Pharmacology - Neurology Flashcards
Levodopa
Indications: Parkinson’s disease
MOA: Anti-Parkinsonian –> prodrug converted into dopamine by dopacarboxylase and crosses BBB. It is given with an extra cerebral dopa-decarboxylase inhibitor to decrease its peripheral conversion therefore more crosses the BBB.
S/E’s: Dyskinesias, on-off phenomena, psychosis, mouth dryness, insomnia, N+V, hypotension, end of dose dyskinesia
CI’s: MAOI’s (–> hypertensive crisis), glaucoma, melanoma
Interactions: MOAI’s, effects decreased by antipsychotics, antihypertensives enhance the drop in BP
Other: Loss of response within 2-5years. Give domperidone for N+V. Short half life therefore take TDS.
Levodopa + periph dopadecarbox inhib = Carbidopa
Apomorphine
Indications: Parkinson’s disease - refractory motor fluctuations inadequately controlled by carbidopa - for ‘off’ episodes
MOA: Anti-parkinsonian –> non selective DA agonist (both D1 and D2)
S/E’s: Very emetogenic so give 2 days of domperidone before starting, injection site reactions
CI’s: Dementia, respiratory depression, hypersensitivity to opiods, psychosis, pregnancy
Interactions: Ondansetron
Other: Give S/C. Rescue pen for ‘off freezing’.
Bromocriptine
Cabergoline
Pergolide
Indications: Parkinson’s disease, endocrine disorders e.g. hyperprolactinaemia
MOA: Anti-Parkinsonian –> Ergot derived DA agonists
S/E’s: Fibrosis (lung/heart/valves), vasospasm (digits/coronaries), GI upset, postural hypotension, drowsiness, neuropsych syndromes
CI’s: Cardiac valvulopathy, porphyria, psychosis
Interactions: Increased levels with ocreotide and macrolides
Other: Not often used in Parkinson’s due to S/E’s
Ropinirole
Rotigotine
Pramipexole
Indications: Parkinson’s disease alone or with L-Dopa
MOA: Anti-Parkinsonian –> Non ergoline Synthetic Da agonists
S/E’s: GI upset, GORD, hypotension, drowsiness, neuropsych syndromes e.g. hallucinations
CI’s: Severe cardiovascular disease, psychotic disorders, elderly, hepatic/renal impairment, pregnancy
Interactions: Antipsychotics, metoclopramide
Other: Delays the need to start L-Dopa
Selegiline
Rasagiline
Indications: Parkinson’s disease alone or with Carbidopa
MOA: Anti-Parkinsonian –> Selective MAO-B inhibitors therefore prevents intraneuronal degredation of DA. No cheese reaction!
S/E’s: GI upset, insomnia, postural hypotension, bradycardia
CI’s: Active PUD, uncontrolled HTN, arrhthymias
Interactions: TCA’s, MOAI’s, antidepressants
Other: Buccal preparations have better bioavailability. Use alone to delay need for L-Dopa or can be used as an adjunct to lower dose of L-Dopa.
Entacapone
Tolcapone
Indications: Parkinson’s disease - adjunct to other drugs to help with ‘end of dose’ motor fluctuations
MOA: Anti-Parkinsonian –> COMT inhibitor - prevents peripheral DA degredation so DA can cross the BBB
S/E’s: N+V+D, red-brown urine, dyskinesias, hepatotoxic
CI’s: Phaeochromocytoma, hx of neurolepmaligsyndrome or rhabdo
Interactions: MAOI’s, warfarin, sympathomimetics
Other: Decreases the ‘off’ period of L-Dopa
Amantadine
Indications: Parkinson’s disease
MOA: Anti-Parkinsonian –> weak DA agonist and weak anti-cholinergic
S/E’s: GI upset, sleep disturbance, livedo reticularis, neuropsychsyndromes
CI’s: Gast
Interactions:
Other: Can be used in PD for late onset dyskinesia
Procyclidine
Benzhexol
Indications: Parkinson’s disease, drug induced extra-pyramidal side effects
MOA: Anti-parkinsonian –> Procyclide = anticholinergic Benzhexol = antimuscarinic (muscarinic antagonists)
S/E’s: Anti-AchM (dry mouth/constipation/urine reten), memory impairment, confusion
CI’s: Myaesthenia gravis, hepatic/renal impairment
Interactions:
Other: Reduces tremors
Valproate
(Sodium valproate)
Indications: All forms of epilepsy. 1st line in generalised seizures. Mania.
