Ch 15 - Drugs Used to Treat CNS Degenerative Disorders - DONE

Question 1

What is Parkinson´s disease?

Answer 1

A movement disorder that has the four following characteristics:

1. Resting tremors
2. Muscle rigidity
3. Bradykinesia
4. Abnormal posture and gait

Question 2

What is the pathophysiology of Parkinson’s disease?

Answer 2

• The disorder is thought to occur because of a loss of dopamine in the nigrostriatal pathway.
• The loss of dopamine disrupts the delicate balance between cholinergic and dopaminergic systems within the stratum and basal ganglia.

Question 3

What are the pharmacological treatment options for Parkinson´s disease?

Answer 3

1. Dopamine agonists
2. MAO inhibitors
3. Amantadine
4. Antimuscarinic agents
5. Catechol-O- Methyltransferase (COMT)

Question 4

Give examples of Dopamine agonists:

Answer 4

• levodopa/carbidopa
• bromocriptine
• pergolide
• pramipexole
• ropinirole

Question 5

Give examples of MAO inhibitor:

Answer 5

selegiline

Question 6

Give examples of Catechol-O- Methyltransferase (COMT):

Answer 6

• entacapone

- tolcapone

Question 7

Can we use drugs to cure Parkinson´s disease?

Answer 7

Nope. They neither revers or arrest the disease. And they can offer temporary relief.

Question 8

What is the treatment strategy for Parkinson´s disease?

Answer 8

• The ultimate goal is to reestablishing the balance between dopamine and acetylcholine in the brain.
• This can be accomplished by either:
  
  1. increasing dopamine int he nigrostriatal system
     2. reducing the cholinergic output of the stratum

Question 9

What is Levodopa?

Answer 9

• metabolic precursor of dopamine

- first-line drug for the treatment of Parkinson´s disease

Question 10

What is the advantages in using a precursor dopamine?

Levodopa

Answer 10

Dopamine itself does not cross the blood-brain barrier. However, Levodopa is transported to the brain and subsequently converted to dopamine in the basal ganglia.

Question 11

What are the disadvantages of using Levodopa alone?

Answer 11

Large doses of Levodopa is required if used alone because this drug is decarboxylated in the periphery to dopamine

Question 12

What is Levodopa usually used in the combination with?

Answer 12

another drug, such as Carbidopa

Question 13

What are the pharmacokinetics of Levodopa?

Answer 13

Levodopa is absorbed well in the GI tract.
However, if it is ingested with high protein meals, its transport across the blood-brain barrier is impaired because of competition from neutral amino acids.

Question 14

What is the on-off phenomenon?

Levodopa

Answer 14

Because Levodopa has an extremely short half-life, plasma levels may drop suddenly.

This may cause sudden immobility, tremors, and cramps.

These rapid changes are called the on-off phenomenon.

Question 15

**What drugs should NOT be given with Levodopa?

page 113. read for more

Answer 15

• nonselective monoamide oxidase inhibitors
• pyridoxine
• antipsychotics

Question 16

Levodopa AE:

Answer 16

• Nausea, vomiting, arrythmias, and postural hypotention: due to the conversion of Levodopa to dopamine in the periphery
• Dyskinesia, hallucinations, restlessness, and confusion: due to overstimulation of central dopamine receptors

Question 17

What is Carbidopa?

Answer 17

A dopamine decarboxylase inhibitor that does not cross the blood-brain barrier.

Question 18

Why do we use Carbidopa?

Answer 18

When administered with Levodopa, Carbidopa reduces the metabolism of dopamine in the periphery and therefore increases the availability of dopamine in the CNS.

• With the use of Carbidopa we need less Levodopa.
• Carbidopa also reduces the side effects of Levodopa, such as nausea and vomiting

Question 19

What is the efficacy of levodopa/Carbidopa (Sinemet) treatment?

Answer 19

• The treatment efficacy declines as the disease progresses. This occurs because Levodopa requires some healthy dopaminergic neurons to be effective

Question 20

What is Bromocriptine?

Answer 20

• Bromocriptine is an ergotamine derivative that acts as a dopamine receptor agonist at D2 receptors.
• It is a second-line drug after Levodopa.

Question 21

What is the therapeutic use of Bromocriptine?

Answer 21

Bromocriptine is used in conjunction with Levodopa. It may allow reduction in the maintenance dosage of Levodopa and therefore reduce the occurrance if side effects associated with long-term Levodopa use.

Question 22

How is Bromocriptine when used alone?

Answer 22

Bromocriptine has very little effect on parkinsonian symptoms when used alone

• however when used in conjunction with Levodopa, it helps relieve rigidity and tremor. It has minimal effects on bradykinesia.

Question 23

What is the adverse effects of Bromocriptine?

Answer 23

• Hallucinations and delurium occure more often with Bromocriptine than with Levodopa
• Nausea and vomiting
• Cardiac arrythmia, postural hypotention
• Erythromelagia; a condition characterized by red, painful, and swollen feet or hands

Question 24

What, other than Parkinson´s disease, is Bromocriptine used for?

Answer 24

hyperprolactinemia!

