Pharmaceutical Basics and Drug-Induced Harm

Which of the following statements about the fundamental nature of medicines is correct?

1. Medicines, too, are foreign substances (xenobiotics) to the human body, and the actions they exert on it are complex and wide-ranging, not all of which have been elucidated.
2. The actions medicines exert on the human body are simple, and in the present day all of them have been elucidated.
3. Because medicines are not foreign substances to the human body, they never cause undesirable reactions (side effects).
4. Because over-the-counter (OTC) drugs carry relatively lower risk than prescription drugs, they never carry any risk to public health and hygiene.

Which of the following statements about medicines that are not used on the human body is correct?

1. Because insecticides and test kits are not used directly on the human body and do not count as life-related products, the Guide does not address them.
2. Medicines that are not used on the human body never affect human health.
3. Some insecticides can harm health if a person is accidentally exposed to them.
4. Even if the interpretation or judgment of a test kit's result is mistaken, it never affects the person's chance of visiting a medical institution.

Which of the following statements about the relationship between medicines and information is correct?

1. Because OTC drugs are selected by the purchaser at their own discretion, the law imposes no requirement whatsoever to state efficacy, dosage and administration, or side effect information on the package insert or product labeling.
2. Even without information such as efficacy, dosage and administration, and side effects, a medicine fully performs its role merely by containing an active ingredient, rather than being a mere drug substance.
3. The Guide describes a medicine lacking necessary information as a 'food with health claims' and treats it within the same framework as health foods.
4. A medicine performs its role fully only once necessary information such as efficacy, dosage and administration, and side effects has been properly conveyed and the purchaser and others use it appropriately.

Which of the following statements about the involvement of professionals in the sale of OTC drugs is incorrect?

1. Ordinary members of the public may develop misunderstandings or insufficient awareness of efficacy or side effects merely by looking at the content of the package insert or product labeling.
2. For purchasers and others to select and properly use OTC drugs appropriately, the involvement of a professional in their sale is essential.
3. Professionals must provide appropriate information, such as conveying technical terms in easily understandable language.
4. Because OTC drugs are selected and used by ordinary members of the public on their own, there is no need to respond to inquiries from purchasers and others.

Which of the following statements about the handling of medicines after they reach the market is correct?

1. Even when precautions for use are changed, this is understood to remain confined to a notice to the marketing authorization holder and never to be reflected in the package insert or product labeling.
2. Because knowledge accumulates and information is gathered from usage results and the like, with new information added from time to time, professionals engaged in sales must always work to keep abreast of new information.
3. Information on a medicine's efficacy, safety and the like is entirely fixed at the time of approval, and no new information is added even after knowledge accumulates and usage results are gathered afterward.
4. Efficacy and safety are confirmed after marketing based on usage results, but the outcome never leads to a change in risk classification or a review of approval standards.

Which of the following statements about the quality of medicines is correct?

1. Because medicines are closely related to human life and health, a high and uniform standard of quality must be assured.
2. No legal provisions are in place regarding the quality of medicines.
3. A medicine containing a foreign substance or that has deteriorated may be sold as long as there is no possibility of causing health damage.
4. Product recalls are solely a matter for the marketing authorization holder, and those who sell the product need not pay attention to information from the marketing authorization holder and others.

Which of the following statements about the Act on Securing Quality, Efficacy and Safety of Pharmaceuticals, Medical Devices, etc. is correct?

1. The name of this act was changed from the 'Pharmaceutical Affairs Act' in January of Heisei 29 (2017), when the Self-Medication Tax System covering switch OTC drugs was introduced.
2. The Guide abbreviates this act as the 'PL Act', and states that it was enacted separately from the Product Liability Act as Act No. 85 of Heisei 6 (1994).
3. It is Act No. 145 of Showa 35 (1960), and its name was changed from the 'Pharmaceutical Affairs Act' by the Act for Partial Revision of the Pharmaceutical Affairs Act, etc.
4. It is an act enacted as Act No. 85 of Heisei 6 (1994), providing for liability for damages caused by defects in products.

Which of the following statements about the Product Liability Act (the PL Act) is incorrect?

1. The PL Act provides for the liability for damages of manufacturers and others where a defect in a product causes harm to a person's life, body, or property.
2. Products sold as OTC drugs are also subject to the PL Act.
3. The PL Act is Act No. 145 of Showa 35, an act intended to secure the quality, efficacy and safety of medicines and the like.
4. If an OTC drug that was sold has an obvious defect, it can be subject to the PL Act.