MOA: Anti-epileptic –> Na channel blocker, inhibit action potential generation. Is a CYP inhibitor.
S/E’s: GI upset, hepatotoxic, encephalopathy, weight gain, pancreatitis, hair loss, oedema, ataxia, tremor, low plts
CI’s: Hepatic dysfunction, porphyria, pregnancy (teratogenic)
Interactions: Anti-malarials, TCA’s, antipsychotics, aspirin, warfarinm
Other: Monitor FBC + LFTs before and during
Carbamezepine
(Tegretol)
Indications: Focal seizures, 2nd line generalised seizures, trigeminal neuralgia, bipolar (if lithium fails)
MOA: Anti-epileptic –> Stabilises the inactivated state of voltage gated Na channels so they do not open –> inhibits action potential generation. CYP inducer.
S/E’s: Skin reactions (SJS), blood dyscrasias, hyponatremia (SIADH), fetal neural tube defects, GI upset, hair thinning
CI’s: Unpaced AV conduction defects, pregnancy, bone marrow depression, porphyria, liver disease
Interactions: OCP, doxy, steroids, warfarin, macrolides, verapamil/diltizem, ETOH, NSAIDs, rifampicin
Other: Monitor serum levels (half life 10hrs), U+E’s, LFTs and FBC
Phenytoin
Indications: Partial seizures, generalised seizures, status epilepticus
MOA: Anti-epileptic –> Blocks voltage dependent gated Na channels. CYP inducer.
S/E’s: Acute = drowsiness, cerebellar signs, rash. Chronic = gingival hypertrophy, hirsutism/acne, low folate
CI’s: Sinus bradycardia, SANblock, 2/3rd degree heart block, porphyria, pregnancy (cleft palate risk)
Interactions: OCP, doxy, steroids, warfarin, antiepileptics, macrolides, verapamil, EtOH, NSAIDs…
Other: Albumin bound –> zero order kinetics therefore need therapeutic drug monitoring. Monitor FBC.
Lamotrigine
Indications: Focal seizures, generalised seizures, seizures assoc with lennox gastaut syndrom, Bipolar (depression)
MOA: Anti-epileptic –> Na channel blocker, also blocks Ca channel receptor/channels therefore inhibits release of glutamate
S/E’s: Rashes (SJS/TEN/lupus), cerebellar signs, blood dyscrasias, hepatotoxic.
CI’s: Lower dose in renal/liver disease, can exacerbate Parkinson’s disease
Interactions: OCP, phenytoin, TCA’s, SSRI’s, valproate
Other: Monitor U+E’s, LFT’s, FBC, clotting. Stop if any signs of rash!! Safest drug in epilepsy.
Ethosuximide
Indications: Typical/Atypical absence seizures
MOA: Anti-epileptic –> Succinimide anticonvulsant - Ca channel blocker
S/E’s: GI upset
CI’s: Avoid abrupt withdrawal, acute porphyria
Interactions: Phenytoin, antidepressants, antipsychotics
Other: Only used in childhood absence seizures
Vigabatrin
Indications: In combo with other antiepileptics, focal epilepsy. Do not use unless other Rx has failed.
