Intoxications caused by reptiles and insects – local and general manifestations of poisoning (28);

Intoxications with opiates, psycho stimulants and dyspeptic hallucinogens. The “New-born” narcotics.
Drug addiction (30); Drug therapeutic treatment of poisoning – solutions for infusion, organ protective
medications, symptomatic agents (36).

Intoxications caused by reptiles and insects – local and general manifestations of poisoning (28)

A toxicant is any chemical, of natural or synthetic origin, capable of causing a deleterious effect on a living
organism. A toxin is a toxicant that is produced by a living organism and is not used as a synonym for
toxicant — all toxins are toxicants, but not all toxicants are toxins.
The toxin produced by the puffer fishes ( Sphaeroides spp.) is called tetrodotoxin (TTX). TTX is
concentrated in the gonads, liver, intestine, and skin, and poisonings occur most frequently in Japan
and other Asian countries where the flesh, considered a delicacy, is eaten as “ fugu. ” Death occurs
within 5 – 30 min and the fatality rate is about 60%. TTX is an inhibitor of the voltage - sensitive Na
channel (like saxitoxin); it may also be found in some salamanders and may be bacterial in origin.
Venoms are very complex, containing polypeptides, high- and low-molecular-weight proteins,
amines, lipids, steroids, aminopolysaccharides, quinones, glucosides, and free amino acids, as well as
serotonin, histamine, and other substances. Some venoms are known to consist of more than a
hundred proteins. The venom is a source of peptides and proteins that act on myriad exogenous
targets such as ion channels, receptors, and enzymes within cells and on cell membranes.
Snake venoms have been studied extensively; their effects are due, in general, to toxins that are
peptides with 60 – 70 amino acids. These toxins are cardiotoxic or neurotoxic, and their effects are
usually accentuated by the phospholipases, peptidases, proteases, and other enzymes present in
venoms. These enzymes may affect the blood - clotting mechanisms and damage blood vessels.
Bees
The venom contains biologically active peptides, such as melittin, apamine, mast cell–degranulating
peptide, and others, as well as phospholipases A 2 and B, hyaluronidase, histamine, dopamine,
monosaccharides, and lipids. Melittin causes erythrocyte lysis. Melittin also facilitates ion transport
through membranes causing a breakdown of the resting potential and rapid depolarization of
nociceptors, which induces pain The compound apamine is a blocker of calcium-dependent
potassium channels and is thought to be the “lethal factor”. Mast cell–degranulating peptide
stimulates release of histamine and specifically inhibits voltage-dependent potassium channels.
Bee stings typically produce immediate, sharp or burning pain, slight local erythema, and edema
followed by itching. The edema may vary depending on location of the sting. It is said that 50 stings
can be serious and lead to respiratory dysfunction, intravascular hemolysis, hypertension, myocardial
damage, hepatic changes, shock, and renal failure. With 100 or more stings, death can occur.
In patients who are allergic to bee stings, immediate allergic reaction with the risk of anaphylactic
shock requires urgent medical treatment.
Vespidae (Wasps) This family includes wasps and hornets. The venoms contain a high content of
peptides, which include mastoparan in wasps and hornets and crabolin from hornet venom. Other
peptides named wasp kinins cause immediate pain, vasodilation, and increased vascular permeability
leading to edema. These venoms also contain phospholipases and hyaluronidases, which contribute
to the breakdown of membranes and connective tissue to facilitate diffusion of the venom. These
proteins also contribute to the allergenicity of the venoms.
Caterpillars, Moths, and Butterflies
The toxic material found in the venom glands contains aristolochic acids, cardenolides, kallikrein,
and histamine among other substances coagulation defects such as prolonged prothrombin and partial
thromboplastin times have been detected, and decreases in fibrinogen and plasminogen have been
noted. It is thought that the hemorrhagic syndrome cannot be classified as being either totally
fibrinolytic or a syndrome such as disseminated intravascular coagulopathy. In some parts of the
world the stings of several species of Lepidoptera give rise to a bleeding diathesis, often severe and
sometimes fatal. Envenomation by members of the family Saturniidae, generally gives rise to little
more than immediate localized itching and pain, usually described as burning, followed in some
cases by urticaria, edema, and occasionally fever. Contact with other species is related to pain as well
as papules (sometimes hemorrhagic) and hematomas; on occasions there may also be headache,
nausea, vomiting, hematuria, lymphadenitis, and lymphadenopathy.
Scorpions
Many scorpion venoms contain low-molecular-weight proteins, peptides, amino acids, nucleotides,
and salts, among other components. The neurotoxic fractions appear to affect potassium, sodium, or
chloride channels. The symptoms and signs of scorpion envenomation differ considerably depending
on the species.
Lizards
The Gila monster (Heloderma suspectum) is relatively slow moving, and largely nocturnal reptiles.
Their venom is transferred from venom glands in the lower jaw through ducts that discharge their
contents near the base of the larger teeth of the lower jaw. The venom is then drawn up along grooves
in the teeth by capillary action (Brown and Carmony, 1991). The venom of this lizard has serotonin,
amine oxidase, phospholipase A, a bradykininreleasing substance, helodermin, gilatoxin, and low-
