The substance that has been taken may often be determined by asking the person. However, if they will not, or cannot, due to an altered level of consciousness, provide this information, a search of the home or questioning of friends and family may be helpful.

Examination for toxidromes, drug testing, or laboratory test may be helpful. Other laboratory test such as glucose, urea and electrolytes, paracetamol levels and salicylate levels are typically done. Negative drug-drug interactions have sometimes been misdiagnosed as an acute drug overdose, occasionally leading to the assumption of suicide.

The diagnosis of benzodiazepine overdose may be difficult, but is usually made based on the clinical presentation of the patient along with a history of overdose. Obtaining a laboratory test for benzodiazepine blood concentrations can be useful in patients presenting with CNS depression or coma of unknown origin. Techniques available to measure blood concentrations include thin layer chromatography, gas liquid chromatography with or without a mass spectrometer, and radioimmunoassay. Blood benzodiazepine concentrations, however, do not appear to be related to any toxicological effect or predictive of clinical outcome. Blood concentrations are, therefore, used mainly to confirm the diagnosis rather than being useful for the clinical management of the patient.

A specific blood test to verify toxicity is not typically available. An electrocardiogram (ECG) should be included in the assessment when there is concern of an overdose.

People with symptoms are usually monitored in an intensive care unit for a minimum of 12 hours, with close attention paid to maintenance of the airways, along with monitoring of blood pressure, arterial pH, and continuous ECG monitoring. Supportive therapy is given if necessary, including respiratory assistance and maintenance of body temperature. Once a person has had a normal ECG for more than 24 hours they are generally medically clear.

Stabilization of the victim's airway, breathing, and circulation (ABCs) is the initial treatment of an overdose. Ventilation is considered when there is a low respiratory rate or when blood gases show the person to be hypoxic. Monitoring of the patient should continue before and throughout the treatment process, with particular attention to temperature, pulse, respiratory rate, blood pressure, urine output, electrocardiography (ECG) and O saturation. Poison control centers and medical toxicologists are available in many areas to provide guidance in overdoses to both physicians and the general public.

Paracetamol may be quantified in blood, plasma, or urine as a diagnostic tool in clinical poisoning situations or to aid in the medicolegal investigation of suspicious deaths. The concentration in serum after a typical dose of paracetamol usually peaks below 30 mg/l, which equals 200 µmol/L. Levels of 30–300 mg/L (200–2000 µmol/L) are often observed in overdose patients. Postmortem blood levels have ranged from 50–400 mg/L in persons dying due to acute overdosage. Automated colorimetric techniques, gas chromatography and liquid chromatography are currently in use for the laboratory analysis of the drug in physiological specimens.

Medical observation and supportive care are the mainstay of treatment of benzodiazepine overdose. Although benzodiazepines are absorbed by activated charcoal, gastric decontamination with activated charcoal is not beneficial in pure benzodiazepine overdose as the risk of adverse effects would outweigh any potential benefit from the procedure. It is recommended only if benzodiazepines have been taken in combination with other drugs that may benefit from decontamination. Gastric lavage (stomach pumping) or whole bowel irrigation are also not recommended. Enhancing elimination of the drug with hemodialysis, hemoperfusion, or forced diuresis is unlikely to be beneficial as these procedures have little effect on the clearance of benzodiazepines due to their large volume of distribution and lipid solubility.

A person's history of taking paracetamol is somewhat accurate for the diagnosis. The most effective way to diagnose poisoning is by obtaining a blood paracetamol level. A drug nomogram developed in 1975, called the Rumack-Matthew nomogram, estimates the risk of toxicity based on the serum concentration of paracetamol at a given number of hours after ingestion. To determine the risk of potential hepatotoxicity, the paracetamol level is traced along the nomogram. Use of a timed serum paracetamol level plotted on the nomogram appears to be the best marker indicating the potential for liver injury. A paracetamol level drawn in the first four hours after ingestion may underestimate the amount in the system because paracetamol may still be in the process of being absorbed from the gastrointestinal tract. Therefore, a serum level taken before 4 hours is not recommended.

Clinical or biochemical evidence of liver toxicity may develop in one to four days, although, in severe cases, it may be evident in 12 hours. Right-upper-quadrant tenderness may be present and can aid in diagnosis. Laboratory studies may show evidence of liver necrosis with elevated AST, ALT, bilirubin, and prolonged coagulation times, particularly an elevated prothrombin time. After paracetamol overdose, when AST and ALT exceed 1000 IU/L, paracetamol-induced hepatotoxicity can be diagnosed. In some cases, the AST and ALT levels can exceed 10,000 IU/L.