MOA: Anti-epileptic –> Irreversibly inhibits GABA transaminase therefore stops GABA being broken down
S/E’s: Visual field defects, nausea, abdo pain
CI’s: Visual field defects, elderly, psychosis
Interactions: Antidepressants, antipsychotics, st johns wort
Other: Can be prescribed as monotherapy in West’s syndrome (infantile spasms)
Sumatriptan
Rizatriptan
Indications: Acute migraine
MOA: Anti-migraine –> 5HT1B/1D receptor agonist therefore reverses dilation of cerebral vessels (causes vasoconstriction)
S/E’s: Tingling, heaviness, pressure, tightness sensations, flushing, dizziness, fatigue, N+V
CI’s: IHD, prev MI, Prinzmetal’s, uncontrolled HTN, TIA/CVA, PVD
Interactions: SSRI’s, MAOI’s
Other: Don’t use if >2/3 per week/chronic migraines i.e. only for acute migraines!!
Ergotamine
Indications: Acute migraine, migraines unresponsive to analgesics
MOA: Anti-migraine –> Ergot family, partial 5HT1BR agonists causing vasoconstriction of intracranial blood vessels
S/E’s: GI upset, dizziness
CI’s: PVD, IHD, coronary vasospasm, raynauds, uncontrolled HTN, hyperthyroidism
Interactions: Azoles, cimetidine
Other: Use limited by S/E’s
Pizotifen
Indications: Prevention of vascular headache including migraines and cluster headaches
MOA: Anti-migraine –> Serotonin antagonist (mainly 5HY2AR’s + 5HT2CR’s), also some antihistamine activity
S/E’s: Dry mouth, nausea, dizziness, weight gain
CI’s: Urinary retention, closed angle glaucoma, epilepsy
Interactions:
Other: Prophylaxis medicine!!
Amitriptylline
Indications: Depressive illness (not first line), neuropathic pain (unlicensed) and migraine prophylaxis
MOA: Anti-migraine –> 5HT and NA reuptake inhibitor
S/E’s: Arrhythmias, heart block (in OD get long Qt–>Torsadesdp) + anticholinergic, anti-adrenergic and anti-histamine effects
CI’s: Just after MI, arrhythmias, manic phase of BPAD
Interactions: MOAI, amiodarone, SSRI’s
Other: Hepatic metabolism.
Methylprednisolone
Indications: Suppression of inflammation in acute MS relapse, Allergic disorders, Severe IBD, Cerebral oedema assoc with malignancy, Rheumatic diseases
MOA: Inhibits PLA2 –> decreased PG + PAF –> decreased PMN extravasation therefore increased PMN in blood –> lymphopenia, decreased phagocytosis and Ab production + cytokines + proteolytic enzymes
S/E’s: Cushing’s syndrome, DM, central obesity, dyslipidaemia, PUD, OP, hirsuitism, acne
CI’s:
Interactions:
Other: High dose for relapse of MS (1g/day for 3-5days)
Interferon- B1
Indications: MS relapse/prevention
MOA: Balances the expression of pro and anti inflammatory agents in the brain, decreases amount of inflammatory cells crossing the BBB –> decreases neuronal inflammation
S/E’s: Injection site reactions, flu like symptoms, N+V, depression
CI’s: Severe renal/hepatic impairment, cardiac disease, depression/suicide, myelodepression
Interactions:
Other: Monitor LFT’s
Glatiramer
Indications: MS (decreases frequency of relapses)
MOA: Random polymer of 4 a/acids found in myelin basic protein –>?acts as a decoy for the immune system
S/E’s: Hypersensitivity reactions, flushing, chest pain, tachycardia, palpitations, N+D+C, flu like symptoms
CI’s: Cardiac disorders
Interactions:
Other:
Natalizumab
Indications: Active relapsing remitting MS despite Rx with interferon B1
MOA: Monoclonal Ab –> inhibits migration of leucocytes into the CNS therefore decreasing inflammation + demyelination (anti alpha4integrin)
S/E’s: Increased risk of opportunistic infection + PML, N+V, flushing, headache, dizziness, fatigue, pyrexia, anaphylaxis
CI’s: caution if prev Rx with immunosuppression as further immune depression increases risk of PML
Interactions:
Other: Monitor LFT’s
Alemtuzumab
Indications: Used for CLL, cutaneous T cell lymphoma, T cell lymphoma and in clinical trials for MS
MOA: Monoclonal Ab –> Anti CD52
S/E’s:
CI’s:
Interactions:
Other:
Baclofen
Indications: Chronic severe spasticity from disorders such as MS or spinal cord injury
