Psychopharmacology 1

Question 1

2 inputs and 2 outputs of neurons

Answer 1

Inputs:-
- Chemical
- Electrical 
Output:-
- Neurotransmitter release
All-or-nothing (action potential)

Question 2

Permeable and impermeable substances across neuronal cell membrane

Answer 2

Permeable:-

• Water
• Oxygen/carbon dioxide
• Small molecules (ethanol)
• Lipophilic substances

Impermeable:-

• Charged particles (ions)
• Large polar molecules eg sugars

Question 3

Channel at end of synapse

Answer 3

Ca2+ channel

Question 4

Excitation, inhibition membrane outcomes

Answer 4

Membrane depolarisation

Membrane hyperpolarization

Question 5

Blood- brain barrier function

Answer 5

Physiological barrier/interface
Separates CNS and peripheral circulation
Preserves homeostasis for optimal neuronal activity
Deficient around circumventricular organs (diffusion and allows regulation of endocrine/ANS functions)

Question 6

Intraluminal capillary endothelial cells function in BBB

Answer 6

Tight junctions- intramembranous strands

Adhesion/maintenance/regulation

Question 7

Astrocytes function in BBB

Answer 7

Star-shaped neuroglial

Question 8

Pericytes function

Answer 8

Mechanical support
Phagocytosis
Induce tightness

Question 9

Which factors enhance transport across BBB

Answer 9

Lipophiliicity, Low MW,
Facilitated diffusion
Endocytosis

Question 10

Monoamines as neurotransmitters

Answer 10

Dopamine and serotonin

Question 11

Dopamine/Noradrenaline synthesis steps

Answer 11

1) Tyrosine at synaptic terminal synthesised to 2) L-DOPA formed via tyrosine hydroxylase
3) Dopamine via Dopa decarboxylase
Noradrenaline formed from dopamine- beta- hydroxylase

Question 12

Serotonin

Answer 12

Synthesized from tryptophan

1) 5- hydroxytryptophan from Tryptophan hydroxylase- rate limiting enzyme

Question 13

Acetylcholine

Answer 13

Synthesised from choline from acetyl coenzyme A
Catalysed by choline acetyltransferase
stored in vesicles in nerve terminals
Metabolised by AChE to form choline and free acetate

Question 14

Glutamate/GABA

Answer 14

GLUTAMTE: Main excitatory neurotransmitter of CNS
GABA: Main inhibitory neurotransmitter of brain
Synthesized from glucose in krebs cycle
GABA formed from glutamic acid decarboxylase

Question 15

Glycine

Answer 15

Main inhibitory neurotransmitter of spinal cord/PNS
Synthesised from serine
Folate-dependent reaction
Enzymes : serine hydroxymethyltransferase

Question 16

Three ways of neurotransmitter termination

Answer 16

1) Diffusion from synaptic cleft
2) Reuptake into presynaptic neuron (inhibition)
3) Enzymatic degradation (MAO, COMT catechol-O-methyltransferase)
AChe

Question 17

TCA and MAOI drug discoveries (one of each)

Answer 17

Imipramide -TCA

Iproniazid- MAOI

Question 18

Monoamine model

Answer 18

5-HT broken down by MAO into 5-HIAA

Less 5-HT and 5-HIAA in brainstem of suicide deaths

Question 19

Neurogenic model

Answer 19

Chronic stress- hippocampal damage, cortisol levels
HPA axis overactivity , insufficient negative feedback
Elevated cortisol levels

Question 20

Inflammation model

Answer 20

Higher inflammatory marker (Cytokine, CRP)

Decreased response to treatment

Question 21

Glutamate/ GABA

Answer 21

Increased glutamate, decreased GABA in occipital cortex
Decreased glutamate and GABA in prefrontal cortex
Scope for glutamate antagonists- Ketamine, Blocks NMDA receptor
Ketamine separates mind and body

Question 22

Antidepressants MOA

Answer 22

Enhance monaminergic activity in central synapses

• Inhibit reuptake
• Inhibit enzymatic degradation
• Block presynaptic autoreceptors

SSRIS/SRI/NRI

Question 23

Reuptake inhibitors

Answer 23

TCAs, SSRIs, NRI, SNRI

Question 24

NRI examples

Answer 24

Reboxetine

Question 25

SNRI examples

Answer 25

Duloxetine, Venlafaxine

Question 26

Enzyme inhibitor MAOI spends longer in the synaptic cleft. How is this useful?

Answer 26

Redress pre-existing deficit of the monoamine leading to compensatory post-synaptic adaptations

SERT is stopped

Leads to activating effects downstream

Question 27

What is the cheese crisis?

Answer 27

MAO give you hypertensive reactive- tyramine activates sympathetic nervous system
Tyramine is usually blocked by monoamine oxidase but here MAO are blocked by MAOIs and Tyramine

Question 28

Mirtazapine MOA

Answer 28

Noradrenergic and specific serotonergic antidepressant (NaSSa)
Noradrenaline- blocks own release via alpha-2 autoreceptors
Enhances the release of norepinephrine and 5-HT1a-mediated serotonergic transmission- 5HT2, 5HT3 receptors
Feedback loops blocked
HI antagonist: drowsiness, weight gain

Question 29

CY1A2 enzyme inhibitors

Answer 29

Mirtazapine, TCAs

Question 30

CYP2C enzyme inhibitors

Answer 30

TCAs

Question 31

CYP2D6 enzyme inhibitors

Answer 31

TCAs, tazadone, Velafaxine

Question 32

CYP3A enzyme inhibitors

Answer 32

Mirtazapine, TCA, venlaflaxine

Question 33

TCAs, H1 pharmacodynamic effects

Answer 33

Sedation- drugs and alcohol

Question 34

TCA- Anti- Ch effects

Answer 34

dry mouth, blurred vision, constipation - antihistamines, antipsychotics

Question 35

TCA alpha-1 effects

Answer 35

Postural hypotension- anti hypertensives

Question 36

Inhibitors of Monoamine uptake

Answer 36

SSRIS, TCAs, Mixed 5-Ht and noradrenaline reuptake inhibitors, NRIs

Question 37

Examples of SSRIs

Answer 37

Fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram, viladazone

Question 38

TCA example and MOA

Answer 38

Varied activity and selectivity with respect to inhibition of noradrenaline and 5-HT uptake