proteolytic as well as high-hyaluronidase activities, but lacks phosphomonoesterase and
phosphodiesterase, acetylcholinesterase, nucleotidase, ATPase, deoxyribonuclease, ribonuclease,
amino acid oxidase, and fibrinogenocoagulase activities. The clinical presentation of a helodermatid
bite can include pain, edema, hypotension, nausea, vomiting, weakness, and diaphoresis. No
antivenin is commercially available. Treatment is supportive.
Snakes
Venomous snakes primarily belong to the following families: Viperidae (vipers), Elapidae,
Atractaspididae, and Colubridae. These venoms are complex mixtures: proteins and peptides,
consisting of both enzymatic and nonenzymatic compounds, make up over 90% of the dry weight of
the venom. Snake venoms also contain inorganic cations such as sodium, calcium, potassium,
magnesium, and small amounts of zinc, iron, cobalt, manganese, and nickel. The metals in snake
venoms are likely catalysts for metal-based enzymatic reactions. Some snake venoms also contain
carbohydrates (glycoproteins), lipids, and biogenic amines, such as histamine, serotonin, and
neurotransmitters (catecholamines and acetylcholine) in addition to positively charged metal ions.
Actions of snake venoms can be said to be broad ranging in several areas. A simplistic approach
would group toxin components as neurotoxins, coagulants, hemorrhagins, hemolytics, myotoxins,
cytotoxins, and nephrotoxins. Neurotoxins produce neuromuscular paralysis ranging from dizziness
to ptosis; to ophthalmoplegia, flaccid facial muscle paralysis, and inability to swallow; to paralysis of
larger muscle groups; and finally to paralysis of respiratory muscles and death by asphyxiation.
Coagulants may have initial procoagulant action that uses up clotting factors leading to bleeding.
Coagulants may directly inhibit normal clotting at several places in the clotting cascade or via
inhibition of platelet aggregation. In addition, some venom components may damage the endothelial
lining of blood vessels leading to hemorrhage. Bite victims may show bleeding from nose or gums,
from the bite site, and in saliva, urine, and stools. Myotoxins can directly impact muscle contraction
leading to paralysis or cause rhabdomyolysis or the breakdown of skeletal muscle. Myoglobinuria, or
a dark brown urine, and hyperkalemia may be noted. Cytotoxic agents have proteolytic or necrotic
properties leading to the breakdown of tissue. Typical signs include massive swelling, pain,
discoloration, blistering, bruising, and wound weeping. Finally, nephrotoxins can cause direct
damage to kidney structures leading to bleeding, damage to several parts of the nephron, tissue
oxygen deprivation, and renal failure. Proteolytic enzymes that catalyze the breakdown of tissue
proteins and peptides include peptide hydrolases, proteases, endopeptidases, peptidases, and
proteinases. Several proteolytic enzymes may be in a single venom. Some are inactivated by
ethylenediaminetetraacetic acid (EDTA) and certain reducing agents. Metals appear to be
intrinsically involved in the activity of certain venom proteases and phospholipases. The crotalid
venoms examined so far appear to be rich in proteolytic enzyme activity. Viperid venoms have lesser
amounts, whereas elapid and sea snake venoms have minimal, if any, proteolytic activity. Venoms
that are rich in proteinase activity are associated with marked tissue destruction. Collagenase is a
specific kind of proteinase that digests collagen. This activity has been demonstrated in the venoms
of a number of species of crotalids and viperids. Hyaluronidase cleaves internal glycoside bonds in
certain acid mucopolysaccharides resulting in a decrease in the viscosity of connective tissues. The
breakdown in the hyaluronic barrier allows other fractions of venom to penetrate the tissues, causing
hyaluronidase to be called “spreading factor.” The snake venom hemorrhagic metalloproteinases
(SVMP) are enzymes that disrupt the hemostatic system.
Toxicology
In general, the venoms of rattlesnakes and other crotalids produce alterations in the resistances and
often in the integrity of blood vessels, changes in blood cells and blood coagulation mechanisms,
direct or indirect changes in cardiac and pulmonary dynamics, and—with crotalids such as C.
durrissus terrificus and C. scutulatus —serious alterations in the nervous system and changes in
respiration. In humans, the course of the poisoning is determined by the kind and amount of venom
injected; the site where it is deposited; the general health, size, and age of the patient; the kind of
treatment; and those pharmacodynamic principles noted earlier in this chapter. Death in humans may
occur within less than one hour or after several days, with most deaths occurring between 18 and 32
hours. Hypotension or shock is the major therapeutic problem in North American crotalid bites.
Snakebite Treatment
The treatment of bites by venomous snakes is now so highly specialized that almost every
envenomation requires specific recommendations. However, three general principles for every bite
should be kept in mind: (1) snake venom poisoning is a medical emergency requiring immediate
attention and the exercise of considerable judgment; (2) the venom is a complex mixture of
substances of which the proteins contribute the major deleterious properties, and the only adequate
antidote is the use of specific or polyspecific antivenom; and (3) not every bite by a venomous snake
ends in an envenomation. Venom may not be injected. In almost 1000 cases of crotalid bites, 24%
did not end in a poisoning. The incidence with the bites of cobras and perhaps other elapids is
probably higher. The reader is referred to other appropriate texts for appropriate treatment of
snakebites.

