Week 2 Flashcards
What are anaesthetics?
Drugs that cause loss of consciousness, usually with loss of reflexes and some alagesia
What are analgesics?
Drugs that relieve pain
What are psychotropics?
Drugs that affect mood and/or behaviour
What are anxiolytics/ hypnotics/ sedatives/ minor tranquilisers?
Drugs that relieve anxiety and reduce excitability. In higher doses may induce sleep.
What are major tranquilisers/ antipsychotics/ neuroleptics?
Drugs used in humans for the treatment of schizophrenia, in animals used to produce profound sedation
What are antidepressants?
Drugs that alleviate the symptoms of depressive illness in humans and are used in veterinary medicine to treat compulsive behavioural disorders
Where do virtually all drugs act in the CNS?
Virtually all drugs that act in the CNS produce their effects by modifying some step in chemical synaptic transmission
- action potential in presynaptic fibre
- Synthesis of transmitter
- Storage of transmitter
- Metabolism (breakdown) of transmitter
- Release of transmitter
- Reuptake of transmitter
- Degradation of transmitter
- Binding of transmitter to receptor
- Receptor induced increase or decrease in ionic conductance
What are the chemical mediators in the CNS? What kind of effects can they produce?
- Neurotransmitters- released by presynaptic terminals and produce rapid excitatory response in post synaptic neurons
- Neuromodulators- released by neurons, and produce slower pre- or post- synaptic responses, mediated mainly by G-protein coupled receptors
- Neurotrophic factors- released mainly by non-neuronal cells, act on tyrosine-kinase-linked receptors that regulate gene expression
** chemical mediators in the brain have long slow lasting effects, can act diffusely at considerable distances from the site of release and can have diverse effect on transmitter synthesis, on expression of neurotransmitter receptors and on ionic conductance
What are some fast neurotransmitters? What do they operate through?
Glutamate, glycine, GABA, ACh– that operate through ligand gated ion channels
* Speed depends on the receptor that it binds to. E.g. the same agent may act through both ligand gated and GPCR like glutamate or ACh
What are the slow neurotransmitters and neuromodulators? What do they operate through? What ultimately causes a transmitter to be fast or slow?
Dopamine, 5HT, ACh, neuropeptides– operate through G-protein-coupled receptors.
* Speed depends on the receptor that it binds to. E.g. the same agent may act through both ligand gated and GPCR like glutamate or ACh
What is an example of an amino acid neurotransmitters that are excitatory?
Glutamate, the principal fast “classical” excitatory transmitter and is widespread through the CNS. Several different glutamate receptors have been characterized according to particular agonists that bind to them e.g. NMDA, AMPA, kainate
What are three examples of an amino acid neurotransmitters that are inhibitory?
Gamma-amino butyric acid (GABA) is a major inhibitory neurotrasmitter in the CNS. GABA receptors are of two main types GABA (A) receptor is ligand gated to Cl- ion channels and is the site of action of many neuroactive drugs e.g. barbituates, benzodiazepines, steroid anaesthetics GABA (B) receptor is G-protein-coupled receptor, coupled to biochemical processes and regulation of ion channels
* Glycine is an inhibitory transmitter acting mainly in the spinal cord. Strychnine is a competitive glycine antagonist.
* Acetyl choline- ACh is widely distributed in the brain. Both nicotinic and muscarinic receptors occur in the CNS. Muscarinic receptors mediate the main behavioural effects associated with ACh- arousal level, learning and short term memory
What are three examples of monoamines?
* Dopamine- neurotransmitter as well as being a precursor of NA. But distribution of dopamine in the brain is very different from NA. There are two main families of dopamine receptors- D1 and D2. D2 receptors are implicated in the pathophysiology of Parkinson’s disease and schizophrenia.
* Noradrenaline- Pathways for NA neurotransmission in the CNS are essentially the same as in the PNS. Adrenergic receptors in the CNS are alpha1, alpha2, beta. NA is important in the “arousal” system, controlling wakefulness, blood pressure regulation, control of mood. Drugs acting on noradrenergic transmission in the CNS include alpha 2 agonists, antidepressants, cocaine, and amphetamine.
