Pharmacology Flashcards
What is the blood brain barrier?
A specialization of the walls of brain capillaries that limits movement of substances into the ECF of the brain. It restricts access of microorganisms, proteins, cells, drugs into the CNS. Crucua for protection and homeostasis but challenge for drug delivery to brain
What is the blood CSF barrier?
Tight junctions between cuboidal epithelium of choroid plexus that is permeable to some circulating peptides and plasma proteins
What is the function of astrocytes with regards to the BBB?
They induce capillary endothelial cells to form the BBB and maintain tight junctions between them. They have processes with “end feet” that cover more than 95% of the basal lamina adjacent to capillary endothelial cells
What is the function of pericytes with regards to the BBB?
How can substances cross the BBB?
What determines whether a substance will be able to cross the BBB?
Substances should be fairly lipid soluble, need to cross cell membrane
Despite the fact that the BBB is a lipid membrane and substances that are going to cross it should be lipid soluble, many ions and molecules cross that are not lipid soluble. What are some key examples of such molecules?
Glucose
Amino Acids
Vitamin K
Vitamin D
Na+ and K+ cross the BBB through […]
Ion channels
How are drugs removed from the brain?
What is a circumventricular organ?
Structures in the brain that lack normal blood brain barrier function. They have extensive vasculature and fenestrated capillaries so they have a “leaky” BBB. They can be sensory or secretory.
What are the 3 sensory CVOs in the brain?
What is their function?
What are the 5 secretory CVOs in the brain?
What is their function?
What effect does mannitol have on the BBB?
Large / lipid insoluble molecules can be introduced to the brain by transiently disrupting the BBB with a hyperosmotic agent such as mannitol. It opens the BBB by temporarily shrinking the endothelial cells and thus opening the tight junctions between them.
What effect does inflammation have on the BBB?
It disrupts the integrity of the BBB, allowing normally impermeant substances to enter the brain.
What effect does infarction (blood blockage) have on the BBB?
Infarction of brain tissue destroys tight junctions of endothelial cells and results in vasogenic edema, reducing effectiveness of BBB
What is an endorphin?
Endogenous Morphine
Loperamide is an opoid mu-receptor agonist that is permeable to the BBB. However, it really only exerts peripheral effects. Why is this?
It is a substrate for P-glycoprotein which is found in the CNS and uses ATP to remove drugs from the CNS tissue. As such, once it diffuses across the BBB into the CNS, it is removed by the transporter. As such, its actions are peripherally restricted.
What is opium?
The extract of the juice of the poppy that contains many alkaloids related to morphine
What is an opoid?
Any substance that produces morphine like effects that are blocked by antagonists such as naloxone
What is an opiate?
Compounds such as morphine and codeine that are found in the opium poppy
Morphine and Heroin
- What do these stimulate?
- What behavior changes occur?
- Why are the withdrawals so bad?
- neurtransmitters for endorphins
- Decreased pain, euprhoria, warm, happy, withdrawn from world
- Once drug leaves brain, the affected synapses are less responsive, so there is anxiety, pain and exaggerated neurotransmission
What are the 4 classes of opioid receptors?
What type of receptors are they?
Mu, delta, kappa and ORL1
Metabotropic (GPCRs)
Mu Receptors
- Agonists and antagonists
- Effector Mechanism
- Location
- Function
Delta Receptors
- Agonists and antagonists
- Effector Mechanism
- Location
- Function
Kappa Receptors
- Agonists and Antagonists
- Effector Mechanism
- Location
- Function
ORL1 Receptors
- Agonists
- Effector Mechanism
- Location
- Function
- Effects
Additional for effects:
- Nociception
- Anxiety
- Food intake
- Cardiovascular and renal functions
- GI motility