Intoxications with opiates, psycho stimulants and dysleptic hallucinogens. The “New-born” narcotics.
Drug addiction (30)

Page 131 – opiates

The abuse of stimulants such as amphetamine and methamphetamine has been well
known for many years (see Figure 23.1). However, methamphetamine abuse is
largely confined to North America, Japan and Far East. Amphetamine, but not
methamphetamine, is a common inexpensive drug of abuse in the UK. However, the
abuse of some of their newer analogues such as methylenedioxyamphetamine
(MDA), MDMA (“ecstasy”) and methylenedioxyethyl-amphetamine (MDEA) is
increasingly common, although users rarely require hospital care. Admission may be
required following “overdosage” with such drugs or as a result of adverse reactions,
which are most commonly seen as delirium, with cardiovascular manifestations
such as heart rhythm disturbances, hypertension and hyperpyrexia, increased body
temperature and heat stroke. Other adverse effects that have been described include
liver toxicity and neuropsychiatric illness such as depression and suicide linked to
destruction of serotonergic pathways in the brain.
Goldfrank 1111-1115; 1123-1127 –psychostimulants
1201-1203; 1209-1212; 1224-1227 – hallucinogens
New born narcotics: cathinones (“bath salts”, psychostimulants); synthetic cannabinoids,
“crocodile”
Cathinones (“bath salts”)
Bath salts can be ingested, snorted, smoked, or injected. Injection is especially ill-advised as these
products rarely list ingredients, let alone dosage. Bath salts are detrimental to human health and can
cause erratic behaviour, hallucinations, and delusions. Bath salts are often consumed concurrently
with alcohol. A 2015 study has investigated the interrelation between mephedrone and alcohol,
focusing on psychostimulant and rewarding effects. It showed that alcohol, at low (non-stimulant)
doses, significantly enhances the psychostimulant effects of mephedrone. This effect is mediated by
an increase in synaptic dopamine, as haloperidol, but not ketanserin, was capable of blocking the
potentiation by alcohol.
Bath Salts or Monkey Dust comes in a powdered or crystallised form which can be swallowed,
smoked, injected or snorted. Subjective effects are similar to MDMA or cocaine but with a duration
of 5–6 hours. Both substances cause a rapid onset of action in the central nervous system, and
stimulant toxicity. In larger doses this class of substances can cause effects similar to those seen in
cases of serotonin syndrome. Due to their rapid onset, synthetic cathinones are powerful
reward/reinforcers, with high addiction potential. "Monkey dust", "bath salts" or plant food are often
used at the same time as classical psychoactive drugs. Users who have overdosed often display
symptoms of; agitation, delirium, hallucinations, excessive motor activity, seizures, tachycardia,
hypertension, and/or hyperthermia. Bath salt users have reported symptoms that include headache,
heart palpitations, nausea, cold fingers, hallucinations, paranoia, and panic attacks. News media
have reported reactions that include violent behavior, heart attack, kidney failure, liver failure,
suicide, an increased tolerance for pain, dehydration, and breakdown of skeletal muscle tissue.
Visual symptoms similar to those of stimulant overdoses include dilated pupils, involuntary muscle
movement, rapid heartbeat, and high blood pressure.

