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PHAR2002 TERM 2 > SECTION 1 > Flashcards

SECTION 1 Flashcards

1
Q

Name the transporters of glutamate

A

EAAT(1-5) is the transporter on the membranes of neurons and glia
vGlut is the vesicular transporter

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2
Q

Name the transporters of GABA and glycine

A

GAT(1-4) is the transporter on the neuronal membrane
Glycine is taken up from the synapse by GlyT(1 or 2)
VIAAT transports both GABA and glycine into vesicles

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3
Q

Name antagonists of the following receptors:

AMPA, Kainate and NMDA

A

antagonist of AMPA and Kainate –> CNQX

NMDA is blocked by AP5

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4
Q

Name an agonist and antagonist of the GABAa receptor

A

agonist –> Muscimol

antagonist –> Bicuculline

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5
Q

What effect do Benzodiazepines have on the GABAa receptor?

A

they are positive allosteric modulators of the receptor. Used to treat anxiety, insomnia and as sedatives.

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6
Q

Name an antagonist of the Glycine receptor

A

Strychnine

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7
Q

List the chief symptoms associated with Parkinson’s Disease

A

Suppression of Voluntary Movement - Hypokinesia
Tremor at rest
Muscle Rigidity
Cognitive Impairment

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8
Q

List possible factors that could lead to Parkinson’s Disease

A

Head Trauma
Viral Attack
Chemical Agents e.g. MPTP, a toxic opioid metabolite used as a recreational drug

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9
Q

What are the effects of the release of Dopamine by the Substantia NIgra in the Nigrostriatal Pathway

A

Dopamine acts on D1 receptors in the Striatum to turn up the Direct Pathway
DA also acts on D2 receptors in the Striatum to turn down the Indirect Pathway.

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10
Q

What is the purpose of the Direct and Indirect Pathway?

A

Direct Pathway facilitates the initiation of movement

Indirect Pathway prevents unnecessary movement

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11
Q

Name the five Dopamine Pathways in the CNS

A 
Nigrostriatal Pathway 
Mesolimbic Pathway
Mesocortical Pathway
Tuberoinfundibular (aka  Median Eminence to Anterior Pituitary)
Chemoreceptor Trigger Zone
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12
Q

Outline the steps involved in Dopamine Synthesis

A

Tyrosine –> L-DOPA –> Dopamine

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13
Q

Name the enzyme responsible for converting L-DOPA to Dopamine

A

DOPA Decarboxylase

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14
Q

What are the classes of Dopamine Receptors?

A

D1 (includes D5) - Gs coupled

D2 (includes D3 and D4) - Gi coupled

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15
Q

What are the effects of Acetylcholine on the Direct and Indirect Pathways

A

Striatal Cholinergic Interneurons inhibit neurons involved in the Direct Loop while they excite neurons in the Indirect Loop.

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16
Q

Name the pharmacological treatments of Parkinson’s Disease

A

L-DOPA, Carbidopa, Selegiline, Bromocrpitine, Apomorphine, Domperidone, Amantadine

17
Q

What are the effects of L-DOPA in the CNS and the periphery?

A

In the CNS it is converted to dopamine by dopaminergic neurons which goes to activate D1 and D2 receptors. In the periphery, it also is converted to DA, causing nausea (activation of the CTZ) and causes postural hypotension

18
Q

What is the effect of Carbidopa?

A

It’s a DOPA decarboxylase inhibitor in the periphery. the enzyme that converts L-DOPA to Dopamine. Carbidopa is given as an adjunct with L-DOPA

19
Q

What are the effects of Selegiline?

A

Selegiline is a selective MOAB inhibitor and is able to cross the BBB so it prolongs the effects of DA In the CNS

20
Q

Name the Dopamine receptor agonists used to treat Parkinson’s and outline their effects

A

Bromocriptine - selective D2 receptor agonist in the CNS so turns up the Indirect pathway
Apomorphine - a non-selective D1 and D2 agonist in the CNS it’s useful when L-DOPA has a reduced effect.

21
Q

What is the effect of Domperidone? What is it usually administered with?

A

it is a selective D2 receptor antagonist in the periphery (can’t cross the BBB). it is a particularly useful anti-emetic(blocking the D2 receptors of CTZ) so is given with Apomorphine

22
Q

List the 5 possible symptomatic causes of epilepsy

A 
Cerebrovascular lesions 
Perinatal or Postnatal trauma 
CNS infections 
Tumours 
Congenital malformation of the CNS
23
Q

What are the two main classes of epileptic seizures?

A

Partial seizures - local electrical discharge in one brain area
Primary Generalized - widespread discharge involving both hemispheres

24
Q

What are the subtypes of Partial Seizures in Epilepsy?

A

Simple Partial - consciousness is preserved
Complex Partial - consciousness is altered so person has no recollection of the event
Both types can escalate to a Secondary Generalized

25
Q

Describe what is known as status epilepticus

A

A state where seizures follow one another with no intervening periods of normal function. This tends to occur following prolonged Primary Generalized seizures.

26
Q

Explain what is known as Paroxysmal Depolarization Shifts (PDS)?

A

PDS is an abnormal behaviour during which the membrane potential of neurons suddenly decreases by ~ 30mV and remains depolarised before returning normal. A burst of APs usually accompanies this shift

27
Q

Name the 6 cellular modifications that can promote rapid depolarizing bursts

A 
Increase in Ca conductance 
Increase in Na conductance 
Decrease in K conductance 
Decrease in Cl conductance 
Excessive activation of NDMARs 
Reduction of GABAR activity
28
Q

Name the four types of drugs used in the treatment of Epilepsy to decrease excitation in the CNS

A

Phenytoin
Carbamezapine
Valproate
Ethosuxemide

29
Q

What is the mechanism of action of Phenytoin and Carbamazepine

A

Phenytoin and Carbamazepine are use dependent blockers of the Na channel. They preferentially bind block the channels in their active state.

30
Q

What is the mechanism of action of Ethosuxemide?

A

Ethosuximide inhibits the T-type Ca channel particularly in thalamic neurons. It also blocks Na channels. It is particularly useful in absence seizures

31
Q

Name the four types of drugs used in the treatment of Epilepsy to increase inhibition in the CNS

A

Valproate
Benzodiazepines
Barbiturates
Tiagabine

32
Q

Describe the mechanism of action of Valproate

A

It’s a used dependent blocker of Na channels and is an inhibitor of GABA transaminase which metabolizes GABA in neurons.

33
Q

Describe the mechanism of action of Benzodiazepines (BZD) and Barbiturates (BBT)

A

Both are positive allosteric modulators of the GABAa receptor. Diazepam and Clonazepam are BZDs. Phenobarbitone is a BBT

34
Q

Describe the mechanism of Tiagabine

A

It blocks the membrane transporter of GABA, GAT-1, so GABA has prolonged effects in the synapse

35
Q

Describe the mechanism of action of Perampanel

A

it is a non-competitive antagonist of the AMPA receptor and is used to treat epilepsy.

36
Q

What is the mechanism of action of Tolcapone and what is it used to treat?

A

It is a selective reversible inhibitor of the COMT enzyme in the periphery as the drug can’t cross the BBB. COMT breaks down Levodopa in the periphery and dopamine in the CNS.

37
Q

What are the proposed mechanisms of action of the drug Amantadine?

A
  • Enhances the release of DA and inhibits its uptake
  • up-regulates post synaptic D2 receptors
  • non-competitive antagonism of the NMDARs

PHAR2002 TERM 2 (3 decks)

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