MOA: Agonist for GABAB-R’s, inhibits nerve transmission at the spinal level –> skeletal muscle relaxation
S/E’s: GI upset, dry mouth, hypotension, resp/cardio depression, sedation, confusion, decreased tone
CI’s: Caution in psych illness, Parkinson’s, CVA, epilepsy, resp impairment, PUD
Interactions: Increased effects with TCA’s
Other: Rx for painful muscle spasms. Do not stop abruptly –> can cause hyperthermia, convulsions, increased spasticity
Dantrolene
Indications: Chronic severe spasticity of voluntary muscle, malignant hyperthermia
MOA: Depresses excitation - contraction coupling in skeletal muscle by binding to the ryanodine receptor and decreasing free intracellular Ca2+ concentration
S/E’s: N+D+V, anorexia, hepatotoxic
CI’s: Acute muscle spasms, caution in reduced cardiac/resp function
Interactions:
Other: Therapeutic effect can take several weeks –> stop if no response within 6-8weeks
Oxybutynin
Indications: Urinary frequency/urgency/incontinence, neurogenic bladder, nocturnal enuresis
MOA: Anti-muscarinic
S/E’s: Dry mouth, GI upset, blurred vision
CI’s: Myaesthenia gravis, GI/bladder obstruction
Interactions: TCA’s
Other: Used for detrusor instability in MS
Metoclopramide
Prochloperazine
Domperidone
Indications: Symptomatic relief of N+V caused by GORD, chemo, morning after pill, opiates, migraine, vestibular
MOA: Anti-emetics - D2-R antagonist –> blocks dopamine R’s in the chemoreceptor trigger zone. Also gastroprokinetic activity increases tone of LOS.
S/E’s: Extrapyramidal side effects (NB.oculogyric crisis), drowsiness, rash
CI’s: GIT obstruction/perf/haemorrhage, phaeo, prolactinoma, renal/hepatic impairment
Interactions: Antipsychotics increase EPSE’s
Other: Domperidone does not cross the BBB therefore less EPSE’s than the others
Ondansetron
Indications: Post op N+V (Rx and prevention), Chemo
MOA: Anti-emetics - 5HT3R antagonist. CYP metabolism
S/E’s: Constipation, headache
CI’s: Congenital long Qt syndrome
Interactions: Levels decreased by rifampicin, CBZ, phenytoin
Other:
Cyclizine
Cinnarizine
Indications: Nausea, vomiting, vertigo, motion sickness, labyrinthine disorders
MOA: Anti-emetic – Anti-histamines
S/E’s: Drowsiness, headache, anti-muscarinic effects
CI’s: Caution in BPH, urinary retention, closed angle glaucoma, epilepsy, heart failure
Interactions: MAOI’s, opioids (increase sedative effect)
Other:
Hyoscine hydrobromide
Indications: Motion sickness, hypersalivation assoc with clozapine therapy, excessive respiratory secretions
MOA: Anti-emetic - Anti muscarinic
S/E’s: Anti-muscarinic effects, drowsiness
CI’s: Caution in GORD, UC, MI, HTN, BPH, autonomic neuropathy, glaucoma, MG, pyloric stenosis, toxic megacolon, paralytic ileus
Interactions: decreases the effects of GTN
Other:
Dexamethasone
Indications: N+V associated with chemo + surgery
MOA: Steroid –> unknown anti-emetic effect
S/E’s: as per all steroids
CI’s:
Interactions:
Other:
Aprepitant
Indications: Adjunct to dexamethasone and 5HT3R antagonists in preventing N+V assoc with moderate and highly emetogenic chemotherapy
MOA: Anti-emetic - substance P antagonist –> neurokinin 1 receptor blocker
S/E’s: Hiccups, dyspepsia, N+D+C, anorexia, headache
CI’s:
Interactions:
Other:
Paroxetine
Citalopram
Fluoxetine
Sertraline
Indications: Major depression, OCD, panic disorder, suicial thoughts, PTSD, social/generalised anxiety disorder
MOA: Anti-depressants – SSRS’s, increase serotonin levels
S/E’s: GI upset, weight gain, insomnia, headache, sexual dysfunction, SIADH, withdrawal effects
CI’s: Mania, children <18 (except fluoxetine)
Interactions: P450 inhibitor –> increased levels with TCA’s, benzo’s, clozapine, haloperidol, phenytoin, increased bleeding risk with aspirin
Other: SSRI’s + MAOI = serotonin syndrome (headache, agitation, coma, confustion, sweating, tacchy, palpitations, HTN, pyrexia, myolclonus, increased tone. Start SSRI’s 2 weeks after stopping MAOI.
