Digoxin (Cardiac glycoside)

 The chemical formula of Digoxin is C41 H64 O14.

Digoxin (Cardiac glycoside) reversibly inhibits the sodium-potassium-ATPase, causing an increase in intracellular sodium and a decrease in intracellular potassium. The increase in intracellular sodium prevents the sodium-calcium antiporter from expelling calcium from the myocyte, which increases intracellular calcium. The net increase in intracellular calcium augments inotropy. Cardiac glycosides also increase vagal tone, which results in decreased conduction through the sinoatrial and atrioventricular nodes.

Life-threatening digoxin-induced arrhythmias and other toxic manifestations occur at a substantially increasing frequency as the plasma digoxin concentration rises above 2.0 ng/mL. However, toxicity is more likely in the presence of one or more comorbid conditions (eg, hypokalemia, hypomagnesemia, hypercalcemia, myocardial ischemia). Hypokalemia is a particularly important risk factor that can promote digoxin-induced arrhythmias.

PVCs are often the first sign of digoxin toxicity and are the most common arrhythmia due to digoxin toxicity. PVCs can be isolated or occur in a bigeminal pattern. The so-called "digitalis effect" on the ECG consists of T wave changes (flattening or inversion), QT interval shortening, scooped ST segments with ST depression in the lateral leads and increased amplitude of the U waves.

Early recognition of cardiac glycoside toxicity and prompt administration of Fab fragments is essential for the successful treatment of severe poisoning. Fab fragments are highly effective and safe and have transformed the management of cardiac glycoside poisoning.

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Muscle Weakness

 Upper Motor Neuron (UMN) lesions are lesions occurring anywhere in the CNS from the brain up to the spinal cord before the alpha motor neurons arise from the spinal cord. The lesion could arise from the cerebral cortex, internal capsule, midbrain, pons, medulla, and the cortico-spinal tract in the spinal cord.

Lower motor neuron (LMN) lesions may arise from disease processes affecting the anterior horn cell or the motor axon and/or its surrounding myelin. Neuromuscular junction pathology and muscle disorders may mimic an LMN disorder and form part of the differential diagnosis. In an LMN lesion, the muscle becomes hypersensitive to neuro-transmitter as it is denervated. Similarly, the damaged lower motor erratically discharges the neurotransmitter stored within itself as the neuron degrades. So, both increased hypersensitivity and erratic release of neurotransmitter cause fasciculations. However, in UMN lesions, there is regular firing to prevent the atrophy of muscles. LMN syndromes are clinically characterized by muscle atrophy, weakness, and hyporeflexia without sensory involvement.

Neuromuscular Junctions, the junction between a motor neuron and muscle fiber is a specialized synapse. The motor neuron releases a flood of acetylcholine (Ach) neurotransmitters upon stimulation from the axon terminals from synaptic vesicles that bind with the post-synaptic receptors at the plasma membrane. This response is contractile causing muscle contraction and inhibition does not require a neurotransmitter release.

UMC & LMN lesions cause very different clinical findings.

1. UMN lesions are lesions anywhere from the cortex to the descending tracts. This lesion causes hyperreflexia, spasticity, and a positive Babinski reflex, presenting as an upward response of the big toe when the plantar surface of the foot is stroked, with other toes fanning out.
2. LMN lesions are lesions anywhere from the anterior horn of the spinal cord, peripheral nerve, neuromuscular junction, or muscle. This type of lesion causes hyporeflexia, flaccid paralysis, and atrophy.

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