- Nausea
- Constipation
- dizziness
- drowsiness
- Neurological and respiratory depression in overdose
Weak/ Moderate Opioids - Contraindications
- Avoided in epilepsy and controlled epilepsy
Weak/ Moderate Opioids - Caution
- Respiratory disease
- Reduced dose in renal and hepatic impairment + elderly
Weak/ Moderate Opioids - Interactions
-Should not be used with other sedating drugs : antipsychotic, benzodiazepine, tricyclic antidepressants
Weak/ Moderate Opioids - Patient education
Avoid driving or operating heavy machinery if they become drowsy or confused
Strong Opioids - Examples
- Morphine
- Oxycodone
Strong Opioids - Indications
1) Rapid relief of acute sever pain
2) Relief of chronic pain
3) Relief of SOB in end-of-life care & acute pulmonary oedema
Strong Opioids - MOA
- The therapeutic action of opioids arises from activation of opioid µ receptors in the central nervous system (CNS).
- Activation of these G protein-coupled receptors has several effects that, overall, reduce neuronal excitability and pain
Strong Opioids - Side Effects
- Euphoria & detachment
- Nausea & vomiting
- Constipation
- Itching, urticaria, sweating
- Tolerance & dependence
Strong Opioids - Contraindications
- Respiratory Failure
- Biliary colic
Strong Opioids - Caution
- Hepatic + Liver Failure
- Elderly
Strong Opioids - Interactions
- Should not be used with other sedating drugs (e.g. antipsychotics, benzodiazepines & tricyclic antidepressants)
Carbamazepine - Indications
1) Epilepsy = seizure prophylaxis
2) Trigeminal neuralgia –> 1st line
Carbamazepine - MOA
- Inhibits neuronal sodium channels.
- This stabilises RMP and reduces neuronal excitability
Carbamazepine - Side Effects
- GI Upset : N & V
- Neuro effects : dizziness & ataxia
- Carbamazepine hypersensitivity
- Oedema + Hyponatraemia
Carbamazepine - Contraindications
- Prior antiepileptic hypersensitivity syndrome
Carbamazepine - Caution
Hepatic + renal or cardiac disease –> due to increased toxicity
Carbamazepine - Interactions
- Carbamazepine induces CYP enzyme which reduces plasma conc and efficacy of drugs that are metabolised by CYP enzymes (e.g. warfarin + oestrogen)
- CYP inhibitors : increased conc and adverse effects as carbamazepine is metabolised by CYP enzymes.
Carbamazepine - Patient Education
- Started at low dose (100-200mg) and then increased as tolerance to SE develops.
Valproate - Examples
Sodium valproate
Valproic acid
Valproate - Indications
1) Epilepsy - seizure prophylaxis
2) Certain cases of established convulsive status epilepticus
3) Bipolar disorder
Valproate - MOA
- Weak inhibitor of neuronal sodium channels, stabilising RMP and reducing neuronal excitability
Valproate - Side Effects
Common:
- GI upset : Nausea, diarrhoea
- Neuro /psychiatric : tremor, behavioural disturbances
- Thrombocytopenia
Life-threatening:
- Severe liver injury, bone marrow failure
Valproate - Contraindications
- Women of child-bearing age
- 1st trimester of pregnancy
Valproate - Caution
- Hepatic impairment
- Severe renal impairment
Valproate - Interactions
- With Lamitrigine & drugs metabolised by CYP enzymes (warfarin) : inhibit liver enzymes, risk of toxicity and increase plasma conc
- CYP inducers (carbamezepine) : because valproate is metabolised by CYP enzymes, so inducers reduce conc and increase risk of seizures
Valproate - Patient Education
- Take tablets with food to reduce GI irritation
Lamotrigine - Indications
1) Epilepsy : seizure prophylaxis
- -> focal, tonic-clonic, absence
2) Bipolar disorder
Lamotrigine - MOA
- It binds to voltage-sensitive neuronal Na+ channels, interfering with Na+ influx into the neuron.
