Pharmacology of CNS and Breathing

Question 1

What are the potential targets for drug action?

Answer 1

Brain stem

• Peripheral chemoreceptor input
• Central chemoreceptors
• Networks

Question 2

What is the old term for respiratory stimulants?

Answer 2

analeptics

Question 3

1. What are the clinical uses for doxapram?
2. What does it do?
3. What are the adverse effects?

Answer 3

1. Acute ventilatory failure, Post operative respiratory depression, Apnoaea e.g. in premature babies.
   Acts very quickly
2. Stimulates CO2 and O2 receptors
3. cardiac arythmias, convulsion
   - mechically supported ventilation preferred

Question 4

What is the general principle of respiratory depressants?§

Answer 4

Any agent which has a generalised CNS depressant effect has the potential to depress respiration via action at the respiratory centre in the brain stem

Question 5

General anaesthetics

Answer 5

General Anaesthetocs
- volatile anaesthetics e.g. halothane
- decrease response of CO2 chemorecepetors –> increases PaCO2
Mechanism of action? GABA? non specific?

Question 6

Benzodiazepines:
What are they used for?
What do they do?
Describe the mechanism of action of benzodiazepines?
Are they fatal? Why/why not?

Answer 6

Benzodiazapines e.g. diazepam

• used as a presanaesthetic, anxiolytic
• physiological action to decrease hypoxic drive by acting on peripheral chemoreceptors. If high does –> central
• MOA = GABAa receptors

GABA binds to GABAa receptor
Acts as an agonist and open channel
Infux of Cl- –> hyper polarisation (further from threshold)
Benzodiazepine binds to allosteric site and increases affinity for GABA –> more hyper polarisation
Non-fatal because just enhancing effect of GABA which needs to be present in order for BD’s to act

Question 7

State the 5 respiratory depressants and specific examples of each

Answer 7

General anaesthetics e.g. halothane
Benzodiazipines e.g. diazepam
Barbituates e.g. phernobarbital
Alcohol
Opioids e.g. morphine

Question 8

Barbituates
Where do they act?
What is their mechanism of action?
Are they fatal? Why/why not?

Answer 8

physiological action
decrease response to central chemoreceptors
decrease hypoxic drive

mechanism of action

• increase neurotransmission via GABAa receptors
• Cl- channel open time is increased

Anaesthetic dose vs depression dose = very close!
They are fatal as they can work without GABA

Question 9

Alcohol

What is they mechanism of action?

Answer 9

physiological action
increase GABAa transmission –> increases inhibitory effect
decrease NMDA transmission (glutamate receptor) –> decreases excitatory effect

blunts ability to respond to CO2
Voltage gated Ca2+ channels, other NT’s
Fatal dose rarely achieved

Question 10

Opioids
Where do they act?
What is their mechanism of action?
What type of drug can be given to reverse the effects of opioids? Give an example

Answer 10

receptor subtypes - mew, kapa, delta
mew = morphine targer --> pain blocking
AND brainstem respiratory centres 
Act to decrease CO2 receptor response 
cannot separate analgesic and resp action as they act on the same receptor 
medulla = highly sensitive 

MOA
GPCR’s
Open K+ channels –> hyperpolariatsation –> decreased excitability

Opiod receptor antagonist e.g. naloxone

Question 11

Drug interactions:

1. benzodiazipine + alcohol
2. benzodiazipne + general anaethetic

Answer 11

1. potentially fatal
2. requires assisted ventilation
   - give benzodiazipine antagonist e.g. flumazenil

Question 12

What is the one respiratory stimulant drug?

What are the 5 respiratory depressants?

Answer 12

doxapram

general anaesthetics
benzodiazepines
barbiturates
opioids
alcohol