Tetanus, muscle

Strychnine and tetanus (muscle rigidity) Opiates Phenothlazines and antipsychotic dmgs Sedative-hypnotics Tricyclic antidepressants... 

Tetanus is a disease caused by the release of neurotoxins from the anaerobic, spore-forming rod Clostridium tetani. The clostridial protein, tetanus toxin, possesses a protease activity which selectively degrades the pre-synaptic vesicle protein synaptobrevin, resulting in a block of glycine and y-aminobutyric acid (GABA) release from presynaptic terminals. Consistent with the loss of neurogenic motor inhibition, symptoms of tetanus include muscular rigidity and hyperreflexia. The clinical course is characterized by increased muscle tone and spasms, which first affect the masseter muscle and the muscles of the throat, neck and shoulders. Death occurs by respiratory failure or heart failure. 

Twitch is a muscle contraction caused by a single action potential, whereas tetanus is a sustained muscle contraction caused by a series of repetitive action potentials. The amplitude of tetanus contraction is larger than that of twitch, due to mechanical summation. 

Figure 2. Muscle stimulation, a) a single nerve impulse (stimulus) causes a single contraction (a twitch). There is a small delay following the stimulus before force rises called the latent period, b) A train of stimuli at a low frequency causes an unfused tetanus. Force increases after each progressive stimulus towards a maximum, as calcium levels in the myofibrillar space increase. But there is enough time between each stimulus for calcium to be partially taken back up into the sarcoplasmic reticulum allowing partial relaxation before the next stimulus occurs, c) A train of stimuli at a higher frequency causes a fused tetanus, and force is maximum. There is not enough time for force to relax between stimuli. In the contractions shown here, the ends of the muscle are held fixed the contractions are isometric.

Figure 1. Original records of tension and intracellular free calcium concentration Caf ) obtained from a single mouse muscle fiber during a fatigue run (modified from Westerblad and Allen, 1991). A continuous tension record in which each vertical line represents a tetanus. B (Ca ] (measured with fura-2) and tension records obtained from the individual tetani (a, b, and c) indicated above the record in A. Three major features are illustrated 1.) the initial tension decline is accompanied by an increase in tetanic ICa li, 2.) late in fatigue the tetanic [Ca li is reduced, and 3.) the resting [Ca li increases during fatiguing stimulation (dashed line indicates resting [Ca ] in control). Stimulation periods are shown below tension records in B. From Westerblad et al., 1991, with permission from the Amer. Physiol. Society.

Control muscle spasm associated with tetanus... 

Altered release. Tetanus is an infectious disease caused by the bacterium Clostridium tetani. This bacterium produces a neurotoxin active on inhibitory synapses in the spinal cord. Motor neurons, which supply skeletal muscle and cause contraction, have cell bodies that lie in the spinal cord. Under normal circumstances, these motor neurons receive excitatory and inhibitory inputs from various sources. The balance of these inputs results in the appropriate degree of muscle tone or muscle contraction. Tetanus toxin prevents the release of gamma amino butyric acid (GABA), an important neurotransmitter active at these inhibitory synapses. Eliminating inhibitory inputs results in unchecked or unmodulated excitatory input to the motor neurons. The resulting uncontrolled muscle spasms initially occur in the muscles of the jaw, giving rise to the expression lockjaw. The muscle spasms eventually... 

As mentioned previously, a single action potential lasting only 2 msec causes a muscle twitch that lasts approximately 100 msec. If the muscle fiber has adequate time to completely relax before it is stimulated by another action potential, the subsequent muscle twitch will be of the same magnitude as the first. However, if the muscle fiber is restimulated before it has completely relaxed, then the tension generated during the second muscle twitch is added to that of the first (see Figure 11.3). In fact, the frequency of nerve impulses to a muscle fiber may be so rapid that there is no time for relaxation in between stimuli. In this case, the muscle fiber attains a state of smooth, sustained maximal contraction referred to as tetanus. 

Figure 11.3 Muscle twitch summation and tetanus. A single action potential (represented by A) generates a muscle twitch. Because duration of the action potential is so short, subsequent action potentials may restimulate the muscle fiber before it has completely relaxed, leading to muscle twitch summation and greater tension development. When the frequency of stimulation becomes so rapid that no relaxation occurs between stimuli, tetanus occurs. Tetanus is a smooth, sustained, maximal contraction.

Somlyo With a big enough tetanus they will. When we did a tetanus in rat cardiac muscle we added ryanodine and raised extracellular Ca2+ to lOmM, tetanized the muscle sure enough, there was mitochondrial Ca2+ uptake. 

Tetanus Clostridium tetani tetanus toxin Blocks neurotransmitter release in the brain leading to chronic contraction of muscles (See Figure 13.9)... 

Ergot alkaloids contain lysergic acid (formula in A shows an amide). They act on uterine and vascular muscle. Ergo-metrine particularly stimulates the uterus. It readily induces a tonic contraction of the myometrium (tetanus uteri). This jeopardizes placental blood flow and fetal O2 supply. The semisynthetic derivative methylergometrine is therefore used only after delivery for uterine contractions that are too weak. 