Which of the following statements about the risk assessment of medicines is correct?

1. The efficacy and risk of a medicine are assessed based solely on the length of the administration period.
2. The safety standards required of medicines are more lenient than those required of food.
3. The efficacy and risk of a medicine are assessed based on the relationship between dose and potency (the dose-response relationship).
4. A medicine never causes health damage even if used incorrectly.

Which of the following correctly lists, in order of increasing drug dose, the relationship between administered dose and effect or toxicity?

1. No-effect dose → minimum effective dose → therapeutic dose → toxic dose → minimum lethal dose → lethal dose
2. Minimum effective dose → no-effect dose → therapeutic dose → minimum lethal dose → toxic dose → lethal dose
3. No-effect dose → therapeutic dose → minimum effective dose → toxic dose → lethal dose → minimum lethal dose
4. Therapeutic dose → no-effect dose → minimum effective dose → toxic dose → lethal dose → minimum lethal dose

Which of the following is a correct statement in the Guide regarding what happens once the upper limit of the therapeutic dose is exceeded?

1. It first becomes the 'minimum lethal dose', and then, after passing through the 'toxic dose', at which harmful reactions appear more strongly than the effect, it reaches the 'lethal dose'.
2. Once the upper limit of the therapeutic dose is exceeded, the dose reaches the 'lethal dose' immediately, regardless of any further increase, without passing through the toxic dose or the minimum lethal dose.
3. Only the effect is strengthened as the dose increases, and no harmful reaction appears even once the upper limit of the therapeutic dose is exceeded.
4. It eventually becomes the 'toxic dose', at which harmful reactions appear more strongly than the effect, and, after passing through the 'minimum lethal dose', it reaches the 'lethal dose'.

Which of the following statements about the 'no-effect dose' is correct?

1. It refers to a dose lying between the minimum effective dose and the therapeutic dose, at which the effect begins to appear.
2. It refers to the 50% lethal dose (LD50) obtained through animal testing, used as an index of a drug's toxicity.
3. It is the dose at which no effect is detected, from which the dose proceeds through the minimum effective dose to the therapeutic dose.
4. It refers to a dose at which the upper limit of the therapeutic dose has been exceeded and harmful reactions appear more strongly than the effect.

Which of the following statements about the relationship between dose and action is incorrect?

1. The 'minimum effective dose' lies on the way from the no-effect dose to the therapeutic dose.
2. The 'minimum lethal dose' is a smaller dose than the toxic dose.
3. The 'lethal dose' is the dose reached after passing through the toxic dose and then the minimum lethal dose.
4. The 'toxic dose' appears after the upper limit of the therapeutic dose is exceeded.

Which of the following statements about the 50% lethal dose (LD50) is correct?

1. It is obtained through post-marketing surveys and is used as an index of a medicine's quality.
2. It is obtained through animal testing and is used as an index of a drug's efficacy.
3. It is obtained through clinical trials on human subjects and is used as an index of a drug's efficacy.
4. It is obtained through animal testing and is used as an index of a drug's toxicity.

Which of the following statements about the dose and toxicity of medicines is incorrect?

1. Even a small dose can cause chronic toxicity to appear if administered over a long period.
2. Even a small dose of a medicine can cause carcinogenicity, fetal toxicity, or dysfunction of tissues or organs.
3. There is a high risk of toxicity appearing after a single administration of a dose exceeding the therapeutic dose.
4. As long as the dose is small, toxicity never appears even with long-term administration.

Which of the following is the correct standard for nonclinical testing of medicine safety?

1. Good Vigilance Practice (GVP)
2. Good Post-marketing Study Practice (GPSP)
3. Good Laboratory Practice (GLP)
4. Good Clinical Practice (GCP)

Which of the following is the correct standard for conducting clinical trials on human subjects?

1. Good Post-marketing Study Practice (GPSP)
2. Good Vigilance Practice (GVP)
3. Good Clinical Practice (GCP)
4. Good Laboratory Practice (GLP)

Which of the following correctly matches a standard concerning medicines with its content?

1. GVP — the standard for nonclinical testing of medicine safety
2. GVP — the standard for conducting clinical trials on human subjects
3. GPSP — the standard for post-marketing safety management
4. GPSP — the standard for conducting post-marketing surveys and studies

Which of the following statements about so-called health foods is incorrect?

1. They are expected to help promote or maintain health, but remain foods, legally distinguished from medicines.
2. Because they are food, they never interfere with drug therapy through interaction with medicines.
3. Many are sold in a form resembling medicines, such as tablets or capsules, to make them easier to ingest.
4. Cases of health damage caused by incorrect use or individual constitution have also been reported.

