Anti-PDs and Neuroleptics Flashcards
Describe dopamine synthesis
- L-Tyrosine is converted by tyrosine hydroxylase to L-DOPA
- DOPA is converted by DOPA decarboxylase to Dopamine
Describe dopamine metabolism
- Dopamine transporter (DAT) and Noradrenaline transporter (NET) both are reuptake transporters that reuptake dopamine from the synapse back into the presynaptic neurone and once here they are metabolised / degraded
- 3 enzymes are involved in the metabolism / degradation:
- Monoamine oxidase A (MAO-A): metabolises DA, NE, 5-HT
- Monoamine oxidase B (MAO-B): metabolises DA
- Catechol-O-methyl transferase (COMT): wide distribution, metabolises all catecholamines
What are the 4 dopaminergic pathways - describe the pathways and a brief word on their function? Also, what disease states are they important in?
- Nigrostriatal pathway - cell bodies of the nerve are present within the subtantia nigra pars compacta (SNc), and the nerves project up to the striatum. Inhibition of these neurones is important in Parkinson’s Disease
- Mesolimbic pathway - cell bodies are located in the Ventral Tegmental Area (VTA) and the axons project up to the Nucleus Accumbens (NAcc). This is the brain reward pathway. Important in schizophrenia
- Mesocortical pathway - cell bodies are located in the Ventral Tegmental Area (VTA) and the axons project up to the cerebrum. Involved in executive function and complex behavioural patterns. Important in schizophrenia
- Tuberoinfundibular pathway - cell bodies in the arcuate nucleus → projection to the median eminence. Regulates prolactin secretion. Inhibition results in hyperprolactinaemia
Describe the pathophysiology of Parkinson’s Disease
- Severe loss of dopaminergic neurones in the nigrostriatal tract
- Lewy bodies and neurites found within neuronal cell bodies and axons respectively
- Consist of abnormally phosphorylated neurofilaments, ubiquitin & α-synuclein
Describe the clinical symptoms of Parkinson’s Disease - the 3 types of symptoms and the symptoms within these
- Motor symptoms - resting tremor, bradykinesia, rigidity, postural instability
- Autonomic nervous system effects - olfactory deficits, orthostatic hypotension, constipation
- Neuropsychiatric - sleep disorders, memory deficits, depression, instability
What are lewy bodies and lewy neurites, where are they located, and what are their roles in the pathophysiology of parkinson’s disease?
- Lewy bodies are located in the cell bodies
- Lewy neurites are located in the axons and dendrites
- These consist of phosphorylated neurofilaments, ubiquitin and α-synuclein
1) What is the Parkinson’s Disease treatment by dopamine replacement - the name of the drug and its adjuncts? How does this work? No need to describe the basis for these adjuncts yet in this flashcard - it’s in another flashcard
2) What are some side effects seen with this treatment?
1)
- Levodopa + carbidopa (+selegiline)
- This is centrally decarboxylated into dopamine to replace the missing dopamine in the nigrostriatal pathway
2)
- Dyskinesias
- ‘On-and-off treatment’
Name the dopamine replacement therapy commonly used to treat Parkinson’s disease and give the adjuncts given alongside this and the purpose that these serve
- Levodopa
- You give L-DOPA with DOPA decarboxylase inhibitors: Carbidopa
- These do not cross the BBB → prevent peripheral conversion of levodopa but not levodopa in the CNS
- Therefore they reduce required levodopa dosage AND importantly…
- They reduce triggering of the CTZ so prevents nausea and vomiting
- COMT inhibitors: Entacapone & Tolcapone
- MAO-B inhibitors: Selegiline
- Both reduce metabolism of the levodopa to reduce its clearance in order to prolong its effect
Describe the use of dopamine receptor agonists in treatment of Parkinson’s Disease
What are the 2 types of this type of treatment and give 2 example drugs of these. Also what are the side effects of one of these types?
1)
- Dopamine receptor agonists activate the dopamine receptors which is useful because dopamine is low in Parkinson’s (as there is loss of dopaminergic neurones in the nigrostriatal pathway)
2)
- Ergot derivatives - Bromocriptine and Pergolide
* SIDE FX: Cardiac fibrosis and increased risk of valvular disease - Non-ergot derivatives - Ropinirole and Rotigotine
Which receptors do dopamine act on?
- D1,5(Gs linked)
- D2-4 (Gi-linked) receptor
1) Describe the use of MAO-B inhibitors in treatment of Parkinson’s Disease
2) Name 2 anti-PD example drugs that do this
1)
- Remember that one of the enzymes that metabolises dopamine after it has undergone reuptake is MAO-B - it metabolises dopamine
- So by inhibiting this, you are increasing the amount of dopamine
2)
- Selegiline
- Rasagiline
Describe the pathophysiology of…..
1) Positive schizophrenia symptoms
2) Negative schizophrenia symptoms
What are the symptoms of…..
3) Positive schizophrenia symptoms
4) Negative schizophrenia symptoms
1)
- Increased mesolimbic activity
2)
- Decreased mesocortical activity
3)
- Hallucinations - auditory and visual
- Delusions - paranoia
- Thought disorder - self-denial
4)
- Affective flattening - lack of emotion
- Alogia: lack of speech
- Avolition / apathy - loss of motivation
What are the 2 first generation anti-psychotics used to treat schizophrenia?
- Chlorpromazine
- Haloperidol
1) What type of drug is Chlorpromazine, what is it used to treat, and what is its mode of action?
2) What are its side effects?
1)
- First generation anti-psychotic
- Treats positive schizophrenia symptoms
- D2 receptor antagonist
2)
- Anti-cholinergic effects, especially sedation
- Extra-pyramidal side effects
1) What type of drug is Haloperidol and what is it used to treat? What is its mode of action?
2) What are some of the side effects of Haloperidol?
1)
- First generation anti-psychotic
- Treats positive schizophrenia symptoms
- D2 antagonist
2)
- Extra-pyramidal side effects
