nicotinic receptors

Nicotine (tobacco)

Nicotine is… unique again. It enters through your lungs as tar (oh joy! Cancer!), but via this method, it enters the brain in 7 seconds, which is twice as fast as IV, which also explains why nobody really shoots up tobacco.

It’s broken down by CYP2A6, another cytochrome common in the liver, to cotinine. It is excreted 90% in urine and 10% in breath. Ew.

It increases calmness and relaxation in regular smokers who have gone a period of time without smoking (i.e. first smoke of the day, or smoke during lunch break), but in new smokers it’s more likely to cause tension or arousal, lightheadedness, dizziness, nausea.

It has positive motor functioning and cognitive accuracy affects, as well as reduced response latency which… is not what you think of when you think of someone smoking, but I guess it explains the jitters.

What’s actually happening in your brain? Acetylcholine. The neurotransmitter acetylcholine, which is excitatory, binds to nicotinic receptors (nAChRs) in the cortex, limbic system, and base of the brain (so… everywhereish?)

There is also, surprise, a dopamine aspect as it increases dopaminergic firing AS WELL AS presents dopaminergic breakdown via the enzyme MAO.

FINALLY, Norepinephrine and epinephrine, responsible for sympathetic nervous system activation, increase firing.

So tada! Tobacco. Don’t do it, kids. It’s addicting, it sucks, and the cost is worse than the reward is good. The end.

Diseases and their twins.

There a few diseases which quite resemble an other disease in presentation and sometimes pathology.Here’s a list I made-

1. Wolf-Parkinson-White and
   Lown-Ganong-Levine syndrome-

   -What’s similar?
    The tachycardia, short PR    
     interval, pre- excitation

  -What’s different?
    While in WPW syndrome,the
    culprit is a naughty extra pathway,
    the bundle of Kent, in LGL the AV
    node itself is naughty.(The
    hypothesized bundle of James  
    hasn’t been discovered yet)
    Conduction through the AV node
    occurs rapidly.
   
    ECG findings- WPW syndrome has
    a short PR interval and a Delta
    wave on the QRS complex. No
    Delta waves occur in the LGL
    syndrome.
   
    Also, the risk of sudden death
    remains lower in LGL syndrome.


2. Myasthenia Gravis and Lambert
   Eaton syndrome.

   -What’s similar?
    The muscle weakness.

  -What’s different?
   Oh almost everything. In MG,
   autoantibodies are formed against
   the nicotinic receptors whilst in
   LEMS(Lambert Eaton myasthenic  
   syndrome), the antibodies are  
   against ‘pre synaptic voltage  
   gated Calcium channels’.
   
    LEMS is mostly associated with
    underlying malignancies,
    making it a paraneoplastic
    syndrome.

     In contrast to MG, where
     distal musculature is affected
     the most, proximal musculature
     gets involved in LEMS. Arm
     muscles are frequently involved
     while MG prefers muscles of the
     leg.
     
     The autonomic nervous system
     also may be affected in LEMS.

    The most significant difference
    is that the strength actually
    improves on exertion in LEMS,
    known as ’Lambert’s sign’,  
    whereas in MG, weakness  
    prevails on repeated activity.


3. Multiple sclerosis and Devic’s
  disease
   
    -What’s similar?
    The demyelination and
    associated CNS symptoms.

    -What’s different?
     Many things. The optic nerve
     and spinal cord are affected more
     commonly in Devic’s. MS affects
     the CNS as a whole.

     Devic’s runs a more serious
     course than MS, the morbidity
     after an attack is more severe
     compared to it.

    MS is a T cell mediated
    autoimmune disease while IgG
    antibodies mediate Devic’s, more
    specifically the
    NMO(neuromyelitis optica)IgG.
    Oligoclonal bands are rare in
    Devic’s, and disappear after
    an attack.

    Uhthoff’s phenomenon, where
    symptoms worsen after exposure
    to higher temperatures,and the
    Lhermitte’s sign, where sudden,
    shock like sensation travelling
    through the spinal cord is felt,
    occur more commonly in MS.

4.Plague and Tularemia.
   
    -What’s similar?
      Those large, pus filled lymph
       nodes.
   
    -What’s different?
      Everything.Francisella
      tularensis is the causative agent,
      ticks and arthropods are the
      vectors, rabbits are the source,
      so on and so forth!