Pharmacology BBB + Questions

Question 1

Easy Passage BBB:

Answer 1

H2O, gasses (CO2, O2), lipophilic substances (free steroid hormones) ~ all measured by octanol/H2O coefficient

Question 2

Uptake of Rx depends on these factors + if Rx is

Answer 2

substrate for non-specific endothelial tx (~P-gp ATP cassette tx protein)

Question 3

Loss of Barrier BBB:

Answer 3

infection, age, Alzheimer’s Disease ~ note could both worsen Rx effects but also have ↑therapy

Question 4

Consequences of Lipophilic Selectivity:

Duration of Effects:

Answer 4

lipophilic Rx cross BBB easy, but also will cross into adipose tissue out brain easily = Short Duration

Question 5

Consequences of Lipophilic Selectivity:

Elimination:

Answer 5

lipophilic Rx will be stored in adipose = short duration but Long Elimination
Example: IV anesthetic —> blood —> cross BBB with ease —> part in blood eliminated —> Rx flows down concentration gradient out of brain (end effects) —> adipose tissue

Question 6

P-gp:

Answer 6

ABCB1 Apical (blood stream side) Transporter

Question 7

P-gp Inhibitors:

Answer 7

“Vera CAN QUIt” = Verapamil, Cyclosporin, Amiodarone, Nifedipine, Quinidine

Question 8

Brain Tumor Treatment:

Answer 8

difficult to treat because how to target drugs to 1° tumor site?

Question 9

Ineffective Antipsychotic / Antidepressant:

Answer 9

poor efficacy because both are P-gp substrates

• –> Treatment Resistant Disease
  (1) Polymorphisms in both ABCB1 gene and CYP family have effects
  (2) No Rx modulates P-gp activity —> better switch patient to Rx that isn’t a substrate

Question 10

Anterior Pore Closure —>

Answer 10

mental retardation, loss of spinal reflexes (UMNs contribute to this), loss of pain sensation, ↓swallowing

Question 11

Anencephaly —>

Answer 11

think structures above foramen magnum (spinal cord is not 1° affected)

Question 12

Dorsal Column Peripheral Receptor =

Answer 12

Pacinian Corpuscle; Spinothalamic Tract Peripheral Receptor = Free Nerve Ending

Question 13

CSF is made in

Answer 13

JUST the lateral + 4th ventricles

Question 14

Headache: pain source.

Answer 14

a) Brain: insensitive to pain; true brain inflammation/destruction will manifest in disease, but it will not create pain
b) Pain Sources: meninges (CN V), blood vessels, nerves

Question 15

Neck Stiffness Pathophysiology

Differential Diagnosis:

Answer 15

Meningitis + Subarachnoid Hemorrhage

Question 16

Meningitis Neck Stiffness Pathophysiology

Answer 16

Inflammation of Meninges —> root irritation —> PAIN + Muscle Spasm

Question 17

Subarachnoid Hemorrhage Neck Stiffness Pathophysiology

Answer 17

Subarachnoid Hemorrhage —> blood produce degrade —> toxic to nerves —> irritation —> PAIN + Muscle Spasm

Question 18

Meningitis & Subarachnoid Hemorrhage

How to differentiate?

Answer 18

Before testing, look for fever; +fever = meningitis

Question 19

Management for Meningitis:

Answer 19

Antibiotics —> Head CT —> Spinal Tap

a) CT: shows inflamed meninges b/c enlarged meningeal blood vessels allow contrast to leak out
b) Tap: cloudy CSF

Question 20

Papilledema:

Answer 20

swollen optic disks indicates ↑intracranial pressure

Question 21

Papilledema Pathophysiology w/Meningitis:

Answer 21

meningitis —> damaged arachnoid villi/granulations —> ↓CSF absorption —> Hydrocephalus
Hydrocephalus —> ↑Volume —> ↑Pressure —> Papilledema