Pharmacological drugs
This unit introduces pharmacology and the drugs it studies. It follows a new drug from discovery through preclinical and clinical development to regulatory review and post-marketing surveillance, then covers four groups of antibiotics, antivirals and antiretrovirals, and the advantages of monoclonal antibodies over other drug classes.
Learning outcomes (4)
- Explain the drug discovery and development process.
- Define 4 classes of antibiotics (penicillins, tetracyclines, fluoroquinolones and sulfonamides) and describe their mode of action.
- Define antivirals and antiretrovirals.
- Describe advantages of monoclonal antibodies compared to other drug classes.
Pharmacology and drugs
Pharmacology is the scientific study of the effects of drugs and chemicals on living organisms. A drug can be defined as any chemical substance, natural or synthetic, which affects a biological system. A drug is used to diagnose, cure or prevent disease.
- Pharmacology
- The scientific study of the effects of drugs and chemicals on living organisms.
- Drug
- Any chemical substance, natural or synthetic, which affects a biological system. A drug is used to diagnose, cure or prevent disease.
- Pharmacological drug
- In pharmacology, a drug is a chemical substance, typically of known structure, which, when administered to a living organism, produces a biological effect.
- Drug therapy (pharmacotherapy)
- An important part of the medical field. It relies on the science of pharmacology for continual advancement and on pharmacy for appropriate management.
- Diagnose: a drug may be used to find out what disease a person has.
- Cure: a drug may remove the disease.
- Prevent: a drug may stop the disease from developing.
15.1Drug discovery and development processOften examined
Drug discovery and development is a complex, multiphase process. It may take several years, or even up to a decade, and it involves several important steps. These steps fall into five phases: discovery, preclinical development, clinical development, regulatory review and post-marketing surveillance.
15.1.1 Drug discovery
Drug discovery has four steps. Each step builds on the one before it.
- Target identification
- The process begins with the identification of a new target molecule, a protein or other molecule involved in the disease process.
- Target validation
- Experiments confirm that modulating the target can produce a therapeutic effect.
- Hit identification
- Screening large libraries of compounds to find "hits" that interact with the target.
- Hit-to-lead optimization
- Refining the hits to improve their potency, selectivity and pharmacokinetic properties.
- Target identification names a molecule involved in the disease process. At this point it is only a suspect, not a proven cause of the disease.
- Target validation tests the suspect. Experiments confirm that modulating the target can produce a therapeutic effect. If it cannot, the target is dropped.
- Only a validated target is worth screening. Hit identification screens large libraries of compounds, which takes time and money, so screening against a wrong target wastes both.
- Hit-to-lead optimization comes last because it needs hits to work on: it refines the hits to improve their potency, selectivity and pharmacokinetic properties.
| Step | Question it answers | What it produces |
|---|---|---|
| Target identification | What molecule is involved in the disease? | A candidate target |
| Target validation | Does acting on it give a therapeutic effect? | A confirmed target |
| Hit identification | Which compounds interact with the target? | Hits |
| Hit-to-lead optimization | How can the hits be improved? | Better, more potent and selective compounds |
Conclusion: each step needs the result of the previous one, so the order cannot be changed.
15.1.2Preclinical development
In preclinical development the lead compounds are tested before any human receives them. There are four parts.
- In vitro studies
- Testing the lead compounds in a laboratory setting to evaluate their effects on cells and biological systems.
- In vivo studies
- Conducting tests in animal models to assess the safety, efficacy and pharmacokinetics of the compounds. Efficacy is the ability to produce a desired or intended result.
- Toxicology studies
- Evaluating potential toxicology and side effects through rigorous testing.
