Neurological pharmacology

Question 1

Neurones are made up of

Answer 1

Cell body
Nucleus
Dendrites
Axon
Axolemma
Neurolemma
Nucleus of schwann cell
nodes of ranvier
myelin sheath
terminal boutons/synaptic knobs

Question 2

effects of nervous system on the body:

Parasympathetic

Answer 2

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

Question 3

effects of nervous system on the body:

Sympathetic effects

Answer 3

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

Question 4

Generation & Propagation of a Nerve Impulse

Answer 4

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.

Question 5

Synapses and Neurotransmitters

Answer 5

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.

Question 6

Common chemical neurotransmitters:

Answer 6

Norepinephrine
Serotonin
Histamine
Acetylcholine (Ach)
GABA (γ – aminobutyric acid)
Endorphins
Doamine

Question 7

Neuro Drugs of the LAS

Answer 7

Paracetamol
Ibuprofen
Entonox
Morphine
Naloxone
Ondansetron
Diazepam

Question 8

Prostaglandins

Answer 8

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.

Question 9

Fever

Answer 9

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.

Question 10

Analgesia - Ibuprofen

Answer 10

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.

Question 11

Analgesia - Paracetamol

Answer 11

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.

Question 12

Analgesia - Entonox

Answer 12

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.

Question 13

Analgesia - Morphine

Answer 13

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.

Question 14

Pharmacodynamics of Morphine

Answer 14

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:

1. More likely that ion channels will open.
2. This reduces excitability of neurons.
3. Suppresses pain messages to brain and can produce euphoric effect.

Question 15

Analgesia - Naloxone

Answer 15

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

Question 16

Advanced Paramedic Practitioners

Answer 16

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)

Question 17

Ondansetron

Answer 17

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.

Question 18

Pharmacodynamics of Ondansetron

Answer 18

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

Question 19

why treat Nausea and vomiting and with what drug

Answer 19

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

Question 20

Diazepam

Answer 20

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.

Question 21

GABA

Answer 21

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