CNS Drugs Flashcards
Hyoscine hydrobromide drug class
Muscarinic antagonist
Hyoscine hydrobromide indications
Motion sickness
Hyoscine hydrobromide mechanism of action
It competitively blocks Muscarinic acetylcholine receptors in the vestibular nuclei and chemoreceptor trigger zone.
Hyoscine hydrobromide ADR
Sedation Memory problems Glaucoma Dry mouth Constipation
Cyclizine drug class
Histamine 1 receptor antagonists
Cyclizine indications
Motion sickness
Morning sickness
Cyclizine mechanism of action
It acts centrally on the vestibular nuclei and inhibits histaminergic signals from the vestibular system to the chemoreceptor trigger zone in the medulla.
Cyclizine ADR
Sedation Excitation Dry mouth Constipation Urinary retention Cardiac toxicity - long QT interval
Cyclizine caution
Elderly
Children
Ondansetron drug class
5-HT3 receptor antagonist
Ondansetron indications
Nausea and vomiting
Ondansetron mechanism of action
It can centrally on the chemoreceptor trigger zone and peripherally to reduce GI motility and secretions
Ondansetron ADR
Constipation Headache Elevated liver enzymes Long QT syndrome Extra-pyramidal effects - Dystonia, Parkinsonism
D2 receptor antagonists examples
Metoclopramide
Domperidone
Haloperidol
D2 receptor antagonist indications
Nausea and vomiting
Motion sickness
Vertigo
D2 receptor antagonists mechanism of action
It increases acetylcholine at Muscarinic receptors in the gut. It promotes gastric emptying by increasing tone of lower oesophageal sphincter, tone of gastric contractions and decreasing the tone of the pylorus.
Metoclopramide ADR
Galactorrhoea
Extra-pyramidal effects - Dystonia and Parkinsonism
Sedation
Hypotension
Domperidone ADR
Sudden cardiac death due to long QT and VT
Galactorrhoea
Dexamethasone drug class
Corticosteriod
Dexamethasone indications
Nausea and vomiting
Dexamethasone mechanism of action
May act on the chemoreceptor tigger zone
Dexamethasone ADR
Insomnia
Increased appetite
Increased blood sugar
Nabilone drug class
Cannabinoid
Nabilone ADR
Dizziness
Drowsiness
Aprepitant drug class
Neurokinin 1 receptor antagonist
Aprepitant indications
Nausea and vomiting
Aprepitant mechanism of action
It prevents the action of substance P at the chemoreceptor trigger zone and in peripheral nerves. It boosts the effects of 5HT3 receptor antagonists.
Aprepitant ADR
Headache
Diarrhoea
Constipation
Stevens-Johnson syndrome - skin reaction
First line drug for motion sickness
Hyoscine hydrobromide
D2 receptor antagonist cautions
Obstruction
Risk of perforation
First line for Morning sickness in pregnancy
H1 receptor antagonist or D2 receptor antagonist
First line for emesis in chemotherapy
Dexamethasone then Ondansetron
Nociception definition
The non-conscious neural traffic due to trauma or potential trauma to tissue
Pain definition
A complex, unpleasant awareness of sensation modified by experience, expectation, immediate context and culture.
Describe the pain reflex ?
Nociceptors stimulated Release of substance P and glutamate Afferent nerve stimulated Fibres decussate Action potential ascends Synapse in thalamus Projects to post central gyrus
Opioid mechanism of action
Agonist binds which leads to a decreased in cAMP. This causes an efflux of potassium. The membrane then becomes hyper polarised. There is decreased production of substance P and GABA which increases dopamine release causing a euphoric effect.
What are some strong opioid agonist ?
Morphine
Fentanyl
Heroin
Oxycodone
What are some moderate opioid agonist ?
Codeine
What is a partial opioid agonist ?
Buprenorphine
What is a opioid antagonist ?
Naloxone
Which receptor does Morphine have a strong affinity to ?