The treatment of barbiturate abuse or overdose is generally supportive. The amount of support required depends on the person's symptoms. If the patient is drowsy but awake and can swallow and breathe without difficulty, the treatment can be as simple as monitoring the person closely. If the person is not breathing, it may involve mechanical ventilation until the drug has worn off.

Supportive treatment often includes the following:

- Activated charcoal may be given via nasogastric tube.

- Intravenous administration of saline, naloxone, thiamine, and/or glucose.

- Intubation and bemegride, or a hand-breather where these are not available until the patient can breathe under their own power.

- Observation in the Emergency Department for a number of hours or admission to the hospital for several days of observation if symptoms are severe.

- Advise the patient about drug misuse or refer for psychiatric consult.

Although opioid overdose accounts for the leading cause of accidental death, it can be prevented in primary care settings. Clear protocols for staff at emergency departments and urgent care centers can reduce opioid prescriptions for individuals presenting in these settings who engage in drug seeking behaviors or who have a history of substance abuse. Providers should routinely screen patients using tools such as the CAGE-AID and the Drug Abuse Screening Test (DAST-10) to screen adults and the CRAFFT to screen adolescents aged 14–18 years. Other “drug seeking” behaviors and physical indications of drug use should be used as clues to perform formal screenings.

Individuals diagnosed with opioid dependence should be prescribed naloxone to prevent overdose and/or should be directed to one of the many intervention/treatment options available, such as needle exchange programs and treatment centers. Brief motivational interviewing can also be performed by the clinician during patient visits and has been shown to improve patient motivation to change their behavior. Despite these opportunities, the dissemination of prevention interventions in the US has been hampered by the lack of coordination and sluggish federal government response.

Prescription monitoring program allow physicians to view individuals' history of prescribed opioids and other controlled substances to prevent risky behaviors, such as doctor shopping and drug diversion. These programs are operational in 49 states and the District of Columbia, and have generally been found to decrease prescribing of opioids.

Regulative policies, such as Florida’s pill mill law, have also been found to decrease opioid prescribing and use, which are both correlated with opioid overdoses. Florida's pill mill law addressed pill mills, or rogue pain management clinics where prescription drugs are inappropriately prescribed and dispensed, and required these clinics to register with the state, have a physician-owner, created inspection requirements, and established prescribing and dispensing requirements and prohibitions for physicians at these clinics.

Emergency treatment of cocaine-associated hyperthermia consists of administering a benzodiazepine sedation agent, such as diazepam (Valium) or lorazepam (Ativan) to enhance muscle relaxation and decrease sympathetic outflow from the central nervous system. Physical cooling is best accomplished with tepid water misting and cooling with a fan (convection and evaporation), which can be carried out easily in the field or hospital. There is no specific pharmacological antidote for cocaine overdose. The chest pain, high blood pressure, and increased heart rate caused by cocaine may be also treated with a benzodiazepine. Multiple and escalating dose of benzodiazepines may be necessary to achieve effect, which increases risk of over-sedation and respiratory depression. A comprehensive systematic review of all pharmacological treatments of cocaine cardiovascular toxicity revealed benzodiazepines may not always reliably lower heart rate and blood pressure.

Nitric-oxide mediated vasodilators, such as nitroglycerin and nitroprusside, are effective at lowering blood pressure and reversing coronary arterial vasoconstriction, but not heart rate. Nitroglycerin is useful for cocaine-induced chest pain, but the possibility of reflex tachycardia must be considered. Alpha-blockers such as phentolamine have been recommended and may be used to treat cocaine-induced hypertension and coronary arterial vasoconstriction, but these agents do not reduce heart rate. Furthermore, phentolamine is rarely used, not readily available in many emergency departments, and many present-day clinicians are unfamiliar with its use and titratability. Calcium channel blockers may also be used to treat hypertension and coronary arterial vasoconstriction, but fail to lower tachycardia based on all cocaine-related studies. Non-dihydropyridine calcium channels blockers such as diltiazem and verapamil are preferable, as dihydropyridine agents such as nifedipine have much higher risk of reflex tachycardia.

Agitated patients are best treated with benzodiazepines, but antipsychotics such as haloperidol and olanzapine may also be useful. The alpha-2 agonist dexmedetomidine may also be useful for treatment of agitation, but effects on heart rate and blood pressure are variable based on several studies and case reports. Lidocaine and intravenous lipid emulsion have been successfully used for serious ventricular tachyarrhythmias in several case reports.

