Anti-PD, Alzheimers, Anticonvulsants, Antiemetics

Question 1

Why do you give L-DOPA in Parkinson’s treatment

Answer 1

Dopamine cannot dross the BBB

L-DOPA can (TH is rate limiting)

Question 2

Why is L-DOPA not a disease modifying drug?

Answer 2

It improves motor symptoms (quality of life) but it doesn’t improve mortality

Question 3

Why must you give Carbidopa and Benserazide when given L-DOPA?

Answer 3

Inhibits peripheral DOPA decarboxylase as it cannot cross BBB

Peripheral breakdown of L-DOPA to dopamine causes nausea and vomiting

Also means maximal amount of L-DOPA reaches brain hence reduced dosage

Question 4

What are the side effects of Dopamine replacement in Parkinson’s and what improves them

Answer 4

Dyskinesias and on off effects as doesn’t mimic natural release of dopamine in the nigrostriatal pathway

COMT inhibitors increase the gradual effects of L-dopa in the brain

Question 5

Examples of COMT inhibitors used for increased effectiveness for levodopa

Answer 5

Entacapone

Tolcapone

Question 6

What types of GPCR are D1 and D5 receptors?

Answer 6

Gs

Question 7

What types of GPCRs are D2, D3, D4 receptors?

Answer 7

GI

Question 8

What are dopamine receptor angonists?

Answer 8

PD treatment:

• Ergot derivatives (bromocriptine & pergolide)
• non-ergot derivatives (ropinirole)

Question 9

Side effects of ergot derivatives (D2 agonists)

Answer 9

Cardiac fibrosis 
Impulsive disorders (eg gambling)

Question 10

How can D2 agonist side effects be limited?

Answer 10

Non ergot derivatives prevent cardiac fibrosis

Ropinirole and Rotigotine available as slow release gel and patch which stops the on off effects

Question 11

How does selegiline and rasigiline work?

Answer 11

They are MAOB inhibitors, they increase the endogenous levels of L-DOPA before dopamine replacement

Question 12

Alzheimer’s disease drugs

Answer 12

NMDA receptor blockers

Anticholinesterases

Question 13

What anticholinesterases are used in Alzheimer’s disease

Answer 13

Donezepil (long half life)
Rivastigmine (also blocks BchEs)
Galantine (a7 nAchR agonist)

Question 14

What are NMDA blockers used for in Alzheimer’s disease

Answer 14

For severe disease, increased NMDA transmission in neurodegeneration.

Memantine, use dependant non competitive blocker with low channel affinity and long plasma half life

Question 15

Drugs for Chemotherapy induced nausea and vomiting

Answer 15

• Ondansetron (5HT3aR antagonist)
• glucocorticoids (reduce free radicals)
• Ariprepant (neurokinin 1 receptor antagonist)

Question 16

Drugs for motion sickness

Answer 16

• Promethazine (H1 antagonist on vestibular nuclei)

- Hyoscine (non selective muscarinic receptor antagonist)

Question 17

What drugs can be used to reduced GI induced vomiting

Answer 17

Metoclopramide

• D2 receptor antagonist (inhibits CTZ receptor antagonist and prokinetic of stomach)
• 5HT3a receptor antagonist

Question 18

Side effects of ondansetron

Answer 18

(5HT receptor antagonist)

• Constipation
• Headaches

Question 19

Side effects of Promethazine

Answer 19

(H1 antagonist)

• drowsiness

Question 20

Side effects of hyoscine

Answer 20

• dry mouth
• drowsiness

Anti-cholinergic

Question 21

Side effects of Metaclopramide

Answer 21

D2 antagonist

• EPS
• galactorrhea

Question 22

What does carbamazepine do?

Answer 22

• Stabilises inactive state of VG sodium channel hence reduced glutamatergic excitability

Used in tonic clonic and partial seizures

Question 23

Pharmacokinetics of epileptic drugs

Answer 23

• fast onset

- long half life

Question 24

How does lamotrigine work?

Answer 24

Inactivates voltage gated sodium channels hence reducing glutamatergic activity

Used for tonic clonic and absence seizures

Question 25

How does ethosuximide work?

Answer 25

T type calcium channel antagonist hence less exocytosis of glutamate Used in absence seizures

Question 26

How does leviteracetam work?

Answer 26

Binds to SV2A protein preventing exocytosis of glutamate Used in myoclonic seizures

Question 27

How does Topirimate work?

Answer 27

Inhibits NMDA and Kainate glutamate receptors hence decreased sodium influx into the post synaptic membrane Used in myoclonic seizures

Question 28

How does diazepam work?

Answer 28

Given as a rectal gel for fast onset for status epilepticus Positive allosteric modulator hence increased GABA transmission

Question 29

What is sodium valproate (Valium) used for?

Answer 29

Inhibits GABA transaminase hence increasing GABA transmission Used for all types of epilepsy