- This prevents repetitive neuronal firing, which is a characteristic of seizure activity
Lamotrigine - Side Effects
Common:
- headache
- drowsiness
- Irritability
- Blurred vision
- dizziness
- GI symptoms
RASH: urgent review and may need to discontinue due to severe hypersensitivity reaction
Lamotrigine - Contraindications
- Prior hypersensitivity to other anti-epileptic drugs
Lamotrigine - Caution
- Hepatic impairment - metabolised by liver
Lamotrigine - Interactions
- Carbamazepine, phenytoin, oestrogens, rifampicin –> reduce lamotrigine conc –> treatment failure
- Valproate –> increase conc to rise –> toxicity
Lamotrigine - Patient Education
- try not to miss dose
- do not stop treatment abruptly
- Driving is prohibited unless they have been seizure-free for 12 months, and for 6 months after changing or stopping treatment.
Levetiracetam - Indications
1) Epilepsy : seizure prophylaxis
2) Selected cases of established convulsive status epilepticus
Levetiracetam - MOA
- The molecular target of levetiracetam is synaptic vesicle protein 2A (SV2A).
- SV2A is expressed throughout the brain, in both excitatory and inhibitory synapses, as a glycoprotein located within the membranes of synaptic vesicles.
- It is presumably through interfering with synaptic vesicle function that levetiracetam modulates neuronal excitability and reduces the risk of seizures.
Levetiracetam - Side Effects
Most people usually have none.
- Drowsiness
- Weakness
- Dizziness
- Headache
Rare:
- Suicidal ideation
Levetiracetam - Caution
- Renal impairment
Levetiracetam - Interactions
Ver few
Levetiracetam - Patient Education
- try not to miss dose
- do not stop treatment abruptly
- Driving is prohibited unless they have been seizure-free for 12 months, and for 6 months after changing or stopping treatment.
Benzodiazepine - Examples
- Diazepam
- Temazepam
- Lorazepam
- Chlordiazepoxide
- Midazolam
Benzodiazepine - Indications
1) Seizure & SE : 1st line
2) Alcohol withdrawal : 1st line
3) Sedation for interventional procedures
4) Anxiety or insomnia : short-term
Benzodiazepine - MOA
- Benzodiazepines are gamma-aminobutyric acid (GABA) receptor agonists. They enhance the binding of GABA to the GABA receptor
- Benzodiazepine drugs increase the effects of GABA on your brain and body.
Benzodiazepine - Side Effects
- Drowsiness
- Coma
Overdose:
- airway obstruction & death
Repeated:
- dependence
Benzodiazepine - Contraindication
None
Benzodiazepine - Caution
- Elderly
Avoid in:
- Resp impairment
- Neuromuscular disease
- Liver failure
Benzodiazepine - Interactions
- Additive with other sedating drugs - alcohol & opioids
- CYP inhibitors - increase effects
- -> (e.g. amiodarone, diltiazem, macrolides, fluconazole, protease inhibitors)
CYP inhibitors
- amiodarone
- diltiazem
- macrolides
- fluconazole
- protease inhibitors
Benzodiazepine - Patient Education
- Should not drive or operate complex or heavy machinery after taking the drug
- caution them that sometimes sleepiness may persist the following day.
Benzodiazepine - Monitoring
- Pre-treatment: ECG, LFTs, U&Es
- Ongoing: LFTs, U&Es Monitor potential for addiction – lowest possible dose for the shortest time should be given
Serotonin 5-HT1-receptor agonists - Examples
Sumatriptan
Triptan - Indications
1) Acute migraine with or without aura
Triptan - MOA
Triptans constrict cranial blood vessels and inhibit neurotransmission in the peripheral trigeminal nerve and in the trigeminocervical complex.
Triptan - Side Effects
Common:
- Pain or discomfort in the chest and throat
- -> intense but resolve quickly
- N & V
- Tiredness
- Dizziness
RARE: MI
Triptan - Contraindications
- Coronary Artery disease + Cerebrovasulcar disease due to its vasoconstrictor properties
- Hemiplegic or basilar migraines
Triptan - Caution
None
Triptan - Interactions
- Monoamine oxidase inhibitors (e.g. tramadol, SSRI, tricyclic antidepressants) increase the risk of serotonin toxicity
Triptan - Patient Education
- Can be taken with NSAIDs
- Only works when taken after the start of migraine (no preventative of an attack)
Antiemetics, dopamine D2-receptor antagonists - Examples
- metoclopramide
- domperidone
Dopamine D2-receptor antagonists - Indications
Prohpylaxis & treatment of N & V
–> specifically regarding reduced gut motility
Dopamine D2-receptor antagonists - MOA
+ First, the D2 receptor is the main receptor in the chemoreceptor trigger zone (CTZ), which is the area responsible for sensing emetogenic substances in the blood.
