Neurology/Psychiatry Drugs Flashcards
what is a dopamine precursor drug?
levodopa
what is the MoA for levodopa?
pro drug
crosses BBB and is converted to dopamine
striatal dopaminergic neurotransmission increased
what are the indications for levodopa?
PD
list some side effects of levodopa
Dyskinesia Compulsive disorders Hallucinations Nausea GI upset
what is important regarding pharmaco-kinetics/dynamics for levodopa?
Converted to dopamine in peripheries (which can cause the motor side effects)
Given with a dopamine decarboxylase inhibitor or COMT inhibitor to reduce these effects
Short half life – 50 to 90 mins
Rapidly absorbed from the proximal small intestine via the large neutral amino acid (LNAA) transport carrier system
what info should be given to patient before starting levodopa?
Dyskinesia common
Reduced efficacy over time
Avoid abrupt withdrawal
what are some dopamine agonists?
Apomorphine Pramipexole Bromocriptine Pergolide Rotigotine
what is the MoA for dopamine agonists?
Stimulate post synaptic dopamine receptors
Apomorphine: non selective D1 and D2 dopamine subfamily of receptors
Pramipexole: selective D3 receptor
what are the indications for dopamine agonists?
PD
list some side effects of dopamine agonists?
Apomorphine: pain at site of injection, nausea, vomiting
Pramipexole: hallucinations, nausea, drowsiness, involuntary movements
what is important regarding pharmaco-kinetics/dynamics for dopamine agonists?
Apomorphine: highly emetic, hence limited use. Short half life (40 mins). Needs to be via injection.
Pramipexole: Cimetidine increases its toxicity, long half life (8 hrs)
Dopamine Agonists have reduced efficacy over time
what info should be given to patient before starting a dopamine agonist?
Apomorphine can only be injected
Dopamine agonists are weaker then L-DOPA so treatment may be modified in time.
what is an example of a Catechol-o-methyl transferase Inhibitor (COMT)?
Entacapone
what are the indications for a COMT inhibitor?
Parkinson’s Disease in conjunction with L-DOPA and dopamine decarboxylase inhibitor
list the side effects of a COMT inhibitor?
Dyskinesia Nausea Abdominal pain Vomiting Dry mouth Dizziness
what is important regarding pharmaco-kinetics/dynamics for a COMT inhibitor?
Rapidly absorbed
Levodopa dose may need to be reduced by 10-30% when given with Entacapone
what info should be given to patient before starting a COMT inhibitor?
Urine may turn brown – normal
Could become lightheaded/dizzy while doing daily activities
Avoid abrupt withdrawal
give examples of an anti-epileptic drug?
Carbamazepine sodium valproate phenytoin Lamotrigrine Levetiracetam
what is the MoA for Carbamazepine?
Voltage gated Na+ channel blocker on pre-synaptic membrane
Blocks the Na+ influx; reduces neuronal excitability and decreases the action potential
what are the indications for Carbamazepine?
Epilepsy
Trigeminal Neuralgia
Neuropathic pain
list the side effects of Carbamazepine?
Dizziness Dry mouth Ataxia Fatigue Headache Diplopia Blurred vision Hyponatraemia Stevens-Johnson’s syndrome
what is important regarding pharmaco-kinetics/dynamics for Carbamazepine?
Response to the drug can be variable
Enzyme inducer of cytochrome P450; induces metabolism of itself
Interactions with other anti-convulsants
The transporter that can confer drug resistance is RALBP1
Grapefruit can significantly increase serum levels of this drug
HLA-B*1502 allele raises the risk for SJS; avoid in these patients
what info should be given to patient before starting Carbamazepine?
Avoid alcohol
Avoid grapefruit juice
what is the MoA of sodium valproate
Weak sodium ion channel blocker
Inhibitor of GABA degrading enzymes
Increased GABA stops action potential
what are the indications for sodium valproate
Epilepsy
Bipolar disorder
Depression
list the side effects of sodium valproate
Nausea Diarrhoea Gastric irritation Weight gain Hyponatraemia Behavioral disturbances Confusion Stevens-Johnson Syndrome
what is important regarding pharmaco-kinetics/dynamics for sodium valproate
Enzyme inhibitor of cytochrome P450
Rapid absorption from GI tract – varies with formulation administered when administered
Can cause interactions with other anti-epileptic drugs.
what info should be given to patient before starting sodium valproate
Avoid alcohol
Take with food
Do not take with milk
Liver function test must be monitored before and during the initial 6 months
what is the MoA for phenytoin
Acts as a voltage-gated Na+ channel blocker on the pre-synaptic neuronal membrane
Limits action potential transmission
Hence limiting spread of seizure activity
what are the indications for phenytoin?
Epilepsy (including status epilepticus)
Trigeminal neuralgia
list the side effects of phenytoin:
nsomnia Headache Rash Constipation Vomiting Gingival hyperplasia Liver damage
Rare: Stevens-Johnson Syndrome, Leucopenia, Thrombocytopenia
what is important regarding pharmaco-kinetics/dynamics for phenytoin?
Enzyme inducer of cytochrome P450
Can cause interactions with other anti-epileptic drugs
Narrow therapeutic index
Relationship between dose and plasma concentration is non-linear
what info should be given to patient before starting phenytoin?
Avoid alcohol
Do not take calcium, aluminum, magnesium or iron supplements within 2 hours of ingestion
Take with food to reduce irritation
What is the MoA for Lamotrigrine?
Varied mechanism of action
Inhibits voltage-gated Na+ channels and/or Ca2+ channels
Acts on pre-synaptic neuronal membrane
Reduces action potential and excitatory signals
what are the indications for Lamotrigrine?
