PH2113 - Neuropharmacology 7

Question 1

What are the routes across the Blood-Brain Barrier?

Answer 1

Cell migration
- non-polar solutes
- lipid soluble
Passive diffusion
- lipid soluble
- amphiphilic
Carrier-mediated efflux
Carrier-mediated influx
- glucose
- amino acids
- amines
- nucleosides
- monocarboxylates
- small peptides
Receptor-mediated transcytosis
- transferrin
- insulin
- leptin
- cytokines
- viruses
Adsorptive-mediated transcytosis
- histone
- avidin
- cationised albumin
Tight Junction modulation
- polar solutes

Question 2

What are the passive mechanisms for molecules to pass across the Blood-Brain Barrier?

Answer 2

Diffusion

• transcellular
• paracellular

Question 3

What is an ABC transporter?

Answer 3

ATP-binding cassette transporter

Question 4

Where are ABC transporters found in the Blood-Brain Barrier?

Answer 4

Luminal membrane

- restricting solute movement into brain

Question 5

What is P-gp?

Answer 5

P-glycoprotein

- an efflux transporter that is important in drug excretion to prevent/ protect from build up in the body

Question 6

What are MRP?

Answer 6

Multi-drug resistance associated proteins

Question 7

What is the indication of loperamide?

Answer 7

Decrease the frequency of diarrhoea in gastroenteritis, inflammatory bowel disease and short bowel syndrome
- slows the contractions of the intestines

Question 8

How does loperamide work?

Answer 8

Opioid agonist does not cross the Blood-Brain Barrier
- when used at normal doses
Acts on the mu-opioid receptors in the myenteric plexus of the large intestine

Question 9

How can loperamide cross the Blood-Brain Barrier?

Answer 9

Concurrent administration of P-glycoprotein inhibitors such as quinidine allows loperamide to cross the Blood-Brain Barrier and produce central morphine-like effects

Question 10

What are the side effects of taking loperamide with P-glycoprotein inhibitors?

Answer 10

Respiratory depression

- indicative of central opioid action

Question 11

Give examples of first generation H1 receptor antagonists

Answer 11

Mepryamine

Diphenyhydramine

Question 12

What are the side effects of first generation H1 receptor antagonists?

Answer 12

Often cause sedation and other CNS side effects by blocking H1-receptor in the CNS

Question 13

Give examples of second generation H1 receptor antagonists

Answer 13

Cetirizine
Temelastine
Astemizole
Fexofenadine

Question 14

Why are second generation H1 receptor antagonists more readily used?

Answer 14

Good P-glycoprotein substrates and produce few CNS side effects

Question 15

What is drug-resistant epilepsy?

Answer 15

Patients with epilepsy whose seizures do not successfully respond to antiepileptic drug (AED) therapy are considered to have drug-resistant epilepsy

• intractable epilepsy
• medically refractory epilepsy
• pharmacoresistant epilepsy

Question 16

What percentage of patients have refractory epilepsy?

Answer 16

20 - 40%

Question 17

What do Animal Models of temporal lobe epilepsy (TLE) drug-resistant animals show?

Answer 17

Increased expression of P-gp in resistant animals vs drug-sensitive responsive animals
Lower cerebral cortex extracellular fluid (ECF) concentrations for phenytoin in resistant animals than in responsive animals
P-gp inhibitors increase extracellular fluid phenytoin concentrations and restore anti-convulsant responsiveness to phenytoin in the previous resistant animal

Question 18

Give three examples of influx transporters that belong to the SLC family?

Answer 18

Monocarboxylic acid transporter
- MCT
Equilibrative Nucleoside Transporter
- ENT
Concentrative Nucleoside Transporter
- CNT

Question 19

What is MCT?

Answer 19

Monocarboxylic acid transporter

• simvastatin
• lovastatin

Question 20

What is ENT?

Answer 20

Equilibrative Nucleoside Transporter