Mu receptors
Morphine ADR
Respiratory depression Emesis GI tract side effects Cardiovascular side effects Miosis Histamine release
Potency and affinity of Fentanyl compared to morphine
More potent
Higher affinity
Morphine actions
Analgesia
Euphoria
Fentanyl actions
Analgesia
Anaesthetic
Fentanyl ADR
Respiratory depression
Constipation
Vomiting
Potency of Codeine compared to morphine
Less potent
Codeine actions
Mild to moderate analgesia
Cough depressant
Codeine ADR
Constipation
Respiratory depression
Buprenorphine affinity compared to morphine
Very high so not easily displaced
Buprenorphine actions
Moderate to severe pain
Opioid addiction treatment
Buprenorphine ADR
Respiratory depression
Low BP
Nausea
Dizziness
Naloxone affinity compared to morphine and Buprenorphine
Greater than morphine but less than Buprenorphine
Overdose effects
Dependence Vomiting Constipation Hypotension Bradycardia Histamine release Miosis Drowsiness Respiratory depression
Opioid contraindications
Hepatic failure Acute respiratory distress Comatose Head injuries Raised ICP
What does PGE2 contribute to ?
Regulation of acid secretion in parietal cells
What does prostacyclin - PGI2 - contribute to ?
Maintenance of blood flow and mucosal repair
What can enhance prostanoids ?
Autacoids such as bradykinin and histamine
What can a disturbance of prostanoids lead to ?
Hypertension
MI
Stoke
What homeostatic functions does COX-1 do ?
GI protection
Platelet aggregation
Vascular resistance
What homeostatic functions does COX-2 do ?
Renal homeostasis
Tissue repair and healing
Reproduction
Inhibition of platelet aggregation
How do NSAIDs have analgesic effects ?
It blocks PGE2 which reduces peripheral pain fibre sensitivity. This can result in decreased PGE2 synthesis in the dorsal horn causing a decrease in neurotransmitter release. This decreases excitability of neurons in the pain relay pathway.
How do NSAIDs have an anti-inflammatory effect ?
NSAIDs reduce production of prostaglandins released at the site of injury. This decreases vasodilation and capillary permeability reducing local swelling.
How do NSAIDs have an anti-pyretic effect ?
NSAIDs inhibit the hypothalamic COX-2 where cytokine induced prostaglandin synthesis is elevated results in a reduction in temperature.
What has COX-1 selectivity ?
Aspirin
Order of increasing COX-2 selectivity (least to most)
Ibuprofen Naproxen Diclofenac Celecoxib Etoricoxib
NSAIDs ADR
Dyspepsia Nausea Peptic ulceration Bleeding Perforation Decreased GFR
NSAIDs cautions
Elderly Prolonged use Smoking Alcohol History of peptic ulceration H.Pylori infection Heart failure Underlying CKD
NSAIDs DDI
Aspirin Glucocorticoid steriods Anti-coagulants ACEi ARB Diuretics Warfarin - increased risk of bleeding Methotrexate
NSAIDs indications
Inflammatory conditions
Osteoarthritis
Postoperative pain
Menorrhagia
Paracetamol indications
Mild to moderate pain
Fever
Paracetamol mechanism of action
COX-2 selective inhibition in the CNS which decreases pain signals to higher centres
Paracetamol overdose effects
Nausea
Vomiting
Abdominal pain
Liver damage
Paracetamol overdose treatment
Activated charcoal is overdose is very recently
Give N-acetylcysteine
Seizure definition
A transient occurrence of signs and symptoms due to abnormal electrical activity in the brain, leading to a disturbance of consciousness, behaviour, emotion, motor function or sensation.
Most important excitatory neurotransmitter and the receptor is acts on ?
Glutamate on the NMDA receptor
Most important inhibitory neurotransmitter and the receptor it acts on ?
GABA on GABA alpha receptors
What can cause a seizure ?
Loss of inhibitory signals or too strong an excitatory ones
This imbalance can happen in any point in the brain and local changes can lead to generalised effects.
What can cause an imbalance in the brain to cause a seizure ?
Genetic differences in brain chemistry / receptor structure
Drugs
Drug withdrawal
Strokes and tumours
Signs and symptoms of seizures
Shaking and jerking
Loss of consciousness
Tongue biting
Possible aura prior
Epilepsy definition
Epilepsy is a tendency towards recurrent seizures unprovoked by a systemic or neurological insult.
Potential stimuli for seizures
Photogenic Musicogenic Thinking Eating Hot water immersion Reading Orgasm Movement
Where do generalised seizures originate ?
Originate at a point and rapidly engage both hemispheres
Where do focal seizures originate ?
Originate within networks limited to one hemisphere. May be discretely localised or more widely distributed
What is a provoked seizure ?
Seizures that result from another medical condition such as : Drug use or withdrawal Alcohol withdrawal Head trauma Metabolic disturbances CNS infections
How to manage a seizure under 5 mins ?