Takes 4-6 weeks for full clinical effects.
Venlafaxine
Indications: Major depression, generalised anxiety disorder
MOA: Serotonin noradrenaline reuptake inhibitor (SNRI)
S/E’s: GI upset, HTN, palpitations, yawning, long Qt, SIADH, rash
CI’s: High risk of arrhythmias, uncontrolled HTN, caution in heart disease, DM, epilepsy, mania
Interactions: Increased risk of bleeding with aspirin
Other: 2nd line anti-depressant.Stop if any sign of rash. SNRI + MAOI = serotonin syndrome
Amitriptyline
Clomipramine
Imipramine
Doxepin
Nortriptyline
Indications: Depression –> severe, insomnia. Neuropathic pain + migraine prophylaxis
MOA: Anti-depressants - TCA’s, inhibits 5HT and NA uptake
S/E’s: Anti-adrenergic –> postural hypotension, sedation, H1 –> drowsiness, weight gain, AntiAchM –> arrhythmias, heart block
CI’s: MI, arrhythmias, liver disease, mania
Interactions: MAOI’s –> HTN + CNS excitation, SSRI’s, amiodarone, TCA’s decrease seizure threshold therefore decreases effect of AED’s
Other: Do NOT give if suicidal ideation, very dangerous in OD. TCA TOXICITY = metabolic acidosis, dilated pupils, increased tone and reflexes, extenor plantars, seizures, tacchy, long QT/TdeP, hypoventilation. Treatement = NaHCO3
Phenelzine
Isocarboxacid
Moclobemide (MAO-A)
Selegiline (MAO-B)
Indications: Depression
MOA: Anti-depressants - MAOI’s
Phenelzine = non selective
S/E’s: Postural hypotension, dizziness, sedation, anti AchM
CI’s: Cerebrovasc disease, phaeo
Interactions: Hypertensive crisis –> tyramine containing foods (CHEESE REACTION) or opioids esp pethidine.
Other: MAO-A = adrenaline, NA, 5HT, tyramine, DA
MAO-B = DA
Paracetamol
Indications: Mild-Mod pain, anti-pyretic
MOA: Analgesic - COX2 inhibition –>prevents formation of pro-inflammatory molecules, decreases amount of prostaglandin E2 in CNS therefore decreasing the set point in the thermoregulatory centre
S/E’s: Hepatic failure in OD
CI’s: Renal/hepatic impairment incl ETOH dependence
Interactions:
Other: Paracetamol OD = usually asymptomatic or can get abdo pain, low glucose, vomiting. Ix - do ABG, FBC, glu, LFT’s, clotting, U+E. Treatment = remove drug i.e if within 1 hr of ingestion use gastric lavage, if under 8hrs since ingestion use activated charcoal. Start NAC. Consider transferring to specialist liver centre.
