Neuro drugs

Question 1

Used in the treatment of idiopathic PD, symptomatic parkinsonism, CO intoxication, and restless leg syndrome

Answer 1

Madopar/Sinemet

Question 2

L-DOPA/ peripheral decarboxylase inhibitors

Answer 2

Madopar/ Sinemet

Question 3

Side effects of L-DOPA (3)

Answer 3

Dyskinesias, involuntary movements and nausea
Mostly due to activity of dopamine
Reactions can be reduced by lower dose

Question 4

Contraindications of L-DOPA (2)

Answer 4

Narrow angle glaucoma

Suspicious undiagnosed skin lesions of Hx of melanoma (may activate malignant melanoma)

Question 5

How does L-DOPA cross the BBB?

Answer 5

Precursor to dopamine that is able to cross BBB

Question 6

How does L-DOPA become activated?

Answer 6

Converted to dopamine in the periphery AND the CNS by aromatic-L-amino-acid decarboxylase

Question 7

L-DOPA is administered with which drug to inhibit activation in the peripheries

Answer 7

Dopamine decarboxylase inhibitor (DCC) e.g. Carbidopa

Question 8

Excretion of L-DOPA

Answer 8

Renal (70-80%)

Question 9

Metabolism of L-DOPA

Answer 9

95% in stomach, lumen of intestine, kidney, liver and brain

Question 10

Interactions of L-DOPA (4)

Answer 10

Antihypertensives: increase risk of postural hypotension
Antidepressant (TCAs): Hypertension and dyskinesia
Anticholinergics: affect absorption and pt. response
Iron: decrease bioavailability of carbidopa and/or levodopa

Question 11

Control of seizure in status epilepticus when BZDs are ineffective, and to reduced generalised or focal seizures in epilepsy

Answer 11

Phenytoin

Question 12

Side effects of long-term phenytoin Rx

Answer 12

Change in appearance - skin thickening, acne, hirsutism, gum hypertrophy

Question 13

Dose-related side effects of phenytoin (3)

Answer 13

Neurological effects: cerebellar toxicity (nystagmus, ataxia and disco-ordination) and impaired cognition and consciousness

Question 14

Phenytoin causes haematological disorders and osteomalacia by inducing the metabolism of ______ and _____

Answer 14

Folic acid and vitamin D

Question 15

Phenytoin toxicity can cause death through what mechanisms?

Answer 15

Cardiovascular collapse and respiratory depression

Question 16

What is the therapeutic index of phenytoin?

Answer 16

Narrow - increased concentration causes arrhythmia and cerebellar syndrome

Question 17

Exposure to phenytoin in utero causes what? What can be done to avoid this?

Answer 17

Craniofacial abnormalities and reduced IQ - foetal hydantoin syndrome
Women planning pregnancy should take high-dose folic acid prior to contraception

Question 18

MoA of phenytoin

Answer 18

Reduces neuronal excitability and electrical conductance amongst brain cells, inhibiting the spread of seizure activity

Similar effect in cardiac purkinje fibres may account for arrhythmic and cardiotoxic effects

Question 19

Metabolism of Phenytoin

Answer 19

Liver

Question 20

Interactions of phenytoin

Answer 20

Enzyme inducer so reduces plasma conc. and efficacy of drugs metabolised by CYP450 enzymes (warfarin, oestrogen, progesterones)
Metabolised by CYP450, so plasma concentration and adverse effects are increased by CYP450 inhibitors e.g. amiodarone, diltiazem and fluconazole
Complex interactions with other anti-epileptics
Efficacy reduced by drugs lowering the seizure threshold (SSRIs, tricyclic ADs, antipsychotics, tramadol)

Question 21

1st line therapy for focal seizures, Rx of trigeminal neuralgia, Rx of bipolar disease in pts. intolerant to other medications