+ D2-receptor antagonists are therefore effective in nausea and vomiting caused by CTZ stimulation (e.g. by emetogenic drugs).
+ Second, dopamine is an important neurotransmitter in the gut, where it promotes relaxation of the stomach and lower oesophageal sphincter and inhibits gastroduodenal coordination.
+ D2-receptor antagonists therefore have a prokinetic effect, promoting gastric emptying, which contributes to their antiemetic action in conditions associated with reduced gut motility
Dopamine D2-receptor antagonists - Side Effects
Common: Diarrhoea
-QT-interval prolongation & arrhythmias
Dopamine D2-receptor antagonists - Contraindications
Should not be prescribed for more than 5 days.
Avoid:
- neonates, children, young adults
- Intestinal obstruction
- perforation
Avoid metoclopramide:
- Parkinson’s disease
Avoid Domperidone:
- cardiac conduction abnormalities
- severe hepatic impairmentt
Dopamine D2-receptor antagonists - Interaction
- Increased SE with antipsychotics.
- Avoid with dopaminergic agents for parkinson’s
- Avoid with CYP inhibitors - increase SE.
Antiemetics, Histamine H1-receptor antagonists - Examples
- cyclizine
- cinnarizine
- promethazine
Histamine H1-receptor antagonists - Indications
Prohpylaxis & treatment of N & V.
–> especially motion sickness or vertigo
Histamine H1-receptor antagonists - MOA
Nausea and vomiting are triggered by gut irritation, drugs, motion and vestibular disorders, as well as higher stimuli (sights, smells, emotions).
- The various pathways converge on a ‘vomiting centre’ in the medulla, which receives inputs from the chemoreceptor trigger zone (CTZ), & other centres.
- Histamine (H1) and acetylcholine (muscarinic) receptors predominate in the vomiting centre and in its communication with the vestibular system.
- Drugs such as cyclizine block both receptors.
- This makes them useful treatments for nausea and vomiting in a wide range of conditions, particularly when associated with motion or vertigo.
Histamine H1-receptor antagonists - Side Effects
Common: Drowsiness, dry throat and mouth.
- After IV tachycardia, palpitations
Histamine H1-receptor antagonists - Contraindications
- Hepatic encephalopathy
- Prostatic enlargement
Histamine H1-receptor antagonists - Interaction
- Other sedative drugs (benzo , opioids)
- Ipratropium or tiotropium
Antiemetics, serotonin 5-HT3-receptor antagonists - Examples
- ondansetron
- granisetron
Serotonin 5-HT3-receptor antagonists - Indications
Prohpylaxis & treatment of N & V.
–> especially in context of general anaesthesia and chemotherapy
Serotonin 5-HT3-receptor antagonists - MOA
- First, there is a high density of 5-HT3 receptors in the CTZ, which are responsible for sensing emetogenic substances in the blood (e.g. drugs).
- Second, 5-HT is the key neurotransmitter released by the gut in response to emetogenic stimuli.
- Acting on 5-HT3 receptors, it stimulates the vagus nerve, which in turn activates the vomiting centre.
- Thus 5-HT3 antagonists are effective against nausea and vomiting as a result of CTZ stimulation (e.g. drugs) and visceral stimuli (gut infection, radiotherapy).
Serotonin 5-HT3-receptor antagonists - Side Effects
SE are rare
- Constipation
- Diarrhoea
- Headaches
Serotonin 5-HT3-receptor antagonists - Contraindications
Avoid in pt with prolonged AT interval
Serotonin 5-HT3-receptor antagonists - Interactions
Drugs that prolong the QT interval : antipsychotics, quinine, SSRI
