Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology > Anti-parkinsonian drugs and neuroleptics > Flashcards

Anti-parkinsonian drugs and neuroleptics Flashcards

1
Q

What are the three neural pathways involved in dopamine?

A

Nigrostriatal pathway
Mesolimbic pathway
Tuberoinfundibular pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe the nigrostriatal pathway

A

Substantia nigra pars compacta -> striatum

Involved in control of movements

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe the mesolimbic pathway

A

Ventral tegmental area -> limbic system (amygdala, hippocampus etc.), frontal cortex, olfactory tubercle, nucleus accumbens.
Involved in emotion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Describe the tuberoinfundibular system

A

Arcuate nucleus of hypothalamus -> median eminence and pituitary gland
Hormonal regulation, maternal behaviour, sensory processes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Recall the dopamine synthesis pathway

A

L-tyrosine converted to L-DOPA by tyrosine hydroxylase.
L-DOPA converted to dopamine by DOPA decarboxylase.
Packaged into vesicles using VMAT (vesicular monoamine transporter).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which receptors are part of the D1-like family and what is the MOA?

A

D1 & D5 receptors

Activates adenyl cyclase -> increase cAMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which receptors are part of the D2-like family and what is the MOA?

A

D2, 3, 4 receptors

Inhibits adenyl cyclase -> decrease cAMP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the mean age of onset for PD?

A

65years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the cardinal signs of PD?

A 
Resting tremor
Bradykinesia
Rigidity
Postural abnormality
[Reduced arm swing, shuffling gait, unilateral onset and then spreads to other side]
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the motor signs of PD?

A 
Pill-rolling rest tremor
Difficulty of fine movements - micrographia
Poverty of blinking
Impassive face
Monotomy of voice and tone
Loss of arm swing
Loss of balance - lack of righting reflex, retropulsion
Short step, shuffling gait
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the non-motor signs of PD?

A 
Depression
Sleep disturbances
Pain
Taste/smell disturbances
Cognitive decline/dementia
ANS:
Constipation
Postural hypotension
Urinary frequency
Impotence
Increased sweating
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the neuropathology of PD?

A

Principal area: substantia nigra
Other areas affected: locus coruleus, dorsal vagus nucleus, nucleus basalis of mynert

Loss of dopaminergic neurones
Loss of neuromelanin (i.e. pigmentation)
Pathway to putamen (as part of nigrostriatal) is mainly lost
Observation of Lewy bodies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What do lewy bodies consist of?

A

Packed of a-synuclein protein.
A-synuclein is responsible for anchoring the vesicle to the pre-synaptic membrane before release.
Therefore this affects neurotransmission in PD.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Briefly describe the PD staging

A

Stages 1-3 are pre symptomatic; affects the locus coeruleus, raphe nuclei, dorsal motor nucleus of vagus and substantial nigra.
Stage 4 &5: A-synuclein goes up brainstem and travels. Spreading of altered proteins is key process of disease.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the biochemical changes of PD?

A

Marked reduction of dopamine in caudate nucleus/putamen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Why can dopamine not be given directly as a replacement in PD?

A

Dopamine cannot cross the BBB.

17
Q

Why can L-DOPA not be given on it’s own as a replacement in PD?

A

L-DOPA is converted to Dopamine by DOPA decarboxylase. This is also found in the periphery, dopamine is able to cross the BBB at the CTZ and therefore cause nausea and vomiting.
L-DOPA must be given alongside a DOPA decarboxylase inhibitor e.g. Carbidopa, Benserazide

18
Q

What are the side-effects of L-DOPA?