The use of beta-blockers for cocaine cardiovascular toxicity has been subject to a relative contraindication by many clinicians for several years despite extremely limited evidence. The phenomenon of “unopposed alpha-stimulation,” in which blood pressure increases or coronary artery vasoconstriction worsens after blockade of beta-2 vasodilation in cocaine-abusing patients, is controversial. This rarely-encountered and unpredictable adverse effect has resulted in some clinicians advocating for an absolute contraindication of the use of all beta-blockers, including specific, non-specific, and mixed. Many clinicians have disregarded this dogma and administer beta-blockers for cocaine-related chest pain and acute coronary syndrome, especially when there is demand ischemia from uncontrolled tachycardia. Of the 1,744 total patients identified in the aforementioned systematic review, only 7 adverse events were from putative cases of “unopposed alpha-stimulation” due to propranolol (n=3), esmolol (n=3), and metoprolol (n=1). Some detractors of beta-blockers for cocaine-induced chest pain have cited minimal acute mortality and the short half-life of the drug, making it unnecessary to aggressively treat any associated tachycardia and hypertension. However, the long-term effect of cocaine use and development of heart failure, with early mortality, high morbidity, and tremendous demand on hospital utilization should be taken under consideration.

The mixed beta/alpha blocker labetalol has been shown to be safe and effective for treating concomitant cocaine-induced hypertension and tachycardia, without any “unopposed alpha-stimulation” adverse events recorded. The use of labetalol is approved by a recent AHA/ACC guideline for cocaine and methamphetamine patients with unstable angina/non-STEMI.

Barbiturates increase the time that the chloride pore of the GABA receptor is opened for, thereby increasing the efficacy of GABA. This is as opposed to benzodiazepines which increase the frequency that the chloride pore is opened, thereby increasing GABA's potency.

Efforts to prevent poisoning include child-resistant packaging and a lower number of pills per package.

Permanent brain damage may occur due to cerebral hypoxia or opioid-induced neurotoxicity.

Intravenous fluids containing dextrose such as D5W are recommended to keep a urinary output between 2 and 3 ml/kg/h.

Sodium bicarbonate is given in a significant aspirin overdose (salicylate level greater than 35 mg/dl 6 hours after ingestion) regardless of the serum pH, as it enhances elimination of aspirin in the urine. It is given until a urine pH between 7.5 and 8.0 is achieved.

Cocaine intoxication refers to the immediate and deleterious effects of cocaine on the body. Although cocaine intoxication and cocaine dependence can be present in the same individual, these syndromes present with different symptoms.

In general, the simultaneous use of multiple drugs should be carefully monitored by a qualified individual such as board certified and licensed medical doctor, either an MD or DO Close association between prescribing physicians and pharmacies, along with the computerization of prescriptions and patients' medical histories, aim to avoid the occurrence of dangerous drug interactions. Lists of contraindications for a drug are usually provided with it, either in monographs, package inserts (accompanying prescribed medications), or in warning labels (for OTC drugs). CDI/MDI might also be avoided by physicians requiring their patients to return any unused prescriptions. Patients should ask their doctors and pharmacists if there are any interactions between the drugs they are taking.

People who engage in polypharmacy and other hypochondriac behaviors are at an elevated risk of death from CDI. Elderly people are at the highest risk of CDI, because of having many age-related health problems requiring many medications combined with age-impaired judgment, leading to confusion in taking medications.

If there is evidence of overdose or it is suspected, the patient should be given gastric lavage, activated charcoal, or both; this could make the difference between life and death in a close situation. It can however aggravate the patient which should be taken into account.

The first line treatments are diazepam and a non-selective beta blocker; other antihypertensive drugs may also be used. It is important to note that not all benzodiazepines and beta blockers are safe to use in an adrenergic storm; for instance, alprazolam and propranolol; alprazolam weakly agonizes dopamine receptors and causes catecholamine release while propranolol mildly promotes some catecholamine release - each worsening the condition.

Adrenergic storms are often idiopathic in nature; however if there is an underlying condition, then that must be addressed after bringing the heart rate and blood pressure down.

Because the adrenergic storm overlaps with so many other similar conditions, such as hypertensive crises, stimulant intoxication or overdose, or even panic attack, and because the treatments for these overlapping conditions are largely alike, it is not necessary to obtain a differential and definitive diagnosis before initiating treatment. However, analysis of the patient's medical history, checked against the possible causes of the adrenergic storm such as those above, should be done, because some adrenergic storms can be caused by serious underlying conditions. If a patient has an adrenergic storm and all or most of the other factors are ruled out, the adrenergic storm could lead to the discovery of a pheochromocytoma, which can become malignant. However, not all cases of adrenergic storm have an identifiable cause. Like a seizure, sometimes a patient has a single one, or perhaps a few, and then does not for the rest of their life. The mechanisms of idiopathic adrenergic storm are very poorly understood.

