Neuropharmacology Flashcards
which area of the limbic system is associated with the regulation of fear?
amygdala
this area of the limibic system is asosciated with memory, emotional processing, regulation of stress, emotions and mood
hippocampus
fxn of Ach
voluntary muscle movements
major excitatory NT
Glutamate! (gas pedal)
term for too much glutamate?
excitotoxicity - causes damage to the CNS
major inhibitory NT
gaba (brake of car)
drugs that increase GABA produce what? (5)
1) relaxation
2) sedation
3) sleep
4) reduced anxiety
5) muscle relaxation
3 limitations of chemical antidepressant drugs
1) drugs don’t work for all pt’s (only work for 50-70%)
2) takes weeks or months for drugs to start working
3) side effects limit usage
3 current available treatments for depression
psychotherapy, chemical antidepressants, ECT
Monoamine hypothesis of depression
depression may be related to a deficiency of primarily NE and serotonin (also dopamine), therefore drugs aim to increase NE and 5HT
neurotrophic hypothesis of depression
depression may be related t oa loss of neurotrophic growth factors such as brain-derived neurotrophic factor, which leads to neuronal atrophy and death. This all may be due to a decrease in NE and 5HT and increased glucocorticoid levels from stress. Antidepressant drugs aim to increase BDNF
3 types of antidepressant drugs
1) Tricyclics (TCAs)
2) Monoamine oxidase inhibitors (MAOIs)
3) SSRIs/SNRIs
which antidepressant drugs are 1st gen?
TCAs and MAOIs
which antidepressant drugs are 2nd gen?
SSRIs/SNRIs
main difference between 1st and 2nd gen antidep drugs?
side effects are worse in 1st gen drugs
2 mechanisms of antidepressant drugs (lay terms definition)
1) bock re-uptake of NE and seratonin via SSRIs
2) block metabolism of NT’s via MAOIs (MAO is what breaks down NE and serotonin so we block MAO via MAOIs)
2 mechanisms of antidepressant drugs (from slides)
- overall goal is to increase monoamine levels (NE and 5HT in the synapse
1) block enzyme breakdown by monoamine oxidase via MAOIs
2) block re-uptake into presynaptic terminal by inhibition of transporters
Name 3 TCAs
imipramine, desipramine, amitriptyline
TCAs: info about treatment
- used to be standard treatment for depression
- now 2nd or 3rd treatment choice due to bad side effects
mechanism of action of TCAs
- block reuptake of NE and 5HT into the presynaptic terminal
- increase NE and 5HT in synaptic cleft
adverse effects of TCAS
sedation, anticholinergic effects (consitpation etc), arrhythmias, ORTHOSTATIC HYPOTENSION. overdose = fatal
the hip breaker drug
TCAs! due to orthostatic hypotension
name 3 MAOIs
phenelzine, tranylcypromine selegiline
info about MAOIs
- 1st modern class of antidepressants
- not used much now because of toxciity and food issue
mechanism of action of MAOIs
increase synaptic availibility of NE and 5HT by blocking their breakdown via inhibition of MAO enzyme
Adverse effects of MAOIs
- CNS excitation (restless, irritable), anticholinergic effects
- increased BP – hypertensive crisis
- Tyramine-rich foods
expand upon tyramine-rich foods and MAOIs
- tyramine-rich foods trigger the release of catecholamines which cause VC and hypertensive crisis that can be fatal
name 6 SSRIs
- fluoxetine
- sertraline
- citalopram
- escitalopram
- paroxetine
- fluvoxamine
Current 1st line of antideprresant drugs are
SSRIs
SSRI info
- not more effective than older drugs, just fewer side effects
- more useful in long term management of depression
mechanism of action of SSRIs
block reuptake of 5HT (serotonin)
also increase abilibilty of 5HT in synaptic cleft
adverse effects of SSRis
- GI irritation (usually resolves after taking drug 1-2wks), insomnia, sexual dysfunction, nervousness, agitation, weight loss or gain
Concerns for PT’s in patients who are depressed
- be aware of potential comorbid depression
- sedation, muscle weakness, ataxia
- orthostatic hypotension!!
name the 3 subtypes of partial seizures
1) simple partial
2) complex partial
3) partial becoming generalized
define simple partial seizure
the person is alert and can remember what happens. it is limited to one area of the brain. the person whill show minimal signs that the seizure is occurring. it is the least robust type of seizure
define complex partial seizure
starts in a small area of temporal/frontal lobe but can spread to other areas that affect alertness/awakeness
define partial becoming generalized
partial seizure that spreads through the entire brain
which area of the brain is involved in a generalized epileptic seizure?