A

Acute:
Nausea (prevent using domperidone - D2 receptor antagonist)
Hypotension
Psychotic effects (action on mesolimbic system): confusion, disorientation, nightmares
Chronic:
Dyskinesias may occur within 2yrs of treatment
‘On-Off’ effects of clinical state

19
Q

Name examples of dopamine agonists and their MOA

A

Bromocriptine, pergolide, cabergoline
D2 receptor agonist
Longer duration than L-DOPA, less chance of dyskinesia
May be used in conjunction with L-DOPA

20
Q

Side effects of dopamine agonists

A

Nausea and vomiting
Psychosis: dizziness, hallucinations, confusion
Rare- constipation, headaches, dyskinesias

Ergot structure: increased risk of heart valve disease
Non-ergot structure: addictive

21
Q

Name MOA inhibitors

A

Deprenyl (selegine): selective for MAO-B
Acts to preserve natural dopamine in circulation. Can be given alone or with L-DOPA (can reduce the dosage of L-dopa -> fewer possible side effects)
Rare adverse side effects: N&V, hypotension, confusion

Resagiline: promotes anti-apoptotic genes in mice

22
Q

Name COMT inhibitors and MOA

A

Tolocapone (CNS and periphery) and Entacapone (Periphery)
Prevents breakdown of dopamine in the brain.
COMT converts L-DOPA to 3-OMD which compete for same transporter protein in BBB. Inhibiting COMT will mean more L-DOPA crosses BBB.

23
Q

What is the gene found to be associated with synaptic development and plasticity?

A

Neuregulin-1: effects NMDA receptor expression

24
Q

Describe the positive and negative effects of dopamine in terms of schizophrenia

A

Dopamine in excess: acts on D2 receptors in mesolimbic and nigrostriatal pathway leading to positive symptoms

Dopamine deficiency: in pre-frontal region, mediated by D1 receptors leads to negative symptoms

25
Q

What are the positive symptoms in schizophrenia?

A

Symptoms which should not appear.
Hallucinations
Delusions
Disorganised thoughts

26
Q

What are the negative symptoms in schizophrenia?

A

List of characteristics which should be present.

  • Reduced speech
  • Lack of facial and emotional expression
  • Diminished ability to start and sustain activities
  • Reduced enjoyment in everyday
  • Social withdrawal
27
Q

What are the cognitive defects seen in schizophrenia?

A

Memory
Attention
Planning
Decision making

28
Q

What is the glutamate theory in schizophrenia?

A

Reduced glutamate concentrations are found in schizophrenic brains.
Where NMDA receptors are reduced, typical schizophrenic behaviour is shown.
Glutamate exerts excitatory effects on GABA-ergic striata neurons -> thalamus, constitutes a ‘sensory’ gate.

29
Q

What is the MOA of antipsychotics?

A

D2 receptor antagonists: treat positive symptoms but not negative ones
Also able to block 5-HT receptors
Delayed effects (weeks) as there is an initial increase in DA synthesis and neuronal activity

30
Q

List the main side effects of antipsychotics

A 
Extrapyramidal effects
Sedation
Weight gain
Anti-cholinergic
Hyperglycaemia
Orthostatic hypotension
31
Q

What are the extrapyramidal side effects of antipsychotics and why do they occur?

A

Blocking dopamine receptors in the nigrostriatal pathway may lead to Parkinson-like symptoms.

  • Acute dystonia; protruding tongue, muscle spasms, neck spasm, fixed upward gaze
  • Tardive dyskinesia; involuntary movements
32
Q

What is the endocrine effect of anti-psychotics?

A

Blocks dopamine receptors part of the tuberoinfundibulnar system.
Dopamine acts to inhibit prolactin secretion via D2 receptors.
Antipsychotics lead to increase serum prolactin -> breast swelling and sometimes lactation (in women)

33
Q

Why is there a possibility of weight-gain with anti-psychotics?

A

Blockage of 5-HT receptors

34
Q

Why is there a possibility of orthostatic hypotension with anti-psychotics?

A

Blocking of alpha adrenoceptors

35
Q

What is the anticholinergic effect of anti-psychotics?

A

They block muscarinic cholinergic receptors.

Dry mouth, blurry vision, increased intra-ocular pressure, constipation, urinary retention

Pharmacology (19 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions