Module 14a

Question 1

Stud of how drugs affect the function of the CNS.

Answer 1

Neuropharmacology

Question 2

There are many disorders in the CNS, and most of them have a component that is mediated by a ________ imbalance. We treat this imbalance with _____.
Unfortunately, these only treat the ________ of disease, not the ______.

Answer 2

biochemical
drugs
symptoms
cause

Question 3

Cells in the brain that act to process and transmit signals and information.

Answer 3

Neurons

Question 4

The start of information transfer in the neuron begins at the ________, which receives a signal from another neuron.

Answer 4

dendrite

Question 5

The resting membrane potential of cells is approximately ____. This means that the inside of the cell is _______ with respect to the outside.

Answer 5

-70mV

negative

Question 6

During depolarization of a neuron, positively charged ____ ions enter the cell through these.

Answer 6

Na+

voltage-gated Na+ channels

Question 7

During repolarization of a neuron, these ions leave the neuron.

Answer 7

potassium

Question 8

Only a few potassium channels are open. Potassium can freely move in and out of cells. The membrane potential does not change.

Answer 8

Resting potential.

Question 9

IF a depolarizing stimulus is received, it opens a few sodium channels. This allows sodium to enter the cell, until this point is reached.

Answer 9

Threshold

Question 10

If threshold is achieved, other sodium channels open and sodium rushes in. the membrane potential increases further.

Answer 10

rising phase

Question 11

Sodium channels close and potassium channels open. Potassium rushes out of the cell and the membrane potential decreases. As the membrane potential approaches resting potential even more potassium channels open.

Answer 11

Falling phase

Question 12

The membrane potential undershoots the RMP due to excess potassium leaving the cell

Answer 12

Hyperpolarization

Question 13

Describe the transmission of the chemical signal from one neuron, to another.

Answer 13

The action potential reaches the pre-synaptic nerve terminal.
This induces calcium influx into the neuron.
Calcium causes vesicles to fuse with the pre-synaptic membrane, and release NTs into the synpatic cleft.
NTs travel through the synaptic cleft and bind to receptors on the post-synaptic membrane, inducing an action potential in the post-synaptic neuron

Question 14

What are the major NT classes?

Answer 14

Monoamines (Epinephrine, NE, Dopamine, Serotonin)
Amino acids (Glutamate, GABA, aspartate, glycine)
Other (ACh)

Question 15

What NTs fall in the monoamine class?

Answer 15

Serotonin, Epinephrine, NE, Dopamine

Question 16

What NTs fall in the amino acid class?

Answer 16

Glutamate, GABA, aspartate, glycine

Question 17

What NT falls in the other class?

Answer 17

ACh (acetylcholine)

Question 18

Excitatory amino acid NTs.

Answer 18

Glutamate, aspartate

Question 19

Inhibitory amino acid NTs

Answer 19

GABA, glycine

Question 20

5 ways in which drugs that treat CNS disorders may act.

Answer 20

Replacement
Agonists/Antagonists
Inhibiting NT breakdown
Blocking reuptake
Nerve stimulation

Question 21

The drug acts to replace NTs that are low in diseases

Answer 21

Replacement

Question 22

A drug that directly binds to receptors on the post-synaptic membrane

Answer 22

Agonists/Antagonists

Question 23

NT metabolism is inhibited

Answer 23

Inhibiting NT breakdown

Question 24

NT reuptake into the pre-synaptic membrane is blocked

Answer 24

Blocking reuptake

Question 25

The drug directly stimulates the nerve causing it to release more NT

Answer 25

Nerve stimulation

Question 26

Parkinson's was first described in 1817 by ______ Parkinson.

Answer 26

James

Question 27

PD is caused by a progressive loss of _________ neurons in the ________ _______ of the brain.

Answer 27

dopaminergic | substantia nigra

Question 28

Is progressive loss of dopaminergic neurons a normal process of aging?

Answer 28

yes, however in PD, this number is very elevated

Question 29

There are distinct symptoms of Parkinsons, these are? (6)

Answer 29

``` Tremor Rigidity Bradykinesis Masklike face Postural instability Dementia ```

Question 30

Slowness of movement, especially slow to initiate movements

Answer 30

Bradykinesia

Question 31

Patient's cannot show facial expression and have difficulty blinking and swallowing

Answer 31

Masklike face

Question 32

Balance is impaired; patients have difficulty balancing while walking

Answer 32

Postural instability

Question 33

Pd is a chronic movement disorder that is caused by an imbalance between ____ and _______ in the brain.

Answer 33

ACh, dopamine

Question 34

In healthy patients (i.e. without PD, there is a normal balance of ACh and dopamine which results in normal ________ release.

Answer 34

GABA

Question 35

Describe the NT imbalance, the result of this imbalance and the overall manifestation as a result of the imbalance, in PD.

Answer 35

Decreased dopamine release, thus Ach release exceeds it greatly GABA release is not inhibited by dopamine, but stimulated by ACh. Excess GABA release causes the movement disorders of PD

Question 36

________ inhibits GABA release; _______ stimulates GABA release.

Answer 36

Dopamine | ACh

Question 37

The etiology of PD is largely _______.

Answer 37

idiopathic

Question 38

Describe how drugs may play a role in development of PD.

Answer 38

A by-product of illlicit street drug synthesis is MPTP - which causes irreversible death of dopaminergic neurons

Question 39

Genetics plays a role in predisposing patients to PD, mutations in these 4 genes have been implicated.

Answer 39

Alpha synuclein, parkin, UCHL1, DJ-1

Question 40

Certain environmental toxins, ________, have been associated with PD

Answer 40

Pesticides

Question 41

Trauma to the brain predisposes patients for PD. _____ are known to cause degeneration to dopaminergic neurons. There is a link between _______ induced ______ damage. and Parkinson's.

Answer 41

ROS diabetes oxidative

Question 42

The main treatment modality in Parkinson's is what?

Answer 42

Improve the balance between ACh and Dopamine

Question 43

There are 5 different major classes of drugs that act by increasing dopamine neurotransmission, what are they?

Answer 43

``` Dopamine replacement - L-DOPA Dopamine agonist Dopamine release Catecholamine-O-Methyltransferase inhibitor Monoamine oxidase-B inhibitor ```

Question 44

the most effective drug for PD treatment.

