15. Drugs that Target Diseases of the Brain

Question 1

What is the function of carbidopa?

Answer 1

Stops levodopa being broken down peripherally so more is available in the brain

Question 2

What are the side effects of levodopa?

Answer 2

Dizziness, nausea and insomnia
Serious: disorientation, psychosis
Long term: dyskinesia, motor fluctuations

Question 3

What drug is used as a rescue therapy for patients with motor fluctuations?

Answer 3

Apomorphine (dopamine agonist)

Question 4

What is dopamine dysregulation syndrome?

Answer 4

Addiction to dopamine therapy

Patient craves medication, shows impulse control disorders

Question 5

How is dopamine dysregulation syndrome treated?

Answer 5

Reduce L-dopa dose

Question 6

When are dopamine agonists used?

Answer 6

First line in patients under 65 as fewer motor complications than L.dopa
Later in the progression of Parkinsons as nerve terminals aren’t required to convert L.dopa

Question 7

Why are ERGOT dopamine agonists no longer used?

Answer 7

Caused fibrotic reactions in the lungs and pericardium as they were non-selective D1 and D2 agonists

Question 8

Name 3 non-ERGOT dopamine agonists

Answer 8

Ropinirole
Apomorphine
Rotigotine as a patch

Question 9

When are MOA-B inhibitors used?

Answer 9

Less severe, newly diagnosed Parkinsons

Question 10

What are the side effects of MOA-B inhibitors?

Answer 10

Orthostatic hypotension, sleep disorders
Can’t have tyramine containing foods
Serotonin syndrome

Question 11

What is the MOA of COMT inhibitors?

Answer 11

Entacopone inhibits peripheral COMT

Tolcapone inhibits central and peripheral COMT

Question 12

What are the side effects of COMT inhibitors?

Answer 12

Urine discolouration, severe diarrhoea
Hepatic toxicity
CV risk with stalevo

Question 13

What drugs are used in mild alzheimer’s disease?

Answer 13

Cholinesterase inhibitors

Eg. donepezil, rivastigmine, galantamine

Question 14

What is the metabolism of donepezil and galantamine?

Answer 14

CYP450

Question 15

What drug is used in severe Alzheimer’s disease?

Answer 15

NMDA antagonists eg. memantine

Question 16

What anti-convulsants are sodium channel inhibitors?

Answer 16

Phenytoin
Carbamazepine
Lamotrigine

Question 17

What type of seizures is phenytoin used for?

Answer 17

Focal and secondary generalised

Question 18

What is the MOA of phenytoin?

Answer 18

Slows rate of channel recovery from inactivated state ie. prevents repetitive firing

Question 19

What are the pharmacokinetics of phenytoin?

Answer 19

Zero order kinetics

CYP450

Question 20

What is the difference between zero order and first order kinetics?

Answer 20

Zero order: same amount eliminated independent of blood conc

First order: dependent on blood conc

Question 21

What are the side effects of phenytoin?

Answer 21

Nystagmus, diplopia, ataxia
Sedation, gingival hyperplasia
Hirsutism

Question 22

What are the long term effects of phenytoin?

Answer 22

Coarse facial features

Mild peripheral neuropathy

Question 23

What type of seizures is carbamazepine useful in?

Answer 23

Generalised

Question 24

What are the pharmacokinetics of carbamazepine?

Answer 24

1st order

CYP450

Question 25

What are the side effects of carbamazepine?

Answer 25

Diplopia Ataxia Agranulocytosis

Question 26

What are the side effects of lamotrigine?

Answer 26

Steven-Johnson syndrome TEN skin syndrome Anaemia

Question 27

Which anti-convulsants are calcium channel inhibitors?

Answer 27

Ethosuximide | Sodium valproate

Question 28

What is the MOA of ethosuximide?

Answer 28

Block global T-type calcium channels

Question 29

What seizures is ethosuximide used for?

Answer 29

Absence

Question 30

What are the side effects of ethosuximide?

Answer 30

``` Fatigue GI distress Headache Itching Stevens-Johnson ```

Question 31

What is the MOA of sodium valproate?

Answer 31

Slows rate of Na+ channel recovery Limits T ca++ channel activity Inhibits GABA metabolism

Question 32

What seizures is sodium valproate used for?

Answer 32

Generalised

Question 33

What are the side effects of sodium valproate?

Answer 33

``` GI distress Hepatotoxicity Neural tube defects Tremor Weight gain ```

Question 34

Which drugs are GABA-A receptor modulators?

Answer 34

Benzodiazepines | Barbituates

Question 35

Which seizure types are benzodiazepines used for?

Answer 35

Focal Tonic clonic Status epilepticus

Question 36

How is a benzodiazepine overdose reversed?

Answer 36

Flumazenil

Question 37

Name 2 drugs that inhibit GABA metabolism

Answer 37

Tiagabine (competitive) | Vigabatrin (irreversible)

Question 38

Name a GABA analogue

Answer 38

Gabapentin