1- Principles

Question 1

Pharmacology

Answer 1

Study of interaction of exogenous substances and the body

Question 2

Xenobiotic

Answer 2

Foreign substance that is administered to the body

Not all are pharmacologically active

Question 3

Pharaceutical

Answer 3

Pharmacological agent administered for a medical purpose

Question 4

Oral Administration- Advantage

Answer 4

Compliance/easy to take

Easier to excrete during overdose

Question 5

Oral Administration- Disadvantage

Answer 5

First pass
Taste (compliance?)
Slow absorption

Question 6

Sublingual- Advantage

Answer 6

Fas absorption (goes directly to blood stream)

Bypasses first pass effect

Question 7

Dermal- Advantage

Answer 7

Compliance

Slow release (lasts longer)

Targets specific area

Bypasses first pass effect

Question 8

Inhalation- Advantage

Answer 8

Very fast absorption

Avoid first pass effect

Question 9

Inhalation- Disadvantage

Answer 9

High potential for overdose

Question 10

Dermal- Disadvantage

Answer 10

Potential for allergic reaction

Question 11

P Glycoprotein

Answer 11

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

Question 12

Characteristics of Drugs that Cross BBB

Answer 12

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

Question 13

Paracellular Transport

Answer 13

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

Question 14

Transporter Mediated Transport

Answer 14

Mimic endogenous entities like glucose and insulin

Question 15

Lipophilic Diffusion

Answer 15

Many brain penetrant xenobiotics are lipophilic

i.e. ethanol, nicotine, BCZ, opiates

Question 16

Receptor Mediated Transytosis

Answer 16

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

Question 17

Adsorptive Mediated Transcytosis

Answer 17

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

Question 18

Positive cell-penetrating peptides

Answer 18

i..e Penetratin

Transportan

Question 19

Intracerebroventricular

Answer 19

Drug injected into lateral ventricle

Question 20

Convection Enhanced Delivery

Answer 20

Stick canula into tissue

Attache pressure pump to administer drug into tissue

Question 21

Intraparenchymal/Intracerebral

Answer 21

Drug delivered into parenchyma

Question 22

Intranasal

Answer 22

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

Question 23

Intratympanic

Answer 23

Pierce tympanic membrane with needle, deliver drug, reaches CSF, then brain