Module 50 Flashcards
Why is it so common that different reports of the incidence of a specific adverse drug reaction to a specific drug will vary by more than an order of magnitude?
Incidence is based on knowing how many people develop an adverse reaction to the drug divided by how many people were treated with the drug. Both the numerator and denominator of this ratio are very difficult to determine accurately
- Only about 10% of severe adverse reactions are reported, and most of the reports are so poor that it is often difficult to determine what the adverse event was, let alone whether it was cause by a drug or some other disease
It is somewhat easier to guess how many people have been treated with a drug based on the number of prescriptions, but you do not know whether the patient took it, or if based on the amount of drug sold, whether some people took the drug for a long time or a larger amount of people took if for a shorter time.
When is it appropriate to induce vomiting to eliminate a toxin and when is it not appropriate?
- There are several contraindications for induction of vomiting
○ The patient must have a high level of consciousness so that they do not aspirate. Things like gasoline also cause severe lung damage if they get into the lungs during vomiting
○ If the toxin causes more damage to the esophagus during vomiting, e.g., with strong alkali such as Drano, it would be inappropriate to induce vomiting
○ Vomiting will not help if a long period of time has passed, and the toxin is no longer in the stomach- In most cases, supportive treatment is sufficient to deal with toxins
What is the most common cause of acute liver failure in the developed world?
Acetaminophen
Is the recommended dose of acetaminophen safe?
- There is a study that found that a dose of 4g of acetaminophen/day (2 extra strength acetaminophen QID) led to a significant increase in ALT in 81% of subjects > 2X the baseline ALT, and in a few cases the increase was marked (ALT >600). These subjects did not develop liver failure, and other studies have not found quite as high an incidence of ALT increases with this dose, but it is worrying.
- Acetaminophen has become the most common cause of liver failure, in many cases due to unintentional overdose. This has led regulatory agencies to review the guidelines for the upper end of the therapeutic dose. The recommended upper limit was decreased in the US to 3g/day, but Canada did not respond as quickly
What is the treatment for an acetaminophen overdose and how does it work?
- The antidote is N-acetylcysteine. It is usually effective if given less than 8 hours after the overdose, but the earlier the better, and it can have some beneficial effects after 8 hours.
- It works by acting as a precursor for the synthesis of glutathione that is depleted by scavenging the acetaminophen reactive metabolite. Some have hypothesized that it decreases covalent binding of the reactive metabolite, but it still works after most of the covalent binding has occurred. It is more likely that, at least in part, it works to help reduce many protein disulfides formed by acetaminophen reactive metabolite-mediated oxidation back to the active thiol form of the protein (in addition to covalently binding to proteins, the reactive metabolite also causes oxidation of protein thiols)
Overdoses of benzodiazepines are rarely fatal, but there are exceptions. In what setting are the risks of benzodiazepines markedly increased?
- The setting is almost always in combination with alcohol or another drug. Benzodiazepines do not cause as much respiratory depression as most other sedatives, but in combination with other CNS depressants, it can easily result in death
How would you treat a child that had ingested rat poison?
- The most common rat poison is warfarin
- The amount of warfarin in rat poison is unlikely to cause significant toxicity to a child. It does not do any good to check the INR soon after the ingestion because it takes time for the warfarin to deplete clotting factors.
- However, there are also “superwarfarins” such as brodifacoum, which has a very long half-life and can cause increased bleeding for months. If the dose is sufficient it may require treatment with vitamin K for a very long time.
That is one situation where induction of vomiting may be appropriate, but fortunately poisonings with superwarfarin are rare
What is in mothballs and what sort of toxicity do they cause?
- There are two types of mothballs: naphthalene and p-dichlorobenzene
- Naphthalene has a very characteristic and unpleasant smell, so it is less commonly used today. It forms an epoxide, which is converted to the catechol. The catechol redox cycles and can lead to hemolytic anemia, especially in individuals who are genetically deficient in G6PD. With more chronic exposure, it can cause cataracts
- P-dichlorobenzene is more commonly used because its odor is less objectionable, and the acute toxicity is less; however, halogenated aromatic systems have a bad reputation and are worrisome
Why shouldn’t you mix hypochlorite bleach with a cleaner containing ammonia?, how about mixing an acid?