the entire brain
2 types of generalized seizures
absence (petit mal) and tonic-clonic (grand mal)
absence/petit mal seizure
sudden, brief loss of consciousness, ranges from no motor signs to symetrical jerking mvmt of entire body
tonic-clonic grand mal
major convulsions of entire body and loss of consciousness
tonic = loss of consciousness and mucle tension
clonic = muscle contracts and relaxes aka convulsions
4 phases of tonic clonic seizure
1) aura: visual distrubances that occur before the seizure. tells person seixure is coming
2) tonic: muscle contractions
3) clonic: convulsions
4) sleep
goals of antiepileptic drugs
inhibit firing of hyperexcitable cerebral neurons
3 ways antiepileptic drugs work
1) increase inhibitory effects of gaba
2) decrease glutamate
3) alter neuron acitvation by altering mvmt of Na Ca (this is needed for depolarization of neurons) (blockks APs)
name 6 epileptic durgs
phenobarbital, diazepam, phenytoin, carbamazepine, ethosuximide, valproic acid
these 2 epileptic drugs produce sedation by increasin gaba
phenobarbital and diazepam (valium and zanex)
this drug is used to treat status epilepticus (ongoing seizure)
diazepam
these 2 drugs can be used to treat a variety of seizures
phenytoin, carbamazepine (work by blocking sodium channels)
these 2 drugs are most commonly used for petit mal seizures
ethosuximide and valproic acid
side effects of epileptic drugs PT’s need to be aware of
dizziness, ataxia, sedation, rashes
simple pathology of parkinson’s
loss of dopaminergic neurons in basal ganglia.. also includes misfolded proteins that build up and eventually destroy cells
main protien involed in parkison
alpha-synuclein
parkinsons pts lose neurons that contain what NT
dopamine!
4 sx/sy of PD
bradykinesia, muscle rigidity, resting tremor, postural instability
pathophys of PD from slide
degeneration/loss of dopamine nuerons in substantia nigra that project to striatum. accompanied by increased activity of ACH in BG. result = decreased ability of BG to modify muscle cotnraction and activiation
basic idea of PD treatmetn
increase dopamine and decrease ACH
genetic factors of PD
alpha synuclein accumulation (protein), formulation of LEwy bodies and increased production of free rads all itnerfere with neuron fxn leading to neuron death
more pathopys of PD
degeneration of SN leads to overactivity in indirect pathway. Net effect = neruons in SN become mroe active and increase inhbition to the thalamus
PD: you lose dopamine in SN. These effect the indrect pathway, so you are losing inhibiton, causing the indirect pathway to be over-active. the end result is increased activation of GP and pars reticulata of the SN which increase gaba input to the thalamus.. this results in decreased excitatory input to the cortex for motor mvmts
:)
most common drug given for PD
L-DOPA. Can’t give dopamine b/c it doesn’t cross BBB, but L-DOPA does.
downsides of L-DOPA
- some patient’s can’t tolerate the drug or don’t respond to it
- benefits of treatment decrease after 3-4 years
L-DOPA is usually given with what drug
Carbidopa, which inhibits dopa decarboxylase (the substance that breaks down Ldopa) so that it can make it into the brain so less is metabolized in the periphery
adverse effects of LDOPA
- dyskinesias that increase the longer you are on the drug
- response fluctuations (wearing off)
dyskinesias from ldopa include what
choreiform mvmts, athetosis, ballismus, dystonias
describe the wearing off of LDOPA
drug wears off after it is given (after a certain amount of time) so time your treatments to shortly after the drug has been given (don’t wait to treat until the end of the day)
idea of combating effects of LDOPA
drug holiday! stop taking drug for a period of time to improve response fluctuation issue
main sx to be worreid about with LDOPA
orthostatic hypotension
2 types of drugs for spasms
diazepam and polysnaptic inhibitors
how does diazepam work
increases gaba in the spinal cord and shuts down acivity of motor neurons to decrease spasm
name 3 drugs for spasms
Carisoprodol, cyclobenzaprine, methocarbamol
- decrease MN activity
- adverse effects = sedation, dizziness, ataxia
6 drugs for spasticity
baclofen, diazepam, dantrolene, gabapentin, tizanidine, botulinum toxin
MOA of baclofen
gaba B receptor agonist
dantrolene works at the ____
muscle to decrease spasticity
side effects of spasm/spasticity drugs
sedation, muscle weakness, dizziness ataxia orthostatic hypotension
