Sem 2 Flashcards
Pregabalin indication and mechanism of action
Neuropathic pain and adjunct therapy for epilepsy (GAD an unapproved indication).
Binds to T-type voltage gated calcium channels and decreases the release of excitatory neurotransmitters associated with neuropathic pain and seizure propagation.
Pregabalin dosing
Neuropathic pain: 75mg BD, increased, if necessary, after 3-7 days to 150mg BD. Increased further, if necessary, after 7 days to maximum 300mg BD.
Adjuvant treatment for focal seizures with or without secondary generalisation: 75mg BD, increased, if necessary, after 3-7 days to 150mg BD. Increased further, if necessary, after 7 days to maximum 300mg BD.
Pregabalin adverse effects
Relatively side effect free, sedation and ataxia.
Cognitive issues may be significant in elderly.
Pregabalin precautions and safety in special populations
Renally cleared. >60 max dose is 600mg.
>30-60 max dose is 300mg.
>15-30 max dose is 150mg.
>15 max dose is 75mg.
Pregabalin advice and self care
Two forms of contraception should be used.
Take with a large glass of water.
Atypical antipsychotics examples (8)
amisulpride, aripiprazole, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, and clozapine
Atypical antipsychotics indication and mechanism of action
Schizophrenia, bipolar and other severe mental illnesses.
D2 PLUS 5HT-2A antagonists.
Atypical antipsychotics adverse effects
Weight gain (particularly olanzapine)
Increased risk of diabetes.
Elevated lipids.
QT prolongation (particularly ziprasidone).
Postural hypotension and hypertension (risperidone, olanzapine, and quetiapine).
Movement disorders (less likely than typicals)
Sexual dysfunction/hyper gynaecomastia + osteoporosis (risperidone, paliperidone and amisulpride).
Sedation (clozapine, olanzapine + quetiapine).
Anticholinergic effects (clozapine + olanzapine).
Rare: Neuroleptic Malignant Syndrome (NMS). Muscular rigidity, pyrexia, confusion, urinary incontinence, disorientation, tachycardia and sweating. More common in young men on higher doses and associated with hot weather and exercise.
Atypical antipsychotics contraindications
Contraindicated in comatose states, CNS depression and phaeochromocytoma.
Atypical antipsychotics precautions and safety in special populations
Caution in CVD, potential for QT prolongation.
Caution in Parkinson’s/elderly – dopamine antagonist effects.
Atypical antipsychorics monitoring
FBC, urea + electrolytes, LFTs initially then annually.
Lipids initially, at 3 months then annually.
Weight initially, regularly during first 3 months then annually.
FBG initially, at 4-6 months then annually.
ECG if CV risk factors.
BP initially and during dose titration.
Prolactin initially, 6 months, then annually if there are clinical concerns.
CVDRA annually.
Citalopram and escitalopram indication and mechanism of action
Depression, anxiety, OCD
Inhibits reuptake of serotonin in the pre-synapse, increasing the available serotonin in the brain.
Citalopram and escitalopram dosing
Escitalopram: 10mg daily, increased if necessary to 20mg.
Citalopram: 20mg daily, increased if necessary to 40mg.
Citalopram and escitalopram adverse effects
QT prolongation (rare but serious)
Nausea, anxiety, insomnia, agitation, hypomania, worsening of depression and suicidal ideation can occur in first days to weeks.
Dose-related adverse effects include fatigue, impotence, increased sweating, somnolence, and insomnia.
Increased risk of bleeding.
Sexual dysfunction.
Serotonin syndrome (rare but serious).
Hyponatremia – monitor in high risk individuals. Most likely to occur during the first 4 weeks. Signs include dizziness, nausea, lethargy, confusion, cramps and seizures.
Citalopram and escitalopram interactions and contraindications
Lithium, sotalol, omeprazole increases risk of QT prolongation (double up)
Lithium, st johns wort, sumatriptan, tramadol and pethidine increase the risk of serotonin syndrome.
Citalopram and escitalopram precautions and safety in special populations
No information available for CrCl <20mL/min
Clozapine indication and mechanism of action
Treatment-resistant schizophrenia
D1, D2, 5HT-2a and muscarinic receptor antagonist
Clozapine adverse effects
Tachycardia, hypotension, myocarditis, fever, headache, sedation, seizures, constipation, nausea, vomiting, hypersalivation, weight gain, raised lipids, glucose impairment, blurred vision, urinary incontinence, agranulocytosis (leukopenia), eosinophilia, thrombocytopenia.
Clozapine monitoring
Regular blood monitoring required for dispensing. Baseline FBC 10 days prior to commencing, then weekly FBC for 18 weeks. 28-day monitoring required thereafter and for 4 weeks discontinuation. Agranulocytosis tends to develop within the first 6 months of treatment and is not dose related. Neutropenia can occur at any time.
Constipation. Treat proactively.
Myocarditis symptoms develop within 1 month of starting, whereas cardiomyopathy has a latent onset of after 1 year but can occur at any time.
Clozapine interactions and contraindications
Increased risk of neutropenia: antibiotics (co-trimoxazole, trimethoprim, nitrofurantoin), carbamazepine and antineoplastics associated with BMS.
