Flashcards in Neuropharm - lets do this Deck (44):
inhibits Glutamic acid dehydrogenase
Inhibits GABA transaminase
what causes a stroke?
interrupted blood flow to the brain either by haemorrhage - high BP, weakened blood vessels, amphetamine/cocaine (15%) or by occlusion - atheroscloerisis, thrombosis, embolism (85%).
what happens during a stroke to cause brain damage?
hypo perfusion, electric failure, ionic pump failure, Na influx, K efflux, depolarisation - huge Ca influx. Oxidative stress - free radicals, degrade membranes and proteins. cell death and cerebral damage. also bbb dysfunction
what are the 7 main treatments/preventions for stroke?
treatments (4): Aptiganel - GluR antagonist, Nicardipine - Ca channel blocker, Lamotrignine - Na channel blocker, Clot busters - Alteplase (desmoteplase still in trials) - must be thrombotic. preventatives (3); antihypertensives, statins or aspirin
why are there different symptoms of epilepsy and which brain area is responsible for each?
The symptoms depend on the location of the epileptic foci in the brain. Motor cortex - convulsions. Reticular formation - unconsciousness. Temporal lobe - psychomotor epilepsy. Hypothalamus - peripheral autonomic discharge.
what can trigger epilepsy?
stress, drop in pH, drop in blood glucose, fatigue, infection, gaming, antihistamines
what is a proposed mechanism for epilepsy?
mismatch between GABA and Glut that causes a paroxysmal depol shift. AP spreads from focus - synchronous wave of depol.
what are the 4 main targets for epilepsy treatment?
enhancement of GABAergic transmission. inhibition of na channels. inhibition of ca channels. inhibition of glutamate receptors.
enhancement of GABAergic transmission?
Vigabatrin - inhibits Gaba transaminase, tiagabine - inhibits GAT, valproate - SSADH inhibitor, barbiturates - GABAa receptor enhancement, may also prevent seizures at the initial site e.g. phenobarbital.
na channel inhibitors?
ca channel inhibitors
mainly used in absence seizures, t-type ca channels - ethosuximide, gabapentin
What is anxiety?
fear is a physiological response to fearful stimuli - anticipation of these events
What is the correlation between anxiety and GABA?
People with anxiety have reduced GABAa receptors.
What are the five main categories of anxiety?
General anxiety disorder. Panic disorder - sudden attacks of terror. Phobias - irrational fear of object/situation. PTSD - anxiety caused by recall of previous stressful event. OCD - recurrent and persistent thoughts in which the individual responds by performing ritualised excessive actions.
What are the main treatments for each type?
GAD - benzodiazepines and buspirone. Panic disorder - benzodiazepines and antidepressants. Phobias - benzodiazepines. PTSD - antidepressants and b-blockers. OCD - antidepressants.
How do we study fear and anxiety?
Innate (movement from dark to light) or learnt (e.g. electric shock in response to stimulus). apply stimulus or give environment and observe. elevated plus maze.
How does the HPA axis regulate anxiety?
Hippocampus and amygdala. Amygdala is the on signal and stimulates PVN in hypothalamus. Causes release of CRF. Stimulates release of adrenocorticotropic factor. Stimulates adrenal medulla to release glucocorticoids. glucocorticoids inhibit all but amygdala and ACTF.
What are the four main treatments for anxiety?
Benzodiazepines, buspirone, beta-blockers and antidepressants.
allosteric modulators of GABAa receptor. require gamma2 for binding. increase affinity for gaba so only potentiate gaba already released. ideally would be selective for alpha2.
give two examples of benzodiazepines
beta-blockers used for anxiety?
e.g. propanolol. used to reduce peripheral effects of panic attacks
used to treat anxiety - dirty pharm - 5-HT1a, D2, D3 etc. can take weeks to take effect
4 main treatments for insomnia?
benzodiazepines, antihistamines, tricyclic antidepressants and zolpidem
inability to cope
what are the two main types of depression?
unipolar - 90% - mood swings always down. bipolar (10%) - alternating periods of manic and depressive behaviour
what are other categories of depression?
reactive (75%) - in response to a stressful life, unipolar. endogenous (25%) - unipolar and most bipolar, often familial susceptibility.
how does functional imbalance in the limbic system correlate with depression?
Amygdala - increased dendritic growth and spine formation - hyper-responsive. Hippocampus - dendritic atrophy and decrease in neurogenes - reduction in volume. medial pre-frontal cortex - dendritic atrophy and spine loss - hyporesponsive
how does stress affect depression? how do antidepressants counter act this?
stress stimulates release of glucocorticoids which reduces BDNF secretion. this increases atrophy and decreases survival causing an increase in vulnerability. antidepressants increase NA and 5-HT secretion, increasing BDNF secretion and stimulating survival and growth.
evidence for/against monoaminergic hypothesis
reserpine - irreversible VMAT inhibitor induces depression. drugs that reduce NA and 5-HT storage depress mood and drugs that inhibit NA and 5-HT uptake elevate mood. some effective antidepressants have no effect on monoamines - monoamines are perhaps the symptoms but not the cause
what are the 3 main pathways influenced by dopamine?
niagrostriatal pathway - control of movement. mesolimbic/mesocortical pathway - cognition, memory, attention etc. tubers-infundibular system - endocrine.
what are the different classes of 5-HT receptor?
5-HT1, 2, 4, 6 and 7 are GPCRs. 1 - Gi, 2 - Gq, 4, 6, 7 - Gs. 5-HT3 is a LGIC.
types of ssri?
reserpine - blocks VMAT. fluoxetine - inhibits SERT. busprione - 5-HT1A agonist.
what does serotonin do in the brain?
mood, wakefulness, sleep, feeding
give examples of maoi and explain how they work
selegiline - inhibit mao-b and iproniazid - non-selective. prevent breakdown of monoamines. side effects such as urinary retention and tremor due to inhibition of tyramine breakdown. irreversible
name 6 tricyclic antidepressants and their moa
amitriptyline and imipramine - non-selective NET/SERT inhibitors. citalopram, sertraline and fluoxetine - SERT selective. disipramine - NET selective
what are side effects of tricyclic antidepressants?
sedation and fatigue, postural hypotension
what are the three main symptom types for schizophrenia?
positive, negative and cognitive
what are the 4 main things shown in brain imaging studies for people with schizophrenia?
thinner prefrontal and temporal cortex. enlarged ventricles. increased activity in the subcortical areas. decreased activity in the prefrontal areas.