Neurology Flashcards
Dopaminergic drugs for PD
E.g. co-beneldopa, co-careldopa, pramipexole, ropinirole
Use: Parkinson’s (ropinirole and pramipexol may be preferred in early disease but in later disease levodopa is an integral part of management), secondary Parkinsonism
MOA: increases dopaminergic stimulation to the striatum, increasing DA in the nigrostriatal pathway (links substantia nigra to corpus striatum). Levodopa is a precursor of DA; ropinirole and pramipexol are selective agonists for the D2 receptor which predominates in the striatum. Levodopa is combined with a DOPA decarboxylase inhibitor (reduces its conversion to DA outside the brain)
Adverse effects: nausea, drowsiness, confusion, hallucinations and hypotension. Levodopa has a wearing off effect (symptoms worsen towards end of dosage interval) which gets worse as duration of therapy increases. Too high a dose may cause dyskinesias.
Cautions: elderly, cognitive or psych disease (increases confusion and hallucinations) and CVD (risk of hypotension)
Interactions: do not combine with first-gen antipsychotics or metoclopramide
Rasagiline, selegiline
Use: PD (mono therapy or as an adjunct in advanced cases)
MOA: irreversible inhibitors of monoamine oxidase B
Adverse effects: abdo pain, angina, anthralgia, arthritis, conjunctivitis, depression, dermatitis, dry mouth, fall, fever, flatulence, hallucinations, headache, increased risk of infection, nausea, pain, postural hypotension, sleep disorder, urinary urgency, vertigo, vomiting
Cautions: breast feeding, mild hepatic impairment (R). Heart problems, ulceration, psychosis (S).
CI: pregnancy and moderate-severe hepatic impairment (R). Active GI ulceration, postural hypotension (S).
Interactions: adrenaline (risk of HTN crisis), increase risk of 5HT syndrome with other serotinergic drugs. Tyramine-rich foods with S.
Entacapone
Use: adjunct to co-beneldopa or co-careldopa in PD with ‘end of dose’ motor fluctuations
MOA: catechol-O-methyltransferase (COMT) inhibitor. When given with levodopa and a decarboxylase inhibitor, plasma levels of levodopa are higher and more sustained. Results in more constant dopaminergic stimulation in the brain.
Adverse effects: abdo pain, confusion, constipation, diarrhoea, dizziness, dry mouth, fall, fatigue, hallucination, hyperhidrosis, IHD, movement disorder, nausea, sleep disorder, urine discolouration, vomiting
Cautions: IHD, levodopa dose may need reducing
CI: hx of neuroleptic malignant syndrome, hx of non-traumatic rhabdomyolysis, pheochromocytoma
Interactions: increased risk of CV events with adrenaline, dobutamine, DA. Decreases absorption of oral iron.
orphenadrine, procyclidine
Use: Parkinsonism, drug-induced extrapyramidal symptoms (not tar dive dyskinesia)
MOA: muscarinic antagonists which can cross the BBB
Adverse effects: constipation, dry mouth, urinary retention, vision blurred
Cautions: CVD, elderly, HTN, BPH, psychotic disorder, pyrexia, those susceptible to angle-closure glaucoma
CI: GI obstruction, acute porphyrias
Interactions:
GABA receptor agonists
E.g. clonazepam, diazepam, lorazepam, phenobarbital Use: epilepsy MOA: Adverse effects: Cautions: CI: Interactions:
Sodium valproate
Use: seizure prophylaxis in epilepsy (first-line for generalised tonic-clonic, absence, focal seizures, myoclonic), established convulsive status epilepticus not responding to benzos, bipolar (acute mania and prophylaxis)
MOA: weak inhibitor of neuronal Na+ channels, stabilising resting membrane potentials and reducing neuronal excitability. Also increases GABA.
Adverse effects: GI upset, neurological and psych effects (tremor, ataxia, behaviour disturbance), thrombocytopenia, transient increase in liver enzymes. Hypersensitivity reactions incl. hair loss.
