CNS Flashcards
Which drugs can target the CNS directly without peripheral effects?
Morphine. receptor is on surface of spinal cord - can slip needle between vertebrate, cannula delivered epidural injection to deliver morphine post surgery
Drug to treat spasticity can also be given spinally
Which neurotransmitters are excitatory and inhibitory?
Glutamate is excitatory Ach, NA, 5ht, DA mixed effects Peptide substance P is excitatory Opioids inhibitory Nitric oxide and adenosine inhibitory
What kinds of pathways is glutamate found in?
Often long pathways, neuron to neuron across body
periphery->cortex
often long term effects via receptors
Which receptor is overactive during a stroke?
NMDA
NMDA allows Na and Ca to enter, causing large bursts of activity.
Calcium entry brings water, osmotic pressure → cell death.
NO is increased. NO → free radicals → cell death
How are peptide neurotransmitters synthesised and transported?
Nuclear synthesis as large precursors/polypeptides, which are called pre-propeptides. These are then processed and cut down.
Peptide-containing vesicles are moved along microtubule “tracks” by ATP-requiring “motor” proteins such as kinesin. Microtubules are long, cylindrical filaments, 25 nm in diameter, present throughout neurons and other cells. This may be very slow.
With which other neurotransmitters do peptides coexist?
glutamate (sub P)
NA (NPY)
DA (CCK)
Are peptide nts uptaken?
No - they are broken down
What is the therapeutic index of general anaesthetics?
4
side effects are mild to fatal eg respiratory depression
What are the 4 stages of general anaethesia?
1) analgesia
2) excitement/delirium
3) surgical anaethesia
4) respiratory depression, severe brainstem depression –> death
What are the 4 planes of surgical anaethesia?
- eyes rolled, then fixed
- corneal and laryngeal reflexes lost
- pupil dilation and lost light reflex
- intercostal paralysis, shallow amdominal respiration
What are some examples of intravenous general anaesthetics?
thiopentone, propofol, etomidate
What is the benefit of propofol?
no “hangover” so it enables day surgery after which patients can go home
What is the general structure of general anaesthetics?
there is no common structure. they are generally small and must be lipid soluble
Which features increase or decrease potency of a GA?
unsaturation increases potency
halogen substitution increases potency
ether group increases potency
hydrophilic groups decrease potency
What is the most accepted theory of mechanism of GAs?
they bind proteins having effect on neuronal function.
CNS is most sensitive - cortex first, brainstem later (which causes respiratory depression etc)
How does xenon affect NMDA Rs?
inhibits the glycine binding site of the NMDA R reducing its excitation
Which receptor does halothane and propofol affect?
GABA-A
cause massive inhibitory potentiation
What other effect do halothane and propofol cause?
increased current through 2 pore leak K channels (hyperpolarisation)
What is a measurement of GA potency?
Minimum alveolar concentration/ MAC
The concentration in lungs required to prevent movement in 50% of patients in response to surgical stimulus ie pain
What factors influence speed of induction/recovery of general anaesthetics?
Solubility in blood
Solubility in fats
What are the features of ideal GA?
low MAC - high potency
low blood solubility - rapid onset and recovery
What is remifentanil?
a potent, short-acting synthetic opioid analgesic drug given as adjunct to anaesthetic (propofol)
What vehicle is used for propofol?
Cremophor EL –> anaphylactic reaction
now emulsion with soy oil, egg phospholipid, glycerol as tonicity-adjusting agent, NaOH to adjust pH
What is carbamazepine used to treat?
epilepsy and pain
How does Gabapentin work?
Gabapentin blocks calcium channels, treating pain
Which receptors are recruited by “wind up” with chronic pain?
NMDA R
What is heroin’s chemical name?
diacetylmorphine
What are the names of the opioid receptors?
mu
delta
kappa
ORL-1
What is Fentanyl?
rapid on/off opioid pain relief
Which drug is an opioid antagonist?
Naloxone
Are most opioid receptors pre or post synaptic?
75% are pre synaptic
Is substance P excit or inhib?
excitatory
Is nitric oxide excit or inhib?
inhibitory neurotransmitter
