Craviso: Drug Action in the CNS

Question 1

Belongs to a family of membrane transporters that modulate drug distribution; capillary endothelial cells of the BBB have high levels compared to other tissues

Answer 1

P-glycoprotein

Question 2

What does transport of drugs through membranes by passive diffusion depend on?

Answer 2

the lipid solubility of the drug

Question 3

The greater the lipid solubility, the (blank) a drug enters the CNS

Answer 3

faster

Question 4

What are two drugs that have a high lipid solubility, but do not get across the BBB efficiently?

Answer 4

phenobarbital

phenytoin

Question 5

What are two drugs that have a low lipid solubility, but diffuse across the BBB more readily?

Answer 5

glucose

L-DOPA

Question 6

List some regions where the BBB is more permeable

Answer 6

area postrema*
median eminence
pituitary gland
pineal gland
choroid plexus capillaries

Question 7

These can cause an increase in BBB permeability

Answer 7

bacterial and viral infections

Question 8

What is the most promising method for global drug delivery?

Answer 8

vascular route

**each neuron has its own capillary for O2 supply, for the supply of other nutrients, and for removing metabolic waste

Question 9

How do drugs that influence behavior and improve the functional status of patients w neurological/psych diseases act?

Answer 9

by enhancing or blunting neural excitability, usually by targeting specific transmitter systems

Question 10

What are some ways that drugs affect the neurons pre-synaptically?

Answer 10

synthesis
storage
release
reuptake/degradation of neurotransmitters

Question 11

What are some ways that drugs affect neurons post-synaptically?

Answer 11

receptor agonists, antagonists

degradation of neurotransmitters

Question 12

What is the main goal of antiemetic therapy?

Answer 12

block neurotransmission at the chemoreceptor trigger zone, at afferent inputs to the emetic center and in the emetic center

Question 13

3 receptors in the chemoreceptor trigger zone?

Answer 13

5HT3
D2
M1
NK1

Question 14

Antiemetic drug; 5HT3 receptor antagonist; also acts peripherally to block intestinal vagal afferents

Answer 14

ondansetron (Zofran)

granisetron (Kytril)

Question 15

Antiemetic drug; NK1 receptor antagonist

Answer 15

aprepitant (Emend)

Question 16

5HT3 receptors are (blank) channels

Answer 16

Na+

Question 17

Corticosteroid used with antiemetic drugs

Answer 17

dexamethasone

Question 18

D2 receptor antagonist; may also act peripherally to enhance GI motility; alone or in combo for treating CTI nausea and vomiting; also used for treating unproductive nausea and vomiting

Answer 18

Metoclopramide (Reglan)

Question 19

Side effects of Metoclopramide?

Answer 19

dystonias

tardive dyskinesia

Question 20

Oral cannabinoid; thought to act in higher cortical centers; approved for use in patients not responding to other antiemetic agents; can be used for breakthrough or refractory emesis

Answer 20

Dronabinol (Marinol)

**synthetic form of THC

Question 21

What is smoking marijuana used for medically? Side effects?

Answer 21

pain, inflammation, spasticity;

euphoria, dysphoria, hallucinations, abuse potential

Question 22

There are two antiemetic drugs used to control non-productive nausea and vomiting. What are they?

Answer 22

Promethazine - D2 receptor antagonist
Doxylamine - H1 receptor antagonist

**both also block mACh receptors

Question 23

Two H1 receptor antagonists that provide short-term, immediate relief for motion sickness

Answer 23

Dimenhydrinate (Dramamine)

Meclizine (Antivert)

Question 24

A muscarinic receptor antagonist that is used for long-term, sustained control of motion sickness; skin patch placed behind the ear that produces less side effects than via the oral route

Answer 24

Scopolamine

Question 25

What are four strategies for antiseizure therapy?

Answer 25

1. enhance synthesis of GABA 2. block degradation of GABA 3. block reuptake of GABA 4. enhance postsynaptic GABA-A receptor activity

Question 26

So, one way to prevent seizures is to upregulate GABA activity. What is one other neurotransmitter that you could alter?

Answer 26

glutamine (downregulate it)

Question 27

Besides GABA and glutamine, what is another way you could decrease seizures?

Answer 27

block ion conductance through channels (block Ca++ and Na+ influx, or K+ efflux)

Question 28

Loss of basal forebrain cholinergic neurons that cause a striking deficiency in ACh

Answer 28

Alzheimer's disease

Question 29

How to treat Alzheimer's?