- Formulation development
- Developing the drug formulation for stability, delivery and dosage.
| Feature | In vitro studies | In vivo studies |
|---|---|---|
| Where | In a laboratory setting | In animal models |
| What is tested | Effects of the lead compounds on cells and biological systems | Safety, efficacy and pharmacokinetics of the compounds |
| Stage | First test of the lead compounds | Follows the laboratory work, still before human trials |
15.1.3Clinical developmentOften examined
The investigational new drug application is the submission of data from preclinical studies to regulatory authorities (like the FDA) to obtain permission to begin clinical trials. Clinical trials are composed of four phases: Phase 1, 2, 3 and 4.
| Phase | Participants | Purpose |
|---|---|---|
| Phase 1 | Small group of healthy volunteers (20 to 100) | Assess safety, dosage and pharmacokinetics |
| Phase 2 | Larger group (100 to 500) of patients | Evaluate efficacy and further assess safety |
| Phase 3 | Large-scale studies (1000 to 3000 participants) | Confirm efficacy, monitor side effects and compare with standard treatment |
| Phase 4 | The public after marketing | Post-marketing surveillance monitors drug side effects |
| Study | Phase | Reason |
|---|---|---|
| A: 60 healthy volunteers, safe dose | Phase 1 | Small group of healthy volunteers (20 to 100) testing safety and dosage |
| B: 300 patients, does it work? | Phase 2 | Larger group of patients (100 to 500) evaluating efficacy and further assessing safety |
| C: 2000 participants, compared with standard treatment | Phase 3 | Large-scale study (1000 to 3000) that confirms efficacy and compares with standard treatment |
| D: people taking the drug after sale | Phase 4 | Post-marketing surveillance of drug side effects |
Method: first look at who takes part (healthy volunteers or patients), then at how many, then at the purpose.
15.1.4Regulatory review
After the clinical trials, the drug must be approved before it can be sold.
- New drug application
- Submitting comprehensive data from all studies to regulatory authorities for approval to market the drug.
- Review process
- Regulatory agencies evaluate the data for safety, efficacy and quality before granting approval.
| Feature | Investigational new drug application | New drug application |
|---|---|---|
| Stage | Before clinical development | After the clinical trials, at regulatory review |
| Data submitted | Data from preclinical studies | Comprehensive data from all studies |
| Permission sought | To begin clinical trials | To market the drug |
15.1.5Post-marketing surveillance (Phase 4)
Approval is not the end of the process. Two activities continue after the drug reaches patients.
- Monitoring
- After approval, the drug is continuously monitored for long-term effects, rare side effects and overall effectiveness in the general population.
- Additional studies
- Conducting further studies to explore new uses, dosage adjustments or combinations with other drugs.
Throughout the whole process, collaboration across disciplines such as biology, chemistry, pharmacology and regulatory affairs is essential. The drug discovery and development process is expensive and time consuming, with a high rate of failure at each stage, but it ultimately aims to bring safe and effective medications to patients.
| Phase (Figure 15.1) | Main activities in the book |
|---|---|
| 1. Discovery and development | Target identification, target validation, hit identification, hit-to-lead optimization |
| 2. Preclinical research | In vitro studies, in vivo studies, toxicology studies, formulation development |
| 3. Clinical research | Investigational new drug application, then clinical trial phases 1, 2, 3 and 4 |
| 4. FDA review | New drug application and review process |
| 5. FDA post-market safety monitoring | Monitoring and additional studies (Phase 4) |
15.2Antibiotics and their mode of actionOften examined
Antibiotics are used to treat or prevent some types of bacterial infections.
- Antibiotics
- Medicines that help stop infections caused by bacteria.
Antibiotics work by killing bacteria or stopping them from multiplying.
- Killing bacteria: antibiotics can kill bacteria by destroying crucial parts they need to survive, like their cell walls or DNA.
- Stopping growth: antibiotics can stop the growth of bacteria by preventing them from making certain proteins they need to multiply.
- Antibiotic resistance
- The ability of bacteria that have adapted over time (superbugs) to survive and thrive despite the presence of antibiotics that would normally kill them.
- Genetic mutations leave a few bacteria in the population able to survive a standard antibiotic.