Start a timer and usually seizures will self-terminate without use of drugs
What is status epilepticus ?
A seizure lasting more than 5 minutes or more, or multiple seizures without a complete recovery between them.
Drug management for Status epilepticus
0-5 mins - Full dose of benzodiazepine
0-15 mins - 2nd full dose of benzodiazepine
15-45 mins - phenytoin or levetiracetam
45 mins + - thiopentone / anaesthesia
Investigations for a diagnosis of epilepsy
EEG- record the electrical pattern of activity in the brain
Imaging - MRI
Benzodiazepine drug class
GABA alpha agonist
Benzodiazepine indications
Termination of a seizure
Benzodiazepine mechanism of action
There is increased chloride conductance resulting in more negative resting potential so the action potential is less likely to fire.
Benzodiazepine examples
IV lorazepam
Diazepam rectally
Buccal or intranasal midazolam
Carbamazepine drug class
Sodium channel blocker anti-epileptic drug
Carbamazepine indication
Epilepsy
Carbamazepine mechanism of action
Blocking sodium channels in the central neurones which slows recovery of neurones from inactive to closed states. This reduces neuronal transmission.
Carbamazepine ADR
Suicidal thoughts
Joint pain
Bone marrow failure
Phenytoin drug class
Sodium channel blocker anti - epileptic drug
Phenytoin indications
Epilepsy
Mainly used in status epilepticus
Phenytoin cautions
Exhibits zero order kinetics so there must be care in adjusting doses
Phenytoin ADR
Bone marrow supression
Hypotension
Arrhythmia with IV use
Sodium valproate drug class
Anti - epileptic
Sodium valproate indications
1st line for generalised epilepsies
Sodium valproate ADR
Liver failure
Pancreatitis
Lethargy
Sodium valproate mechanism of action
Mixed GABA alpha effects and sodium channel blockade
Lamotrigine drug class
Sodium channel blocker anti - epileptic drugs
Lamotrigine indications
Focal epilepsy
Used for generalised epilepsy when sodium valproate is contraindicated
Levetiracetam indications
Focal seizures
Generalised seizures
Positives of levetiracetam
Safe in pregnancy
Levetiracetam mechanism of action
It stops the release of neurotransmitters into synapse and reduces neuronal activity.
Levetiracetam drug class
Synaptic vesicle glycoprotein binder - AED
Anti-epileptic drug ADR
Tiredness Drowsiness Nausea Vomiting Mood changes Suicidal ideation Osteoporosis
AED DDI
Warfarin
Alcohol
Decreases effectiveness of oral contraceptive pill and antibiotics
CYP inducers - phenytoin, carbamazepine and barbiturates
CYP inhibitors - valproate
Dopamine receptor agonist examples
Levodopa
Co-careldopa
Amantadine
What is special about co-careldopa ?
Levodopa is used in combination with a peripheral dopa decarboxylase inhibitor. This reduces the dose and side effects. It also increases levodopa reaching the brain.
Dopamine receptor agonist indications
Parkinson’s disease
Levodopa side effects
Nausea
Hypotension
Psychosis
Tachycardia
Levodopa mechanism of action
Levodopa is a prodrug that is converted to dopamine by DOPA decarboxylase. It crosses the blood brain barrier and is decarboxylase to dopamine where it stimulates dopaminergic receptors.
Levodopa DDI
Pyridoxine ( vitamin B6 ) increases peripheral breakdown of levodopa.
MAOI and levodopa increase risk of hypertensive crisis.
Many anti-psychotic drugs block dopamine receptors and have Parkinsonism as a side effect.
COMT inhibitor examples
Entacapone
Opicapone
COMT inhibitors mechanism of action
No therapeutic effect alone and used alongside levodopa. They reduce the breakdown of levodopa so prolong motor response to levodopa.
COMT inhibitor indications
Used alongside levodopa for Parkinson’s disease
Examples of impulse control disorders
Pathological gambling
Hyper-sexuality
Compulsive shopping
Punding
Dopamine receptor agonist ADR
Sedation Hallucinations Confusion Nausea Hypotension
MAOI examples
Selegiline
Rasagiline
MAOI actions
Can be used alone
Prolongs the action of levodopa
Smooths out motor response
Anti-cholinergics examples
Orphenadrine
Procyclidine
Anti-cholinergic ADR
Confusion
Drowsiness
Anti-cholinergic positive
Treats the tremor
