Psychopharmacology 1

Question 1

How is resting potential established?

Answer 1

• Inside of neuron more -ve than outside
• Poorly permeable to Na+
• Moderately permeable to K+
• 3Na+ out, 2K+ in

Question 2

Where is the BBB deficient?

Answer 2

• Around circumventricular organs

- Permits diffusion, allows regulation of endocrine/ANS functions

Question 3

How permeable are the intraluminal capillary endothelial cells?

Answer 3

• Tight junctions = adhesion, maintenance, regulation

- Restricts paracellular diffusion

Question 4

What are the functions of pericytes?

Answer 4

• Mechanical support
• Phagocytosis
• Induce tightness

Question 5

What does BBB failure lead to?

Answer 5

• Loss of tightness
• Upreg water transport
• Pore formation

Question 6

How is Dopamine/Noradrenaline synthesised?

Answer 6

From Tyrosine

Tyrosine > L-DOPA > Dopamine > Noradrenaline

Question 7

How is serotonin synthesised?

Answer 7

From Tryptophan

Tryptophan > 5-hydroxytryptophan > 5-HT (serotonin)

Question 8

How is acetylcholine synthesised?

Answer 8

• From choline + acetyl co A
• Stored in vesicles in nerve terminals
• Metabolised by AChE to form choline + free acetate

Question 9

How is Glutamate/GABA synthesised?

Answer 9

From glucose in Krebs cycle

Question 10

What is the role of Glutamate & GABA?

Answer 10

Glutamate = main excitatory NT of CNS
GABA = main inhibitory NT of brain

Question 11

What is the role of Glycine and how is it synthesised?

Answer 11

• Main inhibitory NT of spinal cord/PNS
• Synthesised from serine
• Folate dependent reaction

Question 12

How are NT’s terminated?

Answer 12

Enzyme degradation:
MAO - Monoamine oxidase
COMT - Catechol-O-methyltransferase
AChE - Acetylcholinesterase

Question 13

What are the theories of depression?

Answer 13

• Monoamine model
• Neurogenic model
• Inflammation
• Glutamate

Question 14

Summarise the monoamine model of depression

Answer 14

• Too little serotonin
• Indirect measurements
• 5-HT broken down by MOA into 5-HIAA
• Both found to be low in brainstem of suicide death
• Also increased tryptophan hydroxylase

Question 15

Summarise the neurogenic model of depression

Answer 15

Elevated cortisol levels / non-suppression of cortisol

Question 16

Summarise the inflammation model of depression

Answer 16

Association with higher inflam markers (cytokines, CRP)

Question 17

Summarise the glutamate model of depression

Answer 17

Abnormalities:

• Increased glutamate, reduced GABA in occipital cortex
• Decreased glutamate & GABA in prefrontal cortex

Question 18

How do glutamate antagonists work?

Answer 18

Block NMDA receptor

Question 19

How do antidepressants work?

Answer 19

Enhance monoaminergic activity in central synapses

1) Inhibit reuptake
2) Inhibit enzymatic degradation
3) Block presynaptic auto receptors

Question 20

What are reuptake inhibitors and how do they work?

Answer 20

• Tricyclics: serotonin/noradrenaline reuptake inhibitors (SERT vs NET)
• Selectively: act on other receptors = side effects
• SSRIs
• NRI: Reboxetine
• SNRI: Duloxetine, Venlafaxine

Question 21

What are enzyme inhibitors and how do they work?

Answer 21

• MAOI
  = Longer time in synaptic cleft
• Can cause hypertensive reaction: flushing, headache, HTN, CVA
• Moclobemide (MAOI) = reversible = safer

Question 22

What is Mirtazapine and how does it work?

Answer 22

• Works on noradrenergic + specific serotonergic
• Noradrenaline - blocks own release via alpha-2-autoreceptors, inhibits serotonin release via same mechanism on serotonergic
• Blocks some 5HT

Question 23

Name CYP450 enzyme inducers/inhibitors

Answer 23

• Drug interferes with another

- Mirtazapine, TCAs, Trazadone, Venlafaxine

Question 24

What are the physiological mechanisms of pharmacodynamics?

Answer 24

• Direct competition @ receptor site
• Augmentation of same NT pathway
• Different effect on organ

Question 25

What are the pharmacodynamics of TCA’s?

Answer 25

• H1 : sedation - drugs + alcohol
• Anti-Ch : dry mouth, blurred vision, constipation - antihistamines, antipsychotics
• Alpha-1 : postural hypotension - antihypertensives

Question 26

What are the pharmacodynamics of SSRI’s?

Answer 26

• Increase serotonergic activity > Serotonin syndrome
• Inhibit platelet aggregation > risk gastric bleeding with aspirin/NSAIDs
• Hyponatraemia > Diuretics

Question 27

What are the pharmacodynamic of MAOI’s?

Answer 27

• Sympathomimetic + dopaminergic drugs

- Serotonin syndrome

Question 28

What is serotonin syndrome?

Answer 28

• Increased 5-HT activity in CNS
• Mental state - anxiety, agitation, disorientation
• Autonomic instability - daphoresis, raised HR/RR/BP/temp/vomiting/diarrhoea
• Neuromuscular - tremor, rigidity, hyperreflexia, bilateral babinski
• Differentiators from NMS - hypereflexia, dilated pupils, increased bowel sounds