Depression Flashcards Preview

pharmacology > Depression > Flashcards

Flashcards in Depression Deck (25):
0

What is depression

Sad mood, loss of interest, abnormalities of sleep, appetite, energy
Frequently comorbid with anxiety disorders
Associated neuroendocrine disruption,
excessive CRF release

1

Depression neurocircuitry

May share anxiety neurocircuitry
Orbital and pfc
Amygdala
Ventral striatum
Hippocampus
Hypothalamus
Cingulate gyrus

2

Role of serotonin

Made from l typtophan
Metabolised by monoamine oxidase
Made in raphe nuclei
1abdefR activated by triptans
2abcR activated by hallucinogenic drugs
3-7 ionotroohic, blocked by ODANSERON LIKE ANTIMEMTICS

3

Role of noradrenaline

Tyrosine to dopamine to na
Made in locus coeruleus
Alpha and beta are metabotrophic

4

Role of dopamine

Made in ventral midbrain,
Sub nigra= movement
Ventral tegmentum area= reward, novelty, motivation
Innervates striatum, limbic and pfc.
Metabotrophic
1= excit galphas
2= inhib galphai

5

Tricyclic drugs

AMITYPTYLINE, IMIPRAMINE, CLOMIPRAMINE
inhibit serotonin and na reuptake
Block mAch, dry mouth, no tears
Histamine= drowsy
Alplha 1 adrenic= vasodilation, hypotension

6

Drug drug interactions with tricyclic drugs

+ adrenergic vasoconstrictors = arrhythmia
+ barbituates ='severe respiratory depresion
+ acetominophen = reduces tca metabolism leads to toxicity.

7

SSRIs

CITALOPRAM
FLUOXETINE
FLUVOXAMINE
PAROTEXETINE
SERTRALINE
selectively inhibit 5ht transporter, sexual dysfunction, weightgain
Decrease metabolism of codeine, benzos

8

NRIs

REBOXETINE
ATOMOXETINE
inhibit na uptake

9

Atypical antagonist

BUPROPRION
poorly understood mechanism
Inhibits da reuptake, minimally occupies dat
MITRAZAPINE
antagonist at alpha 2 5ht2a and 3rs
Mechanism unknown

10

SNRIs

VENLAFAXINE, DULOEXTINE
inhibit 5ht and na uptake
Used for ptsd

11

Monoamine oxidase inhibitor

IDRONIAZID
inhibits breakdown of monoamines,
Maob breaks down 5ht and histamine
TRANYLCYPROMINE, PHENELEZINE,
Tyramine containing foods cause adrenic storms with maois, keeps na in synapse for longer

12

Problems with monoamine antidepressants

Probably dont work by known mechanism
Only half patients respond to them
Clinical benefit seen after 7-8 weeks

13

Antidepressants are bad with what?

St johns wort (hyperforin)
Induces drug metabolising enzymes
Amount of active ingredient varies between different preparations

14

Animal models of depression

Models of stress not depression,
Swim, tail
Observe social isolation and decrease grooming
Reversed with antidepressants?

In vivo models are difficult

15

Monoamine hypothesis

Reduced levels of monoamine causes depression
Antidepressants dont work by their "known" mechanism
Half patients respond to treatment
Effects of monoamine transport is immediate, several weeks to see benefit.
Low tryptophan diet does not produce depression in healthy people

16

Chemical hypothesis

Depression caused by impaired function of particular receptors/channels
Genetic studies
Pathways altered by maois and ssris

17

Network hypothesis

Explains why antidepressants may take weeks to work when effect on nts is immediate

Depression due to long term malfunctions in neural network
Long term alterations in mants, leads to impaired network
Ma's play a role in neuronal growth and development

18

For network hypothesis

Alterations in ma function early postnatal in animal cause permanent organisational and behavioural disturbances, not seen in adults

Increase new neurone production in hippocampus

Sprouting of axons and dendrites

19

Against network hypothesis

Very low tryptophan levels causes depressive symptoms

20

ECT

Muscle relaxant administered
25-45s convulsion
Safe
May have ltm defects
Most effective antidepressant, stimulates neurogenesis

21

Deep brain stimulation

Of subgenual cingulate cortex
Used when all else fails
Dont know how it works, atp release?

22

Future treatments?

Multi-modal serotonergics
Triple uptake inhibitors
Neurokinin r antagonists
Nmda antagonists, may induce bdnf
Crf receptor antagonists

23

What is agomelatine?

Melatonin r agonist
Increase dopamine and na in pfc
Sleep phase shifts in depression
No weight gain
But melatonin not a great antidepressant

24

Bipolar

Mood stabilisers:
Lithium carbonate ( inhibits release of da and na)
Carbamazepine ( anticonvulsant blocks na+ channels interacts with adenosine r)
Valproate na (anticonvulsant, increases gaba, blocks na channels)
Antidepressants
Antipyschotics and benzodiazepines