PH2113 - Neuropharmacology 7 Flashcards
What are the routes across the Blood-Brain Barrier?
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
What are the passive mechanisms for molecules to pass across the Blood-Brain Barrier?
Diffusion
- transcellular
- paracellular
What is an ABC transporter?
ATP-binding cassette transporter
Where are ABC transporters found in the Blood-Brain Barrier?
Luminal membrane
- restricting solute movement into brain
What is P-gp?
P-glycoprotein
- an efflux transporter that is important in drug excretion to prevent/ protect from build up in the body
What are MRP?
Multi-drug resistance associated proteins
What is the indication of loperamide?
Decrease the frequency of diarrhoea in gastroenteritis, inflammatory bowel disease and short bowel syndrome
- slows the contractions of the intestines
How does loperamide work?
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
How can loperamide cross the Blood-Brain Barrier?
Concurrent administration of P-glycoprotein inhibitors such as quinidine allows loperamide to cross the Blood-Brain Barrier and produce central morphine-like effects
What are the side effects of taking loperamide with P-glycoprotein inhibitors?
Respiratory depression
- indicative of central opioid action
Give examples of first generation H1 receptor antagonists
Mepryamine
Diphenyhydramine
What are the side effects of first generation H1 receptor antagonists?
Often cause sedation and other CNS side effects by blocking H1-receptor in the CNS
Give examples of second generation H1 receptor antagonists
Cetirizine
Temelastine
Astemizole
Fexofenadine
Why are second generation H1 receptor antagonists more readily used?
Good P-glycoprotein substrates and produce few CNS side effects
What is drug-resistant epilepsy?
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
What percentage of patients have refractory epilepsy?
20 - 40%
What do Animal Models of temporal lobe epilepsy (TLE) drug-resistant animals show?
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
Give three examples of influx transporters that belong to the SLC family?
Monocarboxylic acid transporter - MCT Equilibrative Nucleoside Transporter - ENT Concentrative Nucleoside Transporter - CNT
What is MCT?
Monocarboxylic acid transporter
- simvastatin
- lovastatin
What is ENT?
Equilibrative Nucleoside Transporter
