Neurological pharmacology Flashcards
Neurones are made up of
Cell body Nucleus Dendrites Axon Axolemma Neurolemma Nucleus of schwann cell nodes of ranvier myelin sheath terminal boutons/synaptic knobs
effects of nervous system on the body:
Parasympathetic
Eyes - constrict
Salivary glands - stimulates secretion
Heart muscle - decrease rate
Bladder - contracts promoting voiding
Digestive tract organs - increase motility
Blood vessels - little or no effect
effects of nervous system on the body:
Sympathetic effects
Eyes - dilates
Salivary glands - inhibits secretion
Sweat glands - stimulates sweating
Adrenal medulla - stimulates excretion of epinephrine and norepinephrine
Arector pili muscles (hair follicles) - contracts (goosebumps)
Heart muscle - increase force and rate
Bladder - Relaxes inhibiting voiding
Digestive tract organs - decrease activity
Blood vessels - constricts most vessels
Generation & Propagation of a Nerve Impulse
Signals are sent along neurones by generating and propagating action potentials.
In a resting neurone, the outside of the cell is more positive than the inside of the cell (membrane potential).
The neurone is excited by some form of energy or neurotransmitter.
This generates a graded potential.
The graded potential changes the voltage across the cell membrane, thereby generating an action potential.
The action potential is propagated along the length of the neurone in a forward direction.
Synapses and Neurotransmitters
A synapse is a junction between 2 neurones.
Information is relayed across the synapse.
the terminal boutons contain vesicles which contain neurotransmitters that get released into the synaptic cleft. and interact with the dendrites.
Action potential reaches the axon terminal and causes release of chemical neurotransmitters.
Neurotransmitters travel across the synaptic cleft.
The neurotransmitters then bind to neuro receptors post synaptically.
Common chemical neurotransmitters:
Norepinephrine Serotonin Histamine Acetylcholine (Ach) GABA (γ – aminobutyric acid) Endorphins Doamine
Neuro Drugs of the LAS
Paracetamol Ibuprofen Entonox Morphine Naloxone Ondansetron Diazepam
Prostaglandins
Prostaglandins (PGs) are mediators of inflammation, pain and fever.
Prostaglandins enhance nociception (feeling pain).
Prostaglandins are made by the enzymes COX-1, COX-2, COX-3.
Fever
As a general rule a temperature of over 37.5oC is defined as a fever.
some say that over 38.5oC is a “high-fever”, but clear references are hard to find.
In the pre–hospital environment, it is sensible to treat a fever documenting clearly that you have done so. NICE Guidance suggests using paracetamol or ibuprofen if the patient is “distressed”.
NICE also warn against using both agents simultaneously in children < 5 as antipyretics.
Analgesia - Ibuprofen
Non-steroidal anti-inflammatory drug (NSAID)
Analgesic, Anti-inflammatory, Antipyretic
It blocks the enzymes cyclo-oxygenase (COX) 1 and 2 which control the production of prostaglandins
If prostaglandin production is inhibited, this will reduce inflammation, fever and pain.
Analgesia - Paracetamol
Paracetamol primarily blocks COX-3.
COX-3 is found in the brain and spinal cord.
It’s a splice variant of COX-1.
Cox-3 is primarily found in the cerebral cortex and is involved in centrally mediated pain
IV paracetamol has been shown to reduce the opioid requirement.
Does not have the same potential for toxicity as opiods.
Does not have the same legislative requirements as controlled drugs.
Analgesia - Entonox
Action of entonox is not yet fully understood.
It is believed that the nitrous oxide may release endorphins and serotonin.
Entonox works centrally and inhibits pain by altering the pain pathways.
Analgesia - Morphine
Morphine is a strong opioid analgesic drug.
Given for severe pain and pain associated with myocardial infarctions.
Morphine must be diluted with NaCl to make 10mg in 10ml of solution.
10mg of morphine is given to adults (IV) but this can be reduced in the elderly.
Larger doses may be used in trauma (up to 20mg).
Naloxone must be given if there is any cardiovascular or respiratory depression.
Pharmacodynamics of Morphine
Morphine works on the CNS.
It binds to the same receptor sites as our endogenous opioids.
Receptors are mu, kappa and delta.
These receptors are found in stomach, brain and spine.
When morphine binds to the opioid receptors:
- More likely that ion channels will open.
- This reduces excitability of neurons.
- Suppresses pain messages to brain and can produce euphoric effect.
Analgesia - Naloxone
Naloxone is an antagonist
It simply blocks the opioid receptors and Morphine or Heroin cannot get into the receptor to have its effect
Naloxone does have a short half-life (2-4 hours) and opioids will get in there if the dosages are not repeated after an hour or so
Advanced Paramedic Practitioners
Ketamine
IV, IO, IM
Midazolam
IV, IO, IM
Ketamine can be analgesic at lower doses, anaesthetic at higher doses, but APPs use it for analgesia.
As it can induce some unpleasant feeling for the patient, Midazolam may be used alongside for sedation (but not as an analgesic)
Ondansetron
An anti-emetic that blocks 5HT receptors centrally and in the GI tract.
Ondansetron is the principle anti-emetic within the LAS.
Works on serotonin receptors within the medulla oblongata
Serotoninis believed to help regulate mood and social behaviour, appetite, digestion, sleep and memory
Ondansetron blocks serotonin receptors in the chemoreceptor trigger zone (CTZ)
The CTZ communicates with the vomiting centre to initiate vomiting.
By blocking serotonin receptors, less serotonin enters the CTZ which decreases communication with the vomiting centre
prolongs QT interval. Other Drugs that prolong QT include adrenaline, amiodarone, amphetamine, tri-cyclic antidepressents.
Pharmacodynamics of Ondansetron
Acts on the chemo-receptor trigger zone (CTZ) in the medulla oblongata
Blocks the action of the 5HT neurotransmitter (aka serotonin)
Specifically blocks the action of 5HT3
Normal action of 5HT is to mediate the vomiting reflex
why treat Nausea and vomiting and with what drug
Both common – better out than in usually, but at times it needs stopping – eg hyperemesis of infection (food poisoning) or managing a patient supine.
Predictable events (e.g. pat predisposed to nausea from opioids)
Give Ondansetron slowly over 2 mins
Diazepam
Diazepam is a benzodiazepine
It’s a CNS depressant
It’s an anti-convulsant
It’s an anxiolytic
It is given to patients who have been fitting for >5mins and still fitting, repeated fits, status epilepticus, eclamptic fits and cocaine toxicity
diazepam goes into GABA receptors
Diazepam can be given intravenously or rectally.
Diazemuls (IV diazepam) should be the route of choice.
Stesolids (rectal diazepam) should be used if IV access cannot be gained rapidly and safely.
Adults are given 10mg initially – repeated once if necessary.
Alcohol and drugs like GHB and GBL also enhance GABA so you have to expect an increased effect if these are already in the patient.
What are the side-effects?
Too much sedation leads to depression of CVS and Respiratory systems – ensure the patient is breathing or being ventilated adequately.
If respiratory depression occurs after administration of diazepam:
Assist ventilations (if resp rate < 10/min)
Monitor the patient.
Document all treatment on PRF.
GABA
GABA works as the primary inhibitory neurotransmitter in the brain and diazepam enhances GABA.
GABA blocks certain brain signals and decreases activity in the nervous system
GABA receptors will produce a calming effect – helping with feelings of stress, anxiety… and prevent seizures
It reduces the excitability of neurons and prevents neurons from firing