Synthetic cannabinoids (SC)

MDMB-CHMICA (methyl 2-{[1-(cyclohexylmethyl)-1H-indol- 3-yl]formamido}-3,3-
dimethylbutanoate) is an indole based cannabinoid that shares some structural similarities with AB-
CHMINACA. It was initially sold under the wrong name MMB-CHMINACA and sometimes it is
mistakenly referred to as this compound. In Europe it was seized (in herbal product) for the first time
in Hungary in September 2014. Towards the end of 2014, this substance had also been detected in
seizures of powders in Romania, Sweden, and the United Kingdom. MDMB-CHMICA is mostly
smoked (e.g. after dissolving in acetone, mixing with herbs and evaporating solvent) in order to get
‘high’. It can also be taken orally, sublingually, intranassally or vaporized and inhaled. However,
using these methods it is very difficult to measure doses, which in the case of this compound are
generally very low. Starting MDMB-CHMICA doses are reported by users as 0.05 mg, and typical
doses range between 0.1 and 0.3 mg. Some users repeat doses to prolong the experience (e.g. every 2
h) leading to a few milligrams smoked throughout the day. Users reported that the effects of this
cannabinoid are delayed and typically start 0.5–5 min after smoking, and end after approximately 2–
4 h (but negative effects may last for up to 15 h). Users claim that the effects of MDMB-CHMICA
are stronger than other SCs (data reported on Internet forums). Reported symptoms were stimulation,
euphoria, hallucinations, amnesia, aggression, insomnia, anxiety, depression, apathy, delusions, and
disturbance of attention. Respiratory, circulatory, heart, kidney and liver failures as well as hypoxic-
ischemic damage of the CNS are potentially fatal. The cause of death accepted by the medical
examiner was multiple organ failure. The effects of many of SCs are stronger when compared to
THC. SCs are substances with structural features which allow binding to cannabinoid receptors (i.e.
CB1 or CB2). The CB1 receptor is responsible for the physiological and psychotropic effects [3].
The first SCs, i.e. JWH-018 and JWH-073, were approximately three to four times more potent as
cannabinoid CB1 receptor agonists when compared to the THC. SCs use has been reported to
produce unpredictable and serious adverse health effects. Common symptoms of the cardiovascular
system were tachycardia and hypertension [13]. Overdose of SCs may cause, myocardial infarction
and cerebral infarction, as well as loss of consciousness [14–16]. Changes of perception,
hallucinations and agitation were frequently reported symptoms of the nervous system. Seizures,
somnolence, and anxiousness also seemed to be characteristic to the SCs [13]. Nausea and vomiting
were the most reported gastrointestinal symptom [13,17]. The use of SCs has been associated with
nephrotoxic effects. Acute kidney injury has been reported by some authors [17–20]. Similarly, liver
failures may occur [21]. Administration of MDMB-CHMICA can also lead to serious adverse
effects. These were observed even after inhaling two or three times from a joint containing MDMB-
CHMICA [22,23]. Reported symptoms were dizziness, tremor, nausea, slurred speech, difficulty in
movement, mucosa dryness, shortness of breath, chest pains, tachycardia, irregular heart beat,
increased blood pressure, increased temperature, collapse, seizures and convulsions [5,6,22]. Non-
fatal intoxications have been characterised by loss of consciousness [22].
Krokodil
Krokodil is a street name for desomorphine, a semi-synthetic drug that has similar effects to heroin
and morphine. It's called semi-synthetic because it is created in a chemical process but it's made
primarily from a drug, usually codeine, that comes from the opium poppy. The short-term effects of
Krokodil include relaxation, euphoria, slow and shallow breathing, and pain and swelling at the
injection site. The long-term effects can include blood clots, swollen veins, severe tissue damage,
skin and muscle infections that cause black or green scaly skin around injection sites, sleeplessness,
exhaustion, physical and psychological dependence, memory loss, speech problems, gangrene and
death. People who use Krokodil are usually injecting opioid drugs such as heroin or prescription
painkillers. Tests for dependence on desomorphine found that tolerance increased rapidly, so more
was needed for the same effect. It causes physical dependence after about 10 days of regular use and
leads to similar withdrawal symptoms to morphine and heroin. Medical case reports have identified
infections and rotting skin down to the bone at injection sites. This can include jaw osteonecrosis
(jawbone exposure in the mouth) where ulcers and skin infections have affected a person's gums.
Many people who have injected Krokodil into their mouths require surgery to cut away the tissue and
sometimes infected parts of the jawbone. Some people have died within three years of starting to use
the drug because of infections.

