Drug Action in the CNS - Craviso Flashcards
Tight junctions in the BBB exist between (astrocytes/endothelial cells)
endothelial cells
What types of things pass through channels in the BBB?
small ions and water
Na, K and Cl
What things travel via membrane transport (aka passive diffusion) through the BBB?
- Small lipophilic molecules (O2 and CO2)
- Anesthetics, barbiturates
- ethanol
- nicotine
- caffeine
(all the things that make you feel good)
What things travel via carrier mediated transport (aka solute carriers) through the BBB?
Metabolism products
- energy transport systems
a. (Glucosde via. GLUT-1)
b. monocarboxylates, lactate, pyruvate (MCT1)
c. creatine (CrT) - amino acid transport systems
a. large neutral amino acids (LAT1) - organic cation/anion transporters, aka nucleosides
What things travel via receptor mediated transport through the BBB?
HORMONES HAVE RECEPTORS insulin transferrin leptin IgG TNFa
what things travel via adsorption-mediated transcytosis sytems?
histone and albumin
What things are ACTIVELY EFFLUXED from the brain via the BBB?
P-glycoprotein
BRCP
MRP 1,2,4,5
What is the role of P-glycoprotein? (P-gp)
membrane transporter that modulates drug distribution
What types of cells express high levels of Pgp?
capillary endothelial cells of the BBB
Which drugs are substrates for Pgp?
chemo agents (vinca alkaloids, doxorubicin), abx like rifampin anti-epileptics
How does high levels of Pgp expression effect drug transmission to the brain?
low levels of drug in the brain
it is a hypothesis for refractory epilepsy and multidrug resistance in general
membrane transport of drugs via passive diffusion relies on (blank) solubility
lipid solubility
the greater the lipid solubility, the faster the penetration
Which two compounds have higher than expected concentration in the brain for their lipid solubility?
glucose
L-DOPA
Which two compounds have lower than expected concentration in the brain for their lipid solubility?
phenobarbitol and phenytoin
What are the areas of the brain where the bbb is more permeable?
P-CAMP AREA POSTREMA Median eminence Pituitary gland Pineal gland Choroid plexus capillaries
T/F: viral and fungal infections can increase bbb permeability
false; viral and bacterial
What is the best route of drug admin for global delivery?
vascular route
T/F: each neuron has it s own capillary
true
Drugs that influence behavior and improve the functional status of patients with neurological or psychiatric diseases act by (blanking or blanking) neural excitability, usually by targeting specific transmitter systems.
enhancing or blunting
drugs that effect synthesis, storage, release, reuptake and/or degradation of neurotransmitters; agonist or antagonist activity at nerve terminal autoreceptors
are (pre/post) synaptic modifiers
presynaptic
drugs that are receptor agonist, antagonist or modulatory activity; degradation of neurotransmitters are (pre/post) synaptic modulators
post-synaptic
T/F: drugs may have direct effects on voltage gated ion channels
true
T/F: drugs may have non-specific effects on membranes overall
true
what is the chemoreceptor trigger zone for vomiting?
area postrema
What four chemicals does the area postrema sense that induces vomiting?
5-HT3
D2
M1
NK1
can antiemetic drugs be used for post operative and radiation induced emesis?
yes
How do 5-HT3 receptor antagonsists work?
serotonin reeptors are Na channels, peripherally block intestinal vagal afferents
What are the common 5-HT3 receptor antagonist
ZOFRAN KYTRIL Anzemet Lotronex Aloxi
What is the only NK1 receptor antagonist
Emend, can give oral or IV
Do corticosteroids act directly on neurotransmitters?
nope
Which corticosteroids are used to treat nausea?
dexamethasone
methylprednisone
Substituted benzamides are what class of antagonists?
d2 receptor
what effect to D2 receptor antagonists have on GI motility?
increase GI motility
T/F: d2 receptor antagonists may be used alone in anti emetic therapy
true
What drug class do you use to treat unproductive N/V?
D2 receptors antagonists (phenothiazines) Phenergan Compazine H1 antagonists Doxylamine
What are the common d2 receptor antagonists?
Reglan (oral, IV, IM)
Tigan
What are the side effects of D2 receptor antagonists (think of what they act on!
restlessness, fatigue, headache, insomnia, confusion, dystonias and tardive dyskinesia (
when are oral cannabinoids approved for use?
when the pt. doesn’t respond to other drugs
oral cannabinoids can be used in conjunction with other drugs for (blank) emesis
refractory
What are the common cannabinoid drugs?
marinol
cesamet
What are the side effects of cannabinoids?
euphoria, dysphoria, hallucinations; abuse potential
T/F: smoking marijuana can decrease emesis
true