Which of the following statements about the position of 'foods with health claims' among health foods is correct?

1. There are two types of foods with health claims: Foods for Specified Health Uses, which are permitted following individual government review, and Foods with Nutrient Function Claims, which do not require an individual application for permission.
2. Foods with health claims are so-called health foods classified as medicines, and are legally given the same treatment as medicines.
3. Foods with health claims are foods that meet requirements set by the government, but are not permitted to display any claims of health promotion effects and the like.
4. They are foods among health foods that meet requirements set by the government, and under certain standards are allowed to display claims of health promotion effects and the like.

Which of the following is the correct explanation of what a Food for Specified Health Use is?

1. It is a food that displays claims about the function of nutrients (such as vitamins or minerals), and this labeling is done in accordance with standards set by the government.
2. It contains health-function ingredients that affect the body's physiological functions, but under a self-certification system that requires no individual application for permission, its labeling is displayed at the business operator's own discretion without government review.
3. It contains health-function ingredients that affect the body's physiological functions, and has undergone individual government review (in some cases under standardized criteria) of matters such as the effect it claims to have on a specific health function and its safety, and has been permitted.
4. It is a product notified to the government as one on which the business operator, on its own responsibility and based on scientific evidence, displays a functional claim on the product package; it has not undergone individual government review of the effect it claims to have on a specific health function.

Which of the following statements about a Food with Nutrient Function Claims is correct?

1. It is a product on which the business operator, on its own responsibility and based on scientific evidence, displays a claim about the function of a functional ingredient it contains on the product package, having notified the government of the evidence for that claim before sale.
2. Because it does not meet the requirements to be a food with health claims, it is not included among them, and it is classified as a so-called health food that also cannot display any claim about a nutrient's function.
3. It contains health-function ingredients that affect the body's physiological functions, and has undergone individual government review (in some cases under standardized criteria) of matters such as the effect it claims to have on a specific health function and its safety, and has been permitted.
4. It is a food that, for a person consuming it to supplement a nutrient in their diet, displays a claim about that nutrient's function, under a self-certification system requiring no individual application for permission.

Which of the following statements about a Food with Function Claims is incorrect?

1. Like a Food for Specified Health Use, it has received individual permission from the government.
2. It is one of the three types of foods with health claims.
3. It is a product notified to the government.
4. It displays, on the product package, a claim about a health-maintaining or health-promoting function possessed by a functional ingredient it contains, on the business operator's own responsibility and based on scientific evidence.

Which of the following statements about the handling of health foods when selling OTC drugs is incorrect?

1. Even when selling OTC drugs, it is important to check whether the customer has been taking any health foods.
2. While respecting the purchaser's own awareness regarding health, guidance on taking health foods should also be given where necessary.
3. Because health foods are food and their safety is assured, there is no need to check whether the customer has been taking any.
4. Health foods differ from medicines both legally and in terms of the scientific data underpinning their safety and effectiveness.

Which of the following statements about the Self-Medication Tax System is correct?

1. It is a system that deducts a set amount from that year's total income based on the price paid for prescription drugs purchased under appropriate health management.
2. From January of Reiwa 9 (2027), in addition to OTC drugs addressing symptoms of low back pain, stiff shoulders, colds and allergies, digestive-system drugs and OTC test kits are also to be excluded from the scope of the tax system.
3. It was introduced in January of Heisei 29 (2017), and where certain conditions are met, it deducts a set amount from that year's total income based on the price paid for switch OTC drugs.
4. It is a system introduced in January of Reiwa 4 (2022), and its scope remains limited today to switch OTC drugs, not covering OTC drugs used for symptoms of low back pain, stiff shoulders, or the common cold.

Which of the following statements about the basic view of side effects caused by medicines is incorrect?

1. Side effects range widely in severity, from relatively common ones such as drowsiness or dry mouth, to serious ones causing death or major disruption to daily life.
2. Because medicines are inherently foreign substances to the human body, it is unavoidable that some harmful action or other arises alongside their therapeutic efficacy.
3. Side effects can include not only those already known through past experience of use, but also unknown ones not yet scientifically elucidated.
4. Harm from medicine side effects can never occur as long as the medicine is used with sufficient care.

Which of the following statements about the Thalidomide litigation is correct?