Morphine
Diamorphine
Fentanyl
Pethidine
Oxycodone
Codeine
Dihydrocodeine
Tramadol
Indications: Mod-severe pain esp if visceral origin
MOA: Analgesic - effects mediated by µ receptor in dorsal horn, periaqueductal grey matter and midline raphe nucleus
S/E’s: CNS –> Resp depression, sedation, N+V, euphoria, miosis, anti-tussive, dependance/tolerance
Non-CNS –> constipation, urine retention, hypotensive and bradycardic, pruritis
CI’s: Acute resp depression, paralytic ileus, raised ICP, head injury, hepatic failure, alcohol intoxification
Interactions: MAOI’s
Other: Opioids decrease pupil size therefore can not assess neurological status when consumed. Treatment in OD = naloxone
Strong opioids = morphine, diamorphine, fentanyl, pethidine, oxycodone
Weak opioids = codeine, dihydrocodeine, tramadol (can cause seizures).
Gabapentin
Pregabalin
Indications: Focal seizures, peripheral neuropathic pain, migrane prophylaxis
MOA: Analgesic - unknown MOA
S/E’s: Sedation, cerebellar signs, dizziness, periph oedema
CI’s: Avoid abrupt withdrawal, caution in eldery/DM
Interactions: Effects decreased by antidepressants and antimalarials
Other: Pregabalin is a more potent gabapentin analogue
Lithium
Indications: Rx/propylaxis of mania, BPAD, recurrent depression, aggression/self harming behaviour
MOA: Unknown –> mood stabiliser
S/E’s: Polyuria, polydipsia (nephrogenic DI), nephrotoxic (renal tubular acidosis), GI upset, fine tremor, hypothyro
CI’s: Dehydration, Addison’s, hypothryoid if unRxed, kidney disease, poor compliance
Interactions: Toxicity increased by NSAID’s, diuretics, ACEi/ARB’s, EToH, low Na, dehydrated
Other: Monitor drug levels, narrow therapeutic range, U+E’s, TFT’s
Chlorpromazine
Haloperidol
Sulpiride
Zuclopenthixol
Indications: Acute pyschosis, acute mania, schizophrenia
MOA: Typical antipsychotics –> DA antagonists, central post synaptic D2 blockade
S/E’s: Sedation, anti-AchM, EPSE’s, neuroleptic malignant syndrome, long QTc, postural hypotension, weight gain, hyperprolactinaemia, sexual dysfunction
CI’s: Comatose states, CNS depression, phaeo
Interactions: lithium, TCA’s
Other: Monitor FBC, U+E, LFT’s
Clozapine
Olanzapine
Quetiapine
Risperidone
Indications: Schizophrenia
MOA: Atypical anti-psychotics –> DA antagonists (no EPSE’s)
S/E’s: Clozapine–> agranulocytosis. All –> weight gain, DM, sedation. Risperidone –> hyperprolactinaemia
CI’s: CVD, PD, epilepsy, MG, BPH, glaucoma, coma’s
Interactions:
Other: Can still get EPSE’s with high doses.
Diazepam
Lorazepam
Indications: Severe anxiety, insomnia
MOA: Anxiolytic –> promote GABA binding to GABAA receptors
S/E’s: Sedation, resp depression, withdrawal, psychomotor impairment
CI’s: Resp depression
Interactions: Antipsychotics, azoles, macrolides, EToH
Other: Rx of OD = Flumazil. Hepatic metabolism. Temporary use only as dependance/tolerance develops very fast.
Phenobarbitol
Indications: Status epilepticus, all other epilepsy except absence seizures
MOA: Anti-epileptic - potentiates GABAA receptors
S/E’s: Sedation, resp depression
CI’s: Severe renal/hepatic impairment
Interactions: TCA’s, CCB’s
Other: CYP inducers
Zopiclone
Indications: Insomnia, short term use only (4 days max)
MOA: Non-benzodiazepine
S/E’s: Taste disturbance, N+V
CI’s: Marked neuromuscular weakness (MG, resp failure, sleep ap)
Interactions:
Other: Highly addictive!!!
