Pharmacology Flashcards
What does each branch of motor neuron axon innervate?
Each branch innervates an individual skeletal muscle cell (muscle fibre) within a muscle. The neurone and the number of fibres that it innervates are known as a motor unit
Where are the cell bodies of motor neurones located?
In the ventral/anterior portion of the spinal cord
What type of receptors are located on the end plate of the muscle cells at the neuromuscular junction?
What are these receptors compose of?
Nicotinic ACh receptors - each receptor is composed of 5 glycoprotein subunits, which assemble to form a pentomeric complex, with each subunit totally spanning the plasma membrane. They surround the cation selective pore (formed by five M2 helices).
What is a “quantum” in terms of the NMJ?
A quantum is a roughly fixed umber of ACh molecules; the content of each vesicle tends to be rather uniform e.g. around 1000 molecules
What causes the end plate potential?
What type of response is this?
The e.p.p. is caused by the activation of nicotinic acetylcholine receptors at the endplate and is a graded response
If the epp is large enough, what does it trigger?
The e.p.p., if large enough, triggers the opening of voltage-activated Na+ channels around the end plate causing an action potential which is an ‘all or none response’
What does the term “safe synapse” mean?
Normally one action potential in the motor nerve triggers one action potential in the muscle (one to one coupling) and a subsequent ‘twitch’ (contraction) of the muscle
I.e. there is a 1:1 relation ship – “safe synapse” – where post synaptic activity faithfully follows presynaptic activity
How do drugs that reduce the epp work?
Drugs, or toxins, that reduce the amplitude of the e.p.p., such that it does not reach threshold for the opening of voltage-activated Na+ channels, block neuromuscular transmission because no muscle action potential is generated
What path does the AP take from propagation at the NMJ ro causing Ca2+ to flood out of the sacroplasmic reticulum?
Action potential propagates over the surface membrane (sarcolemma) of skeletal muscle fibre and enters transverse (T) tubules (invaginations of the sarcolemma that dip deeply into the muscle cell). T-tubules are in close apposition to the sarcoplasmic reticulum (SR, Ca2+ store)
Action potential arriving at the T-tubule triggers release of Ca2+ from the SR which in turn causes contraction by interacting with troponin associated with the myofibrils
What does flooding for Ca2+ out of the sacroplasmic reticulum and into the cytoplasm cause?
It causes an increase in intracellular concentration of Ca2+, which binds to troponin, which slides out of the way, allowing actin and myosin to crossbridge over each other, shortening the length of the skeletal muscle
What is Neuromyotonia and what causes it?
What is the treatment an how does it work?
Symptoms include multiple disorders of skeletal muscle function including cramps, stiffness, slow relaxation (myotonia), and muscle twitches (fasiculations)
In the acquired form (most common) is considered to have an autoimmune origin: antibodies against voltage-activated K+ channels in the motor neurone disrupt function resulting in hyperexcitability (repetitive firing)
Drug treatment includes anti-convulsants (e.g. carbamazepine, phenytoin) which block voltage-activated Na+ channels
What is Lambert-Eaton Myasthenic syndrome and what causes it?
How does drug treatment work?
Characterised by muscle weakness in the limbs, very rare and associated with small cell carcinoma of the lung
Has an autoimmune origin: antibodies against voltage-activated Ca2+ channels in the motor neurone terminal result in reduced Ca2+ entry in response to depolarization and hence reduced vesicular release of ACh
Drug treatment includes anticholinesterases (e.g. pyridostigmine) and potassium channel blockers (e.g. 3,4-diaminopyridine) which increase the concentration of ACh in the synaptic cleft
What is Myasthenia Gravis characterized by and what causes it?
Hoe do drug treatments work?
Characterised by progressively increasing muscle weakness during periods of activity (fatiguability, contrast with LEMS that may transiently improve upon exertion). Often weakness of the eye and eyelid muscles is a presenting feature
In the majority of cases has an autoimmune origin: antibodies against nicotinic ACh receptors in the endplate result in reduction in the number of functional channels and hence the amplitude of the e.p.p.
Drug treatment includes anticholinesterases (e.g. edrophonium for diagnosis, pyridostigmine for long term treatment) and a variety of immunosuppressant agents (e.g. azathioprine). Anticholinesterase increase the concentration of ACh in the synaptic cleft
Define pain
“An unpleasant sensory and emotional experience, associated with actual tissue damage or described in terms of such damage”
What are the three types of pain?
(i) Nociceptive pain - adaptive
(ii) Inflammatory pain - adaptive
(iii) Pathological pain - maladaptive
What does the term maladaptive pain mean?
Pain has outlived its initial prupose
What are nociceptors?
Nociceptors are specific peripheral primary sensory afferent neurones normally activated preferentially by intense stimuli (e.g. thermal, mechanical, chemical) that are noxious
There are dedicated neurones in the PNS which act to detect Noicious stimuli; only normally activated by intense stimuli
Nociceptive pain is adaptive - what does this mean?
Does it have a high or low threshold?
It serves as an early warning system to detect and minimise contact with damaging stimuli (noxious events)
High threshold – provoked only by intense stimuli that activate nociceptors
Is there such thing as a pain receptor?
Pain only occurs one it is consciously perceived – there is no such thing as a pain fibre in the periphery; there are Nociceptive fires which sense Nociceptive stimuli
What is inflammatory pain caused by?
Caused by activation of the immune system in injury, or infection
This is adaptive and is provoked by moderate stimulation e.g. tendonitis
What two things does inflammatory pain cause?
- Hypersensitivity (heightened sensitivity to noxious stimuli)
- Allodynia - a non-noicious stimulus now becomes painful
