1- Principles Flashcards
Pharmacology
Study of interaction of exogenous substances and the body
Xenobiotic
Foreign substance that is administered to the body
Not all are pharmacologically active
Pharaceutical
Pharmacological agent administered for a medical purpose
Oral Administration- Advantage
Compliance/easy to take
Easier to excrete during overdose
Oral Administration- Disadvantage
First pass
Taste (compliance?)
Slow absorption
Sublingual- Advantage
Fas absorption (goes directly to blood stream)
Bypasses first pass effect
Dermal- Advantage
Compliance
Slow release (lasts longer)
Targets specific area
Bypasses first pass effect
Inhalation- Advantage
Very fast absorption
Avoid first pass effect
Inhalation- Disadvantage
High potential for overdose
Dermal- Disadvantage
Potential for allergic reaction
P Glycoprotein
Backup system to BBB
If a molecule gets through endothelial cells, P-Glycoprotein transporter will pump it back out so it never reaches the brain
Characteristics of Drugs that Cross BBB
Not hydrophillic
May cross if hydrophobic (i.e. nicotine)
Can depend on octanol/water partition coefficient)- Diphenhydramine vs. Loratadine
Not subject to efflux transporters such as P-Glycoprotein- Morphine vs loperamide
Paracellular Transport
Temporarily disrupt tight junctions via osmotic shock, electric field, focussed ultrasound
Not very practical- don’t want to disrupt for too long or hormones, bacteria…etc will enter brain
Transporter Mediated Transport
Mimic endogenous entities like glucose and insulin
Lipophilic Diffusion
Many brain penetrant xenobiotics are lipophilic
i.e. ethanol, nicotine, BCZ, opiates
Receptor Mediated Transytosis
Receptor mediated endocytosis from vascular lumen. transport through cytoplasm and exocytosis intro brain
Target receptors for known molecules (i.e. insulin, LDL)- make compounds that resemble that endogenous molecule
Attached xenobiotic to known ligands
Adsorptive Mediated Transcytosis
Positive substance bind to negative endothelial cell membrane- will attached to endothelial cell and diffuse across
involves endocytosis, transport across cytoplasm, exocytosis
Not specific to BBB or brain
Positive cell-penetrating peptides may be used as xenobiotic carriers
Positive cell-penetrating peptides
i..e Penetratin
Transportan
Intracerebroventricular
Drug injected into lateral ventricle
Convection Enhanced Delivery
Stick canula into tissue
Attache pressure pump to administer drug into tissue
Intraparenchymal/Intracerebral
Drug delivered into parenchyma
Intranasal
Mucosal layer in nasal cavity have receptors connected to neurons
Trigeminal nerve innervates nasal cavity
Spray drug and take up into nerve and into extracellular diffusion
Intratympanic
Pierce tympanic membrane with needle, deliver drug, reaches CSF, then brain