Answer 44

Levodopa

Question 45

Unfortunately, the beneficial effects of _______ decrease over time as PD progresses.

Answer 45

levodopa

Question 46

L-DOPA crosses the blood brain barrier by an _______ transport protein. L-DOPA is ________, but is converted to dopamine in dopaminergic nerve terminals. Conversion of L-DOPA is mediated by ____________ enzymes in the brain. The cofactor ________ (vitamin ___) speeds up this reaction

Answer 46

``` active inactive decarboxylase pyridoxine vitamin B6 ```

Question 47

What are the reasons why dopamine is not given to treat PD?

Answer 47

Dopamine cannot cross the BBB | Dopamine has a very short half-life in blood

Question 48

L-DOPA may cause nausea and vomitting due to dopamine mediated activation of the _________ trigger zone in the _______.

Answer 48

chemoreceptor | medulla

Question 49

Cardiac dysrhythmias may occur when taking L-DOPA, because its conversion to dopamine in the periphery can result in activation of these receptors.

Answer 49

cardiac beta 1 receptors

Question 50

What are the adverse effects of L-DOPA?

Answer 50

Nausea/vomitting (chemoreceptor trigger zone in the medulla) Dyskinesias Cardiac dysrhythmias (dopamine in periphery - cardiac beta 1 receptors) Orthostatic hypotension Psychosis

Question 51

Only approximately _% of the total L-DOPA dose reaches the brain. The remaining is metabolzied int he peripheral tissues (mostly the _______), before reaching the brain. Thus, L-DOPA is almost always given with ________, a ________ inhibitor that inhibits the peripheral metabolism of L-DOPA. In this case, approximately __% of L-DOPA now reaches the brain.

Answer 51

``` 1% intestine carbidopa carboxylase inhibitor 10% ```

Question 52

Carbidopa allows a _______ dose of L-DOPA to be administered and _______ the incidence of cardiac dysrhythmias and nausea and vomiting. Explain.

Answer 52

lower decreases Lower amount of peripheral metabolism, means there is less dopamine to interact with cardiac beta 1 receptors, and (to a lesser degree), with the chemoreceptor trigger zone int he medulla

Question 53

There are two types of loss of effects that L-DOPA taking patients may expreince, what are they?

Answer 53

Wearing off - gradual loss of effect | On-off - abrupt loss of effect

Question 54

Usually occurs at the end of the dosing interval of L-DOPA and indicates that drug levels might be low.

Answer 54

Wearing off

Question 55

Wearing off of L-DOPA may be minimized by these three methods.

Answer 55

Shortening the dosing interval Administer with a COMT inhibitor (inhibits L-DOPA metabolism) Add a dopamine agonist to the therapy

Question 56

Can occur even when L-DOPA levels are high and is difficult to treat this loss of effect.

Answer 56

On-off

Question 57

What are the three ways in which on-off may be minimized in L-DOPA treatment?

Answer 57

Divide the medication into 3-6 doses per day Use a controlled release formulation Move protein containing meals to the evening

Question 58

Acts to stimulate release of dopamine from dopaminergic neurons and also blocks dopamine reuptake; also blocks the NMDA receptor.

Answer 58

Dopamine releasers

Question 59

Dopamine releasers - Response is ______, usually within _-_ days Usually used in combination with _______, or alone in the case of ______ PD.

Answer 59

fast, 2-3 days L-DOPA mild

Question 60

The blockade of NMDA receptors by dopamine releasers is thought to decrease this side effect.

Answer 60

Dyskinesia

Question 61

Side effects of dopamine releasers.

Answer 61

dizziness, nausea, vomiting, lethargy, and anticholinergic side effects

Question 62

Enzyme that adds a methyl group to dopamine and L-DOPA, making them inactive

Answer 62

COMT

Question 63

Adverse effects of COMT inhibitors are similar to those of L-DOPA, what are they?

Answer 63

Nausea/vomitting orthostatic hypotension vivid dreams and hallucinations

Question 64

Enzyme that oxidatively metabolizes dopamine and L-DOPA, inactivating them. Located in these two areas.

Answer 64

Monoamine oxidase-B | Brain and periphery

Question 65

Inhibiting oxidative metabolism of L-DOPA allows more conversion to dopamine in the brain, and also allows more dopamine to remain in _______ ______ and be released following an action potential.

Answer 65

nerve terminals

Question 66

Adverse effects of MAO-B inhibitors.

Answer 66

insomnia, orthostatic hypotension, dizziness

Question 67

Can patients taking MAO-B inhibitors have tyramine containing foods?

Answer 67

Yes, as at therapeutic levels, these drugs do not inhibit MAO-A in the liver. Thus no hypertensive crisis

Question 68

Excess acetylcholine causes what types of symptoms in PD patients?

Answer 68

Urinary incontinence, salivation, diaphoresis

Question 69

Block the binding of ACh to its receptor.

Answer 69

Anticholinergic drugs

Question 70

Anticholinergic drugs may increase the effectiveness of _____. In doing so, these drugs may decrease the incidence of these ACh related symptoms.

Answer 70

L-DOPA | urinary incontinence, diaphoresis, salivation