Transcript Drugs and Toxins

DRUGS AND TOXINS
Spastic paralysis vs. flaccid paralysis
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SPASTIC VS. FLACCID PARALYSIS
• Flaccid paralysis is when the muscle cannot
contract at all. The muscle stays weak and floppy.
• Spastic paralysis is when the muscle stays in
contraction. You still cannot move the muscle
properly, but in this case, the muscle is too rigid.
SODIUM VGC BLOCKERS
• Lidocaine- used as
topical anesthesia
• Tetrodotoxin-puffer
fish and newts (TTX)
• Saxitoxin- caused
by red tide; a type
of red algae called
dinoflagellates
accumulates in
shellfish (SXT)
• Causes flaccid
paralysis
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SODIUM VGC BLOCKERS
• Na VGC blockers will block the opening of the
sodium, so you can’t have AP at all. Get flaccid
paralysis.
• When preparing a puffer fish for food, if the chef
makes one nick in its liver, it will contaminate the
whole meat with TTX toxin, which paralyzes the
diaphragm.
• Salamanders and newts have this toxin as well.
Sometimes the toxins can get through the skin just
by handling them; get tingling. Don’t lick a
salamander!
VESICLE BLOCKERS
• Clostridium botulinum:
• Bacterium that has a protease
(enzyme that breaks down proteins).
Botulinum breaks down the docking
proteins that anchor vesicles to the cell
membrane)
• Inhibits ACh neurotransmitter release;
muscles can’t contract.
• Botulism is found in undercooked
turkey and dented cans of food. If
ingested orally, will paralyze the
diaphragm; die of suffocation.
• It causes flaccid paralysis
• It is the muscle killer in “BOTOX”
injections. The muscles die so the
wrinkle lines relax. These small facial
muscles can grow back in three
months; need another shot.
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MACH-R BLOCKER/ COMPETITOR
• Atropine
• Flaccid paralysis
• Smooth muscle,
heart, and glands
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MACH-R BLOCKER/ COMPETITOR
• These block the parasympathetic system, so the
sympathetic gets more control.
• Blocking the parasympathetic neurons will cause
flaccid paralysis in the intestines.
• If heart has stopped, inject atropine to block mACH
receptors on cardiac muscles, and heart rate will
increase.
MACH-R BLOCKER/ COMPETITOR
• Your iris has smooth muscle. If we block Ach, the
muscles will pull, opening pupil.
• Opium derivatives block muscarinic Ach receptors,
causes dilated pupils.
• Chemical warfare drugs that stimulate the
muscarinic Ach receptors causes the
parasympathetic system to gain more control;
increase gut motility, sweat, diarrhea, salivation. A
type of mushroom does this, too, and it can kill you.
NACH-R BLOCKER/ COMPETITOR
• Curare
• From tree sap
• Causes flaccid
paralysis
• Large dose:
asphyxiation
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NACH-R BLOCKER/ COMPETITOR
• South American Indians use curare as a poison on
the tips of arrows. Injecting it into the bloodstream
causes death of the animal. However, the digestive
system can deactivate it, so it is safe to eat an
animal that was killed with curare. How does it kill?
• Nicotinic Ach receptors (nACH-R) are mainly found
in skeletal muscle. If you block them with curare,
you block the ability for ionotropic receptors to
open, so Na+ cannot move in. That blocks
excitation, so muscle will not contract, and you get
flaccid paralysis.
ACHE (ACETYLCHOLINE ESTERASE)
BLOCKERS
• Neostigmine
• Physostigmine
• Spastic paralysis
• These drugs are
used to treat
Myasthenia Gravis,
an autoimmune
disease that causes
ptosis (droopy
eyelid)
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MYASTHENIA GRAVIS
• Myasthenia Gravis (autoimmune disorder). The
body’s antibodies attacks the nicotinic Ach
receptors, so there are fewer of them, less Na+
coming in, fewer action potentials.
• Symptoms usually begin in the eyelid and facial
muscles, and manifests as drooping muscles on half
or both sides of the face, drooping eyelids, and
slurred speech.
• Their eyelid muscles are often the first muscles to
become fatigued.
• To test for this, force open the eyelids, have them
look up, and will quickly cause fatigue, and their lids
will droop (ptosis).
MYASTHENIA GRAVIS
• Treatment is to give a medicine to inhibit ACh-ase.
• That way, the ACh will not be deactivated and it can stay
around longer to keep muscles contracting. Too much will
cause spastic paralysis.
• Neostigmine is an anti-cholinesterase drug which reduces the
symptoms by inhibiting Ach-ase activity, preventing the
breakdown of Ach. Consequently, Ach levels in the synapse
remain elevated, so Ach is available to bind to those few
functional Ach receptors that are left.
• Neostigmine is reversible, so you need to keep taking it daily. It is
therefore useful as a medicine.
ACETYLCHOLINE ANTAGONISTS
• Some INSECTICIDES inhibit acetylcholinesterase, so
Ach accumulates in the synaptic cleft and acts as a
constant stimulus to the muscle fiber. The insects die
because their respiratory muscles contract and
cannot relax.
• Other poisons, such as CURARE, the poison used by
South American Indians in poison arrows, bind to the
Ach receptors on the muscle cell membrane and
prevent Ach from working. That prevents muscle
contraction, resulting in flaccid paralysis.
IRREVERSIBLE ACHE INHIBITOR
• Sarin gas
• Spastic paralysis
• Ventilator until AchE turnover
• This is a permanent Ach inhibitor.
The people who survive Sarin gas
attack are hospitalized. They have
to work to breathe (diaphragm
stops working, so they use their
abdominal muscles), so they need
a ventilator and pressure chambers
until there is a turnover in Ach after
enough gene expression (takes a
few weeks).
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INHIBITORY NEURON BLOCKERS
• Tetanus toxin
• Blocks release of
inhibitory
neurotransmitters
• Muscles can’t relax
• Spastic paralysis
• Opposing flexor
and extensor
muscles contract
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INHIBITORY NEURON BLOCKERS
• When you walk, it takes coordination with activating and inhibiting muscles.
Extension of leg activates quadriceps and inhibits hamstrings. Where does this
coordination originate?
• The somatic motor neurons innervate these muscles. When it reaches
threshold, will release ACh onto inhibitory neurons and excitatory neurons. This
causes flexor muscles to contract and extensor muscles to relax, then viceversa, so you can walk.
• If you have a toxin that prohibits release of inhibitory NT, then excitatory will
override, and cause more muscle contraction.
• That is what happens with tetanus toxin. When all of the NT is excitatory and
none are inhibitory, all muscle groups contract, causing back arching, and
diaphragm contracts too, and stays that way. Person dies from suffocation.
• Treatment is Ach-ase blockers like Curare. But you have to be careful with
that medicine…. Not just nicotinic, but muscarinic receptors also bind to ACh
in skeletal muscle. Atropine will also help.
SPIDER VENOM
• Black widow: causes
ACh release
• Lack of inhibitory
neurotransmitters
• Spastic paralysis
• Brazilian Wandering
Spider (banana spider)
• Spider venom increases
nitrous oxide release
• Most venomous of all
spiders/ more human
deaths
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SPIDER VENOM
• Spider venom works like tetanus toxin.
• The Banana spider makes a lot of nitric oxide, which
stimulates receptors of in penis, causing it to flood
with blood, causing erection.
• Pharmaceutical companies decided to modify this
toxin and add it to Viagra, making the Viagra
longer lasting. Spider venom and Viagra both work
by blocking the enzyme that degrades nitric oxide.