Epilepsy (used for both partial and generalized seizures)
Depressive episodes associated with Bipolar disorder
list the side effects of Lamotrigrine:
Nausea Vomiting Diarrhoea Tremor Insomnia Blurred vision Aggression Skin reactions including Sevens-Johnson syndrome and toxic epidermal necrolysis (rare)
what is important regarding pharmaco-kinetics/dynamics for Lamotrigrine?
Half-life doubles in chronic renal impairment so dose adjustment is required.
what info should be given to patient before starting Lamotrigrine
Take without regard to meals
Seek medical advice if any rash or signs/symptoms of hypersensitivity.
What is the MoA for Levetiracetam?
SV2A is a synaptic vesicle protein required for neurotransmitter release
Levetiracetam blocks this and reduced neurotransmitter release
Induces an anti-epileptic effect
what are the indications for Levetiracetam?
Epilepsy
list the side effects of Levetiracetam?
Headache Fatigue Anxiety Irritability Drowsiness Constipation
what is important regarding pharmaco-kinetics/dynamics for Levetiracetam?
Rapidly and almost completely absorbed after oral administration (99%)
Food does not affect bioavailability
Cytochrome P450 is not involved in its metabolism
what info should be given to patient before starting Levetiracetam?
It might affect your ability to drive or operate machinery
Not recommended during pregnancy and breastfeeding
what are some examples of selective serotonin reuptake inhibitors (SSRIs)?
Citalopram Fluoxetine Paroxetine Escitalopram Sertraline
what is the MoA for SSRIs?
Inhibition of reuptake of serotonin at the serotonin reuptake pump of the synaptic cleft (in the central nervous system)
Increases serotonin stimulation of somatodendritic 5-HT1A and terminal autoreceptors
what are the indications for SSRIs?
Depression
Bulimia
Obsessive Compulsive Disorder
list the side effects of SSRIs:
Dry mouth Nausea Insomnia Anxiety Decreased libido Seizures (rare) Dyskinesia (rare)
what is important regarding pharmaco-kinetics/dynamics for SSRIs?
SSRIs bind with less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs. This leads to fewer side effects.
Less dangerous in overdose than tricyclic antidepressant drugs.
what info should be given to patient before starting a SSRI?
Be wary with alcohol - toxicity possible
Improvement in depressive symptoms may take several weeks to occur.
Abrupt discontinuation from SSRIs may cause withdrawal symptoms (fatigue, tremor, sweating)
what are some examples of tricyclic antidepressants?
Amitriptyline
Imipramine
Doxepin
what is the MoA for tricyclic antidepressants?
Stops the reuptake of monoamines
Binds to monoamine pump at pre-synaptic cleft
The reduced reuptake of norepinephrine and/or serotonin combats depression
what are the indications for tricyclic antidepressants?
Depression
Panic disorders
Neuropathic pain
list the side effects of tricyclic antidepressants
Sedation (anti-histaminergic effects)
Postural hypotension, tachycardia (anti-adrenergic effects)
Urinary retention, dry mouth, blurred vision / diplopia (anti-cholinergic effects)
overdose can be serious - causing seizures and cardiac arrhythmias
what is important regarding pharmaco-kinetics/dynamics for tricyclic antidepressants?
Blocks histamine-H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects
Well absorbed orally
First pass effect (liver)
what info should be given to patient before starting tricyclic antidepressants?
Reduction in depressive symptoms may take several weeks to appear.
what are some examples of anti-psychotic drugs?
- First generation anti-psychotics.
Act non selectively on D1-like and D2-like receptors = Haloperidol; Chlorpromazine - Atypical anti-psychotics.
Varying effects on dopamine and serotonin receptors = Olanzapine; Clozapine
what is the MoA for anti-psychotic drugs?
Block dopamine receptors
Action on mesolimbic and nigrostriatal parts of brain
Also have anti-histaminergic and anti-cholinergic effects
These effects reduce positive symptoms of schizophrenia and can cause sedation and provide anti-emetic activity.
what are the indications for anti-psychotic drugs?
Schizophrenia Mania Delusions, hallucinations Behavioral problems Anti-emetic (Haloperidol)
list the side effects of anti-psychotic drugs
Sedation (anti-histaminergic effect)
Postural hypotension, tachycardia (anti-adrenergic effect)
Urinary retention, dry mouth, blurry vision (anti-cholinergic effect)
what is important regarding pharmaco-kinetics/dynamics for anti-psychotic drugs?
Have effects on numerous receptor systems within the CNS
what info should be given to patient before starting anti-psychotic drugs?
Symptoms may not always disappear while on medication
Dosage may have to be increased if no improvement after a few weeks
what are 3 examples of benzodiazepines?
Diazepam
Lorazepam
Midazolam
what is the MoA for benzodiazepines?
Increases GABA affinity for GABA receptor
GABA binding to receptor increases chloride flow through chloride channels
Hyperpolarization occurs - reducing activity of limbic, thalamic and hypothalamic areas of the brain.
what are the indications or benzodiazepines?
Anxiety
Epilepsy
Muscle spasm
Alcohol withdrawal
list the side effects of benzodiazepines
Sedation
Ataxia
Altered mental status
Insomnia
what is important regarding pharmaco-kinetics/dynamics for benzodiazepines?
Diazepam is a long acting benzodiazepine with active metabolites. Can accumulate in longer term use and in patients with liver failure. Can be oral, rectal or parenteral.
Lorazapam accumulates less with long term use or in patients with liver failure so is preferred in this setting. It cannot be given rectally.
Midazolam is a potent and short acting benzodiazepine typically given parenterally, although buccal preparations exist.
what info should be given to patient before starting benzodiazepines?
Monitor breathing and report if severe breathlessness or palpitations
Only prescribed for short terms – risk of addiction