The combination of hypochlorite and ammonia produces chloramines (NH2Cl, NHCl2, NCl3), which are volatile and very toxic. The combination of hypochlorite and acid produces chlorine gas (Cl2), which is also very toxic and was used as a war gas in WWI
A 19-year-old woman is brought to the emergency room with dilated and fixed pupils, shallow respiration and a slow respiratory rate. Examination of the arm shows needle tracks and a narcotic overdose is the preliminary diagnosis. The nurse and house physician frantically begin looking for naloxone. What basic principle of poisoning treatment is being overlooked?
- Always remember the ABCs of resuscitation: airway, breathing, cardiac
- Most patients can be saved by simple supportive treatment, and the patient may sustain brain damage while you are looking for naloxone. You could also be wrong
- Good supportive treatment gives you time to administer a more specific treatment
A student is brought to the emergency room by friends from a RAVE. He is talking incoherently and breathing rapidly. His temperature is 40° and his blood pressure is 100/60. What would you suspect is responsible for the symptoms, and what are the most important aspects of treatment?
3,4-methylenediozymethamphetamine (MDMA or ecstasy) is a common psychoactive drug that is often associated with Raves. It increases the release and slows the reuptake of serotonin, dopamine, and NE in parts of the brain. It can cause an increased sense of empathy and euphoria, but it can also cause paranoia
- The major acute danger is hyperthermia and dehydration. Subjects often drink a lot of fluids to prevent the dehydration, but that can lead to hyponatremia. Therefore, careful monitoring of electrolytes is important in the treatment of MDMA toxicity
An 18-month-old child weighing 10 kg is brought to the local hospital because of fever, irritability, and he has vomited blood. He has been treated for 2 days because of an upper respiratory infection with an antibiotic and antipyretic, but his temperature went up today and he seems more ill. He is noted to be lethargic but arousable. His temperature is 40°, and his respirations are 70/minute. What drug/chemical could cause these signs and symptoms?
- This is typical of aspirin poisoning
- Aspirin is much more toxic in infants. A rapid respiratory rate is indicative of either respiratory or metabolic acidosis. This can be differentiated by measuring the pH and serum bicarbonate.
- If the patient has breathing difficulties, they will have a low pH with a relatively high bicarbonate.
- If it is metabolic acidosis, they will have a very low bicarbonate with an “anion gap”. Normally, the sum of the serum chloride and bicarbonate is almost equal to the sum of the serum sodium and potassium concentrations. If there is a large difference that is referred to as an anion gap. In this case, the missing anion would be salicylate.
- You could also measure arterial blood gases and determine the CO2 concentration, which would be high with respiratory acidosis but low with metabolic acidosis (but this is more invasive)
A 2-year-old child put a leaf from a houseplant into his mouth and immediately started to cry, pointed to his mouth, and indicated that he was in a lot of pain. What plant is likely responsible and what is causing the pain?
- This is the typical response of a child who has put the leaf of dieffenbachia in their mouth (aka Dumb Cane). The symptoms are caused by sharp crystals of calcium oxalate in the leaves.
- It is treated symptomatically, and usually is not serious
- On rare occasion, there could be sufficient swelling to cause airway obstruction
- A 27-year-old Italian woman started having difficulty with talking and swallowing shortly after attending the funeral of her mother-in-law. She was seen by a physician who thought she seemed anxious and attributed her symptoms to emotions surrounding the funeral. Diazepam was prescribed. She developed trouble walking and raising her head, and she was admitted to hospital. It was noted that she had symptoms resembling those of her mother-in-law before she died; the mother-in-law was believed to have died of an MI. She was given IM saline and sent home. She developed difficulty breathing, had a cardiopulmonary arrest, and died. What do you think she died from?
- These were two cases of botulism. It is not common and hard to diagnose
- The bacteria that cause botulism are anaerobic and the most common cause is canned food that has not been sufficiently heated to kill the spores
- The bacteria produce a toxin that blocks the release of acetylcholine at the neuromuscular junction, resulting in paralysis. The cause of death is usually the inability to breathe.
- It is more common if the food contains meat, and much less common in food that is highly acidic such as tomato sauce.
- It is more common in ethnic communities in which canning is common
A patient comes into the pharmacy and complains that something is wrong because he cannot control his movements. He is acting quite strange, and he appears to be writhing, almost as if he is in pain, and yet he does not complain of pain. What is a likely cause and how is it treated?
this is typical of the acute dystonic syndrome caused by some antipsychotic drugs
- The onset is usually 24-48 hours after starting an antipsychotic agent - It is distinct from tardive dystonia but also involves dopaminergic receptors. - It usually responds rapidly to IV Benadryl, because of the anticholinergic effects. - This is another example of the balance between dopamine and acetylcholine