Drug therapeutic treatment of poisoning – solutions for infusion, organ protective medications,
symptomatic agents (36).
Page 81; antidotes

Intravenous therapy is treatment that infuses intravenous solutions, medications, blood, or

blood products directly into a vein (Perry, Potter, & Ostendorf, 2014). Intravenous therapy is an
effective and fast-acting way to administer fluid or medication treatment in an emergency
situation, and for patients who are unable to take medications orally. Approximately 80% of all
patients in the hospital setting will receive intravenous therapy.

The most common reasons for IV therapy (Waitt, Waitt, & Pirmohamed, 2004) include:

1. To replace fluids and electrolytes and maintain fluid and electrolyte balance: The body’s
fluid balance is regulated through hormones and is affected by fluid volumes, distribution
of fluids in the body, and the concentration of solutes in the fluid. If a patient is ill and has
fluid loss related to decreased intake, surgery, vomiting, diarrhea, or diaphoresis, the
patient may require IV therapy.
2. To administer medications, including chemotherapy, anesthetics, and diagnostic reagants:
About 40% of all antibiotics are given intravenously.
3. To administer blood or blood products: The donated blood from another individual can be
used in surgery, to treat medical conditions such as shock or trauma, or to treat a failure in
the production of red blood cells. The infusion restores circulating volumes, improving
the ability to carry oxygen and replace blood components that are deficient in the body.
4. To deliver nutrients and nutritional supplements: IV therapy can deliver some or all of the
nutritional requirements for patients unable to obtain adequate amounts orally or by other
routes.

Examples of IV fluids:

Glucose 10% w/v Solution for Infusion is indicated for:

Supply of carbohydrate alone or, as required, during parenteral nutrition.

Prevention and treatment of hypoglycaemia.

Rehydration in case of water loss and dehydration states in patients with high carbohydrate need.

Dilution of compatible medicinal products.

Ringer’s Solution for Infusion is a solution of the following substances in water:

• sodium chloride

• potassium chloride

• calcium chloride dehydrate

Ringer’s Solution for Infusion is used to treat a loss of body water (dehydration) and chemicals
(e.g. by heavy sweating, kidney disorders)
0.9% Sodium Chloride infusion solutions is indicated:

As a vehicle for the administration of parenteral drugs

Also utilised as an extracellular fluid replacement and in the management of metabolic alkalosis
in the presence of fluid loss, and for restoring or maintaining the concentration of sodium and
chloride ions.

Mannitol 10% Solution for infusion is indicated for use as an osmotic diuretic in the following
situations:

• Promotion of diuresis in the prevention and/or treatment of the oliguric phase of acute renal
failure before irreversible renal failure becomes established.

• Reduction of intracranial pressure and cerebral oedema, when blood-barrier is intact.

• Reduction of elevated intraocular pressure when it cannot be lowered by other means.

• Promotion of elimination of renally excreted toxic substances in poisoning.

Intralipid ® 10% (A 10% Intravenous Fat Emulsion) is a sterile, non-pyrogenic fat emulsion
prepared for intravenous administration as a source of calories and essential fatty acids. It is made
up of 10% Soybean Oil, 1.2% Egg Yolk Phospholipids, 2.25% Glycerin, and Water for Injection.
In addition, sodium hydroxide has been added to adjust the pH so that the final product pH is 8.
pH range is 6 to 8.9. Intralipid ® 10% is indicated as a source of calories and essential fatty acids
for patients requiring parenteral nutrition for extended periods of time (usually for more than 5
days) and as a source of essential fatty acids for prevention of essential fatty acid deficiency.

Similar IV lipid emulsions: Medialipid, Liposyn III.

Aminosyn II (an amino acid injection, combination of essential and non-essential amino acids)
infused with dextrose by peripheral vein infusion is indicated as a source of nitrogen in the
nutritional support of patients with adequate stores of body fat, in whom, for short periods of
time, oral nutrition cannot be tolerated, is undesirable, or inadequate.

Supplemental electrolytes, in accordance with the prescription of the attending physician, must be
added to Aminosyn II solutions without electrolytes.

Aminosyn II can be administered peripherally with dilute (5 to 10%) dextrose solution and I.V.
fat emulsion as a source of nutritional support. This form of nutritional support can help to
preserve protein and reduce catabolism in stress conditions where oral intake is inadequate.