Answer 29

increasing ACh levels using reversible cholinesterase inhibitors

Question 30

List 3 medications for Alzheimer's and how they work

Answer 30

Donepezil (Aricept) and Ravistigmine (Excelon) - reversible cholinesterase inhibitors; Memantine - low affinity open channel blocker of NMDA receptors (inhibits the pathological activation of the receptor)

Question 31

Progressive loss of dopaminergic neurons in substantia nigra leading to shortage of dopamine in extrapyramidal movement circuit

Answer 31

Parkinson's disease

Question 32

Primary treatment for Parkinson's disease

Answer 32

increase dopamine levels (L-DOPA)

Question 33

Why do we treat Parkinson's disease with L-DOPA instead of dopamine?

Answer 33

dopamine doesn't cross the BBB

Question 34

Characterized by chorea – irregular, unpredictable involuntary muscle jerks at different parts of the body that impair voluntary activity that is the result of a loss of neurons from structures of the basal ganglia, imbalances both in GABA functions (diminished) and dopamine functions (enhanced)

Answer 34

Huntington's disease

Question 35

How to treat Huntington's disease?

Answer 35

Tetrabenazine - a selective and reversible centrally-acting dopamine depleting drug D2 receptor antagonists to control abnormal movements and relieve the psychosis that accompanies the disease

Question 36

a selective and reversible centrally-acting dopamine depleting drug (inhibits VMAT2)

Answer 36

tetrabenazine **inhibits the transporter that takes dopamine into vesicles for storage and release

Question 37

Degeneration of spinal, bulbar and cortical motor neurons that leads to muscle weakness, muscle atrophy and fasciculations, spasticity, dysarthria, dysphagia and respiratory compromise

Answer 37

Amyotrophic lateral sclerosis

Question 38

How to treat ALS?

Answer 38

Riluzole - involves glutamate release, blocks NMDA and kainate glutamate receptors to inhibit voltage-dependent Na+ channels

Question 39

Two drugs used to treat spasticity?

Answer 39

Baclofen - a GABA-B receptor agonist Tizanidine - an alpha-2 adrenergic receptor agonist

Question 40

A GABA-B receptor agonist

Answer 40

Baclofen

Question 41

An alpha 2 adrenergic receptor agonist

Answer 41

Tizandine

Question 42

reduced drug effect with repeated use and higher doses required to produce the same effect

Answer 42

tolerance

Question 43

What are two ways to get drug tolerance?

Answer 43

pharmacokinetic - altered metabolism physiologic - long-term alterations (at site where drug acts or at other synpases for other neurotransmitters)

Question 44

tolerance to a drug in one class | e.g., sedative-hypnotics) will lead to tolerance to others in the same class (sedative-hypnotics

Answer 44

cross-tolerance

Question 45

repeated, compulsive use of a drug that deviates from the social norms of a given culture; disregard of harmful interpersonal or social consequences e.g., ethanol, opiate analgesics, cocaine and other recreational drugs

Answer 45

dependence

Question 46

drugs within a pharmacological class (e.g., opiate analgesics) support individuals physically dependent on other drugs in the same class - useful property for “detox”

Answer 46

cross-dependence

Question 47

(All non-research use illegal under federal law) – highest abuse potential

Answer 47

Schedule I

Question 48

(No telephone prescriptions, no refills)

Answer 48

Schedule II

Question 49

(Prescription must be rewritten after 6 months or five refills)

Answer 49

Schedule III

Question 50

(Prescription must be rewritten after 6 months or five refills; differs from Schedule III in penalties for illegal possession)

Answer 50

Schedule IV

Question 51

(As any other non opioid prescription drug may also be dispensed without prescription unless additional state regulations apply)

Answer 51

Schedule V

Question 52

Which schedule of drugs do these fall under? ``` Stimulants Depressants Hallucinogens Narcotics Marijuana ```

Answer 52

Schedule I

Question 53

Which schedule of drugs do these fall under? Opioids Cocaine, Amphetamine, Amphetamine Complex, etc

Answer 53

Schedule II

Question 54

3 important considerations when prescribing CNS drugs?

Answer 54

lipophilicity - drug can accumulate in fatty tissue high degree of plasma protein binding metabolism via the liver

Question 55

Concerns when prescribing CNS drugs for the elderly?

Answer 55

diminished hepatic/liver function paradoxical reactions polypharmacy greater susceptibility to side effects

Question 56

What are some specificity considerations to keep in mind when thinking about CNS drugs?

Answer 56

some CNS drugs don't have an established mechanism; classified according to primary mechanism of action but can have a similar therapeutic effect via another mechanism; classified according to therapeutic use, but can have a variety of uses