The convulsant toxins, tetanus toxin (cause of wound tetanus) and strychnine diminish the efficacy of interneuronal synaptic inhibition mediated by the amino acid glycine (A). As a consequence of an unrestrained spread of nerve impulses in the spinal cord, motor convulsions develop. The involvement of respiratory muscle groups endangers life. 

Skeletal muscle relaxants may be nsed for relief of spasticity in nenromnscular diseases, snch as multiple sclerosis, as well as for spinal cord injnry and stroke. They may also be used for pain relief in minor strain injnries and control of the mnscle symptoms of tetanus. Dantrolene (Dantrium) has been nsed to prevent or treat malignant hyperthermia in surgery. 

Methocarbamol suppresses multisynaptic pathways in the spinal cord. It is used for relieving spasms and skeletal muscle pain as well as for treating tetanus. Synonyms of this drug are delaxin, forbaxin, robamol, robaxin, and tresortil. 

Muscle relaxant As an adjunct for the relief of skeletal muscle spasm because of reflex spasm caused by local pathology, spasticity caused by uppermotor neuron disorders, athetosis, stiff-man syndrome, used parenterally in the treatment of tetanus (diazepam). 

Muscle spasm 5 to 10 mg IM or IV initially then 5 to 10 mg in 3 to 4 hours if necessary. Tetanus may require larger doses. 

An adjunct for the relief of skeletal muscle spasm caused by reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma) spasticity caused by upper motor neuron disorders athetosis stiff-man syndrome. Injectable diazepam may also be used as an adjunct in tetanus. 

Methocarbamol (Robaxin) [Skeletal Muscle Relaxant/ Centrally Acting] Uses Relief of discomfort associated w/ painful musculoskeletal conditions Action Centrally acting skeletal muscle relaxant Dose Adults. 1.5 g PO qid for 2-3 d, then 1-g PO qid maint therapy IV form rarely indicated Peds. 15 mg/kg/dose IV, may repeat PRN (OK for tetanus only), max 1.8 g/mVd for 3 d Caution Sz disorders [C, +] Contra MyG, renal impair Disp Tabs, inj SE Can discolor urine drowsiness, GI upset Interactions T Effects Wf CNS depressant, EtOH EMS May cause blurred vision and orthostatic hypotension use caution w/ CNS depressants concurrent EtOH use can T CNS depression OD May cause drowsiness, light-headedness, syncope, and slow shallow breathing symptomatic and supportive... 

Tetanus immunoglobulin is an example of an antibody preparation used to induee passive immunization against a mierobial toxin. Tetanus (lockjaw) is an infectious disease caused by the bacterium, Clostridium tetani. Bacterial spores can commonly contaminate surface wounds and the resulting bacterial cells produce a toxin as they multiply. The toxin interferes with normal neurological function, particularly at neuromuscular junctions. The result is spasmodic contraction of muscles and, if untreated, mortality rates are high. Treatment with antibiotics and anti-toxin, however, is highly effective if administered promptly. 

Nondepolarizing blockers are used to relax skeletal muscle for surgical procedures, to prevent dislocations and fractures associated with electroconvulsive therapy, and to control muscle spasms in tetanus. They do not produce anesthesia or analgesia. 

Unlabeled Uses Muscle contraction, headache, external sphincter spasticity, muscle rigidity, opisthotonos-associated with tetanus... 

It is indicated as hypnotic, in anxiety, tension, muscle spasm, psychosomatic and behaviour disorders, dysmenorrhoea, cerebral palsy, upper motor neuron spasticity, sedative for surgical procedures, labour, tetanus, eclampsia and epilepsy. 

It is indicated in skeletal muscle spasm, in surgery, orthopaedic procedures, neurological diseases and tetanus. 

Tetanus is an infection caused by a bacteria found in dirt, gravel and rusty metal. It usually enters the body through a cut. Tetanus bacteria causes the muscles to spasm (move suddenly). If tetanus attacks the jaw muscles it causes lockjaw, the inability to open the mouth. Tetanus can also cause spasm of the respiratory muscles, which can be fatal. 

Uses. Diazepam is one of the oldest medications for treating muscle spasms, and has been used extensively in treating spasms associated with musculoskeletal injuries such as acute low-back strains. Diazepam has also been used to control muscle spasms associated with tetanus toxin the use of valium in this situation can be life-saving as well by inhibiting spasms of the larynx and other muscles.51,65... 

Fig. 19. Tension, intensity, and spacing time courses from the rising phase of tetanic contractions in bony fish muscle (from Mok et al., 2005). All changes have been normalized to be 0% in resting muscle and 100% at the tetanus plateau for all changes that are increases, and vice versa for all changes that are decreases. (A) Shows the changes of the tension (T), the Al and A2 actin layer lines, and the All (11) equatorial reflection. (B) Shows the M3 spacing and intensity relative to tension (T). (C) Shows the changes of the myosin layer line ML3 and of ML1 at the All and A20 positions. For details, see text.

---