Answer 21

Carbamazepine

Question 22

Dose-related side effects of Carbamazepine

Answer 22

GI upset

Neurological effects - dizziness and ataxia

Question 23

Hypersensitivity to carbamazepine

Answer 23

Affects 10%, manifests in maculo-papular rash

Question 24

Contraindications of carbamazepine in utero

Answer 24

Neural tube defects, cardiac and urinary tract abnormalities

Take folic acid prior to contraception to avoid

Question 25

MoA of carbamazepine

Answer 25

Inhibition of neuronal Na+ channels, stabilising resting membrane potential and reducing neuronal excitability

Question 26

Treatment efficacy monitoring of carbamazepine

Answer 26

Compare seizure frequency before and after stating treatment

Question 27

Metabolism and excretion of carbamazepine

Answer 27

Hepatic (CYP3A4) | Urinary and faecal excretion

Question 28

CYP450 interactions of carbamazepine

Answer 28

CYP450 inducer, so reduces efficacy of warfarin, oestrogen, progestogens, etc. Metabolised by CYP450 so plasma conc. and adverse effects are increased by CYP450 inhibitors (e.g. marcolides)

Question 29

1st line Rx of epilepsy for controlled generalised or absence seizures, Rx of bipolar disorder for acute treatment of manic episodes

Answer 29

Sodium valproate

Question 30

Neurological side effects of sodium valproate (3)

Answer 30

tremor, ataxia, behavioural disturbances

Question 31

Rare side effects of sodium valproate (4)

Answer 31

severe liver injury pancreatitis bone marrow failure anti-epileptic hypersensitivity syndrome

Question 32

Advice in utero for sodium valproate

Answer 32

Stop taking before conception - more toxic in utero than other anti-convulsants, causes foetal abnormalities

Question 33

MoA of sodium valproate

Answer 33

Weak inhibitor of neuronal Na+ channels, stabilising membrane potential and reducing excitability Also increases brain content of GABA, reducing excitability of neurones

Question 34

Metabolism and excretion of sodium valproate

Answer 34

Hepatic metabolism and mitochondrial beta-oxidation | Urinary excretion

Question 35

CYP450 interactions

Answer 35

As with other anti-convulsants | & CYP450 inducers (phenytoin, carbapenems) may increase seizure risk

Question 36

Adjunctive treatment of partial seizures in epilepsy and maintenance treatment of bipolar disorder and depression

Answer 36

Lamotrigine

Question 37

Side effects of lamotrigine

Answer 37

Skin rash: mild, self-limiting to SJS Clinical worsening and suicide Renal failure - accumulation of glucuronide metabolite Psych: aggression, irritability NS: headache, somnolence, dizziness, tremor, insomnia, agitation

Question 38

MoA of lamotrigine

Answer 38

Chemically unrelated to other AEDs - Phenyltriazene Stabilised presynaptic neuronal membranes by inhibiting sodium current by bind to the inactivated state of the sodium channel Similar action to local anaesthetics

Question 39

Metabolism and excretion of lamotrigine

Answer 39

Hepatic metabolism | Urinary and faecal excretion

Question 40

Drug interactions (2)

Answer 40

Hormonal contraceptive: increase clearance of lamortigine - higher maintenance doses required AEDs: reduction in metabolism - increased concentration

Question 41

Treatment of partial seizures in adults with epilepsy

Answer 41

Levetiracetam

Question 42

Side effects of Levetiracetam

Answer 42

``` AKI Nasopharyngitis Somnolence Headache Fatigue Anorexia Psych. disorders Vertigo ```

Question 43

MoA of levetiracetam

Answer 43

Stimulation of synaptic vesicle 2a (SV2A), inhibiting NT release Inhibition of N-type Ca2+ currents and reduction of Ca2+ release from intraneuronal stores

Question 44

Metabolism and excretion of levetiracetam

Answer 44

Metabolism: enzymatic hydrolysis of acetamide group, no CYP450 metabolism Urinary excretion, unchanged

Question 45

Interactions of levetiracetam (2)

Answer 45

Probenecid: renal tubular secretion-blocking agent, inhibits renal clearance of primary metabolite Methotrexate: decreases methotrexate clearance - potentially toxic blood levels - monitor carefully