* 5-hydroxytryptamine (serotonin)- an important CNS transmitter with complex and varied effects. 5-HT can exert excitatory or inhibitory effects, acting presynaptically or post synaptically. 5-HT pathways are involved in physiological and behavioural functions, namely hallucinations and behaviour changes, sleep, wakefulness, and mood, control of sensory transmission. A variety of new drugs influence 5-HT pathways in selective ways: for example selective serotonin reuptake inhibitors (SSRIs), ondansetron (an anti-emetic) 5-HT3 receptor antagonist, buspirone (anxiolytic) 5-HT1a receptor agonist.
What are four examples of non adrenergic non cholinergic (NANC) transmitters?
* Histamine- fulfills the criteria of CNS neurotransmitter. H1, H2, H3 receptors are widespread in the brain. Many of the functions are unclear, but H1 receptor antagonists are strongly sedative and anti-emetic.
* Purines- (ATP and adenosine)
*nitric oxide
*arachidonic acid metabolites
^all have established roles as CNS transmitters and modulators.
What are neuropeptides? Three examples?
* Many neuropeptides that act on specific CNS receptors.
EX: Opioid peptides that modulate pain pathways, substance P, neuropeptide Y
Why is it difficult to predict the therapeutic effect of a particular pharmacological agent?
Because of the complexity of neuronal interconnections in the CNS and because of secondary adaptive responses. For example, an increase in transmitter release may lead to a decrease in transmitter synthesis, an increase in transporter expression, or in decreased receptor expression.
What are the classes of analgesics used in veterinary medicine?
* local anaesthetics
* NSAIDs
* Opioid analgesics
* Centrally acting non-opioid analgesics
* alpha 2 adrenergic agonists
In nociceptive afferent neurons in a peripheral sensory nerve, what are the two possible fibre types?
* C-fibres that are non-myelinated, have a low conduction velocity (< 1 m/sec) and sense dull pain.
* A fibres that are fine myelinated and have faster conduction velocities (6-30 m/sec). Sense sharp, localized pain. Terminate in the dorsal horn of the spinal cord.
What is the gate control mechanism in the dorsal horn?
This centre modulates pain transmission. Inhibitory interneurons in teh substantia gleatinosa of the dorsal horn act to inhibit the transmission pathway.
* Inhibitory interneurons are activated by descending pathways from the mid-brain and brainstem, as well as non-nociceptive afferent input.
* Inhibitory interneurons are inhibited by persistent C-fibre activity, hence “wind up” phenomenon- increasing duration of stimulation leads to increased transmission of pain signals.
What is the “wind up” phenomenon in regards to pain signals?
* Inhibitory interneurons are inhibited by persistent C-fibre activity, hence “wind up” phenomenon- increasing duration of stimulation leads to increased transmission of pain signals.
What are the two parts of the brain involved in pain modulation?
*Mid-brain/ pons “peri aqueductal grey area”
* Lower pons/ medulla “nucleus raphe magnus”
* initiate descending pathways that exert a strong inhibitory effect on the dorsal horn. This descending inhibition is mediated by enkephalins, 5-HT, noradrenaline, and adenosine.
What are the major inhibitory neurotransmitters in nociceptive pathways?
* Endogenous opioids
There are more than 20 endogenous opioids, the most important of which are beta- endorphin, enkerphalins, and dynorphin
What are the three types of opioid receptors?
1) mu- receptors: two types mu-1 mediate most analgesic effects, euphoria supraspinal; enkephalins are enodgenous mu 1 ligands. mu-2 mediate most of the undesirable side effects such as respiratory depression and constipation
2) delta receptors: are important in the periphery where they contribute to analgesia
3) kappa receptors: mediated analgesia primarily at the spinal cord level and have fewer side effects- less respiratory depression, miosis, etc. They tend to cause sedation and dysphoria rather than euphoria.

