1. It is a lawsuit for damages against the national government and others over a serious, fatal neurological disease resembling dementia, contracted through prion infection via dried human dura mater used in brain surgery and the like.
2. It is a lawsuit for damages over congenital abnormalities such as limb deficiency and ear defects appearing in infants born to women who were pregnant or thought to be pregnant and had used thalidomide preparations sold as a hypnotic sedative and the like.
3. It is a lawsuit for damages over infection contracted by hemophilia patients who received blood coagulation factor products manufactured from source plasma contaminated with a virus.
4. It is a lawsuit for damages over subacute myelo-optico-neuropathy, accompanied by numbness and difficulty walking in the lower body, contracted through the use of clioquinol preparations sold as an intestinal regulator.

Which of the following statements about the action of thalidomide is incorrect?

1. It is held that only the S-form has the action of inhibiting angiogenesis, and only the R-form has the sedative action.
2. Because the R-form and S-form never convert into each other in the body, separating out and formulating the R-form of thalidomide would avoid teratogenicity.
3. Thalidomide was approved as a hypnotic sedative ingredient, and for its sedative effect was also incorporated into stomach medicines.
4. As a side effect it has an action that inhibits angiogenesis, and thalidomide crosses the blood-placenta barrier and transfers to the fetus.

Which of the following statements about the timeline of sale and recall of thalidomide preparations is incorrect?

1. Thalidomide preparations went on sale in West Germany (as it then was) in 1957, and had been on sale in Japan from January 1958.
2. In Japan, once the recommendation from the West German company arrived in December 1961, shipments were halted and the product recalled immediately.
3. In Japan, the halt of shipments was not carried out until May 1962, and the suspension of sales and the recall did not occur until September of that year, drawing criticism for the slowness of the response.
4. In November 1961, Dr. Lenz of West Germany issued a warning about the teratogenicity of thalidomide preparations, leading to the product being recalled in West Germany.

Which of the following statements about the filing and settlement of the Thalidomide litigation is correct?

1. It was filed against the national government and the pharmaceutical company at the Osaka District Court in May 1989 and at the Tokyo District Court in October of that year.
2. It was filed against the pharmaceutical company in June 1963, and further against the national government and the pharmaceutical company in December of the following year, with settlement reached in October 1974.
3. It was filed against the national government, the importer, and the manufacturer at the Otsu District Court in November 1996 and at the Tokyo District Court in September 1997.
4. It was filed against the national government and the pharmaceutical company in May 1971, with a full settlement reached in September 1979.

Which of the following is a correct statement of what was brought about in response to the drug-induced harm incident caused by thalidomide?

1. The creation and expansion of the 'emergency import' system for the swift supply of urgently needed medicines
2. The establishment of the Pharmaceutical and Medical Device Administration Evaluation and Monitoring Committee
3. The development, mainly among WHO member states, of a system in each country for collecting post-marketing side-effect information
4. The creation, by the Pharmaceuticals and Medical Devices Agency (PMDA), of the Relief System for Infection Injuries Caused by Biological Products

Which of the following statements about the SMON litigation is correct?

1. It is a lawsuit for damages over a condition resembling dementia that appeared following prion infection via dried human dura mater used in brain surgery and the like.
2. It is a lawsuit for damages over viral infection contracted through the administration of a particular fibrinogen preparation or blood coagulation factor IX preparation during childbirth or surgery.
3. It is a lawsuit for damages over congenital abnormalities such as limb deficiency and ear defects appearing in infants born to pregnant women who had used thalidomide preparations sold as a hypnotic sedative and the like.
4. It is a lawsuit for damages over subacute myelo-optico-neuropathy contracted through the use of clioquinol preparations sold as an intestinal regulator.

Which of the following statements about the symptoms of SMON is correct?

1. In its early stage it produces abdominal bloating followed by severe abdominal pain and diarrhea, followed in turn by numbness, weakness, and difficulty walking in the lower body.
2. It is characterized by infection with the hepatitis C virus, caused by administration of a preparation during childbirth or surgery.
3. It is caused by use during pregnancy and is characterized by congenital abnormalities such as limb deficiency and ear defects appearing in the infant.
4. It is characterized by a condition resembling dementia that gradually appears and leads to death, caused by prion infection of brain tissue.

Which of the following statements about the timeline of clioquinol preparations and the SMON litigation is correct?