Many interactions as it is a substrate for CYP450 isoenzymes. Carbamazepine, phenytoin, rifampicin, and omeprazole (inducers) can decrease clozapine plasma levels.
Plasma levels affected by smoking.
Erythromycin, ciprofloxacin, paroxetine, and fluoxetine (inhibitors) may increase clozapine effect. So may hormonal contraceptives.
Plasma concentration can also be increased by a high caffeine intake.
Clozapine can enhance the CNS effects of alcohol, CNS depressants and benzodiazepines.
Clozapine precautions and safety in special populations
Liver disease: check LFTs regularly.
Renal: avoid in severe disease
Clozapine advice and self care
Be aware of neutropenia symptoms (fever, sore throat, flu-like symptoms).
Donepezil indication
Mild-severe Alzheimer’s disease and vascular dementia.
Donepezil mechanism of action
Prevents breakdown of Ach, prolonging the effect at the synapse.
Reversible inhibitor, CNS selective
Donepezil dosing
5mg OD at bedtime, increased, if necessary, after at least 1 month to a maximum of 10mg daily.
Donepezil adverse effects
Anorexia, nausea, vomiting, diarrhoea, abdominal pain.
Drowsiness, hallucinations, agitation, dizziness, headache.
Heart block and sinus bradycardia.
Donepezil interactions and contraindications
Beta blockers, amiodarone, digoxin and diltiazem increase the risk of bradycardia.
Anticholinergic drugs: TCAs, sedating antipsychotics, overactive bladder medicines, sedating antihistamines and antiemetics can compete for the same receptors and decrease the effect of donepezil.
Donepezil precautions and safety in special populations
CYP2D6 polymorphisms are more related to response to treatment than drug interactions.
Caution in mild to moderate hepatic impairment.
Donepezil monitoring
Check HR before initiation. If under 60bpm, an ECG is recommended prior to commencing treatment.
Check pulse at monthly intervals during titration and 6-monthly thereafter.
Assess for falls risk.
Monitor body weight at baseline and regularly during treatment.
Fentanyl indication
Chronic cancer pain. For those with stable opioid requirements but cannot tolerate their current opioid due to side-effects such as constipation, have a deteriorating renal function, or cannot tolerate oral opioid administration.
Fentanyl mechanism of action
Agonists at opioid receptors. Specific for mu receptor.
Fentanyl adverse effects
Nausea, vomiting, constipation, sleepiness, visual disturbance, dizziness, skin reactions, sweating and headache.
Serious: respiratory/CNS depression, hallucinations, euphoria, myoclonic jerks.
Fentanyl interactions and contraindications
CYP3A4 inhibitors (ritonavir, ketoconazole, itraconazole, clarithromycin and erythromycin) increase fentanyl plasma levels
SSRIs, SNRIs and MAOIs increase the risk of serotonin syndrome.
Fentanyl precautions and safety in special populations
Metabolised by the liver – may have delayed elimination in hepatic impairment.
Avoid in pregnancy and breastfeeding.
Fentanyl advice and self care
Replace every 72 hours.
Titrate on other opioids then fentanyl started.
Avoid direct heat on the patch – leads to increased absorption and risk of adverse effects/toxicity.
Fluorouracil indication
Malignant and superficial pre-malignant skin lesions. Most oftenly prescribed for actinic keratoses and in-situ squamous cell carcinoma. Also occasionally used to treat superficial basal cell carcinomas.
Fluorouracil mechanism of action
Irreversibly binds to thymidylate synthetase, preventing formation of DNA and RNA and causing abnormal cell death.
Fluorouracil dosage
Apply thinly 1 to 2 times daily for 3-4 weeks.
Sometimes tretinoin is used before treatment to peel off the top layer of skin and allow fluorouracil cream to work best.
Fluorouracil adverse effects
Local irritation (use a topical corticosteroid): dryness, rash, pruritis, pain, erosion, crusting.
Changes in skin colour
Fluorouracil interactions and contraindications
Dihydropyrimidine dehydrogenase (DPD) deficiency. Can develop life-threatening systemic toxicity including neutropenia, stomatitis, diarrhoea, and neurotoxicity. This may present with fever, chills, fatigue, bloody diarrhoea, vomiting and abdominal pain.
Fluorouracil precautions and safety in special populations
Not to be used in pregnancy or breastfeeding
Fluorouracil advice and self care
Wash the area first with water, then dry. Rinse finger thoroughly after applying (Some patients prefer to wear a glove).
If only applying once a day – better to in the morning.
Avoid applying right before bed – cream may get onto bed linen.
Avoid mucous membranes.
Protect yourself from sunlight
Gabapentin indication and mechanism of action
Epilepsy and neuropathic pain
Binds to T-type voltage-gated calcium channels, reducing influx and decreasing the release of excitatory neurotransmitters associated with neuropathic pain and seizure propagation.
Gabapentin dosing
Epilepsy: Initially 300mg TDS, then increased according to response in steps of 300mg (in 3 divided doses) every 2-3 days. Usual dose 900-1800mg daily in 3 divided doses. Up to 3600mg daily in some patients.
