Psychopharmacology 1 Flashcards
How is resting potential established?
- Inside of neuron more -ve than outside
- Poorly permeable to Na+
- Moderately permeable to K+
- 3Na+ out, 2K+ in
Where is the BBB deficient?
- Around circumventricular organs
- Permits diffusion, allows regulation of endocrine/ANS functions
How permeable are the intraluminal capillary endothelial cells?
- Tight junctions = adhesion, maintenance, regulation
- Restricts paracellular diffusion
What are the functions of pericytes?
- Mechanical support
- Phagocytosis
- Induce tightness
What does BBB failure lead to?
- Loss of tightness
- Upreg water transport
- Pore formation
How is Dopamine/Noradrenaline synthesised?
From Tyrosine
Tyrosine > L-DOPA > Dopamine > Noradrenaline
How is serotonin synthesised?
From Tryptophan
Tryptophan > 5-hydroxytryptophan > 5-HT (serotonin)
How is acetylcholine synthesised?
- From choline + acetyl co A
- Stored in vesicles in nerve terminals
- Metabolised by AChE to form choline + free acetate
How is Glutamate/GABA synthesised?
From glucose in Krebs cycle
What is the role of Glutamate & GABA?
Glutamate = main excitatory NT of CNS GABA = main inhibitory NT of brain
What is the role of Glycine and how is it synthesised?
- Main inhibitory NT of spinal cord/PNS
- Synthesised from serine
- Folate dependent reaction
How are NT’s terminated?
Enzyme degradation:
MAO - Monoamine oxidase
COMT - Catechol-O-methyltransferase
AChE - Acetylcholinesterase
What are the theories of depression?
- Monoamine model
- Neurogenic model
- Inflammation
- Glutamate
Summarise the monoamine model of depression
- 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
Summarise the neurogenic model of depression
Elevated cortisol levels / non-suppression of cortisol
Summarise the inflammation model of depression
Association with higher inflam markers (cytokines, CRP)
Summarise the glutamate model of depression
Abnormalities:
- Increased glutamate, reduced GABA in occipital cortex
- Decreased glutamate & GABA in prefrontal cortex
How do glutamate antagonists work?
Block NMDA receptor
How do antidepressants work?
Enhance monoaminergic activity in central synapses
1) Inhibit reuptake
2) Inhibit enzymatic degradation
3) Block presynaptic auto receptors
What are reuptake inhibitors and how do they work?
- Tricyclics: serotonin/noradrenaline reuptake inhibitors (SERT vs NET)
- Selectively: act on other receptors = side effects
- SSRIs
- NRI: Reboxetine
- SNRI: Duloxetine, Venlafaxine
What are enzyme inhibitors and how do they work?
- MAOI
= Longer time in synaptic cleft - Can cause hypertensive reaction: flushing, headache, HTN, CVA
- Moclobemide (MAOI) = reversible = safer
What is Mirtazapine and how does it work?
- Works on noradrenergic + specific serotonergic
- Noradrenaline - blocks own release via alpha-2-autoreceptors, inhibits serotonin release via same mechanism on serotonergic
- Blocks some 5HT
Name CYP450 enzyme inducers/inhibitors
- Drug interferes with another
- Mirtazapine, TCAs, Trazadone, Venlafaxine
What are the physiological mechanisms of pharmacodynamics?
- Direct competition @ receptor site
- Augmentation of same NT pathway
- Different effect on organ
What are the pharmacodynamics of TCA’s?
- H1 : sedation - drugs + alcohol
- Anti-Ch : dry mouth, blurred vision, constipation - antihistamines, antipsychotics
- Alpha-1 : postural hypotension - antihypertensives
What are the pharmacodynamics of SSRI’s?
- Increase serotonergic activity > Serotonin syndrome
- Inhibit platelet aggregation > risk gastric bleeding with aspirin/NSAIDs
- Hyponatraemia > Diuretics
What are the pharmacodynamic of MAOI’s?
- Sympathomimetic + dopaminergic drugs
- Serotonin syndrome
What is serotonin syndrome?
- 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