1. In the United States, a 1970 recommendation limited the use of clioquinol preparations to amebic dysentery, and in response, sales were also halted in Japan.
2. Following the filing in May 1971, a settlement was reached at the Tokyo District Court in October of that year, constituting a full settlement.
3. Clioquinol preparations began to be sold as an intestinal regulator in 1958, and reports of distinctive neurological symptoms began around that time.
4. In Japan, the theory that clioquinol was the cause of SMON was announced in August 1970, and sales were halted in September of that year.

Which of the following statements about the background to the creation of the Relief System for Adverse Drug Reaction Injuries is correct?

1. In response to the Thalidomide and SMON litigations, it was created in 1980 to provide swift relief for health damage caused by medicine side effects.
2. In response to the hepatitis C litigation, it is a system created by the 2008 revision of the Pharmaceutical Affairs Act to provide early and full relief for infected victims.
3. It was created in 1996, in response to the HIV litigation, to provide swift relief for infection injuries.
4. In response to the CJD litigation, it was created in 2002 by the Pharmaceuticals and Medical Devices Agency to provide swift relief for infection injuries caused by biological products.

Which of the following statements about the HIV litigation is correct?

1. It is a lawsuit for damages, against the national government and pharmaceutical companies, over infection with the hepatitis C virus contracted through the administration of a particular fibrinogen preparation or blood coagulation factor IX preparation during childbirth or surgery.
2. It is a lawsuit for damages over subacute myelo-optico-neuropathy contracted through the use of clioquinol preparations sold as an intestinal regulator.
3. It is a lawsuit for damages over infection contracted by hemophilia patients who received blood coagulation factor products manufactured from source plasma contaminated with the human immunodeficiency virus (HIV).
4. It is a lawsuit for damages against the national government and others over a serious, fatal neurological disease resembling dementia, contracted through prion infection via dried human dura mater used in brain surgery and the like.

Which of the following statements about the course of the HIV litigation and the response that followed is incorrect?

1. It was filed against the national government and the pharmaceutical companies at the Osaka District Court in May 1989 and at the Tokyo District Court in October of that year.
2. On August 24, 1999, a completion ceremony for the 'Monument of Vows' was held, attended by the Minister of Health and Welfare and with relevant patient groups invited.
3. The Osaka and Tokyo District Courts recommended settlement in October 1995 and March 1996 respectively, and settlement was reached at both courts in March 1996.
4. The revised Pharmaceutical Affairs Act reflecting this litigation was enacted in 2002, strengthening safety measures for biological products.

Which of the following statements about the CJD litigation and Creutzfeldt-Jakob disease (CJD) is correct?

1. The cause of CJD is held to be bacteria contaminating dried human dura mater, and infection of brain tissue by that bacteria produces a serious, fatal neurological disease with a gradually appearing dementia-like condition.
2. The CJD litigation was filed against the national government and pharmaceutical companies at the Osaka District Court in May 1989 and at the Tokyo District Court in October of that year.
3. The CJD litigation is a lawsuit for damages over infection contracted by hemophilia patients who received blood coagulation factor products manufactured from source plasma contaminated with the human immunodeficiency virus.
4. CJD is held to be caused by a prion, a type of protein that is neither bacterium nor virus; the prion infects brain tissue, and a dementia-like condition gradually appears, leading to a serious, fatal neurological disease.

Which of the following correctly matches a litigation with a measure subsequently taken?

1. SMON litigation — the establishment of the Pharmaceutical and Medical Device Administration Evaluation and Monitoring Committee, as a third-party body evaluating and monitoring pharmaceutical administration
2. CJD litigation — the creation, by the Pharmaceuticals and Medical Devices Agency, of the Relief System for Infection Injuries Caused by Biological Products
3. CJD litigation — the 1980 creation of the Relief System for Adverse Drug Reaction Injuries, to provide swift relief for health damage caused by medicine side effects
4. HIV litigation — the strengthening of safety measures for biological products under the 2002 revision of the Pharmaceutical Affairs Act, and measures such as the creation of a relief system for infection injuries

Which of the following statements about the hepatitis C litigation is incorrect?

1. It was filed against the national government and pharmaceutical companies at five district courts between 2002 and 2007.
2. It is a lawsuit for damages over infection with the hepatitis C virus contracted through the administration of a particular fibrinogen preparation or blood coagulation factor IX preparation during childbirth or surgery.
3. In January 2008, a special measures act concerning the payment of benefits to relieve victims infected with hepatitis C through the particular fibrinogen preparation and the particular blood coagulation factor IX preparation was enacted and enforced.
4. The five rulings handed down between 2006 and 2007 all reached the same conclusion regarding matters such as the period for which the national government and the pharmaceutical companies should bear responsibility.