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PHRX 3009: drug action > 31: Drug Action Dopamine > Flashcards

31: Drug Action Dopamine Flashcards

1
Q

Draw the structure of dopamine.

A
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2
Q

Describe the function of dopamine in the brain.

A

Dopamine plays a major role in the motivational component o reward-motivated behavior in the brain.
* signals the perceived motivational desirability of an outcome and behavior towards or away from achieving it.
* pleasure chemical

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3
Q

Describe the function of dopamine in the PNS: blood vessels.

A

Inhibit norepinephrine release and acts as a vasodilator.

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4
Q

Describe the function of dopamine in the PNS: digestive system.

A

Reduces sodium excretion and urine output.

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5
Q

Describe the function of dopamine in the PNS: pancreas.

A

Reduces insulin production.

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6
Q

Describe the function of dopamine in the PNS: immune system.

A

Reduces the activity of lymphocytes.

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7
Q

Explain the outcomes of excess dopamine.

A
  • excess movement (involuntary movement)
  • euphoria, hallucinations, and psychosis
  • inhibition of prolactin
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8
Q

Explain the outcomes of regular, normal regulated levels of dopamine.

A
  • motion
  • emotion and reward
  • hormones
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9
Q

Explain the outcome of not enough dopamine.

A
  • less movement; parkinson’s disease
  • lack of emotion; anhedonia, feeling flat
  • increased prolactin; amenorrhea in women; impotence in men
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10
Q

What is the association of dopamine with Parkinson’s Disease?

A

Loss of dopamine-secreting neurons in an area of substantia nigra.

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11
Q

What is the association of dopamine with Restless legs syndrome?

A

Decrease dopamine activity.

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12
Q

What is the association between dopamine and ADHD?

A

Decreased dopamine activity.

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13
Q

What is the association between dopamine and heart failure/shock?

A

Decreased dopamine activity.

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14
Q

What is the association between dopamine and schizophrenia?

A

Increased levels of dopamine activity.

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15
Q

Describe effects of drug action on dopamine.

A

Altered…
* biosynthesis in presynaptic neuron
* release from a presynaptic neuron to a synaptic cleft
* reuptake back to a presynaptic neuron
* removal in a synaptic cleft

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16
Q

Explain step 1 of dopamine biosynthesis.

A

Starts from L-tyrosine
* L-tyrosine is taken into the presynaptic neuron by Na+-dependent tyrosine transporter (TryP)

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17
Q

Explain step 2 of dopamine biosynthesis.

A

L-tyrosine is hydroxylated into L-DOPA by tyrosine hydroxylase (TH)
* RATE-LIMITING STEP

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18
Q

What is Metirosine? What does it do?

A

Metirosine is an antihypertensive drug.
* depletes the levels of dopamine

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19
Q

Explain step 3 of dopamine biosynthesis.

A

L-DOPA s converted into dopamine by aromatic L-amino acid decarboxylase (AADC)

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20
Q

What is Carbidopa used for?

A

Used for Parkinson’s disease in conjugation with levodopa.

21
Q

Explain step 4 of dopamine biosynthesis.

A

Dopamine is taken into the presynaptic vesicles for storage by a H+-coupled vesicular monoamine transporter 1 (VMAT1) in the CNS and PNS.
* OR VMAT2 only in the CNS.

22
Q

What is Reserpine used for?

A

Used for high blood pressure treatment
* VMAT1 and VMAT 2 inhibitor

23
Q

Explain step 5 of dopamine synthesis.

A

Vesicles move to the presynaptic terminal, which enforces Ca2+ channel to open and uptake of Ca2+ into the neuron.

24
Q

Explain step 6 of dopamine biosynthesis.

A

Ca2+ ions activate the vesicles to fuse with the presynaptic membrane and release dopamine into synaptic cleft.

25
Q

Explain step 7 of dopamine biosynthesis.

A

A part of dopamine is diffused out of the synaptic cleft.

26
Q

Explain step 8 of dopamine biosynthesis.

A

A part of dopamine is re-uptake by dopamine transporter (DAT) back to the presynaptic cell.

27
Q

What are the functions of altropane and cocaine?

A

Selective DAT inhibitors or selective dopamine reuptake inhibitors (SDRIs)

28
Q

Describe the mechanism of action of DRIs.

A

DRI - dopamine re-uptake inhibitor
* blocks the action of the dopamine transporter (DAT)
* Increases extracellular concentrations of dopamine –> increases dopaminergic neurotransmission

29
Q

What are DRIs used to treat?

A

ADHD, obesity, or binge eating disorder (sometimes - mood disorders)
* high risk for abuse

30
Q

What makes cocaine so addictive?

A

The increased concentration of dopamine in the synapse activates post-synaptic dopamine receptors –> result: drug is rewarding and promotes compulsive use

31
Q

Explain step 9 of dopamine biosynthesis.

A

A part of reuptake dopamine is metabolized into DOPAC by MAO -> forms inactive metabolite secreted into urine.

32
Q

What is Selegiline and what is it used for?

A

Selegiline is an antidepressant
* MAO inhibitor

33
Q

Explain step 10 of dopamine biosynthesis.

A

A part of reuptake dopamine is metabolized into 3-methoxytyramine (MT) by COMT) –> forms an inactive metabolite secreted into urine.

34
Q

What is Entacapone and what is it used for?

A

Entacapone is a COMT inhibitor and it is used for Parkinson’s disease.

35
Q

Explain step 11 of dopamine biosynthesis.

A

A part of dopamine binds to the presynaptic receptor (D2 receptor) on the neuron membrane surface and inhibits dopamine biosynthesis.

36
Q

Metirosine: drug action? target protein? therapeutic indication?

A

drug action: inhibition of biosynthesis
target protein: tyrosine hydroxylase (TH)
therapeutic indication: hypertension

37
Q

Carbidopa: drug action? target protein? therapeutic indication?

A

drug action: inhibition of biosynthesis
target protein: DOPA decarboxylase (DDC)
therapeutic indication: Parkinson’s disease

38
Q

Reserpine: drug action? target protein? therapeutic indication?

A

drug action: inhibition of storage
target protein: VMAT 1 & 2
therapeutic indication: hypertension

39
Q

Tetrabenazine: drug action? target protein? therapeutic indication?

A

drug action: inhibition of storage
target protein: VMAT 2
therapeutic indication: Chorea

40
Q

Altropane: drug action? target protein? therapeutic indication?

A

drug action: inhibition of reuptake
target protein: dopamine transporter (DAT)
therapeutic indication: ADHD

41
Q

Entacapone: drug action? target protein? therapeutic indication?

A

drug action: inhibition of degradation
target protein: COMT
therapeutic indication: Parkinson’s disease

42
Q

Selegiline: drug action? target protein? therapeutic indication?

A

drug action: inhibition of degradation
target protein: MAO
therapeutic indication: antidepressant

43
Q
A

A. Ca2+

44
Q
A

C. Synaptic cleft

45
Q
A

C. Tyrosine - DOPA - dopamine

46
Q
A

E. A and D

47
Q
A

A. Entacapone

48
Q
A

B. Altropane

PHRX 3009: drug action (36 decks)

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