Question 25

How does Peroglide work?

Answer 25

- Like Bromocriptine, it is an ergot derivative | - it is a dopamine agonist at both D1 and D2 receptors

Question 26

What role does Peroglide hav in the treatment of Parkinson´s disease?

Answer 26

It is usually used in combination with levodopa and anticholinergic drugs

Question 27

Peroglide AE:

Answer 27

- Confusion - Hallucination - Orthostatic hypotension - UTIs

Question 28

How do the Pramipexole and Ropinirole work?

Answer 28

- Pramipexole and Ropinirole are non-ergot agonists at dopamine (D2) receptors. - They can be used as first-line therapy or as an adjunct to levodopa treatment

Question 29

How do the Pramipexole and Ropinirole differ from Bromocriptine and Pergolide?

Answer 29

- Unlike Bromocriptine and Pergolide, they can be initiated at therapeutic levels quickly rather than by a slowing increase, - Pramipexole and Ropinirole also cause fewer GI side effects

Question 30

What are the side effects that should be monitored when using Pramipexole and Ropinirole?

Answer 30

- dyskinesia - insomnia or somnolence - dizziness - orthostatic hypotension

Question 31

How are the Pramipexole and Ropinirole eliminated?

Answer 31

Pramipexole and Ropinirole are excreted through the kidneys. | - Ropinirole is much more extensively metabolized than pramipexole

Question 32

What is the mechanism of action of Selegiline?

Answer 32

Selegiline selectively inhibits monoamine oxidase B (MAO-B), which metabolizes dopamine. MAO-A, however, is not affected unless extremely high doses of Selegiline is given.

Question 33

What is the therapeutic use of Selegiline?

Answer 33

Because it decreses the metabolism of dopamine periphery, Selegiline, increases dopamine levels in the brain. The effects of levodopa are enchanced when it is used in conjunction with Selegiline; however, there is a threat of hypertensive crisis when this drug is administered in high dosages.

Question 34

What is the classification of Amantadine?

Answer 34

Amantadine is an antiviral agent used to treat influenza

Question 35

What is the mechanism of action of Amantadine?

Answer 35

The exact mechanism of action is unknown. Amantadine appear to either enhance the release of dopamine from surviving nigral neurons or inhibit the reuptake of dopamine at synapses.

Question 36

What is the therapeutic use of Amantadine?

Answer 36

Amantadine may improve bradykinesia, tremor, and rigidity when used along with Levodopa. It is usually only effective for a few weeks but seems to be more effective with anticholinergic agents.

Question 37

What are the toxic effects of Amantadine?

Answer 37

- Restlessness, agitation, confusion - Orthostatic hypotesion - Peripheral edema - Livedo reticularis (skin rash)

Question 38

Name three examples of Anticholinergic agents:

Answer 38

- The three most commonly used anticholinergic drugs are: 1. Benztropine 2. Biperiden 3. Trihexiphenidyl

Question 39

Why do people use anticholinergic agens?

Answer 39

These drugs help reduce the cholinergic output of the striatum. Again, this is another method to restore balance between dopamine and acetylcholine with nigrostratal system.

Question 40

What is the therapeutic efficacy of anticholinergic agents?

Answer 40

These drugs are less efficacious than levodopa. - They are commonly used adjuvantly in parkinsonian therapy. - They primarily help reduce tremor, rigidity, and akinesia - Secondary symptoms like drooling are also reduced.

Question 41

What are the AE of anticholinergic agents:

Answer 41

The following are cause by decreased parasympathetic response: - sedation - urinary retention - dry mouth - constipation - mental confusion

Question 42

What is drug-induced parkinsonism?

Answer 42

Parkinsonian symptoms can be caused by potent antipsychotic agents such as haloperidol because they block dopamine receptors

Question 43

What is the treatment of drug-induced parkinsonism?

Answer 43

- lower the drug levels - change the drug to a less potent one - use an anticholinergic agent

Question 44

Define Huntington´s disease:

Answer 44

A genetic disorder due to a single defect on chromosome 4

Question 45

What are the the symptoms of Huntington´s disease?

Answer 45

Individuals who have the disease display dementia and/or chorea

Question 46

What is the pathophysiology of Huntington´s disease?

Answer 46

This disease is thought to occur because of excessive dopaminergic activity and diminished γ-aminobutyric acid (GABA) functions in the basal ganglia (caudate and putamen)

Question 47

What is the treatment of Huntington´s disease?

Answer 47

Dopamine blockers such as haloperidol or tetrabenazine are used to treat Huntington´s disease

Question 48

What is Tourette´s syndrome?

Answer 48

A disease characterized by abnormal tics and facial movement

Question 49

What is the treatment of Tourette´s syndrome?

Answer 49

- Clonidine | - Haloperidol has also been used

Question 50

Define Wilson´s disease:

Answer 50

Wilson´s disease is a genetic disorder of copper metabolism. | - Excess copper is deposited in the liver, brain, and other tissues.

Question 51

What is the treatment of Wilson´s disease?

Answer 51

A copper chelating agent known as Penicillamine