Serotonin syndrome, in which an excess of serotonin in the synapses causes a similar crisis of hypertension and mental confusion, could be confused with an adrenergic storm. The difference is that serotonin, being a tryptamine (non-catecholamine) involved in higher brain functions, can cause dangerous hypertension and tachycardia from its effects on the sympathetic nervous system, but as there are no serotonin receptors in the heart or blood vessels there are no direct effects on the heart. Thus, the presence of arrythmia, abnormal echocardiograms, or chest pain indicates an adrenergic crisis and rules out serotonin syndrome.

The symptoms of an anticholinergic toxidrome include blurred vision, coma, decreased bowel sounds, delirium, dry skin, fever, flushing, hallucinations, ileus, memory loss, mydriasis (dilated pupils), myoclonus, psychosis, seizures, and urinary retention. Complications include hypertension, hyperthermia, and tachycardia. Substances that may cause this toxidrome include the four "anti"s of antihistamines, antipsychotics, antidepressants, and antiparkinsonian drugs as well as atropine, benztropine, datura, and scopolamine.

Due to the characteristic appearance and behavior of patients with this toxidrome, they are colloquially described as "Blind as a bat, mad as a hatter, red as a beet, hot as Hades (or hot as a hare), dry as a bone, the bowel and bladder lose their tone, and the heart runs alone."

A toxidrome (a portmanteau of "toxic" and "syndrome") is a syndrome caused by a dangerous level of toxins in the body. The term was coined in 1970 by Mofenson and Greensher. It is often the consequence of a drug overdose. Common symptoms include dizziness, disorientation, nausea, vomiting, and oscillopsia. A toxidrome may indicate a medical emergency requiring treatment at a poison control center. Aside from poisoning, a systemic infection may also lead to a toxidrome. "Classic" toxidromes are presented below, but they are often variable or obscured by the co-ingestion of multiple drugs.

CNS depression is treated within a hospital setting by maintaining breathing and circulation. Individuals with reduced breathing may be given supplemental oxygen, while individuals who are not breathing can be ventilated with bag valve mask ventilation or by mechanical ventilation with a respirator. Sympathomimetic drugs may be used to attempt to stimulate cardiac output in order to maintain circulation. CNS Depression caused by certain drugs may respond to treatment with an antidote.

There are two antidotes that are frequently used in the hospital setting and these are Naloxone and Flumazenil. Naloxone is an opioid antagonist and reverses the central nervous depressive effects seen in opioid overdose. In the setting of a colonoscopy, Naloxone is rarely administered but when it is administered, its half life is shorter than some common opioid agonists. Therefore, the patient may still exhibit central nervous system depression after Naloxone has been cleared. Typically, Naloxone is administered in short intervals with relatively small doses in order to prevent the occurrence of withdrawal, pain, and sympathetic nervous system activation. Flumazenil is a benzodiazepine antagonists and blocks the binding of benzodiazepines to GABAa. Similarly to Naloxone, Flumazenil has a short half life, and this needs to be taken into account because the patient may exhibit central nervous depression after the antidote has been cleared. Benzodiazepines are used in the treatment of seizures and subsequently, the administration of Flumazenil may result in seizures. Therefore, slow administration of Flumazenil is necessary to prevent the occurrence of a seizure. These agents are rarely used in the setting of a colonoscopy as 98.8% of colonoscopies use sedatives but only 0.8% of them result in the administration of one of these antidotes. Even if they are rarely used in colonoscopies they are important in preventing the patient from entering a coma or developing respiratory depression when sedatives are not properly dosed. Outside of the colonoscopy setting, these agents are used for other procedures and in the case of drug overdose.

In the United States, cocaine use results in about 5,000–6,000 deaths annually.

The level of digoxin for treatment is typically 0.5-2 ng/mL. Since this is a narrow therapeutic index, digoxin overdose can happen. A serum digoxin concentration of 0.5-0.9 ng/mL among those with heart failure is associated with reduced heart failure deaths and hospitalizations. It is therefore recommended that digoxin concentration be maintained in approximately this range if it is used in heart failure patients.

High amounts of the electrolyte potassium (K+) in the blood (hyperkalemia) is characteristic of digoxin toxicity. Digoxin toxicity increases in individuals who have kidney impairment. This is most often seen in elderly or those with chronic renal insufficiency or end-stage kidney disease.