(including ptosis) progressing to flaccid paralysis Nicotinic effects on sympathetic activity may also result in tachycardia, hypertension, and metabolic aberrations (e.g., hyperglycemia, hypokalemia, metabolic acidosis) Muscarinic toxicity is manifested by ocular findings (miosis, visual blurring, eye pain, lacrimation), respiratory distress (watery rhinorrhea, bronchospasm, increased bronchial secretions causing cough, wheezing, dyspnea), dermal involvement (flushing, sweating, cyanosis), GI signs and symptoms (salivation, nausea, vomiting, diarrhea progressing to fecal incontinence and abdominal cramps), genitourinary complaints (frequency, urgency, incontinence), and cardiovascular findings (bradycardia, hypotension, atrioventricular block) Because muscarinic effects on the heart are opposed by the cardiovascular effects of nicotinic hyperstimulation at autonomic ganglia, heart rate and blood pressure may be either elevated or depressed and are not reliable indicators of the severity of nerve-agent intoxication Clinical Presentation The clinical presentation in a given patient depends on dose and route of exposure For vapor exposures, mild toxicity would be suggested by miosis, rhinorrhea, mild dyspnea, and wheezing—all local effects caused by contact of vapor with epithelial surfaces As the dose increases and systemic distribution of the agent occurs, the victim might experience increased respiratory secretions and dyspnea, nausea, vomiting, and muscle weakness In the Tokyo experience with sarin vapor exposure, miosis (99%), dyspnea (63%), nausea (60%), and headache (74%) were particularly common among moderately symptomatic patients at hospital admission In severe cases with exposure to high vapor concentrations, paralysis, and seizures leading to death from respiratory arrest may occur within minutes and sometimes nearly instantaneously In the Tokyo incident, of 640 patients presented to one ED in cardiopulmonary arrest The asymptomatic period between exposure and the onset of signs and symptoms is termed the latent period It is important to stress two aspects of this concept with respect to nerve agents: First, the onset of clinical effects is immediate or nearly immediate after the inhalation of a substantial dose of vapor, whereas there is a delay after skin exposure This is because it takes time for nerve agent to pass through the stratum corneum (where it forms a temporary depot) and reach the dermal capillaries for introduction into the systemic circulation Second, the length of the latent period, whether for inhalation or dermal exposure, is inversely correlated with dose For example, a very small drop of VX applied to the skin may cause rapid local effects (localized sweating and then fasciculations of underlying muscle fibers) but may take up to 18 hours