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!!!