Neurology

Question 1

Levodopa

Answer 1

**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

Question 2

Apomorphine

Answer 2

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’.

Question 3

Bromocriptine

Cabergoline

Pergolide

Answer 3

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

Question 4

Ropinirole

Rotigotine

Pramipexole

Answer 4

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

Question 5

Selegiline

Rasagiline

Answer 5

**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.

Question 6

Entacapone

Tolcapone

Answer 6

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

Question 7

Amantadine

Answer 7

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

Question 8

Procyclidine

Benzhexol

Answer 8

**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

Question 9

Valproate

(Sodium valproate)

Answer 9

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

Question 10

**Carbamezepine **

(Tegretol)

Answer 10

**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

Question 11

Phenytoin

Answer 11

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.

Question 12

Lamotrigine

Answer 12

**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.

Question 13

Ethosuximide

Answer 13

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

Question 14

Vigabatrin

Answer 14

**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)

Question 15

Sumatriptan

Rizatriptan

Answer 15

Indications: Acute migraine

MOA: Anti-migraine –> 5HT_1B/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!!

Question 16

Ergotamine

Answer 16

**Indications: **Acute migraine, migraines unresponsive to analgesics

MOA: Anti-migraine –> Ergot family, partial 5HT_1BR 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

Question 17

Pizotifen

Answer 17

**Indications: **Prevention of vascular headache including migraines and cluster headaches

MOA: _Anti-migraine _–> Serotonin antagonist (mainly 5HY_2AR’s + 5HT_2CR’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!!

Question 18

Amitriptylline

Answer 18

**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.

Question 19

Methylprednisolone

Answer 19

**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)

Question 20

Interferon- B₁

Answer 20

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

Question 21

Glatiramer

Answer 21

**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:

Question 22

Natalizumab

Answer 22

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

Question 23

Alemtuzumab

Answer 23

**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:

Question 24

Baclofen

Answer 24

**Indications: **Chronic severe spasticity from disorders such as MS or spinal cord injury

MOA: Agonist for GABA_B-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

Question 25

Dantrolene

Answer 25

**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

Question 26

Oxybutynin

Answer 26

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

Question 27

Metoclopramide

Prochloperazine

Domperidone

Answer 27

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

Question 28

Ondansetron

Answer 28

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:

Question 29

Cyclizine

Cinnarizine

Answer 29

**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:

Question 30

Hyoscine hydrobromide

Answer 30

**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:

Question 31

Dexamethasone

Answer 31

**Indications: **N+V associated with chemo + surgery

MOA: Steroid –> unknown anti-emetic effect

S/E’s: as per all steroids

CI’s:

Interactions:

Other:

Question 32

Aprepitant

Answer 32

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:

Question 33

Paroxetine

Citalopram

Fluoxetine

Sertraline

Answer 33

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.

Question 34

Venlafaxine

Answer 34

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

Question 35

Amitriptyline

Clomipramine

Imipramine

Doxepin

Nortriptyline

Answer 35

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

Question 36

Phenelzine

Isocarboxacid

Moclobemide (MAO-A)

Selegiline (MAO-B)

Answer 36

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

Question 37

Paracetamol

Answer 37

**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.

Question 38

_Morphine

_Diamorphine

_Fentanyl

_Pethidine

_Oxycodone

_Codeine

_{Dihydrocodeine}

_Tramadol

Answer 38

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).

Question 39

Gabapentin

Pregabalin

Answer 39

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

Question 40

Lithium

Answer 40

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

Question 41

Chlorpromazine

Haloperidol

Sulpiride

Zuclopenthixol

Answer 41

**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

Question 42

Clozapine

Olanzapine

Quetiapine

Risperidone

Answer 42

**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.

Question 43

Diazepam

Lorazepam

Answer 43

**Indications: **Severe anxiety, insomnia

MOA: Anxiolytic –> promote GABA binding to GABA_A 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.

Question 44

Phenobarbitol

Answer 44

Indications: Status epilepticus, all other epilepsy except absence seizures

MOA: Anti-epileptic - potentiates GABA_A receptors

S/E’s: Sedation, resp depression

CI’s: Severe renal/hepatic impairment

**Interactions: **TCA’s, CCB’s

Other: CYP inducers

Question 45

Zopiclone

Answer 45

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!!!