Cautions: hepatic impairment and severe renal impairment
CI: women of childbearing age
Interactions: inhibits hepatic enzymes, increasing plasma conc. and risk of toxicity of lamotrigine and drugs metabolised by CYP450 (warfarin). Conc. is reduced by CYP inducers (carbamazepine, phenytoin) and increased by CYP inhibitors (macrolide, protease inhibitors). Efficacy reduced by drugs which lower seizure threshold (antipsychotics, tramadol)
Gabapentin, pregabalin
Use: add-on in focal epilepsy, neuropathic pain, GAD
MOA: Binds pre-synaptic voltage-sensitive Ca2+ channels, inhibiting release of excitatory NTMs, reducing neuronal excitability in the brain.
Adverse effects: drowsiness, dizziness, ataxia
Cautions: dose reduction in renal impairment
Interactions: effects may be enhanced by other sedating drugs
Topiramate
Use: generalised tonic-clonic seizures or focal seizures +/- secondary generalisation, migraine prophylaxis
MOA: stimulates GABA-A receptor activity and reduces glutamate activity
Adverse effects: lots
Cautions: acute porphyrias, risk of metabolic acidosis, risk of nephrolithiasis, pregnancy
Interactions: decreases efficacy of hormonal contraceptives
Ethosuximide
Use: absence seizures, myoclonic seizures
MOA: binds to T-type voltage sensitive Ca2+ channels which mediate entry of Ca2+ ions into excitable cells for neurotransmission
Adverse effects: lots
Cautions: acute porphyrias, hepatic impairment, renal impairment
Interactions: increased risk of myelosuppression
Levetiracetam
Use: focal seizures +/- secondary generalisation
MOA: unclear
Adverse effects: anxiety, appetite decreased, asthenia, behaviour, cough, depression, diarrhoea, dizziness, drowsiness, GI discomfort, headache, increased risk of infection, insomnia, mood altered, movement disorders, nausea, skin reactions
Cautions: hepatic impairment, pregnancy, breast feeding, dose reduction in renal impairment
Interactions: CNS depressant effects when combined with depressants
Sumatriptan, zolmitriptan
Use: acute migraine
MOA: 5-HT1 receptor agonist. Causes constriction of cranial BVs and inhibits neurotransmission in the peripheral trigeminal nerve and in the trigeminocervical complex.
Adverse effects: pain or discomfort in the chest and throat, N&V, tiredness, dizziness and transient HTN
CI: coronary artery disease (angina, MI), cerebrovascular disease (stroke), patients with hemiplegic or basilar migraines
Interactions: may increase risk of serotonin toxicity and serotonin syndrome when given with MOIs, tramadol, SSRIs and TCAs
Zolpidem, zopiclone
Use: short-term insomnia
MOA: facilitate and enhance the binding to GABA to GABAa receptor, causing a widespread depressant effect on synaptic transmission. Causes reduced anxiety, sleepiness and sedation.
Adverse effects: daytime sleepiness, rebound insomnia, headache, confusion, nightmares, amnesia. Zopiclone can cause taste disturbance, Zolpidem causes GI upset. Z-drugs can result in dependence and withdrawal symptoms. In OD they cause drowiness, coma and respiratory depression
Cautions: elderly
CI: OSA, respiratory muscle weakness, respiratory depression
Interactions: enhance effects of alcohol, antihistamines and benzos. CYP inhibitors (macrolides) enhance sedation whereas CYP inducers (phenytoin, rifampicin) impairs sedation
Benzos
Use: seizures, status epilepticus, alcohol withdrawal, short-term insomnia
MOA: facilitate and enhance binding of GABA to GABAa receptor, causing widespread depressant effects incl. reduced anxiety, sleepiness and sedation and anti-convulsive effects
Adverse effects: drowsiness, sedation and coma. OD incl. cardiorespiratory depression. May result in dependence and withdrawal reactions.
Cautions: elderly, respiratory impairment, neuromuscular disease, liver failure (can precipitate hepatic encephalopathy)
Interactions: CYP inhibitors (amiodarone, diltiazem, macrolides, fluconazole, protease inhibitors) increases effects
Antibiotics for bacterial meningitis
Benzylpenicillin
Ceftriaxone - cephalosporin
Cefotaxime - cephalosporin
Ampicillin
Corticosteroid for bacterial meningitis and SOLs with local cerebral oedema
Dexamethasone
