Intro to CNS drugs and Hypnotics

Question 1

Areas in BBB not fully developed

Answer 1

1. Area postrema -vomiting

2. Hypothalamus

Question 2

Early classes of antihistamines

Answer 2

diphenhydramine

Question 3

later classes of antihistamines

Answer 3

Levocetirizine -less lipophilic

Question 4

Dopamine is very polar so it cannot get through the BBB

Answer 4

There are receptors that allow molecules tthat are polar to get into the brain by tricking and by making the molecule look like an amino acid . L dopa is tricking the body to incorporate it into CNS… L-dopa decarboxylase , when L dopa enters, it gets decarboxylated to getit in to the BBB .

Question 5

80-90 % of receptors of CNS drugs focus on proteins of what happens in the synapse other will focus on

Answer 5

propagation of action potential

Question 6

Epilepsy and local anesthesia are targeted by drugs that

Answer 6

Focus on act pot propagation

Question 7

Treatment of epilepsy , which type of ion channel

Answer 7

voltage gatedm

Question 8

Known influx of sodium, efflux of potassium, influx of chloride

Answer 8

depol-Na in
hyper pol-K out
hyper pol -Cl in

Question 9

Ligand gated ion channel are expressed in

Answer 9

pre and post synaptic neurons

Question 10

Two ligand gated ion channels

Answer 10

1. GABA-A receptors

2. Nicotinic receptors

Question 11

GABA-A

Answer 11

inhibitory due to it being a chloride ion channel

Question 12

Nicotinic receptor is

Answer 12

excitatory -triggers rerelease of sodium and calcium

Question 13

Metabotropic receptors have no

Answer 13

ion pores

Question 14

Metabotropic receptors affect opening of voltage gates channels by two mechanisms

Answer 14

1. Causing the beta gamma subunits to open up (adrenoreceptors)
2. Second messengers causes opening of voltage gated ion channels. (DAG, cAMP- these activate kinases to phosphorylate the proteins of ion channels.

Question 15

IPSP

Answer 15

Cl influx

Question 16

EPSP

Answer 16

Na Ca influx

Question 17

When affecting how NT are produced and excreted we can use drugs that are

Answer 17

analogues to certain molecules - these molecules can either increase secretion, synthesis, storage, release.

Question 18

NT are synth in the

Answer 18

presynaptic and stored in vesicles that can degranulate using a calcium dependent mechanism

Question 19

Limitations with NT are

Answer 19

releasing more than what is produced (amphetamines over stimulation)

Not all NT that are released bind to receptors

Question 20

Ach broken down by

Answer 20

Ach-esterase

Question 21

Ach is recycled by

Answer 21

inhibiting Ach esterase

Question 22

Amino acid derivative to know (excitatory)

Answer 22

Glutamate- main excitatory NT in brain– epilepsy drugs block glutamate

Ach -ionotropic ,nicotinic receptors -in flux of Ca Na
and Muscarinic receptor is metabotropic.

Question 23

Receptors for glutamate

Answer 23

Two ionotropic which are NMDR, AMPAR.

One metabotropic which is mGluR

Question 24

Amino acid derivative to know (inhibitory)

Answer 24

GABA-A -main inhibitory - If stimulated will treat anxiety, insomnia

Glycine

Question 25

GABA-A receptor

Answer 25

ionotropic -5 subunits -allows Cl influx

Question 26

Monoamine NT

Answer 26

Dopamine Serotonin Norepi Histamine

Question 27

Neuropeptide NT

Answer 27

``` Substance P Endorphins Somatostatin Neurotensin Orexin ``` *Anandamide- binds to CB1 and CB2 -natural endocannabinoid

Question 28

First drugs used in the 20s, 30s, 40s, had a very narrow therapeutic index. This means there was a narrow range b/t

Answer 28

desired effect and toxic dose

Question 29

Used to treat epilepsy as a last resort when other treatments aren't working?

Answer 29

Phenobarbitial

Question 30

Old gen barbiturates

Answer 30

Phenobarbital , pentobarbital, thiopental, glutethimide, chloral hydrate

Question 31

Features of benzos

Answer 31

benzene ring .. long carbon chain.. halogenated

Question 32

Benzos discussed in class

Answer 32

diazepam , chlordiazepoxide, flurazepam,, flunitrazepam..triazolam,, alprazolam

Question 33

New generation or Z hypnotic

Answer 33

zolpidem, zalepon, eszopiclone

Question 34

Benzo, barb, Z-hyp, all interact with

Answer 34

GABA-A

Question 35

These drugs mimic the effects of melatonin

Answer 35

Ramelteon... Tasimelteon

Question 36

Used to treat depression. Partial agonist of serotonin, used as anxiolytic, safer option.

Answer 36

Buspirone.

Question 37

These CNS lipophilic molecules go through rapid

Answer 37

redistribution --distributed fast to other organs to be excreted from the body

Question 38

Barbituates can

Answer 38

self stimulate their own metabolism --due to this , they may effect other drugs such as oral contraceptives.

Question 39

Benzos can also

Answer 39

self stimulate their own metabolism, and can form active metabolites . Caution with liver.

Question 40

Easy overdose with

Answer 40

barbiturates

Question 41

Speeding up excretion of these molecules such as barbiturates can be done by

Answer 41

giving sodium bicarb because the barbiturates are weak acids.

Question 42

Drugs that affect GABA-A don't bind to

Answer 42

GABA-A

Question 43

GABA sub unit for GABA binding is

Answer 43

b/t alpha and beta subunit

Question 44

Benzos and Z-hyp bind where

Answer 44

to a pocket b/t alpha and gamma subunit. Referred to as benzodiazepine receptors

Question 45

Barbiturates bind to

Answer 45

to more lipophilic AA residues within the membrane

Question 46

Antidote to Z-hyp and benzos

Answer 46

Flumazeril

Question 47

Name the alpha 1 receptors

Answer 47

alpha 1,2,3,5,

Question 48

Benzos bind to which alpha receptors

Answer 48

1,2,3,5

Question 49

Z-hyp bind to which alpha receptors

Answer 49

1

Question 50

alpha 1 receptor is involved in

Answer 50

hypnosis

Question 51

Why is a Z-hyp not used for anesthesia

Answer 51

only binds to alpha 1 which is involved in hypnosis

Question 52

Benzos can cause

Answer 52

anterograde amnesia - loss of men after given drug

Question 53

Tolerance can come about two ways

Answer 53

1. Pharmokinetic mechanism - body speeds up and speeds up metabolism requiring higher and higher dose. 2. Pharmodynamic- overstimulation of NT receptors leads to decrease number of receptors, so dose muse be increased to get the same effect.

Question 54

Two orexin receptors antagonist 1. | Mechanism 2.

Answer 54

almorexant and suvorexant -1. These are antagonist of the orexin receptors which is involved the stimulation of wakefulness, so inhibition would give a hypnotic effect.