Neuropathic pain: 300mg OD on day 1, then 300mg BD on day 2, then 300mg TDS on day 3, OR 300mg TDS on day 1, then increased according to response in steps of 300mg (in 3 divided doses) every 2-3 days. Up to maximum of 3600mg daily.
Gabapentin adverse effects
Drowsiness, dizziness, weight gain, peripheral oedema, ataxia.
Rare but serious: rash (DRESS), suicidality
Cognitive issues may be significant in elderly.
Gabapentin precautions and safety in special populations
Dose adjustment required in impaired renal function
Gabapentin advice and self care
Use 2 types of contraception
Hypnotics (Z drugs) indication and mechanism of action
Short term relief of insomnia
Binds to GABA-A receptor, increasing the amount of GABA (inhibitory neurotransmitter)
Hypnotics (Z drugs) dosing and adverse effects
7.5mg OD at bedtime
Incoordination, dizziness, drowsiness, confusion, amnesia
Hypnotics (Z drugs) precautions and safety in special populations
Reduce to 3.75mg in renal/hepatic impairment + elderly.
IV iron indications
When oral therapy is unsuitable or unsuccessful.
Patient with chronic renal failure who are receiving haemodialysis.
IV iron dosing
Ferric carboxymaltose (ferrinject) is advantageous as it can be given over 15 minutes rather than several hours. Must be administered IV (NOT SC or IM).
Maximum single IV dose 1000mg iron, with no more than 1000mg given per week.
IV iron adverse effects
Anaphylaxis. Make sure to have resuscitation facilities available. Monitor closely for hypersensitivity – especially in the first 5 minutes of administration.
Observe patient for 30-60 minutes following administration. Ferrinject is well-tolerated and associated with minimal risk of adverse reactions.
Most common: headache, dizziness, hypertension, nausea, abdominal pain, constipation, diarrhoea.
Other: hyperphosphataemia – especially in those with hyperparathyroidism or vitamin D deficiency
IV iron interactions and contraindications
Pre-existing hypophosphatemia
IV iron precautions and safety in special populations
Avoid during pregnancy if possible. Contraindicated in the first trimester. If administering, calculate dose based off pre-pregnancy weight.
Safe to use in breastfeeding.
No clinical data to support the use of IV iron carboxymaltose in children under 14 so cannot be recommended for paediatric use.
IV iron advice and self care
Oral iron not to be given for at least 5 days after last injection.
Contact doctor if experiencing: tiredness that is ongoing or getting worse, bone pain, muscle weakness, irritability, or confusion.
Lamotrigine indications
Seizure prevention (age 2 up)
Mood stabiliser in bipolar disorder (age 18 up)
Lamotrigine mechanism of action
Inhibits sodium voltage gated channels, decreasing the release of glutamate and affecting the membrane excitability.
Lamotrigine dosing
Start low and go slow
With valproate: initially 25 mg on alternate days for 14 days, then 25 mg once daily for further 14 days, thereafter increased by maximum 50 mg every 7–14 days; usual maintenance, 100–200 mg daily in 2 divided doses
Depends whether it is with valproate and/or enzyme inducing drugs
Lamotrigine adverse effects
Skin reactions most likely to occur within the first 8 weeks of treatment. Although often mild and self-limiting, can progress to severe and potentially fatal conditions – including SJS and toxic epidermal necrolysis.
Anticonvulsant hypersensitivity syndrome: high spiking fever, rash and/or hepatitis.
Dizziness, blurred vision and headache are common when initiating. Typically these are mild to moderate and resolve within the first few weeks.
Increased risk of anxiety, depression and suicidality.
Lamotrigine interactions and contraindications
Sodium valproate. Inhibits the metabolism of lamotrigine and therefore increases its plasma concentration increased risk of serious side effects.
Phenytoin, carbamazepine, phenobarbitone and primidone induce the metabolism and can result in subtherapeutic concentrations.
Ethinylestradiol/levonorgestrel induces the metabolism of lamotrigine and results in lower plasma concentrations.
Lamotrigine precautions and safety in special populations
Preferred drug (the two L’s) for pregnancy.
Known to deplete folate levels – should take folic acid 5mg per day if wanting to become pregnant for 4 weeks before conception and the first 12 weeks of pregnancy.
Concentration levels known to decrease during pregnancy (increased excretion)
Lamotrigine advice and self care
Seek medical advice immediately if a rash occurs within the first 8 weeks.
Melatonin indications
Short term primary insomnia (aged 55 and older)
Long term use (persistent and distressing insomnia secondary to a neurodevelopmental disorder such as autism, ADHD and have not responded successfully to behavioural or environmental approaches).
Melatonin mechanism of action
Hormone produced in the pineal gland that facilitates sleep onset.
Melatonin dosage
2-3mg 1-2 hours before bedtime
Melatonin adverse effects
Headache, diarrhoea, arthralgia (joint pain)
Melatonin interactions and contraindications
Avoid benzodiazepines and other hypnotics, caffeine and alcohol.
Melatonin precautions and safety in special populations
Not recommended in hepatic impairment