- When the antibiotic is used, it kills the sensitive bacteria, so the resistant bacteria are selected: this is natural selection.
- The survivors multiply, and the new population is resistant. Each unnecessary use of an antibiotic gives this selection another chance, which is why overuse produces superbugs.
Types of antibioticsOften examined
There are hundreds of different types of antibiotics, but most of them can be classified into four groups: penicillins, tetracyclines, fluoroquinolones and sulfonamides.
1. Penicillins
- Use: widely used to treat a variety of infections, including skin infections, chest infections and urinary tract infections.
- Examples: penicillin, amoxicillin, flucloxacillin.
- Mode of action: they inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins, leading to cell lysis.
2. Tetracyclines
- Use: can be used to treat a wide range of infections.
- Examples: tetracycline, doxycycline, minocycline.
- Mode of action: they inhibit protein synthesis by binding to the 30S ribosomal subunit, blocking the attachment of aminoacyl-tRNA to the ribosome.
3. Fluoroquinolones
- Use: broad-spectrum antibiotics that were once used to treat a wide range of infections, especially respiratory and urinary tract infections. They are no longer used routinely because of the risk of serious side effects.
- Examples: ciprofloxacin, levofloxacin.
- Mode of action: they inhibit bacterial DNA replication by targeting enzymes like DNA gyrase and topoisomerase IV.
4. Sulfonamides
- Nature: synthetic, bacteriostatic antibiotics.
- Examples: mafenide, sulfacetamide, sulfadiazine, sulfanilamide, and others.
- Mode of action: they competitively inhibit the conversion of p-aminobenzoic acid (PABA) to dihydropteroate, which bacteria need for folate synthesis and ultimately purine and DNA synthesis. Humans do not synthesize folate but acquire it in their diet, so their DNA synthesis is less affected.
| Group | Examples | Mode of action | Target |
|---|---|---|---|
| Penicillins | Penicillin, amoxicillin, flucloxacillin | Inhibit cell wall synthesis by binding to penicillin-binding proteins, leading to cell lysis | Cell wall |
| Tetracyclines | Tetracycline, doxycycline, minocycline | Inhibit protein synthesis by binding to the 30S ribosomal subunit and blocking attachment of aminoacyl-tRNA | Ribosome (protein synthesis) |
| Fluoroquinolones | Ciprofloxacin, levofloxacin | Inhibit DNA replication by targeting DNA gyrase and topoisomerase IV | DNA replication |
| Sulfonamides | Mafenide, sulfacetamide, sulfadiazine, sulfanilamide | Competitively inhibit conversion of PABA to dihydropteroate, blocking folate, purine and DNA synthesis | Folate synthesis |
| Drug | Clue in the description | Group | Process stopped |
|---|---|---|---|
| X | PABA to dihydropteroate | Sulfonamides | Folate synthesis, and so purine and DNA synthesis |
| Y | 30S ribosomal subunit | Tetracyclines | Protein synthesis |
| Z | DNA gyrase and topoisomerase IV | Fluoroquinolones | DNA replication |
Method: look for the enzyme or structure named in the description and match it to the mode of action in the table. Penicillins would be the answer for a drug that stops cell wall synthesis and causes cell lysis.
- Bacteria make folate themselves. A step on the way is the conversion of PABA to dihydropteroate.
- Sulfonamides competitively inhibit this conversion, so less dihydropteroate is made.
- Without folate, bacteria cannot complete purine synthesis, and so cannot make DNA. They cannot multiply, which is why sulfonamides are bacteriostatic.
- Humans do not synthesize folate. They acquire it from their diet, so the step that sulfonamides block is not part of human folate supply, and human DNA synthesis is less affected.
Conclusion: the drug attacks a pathway that bacteria have and humans do not make use of, so it is selective for the bacteria.
15.3Antivirals and antiretroviralsOften examined
Antivirals and antiretrovirals are a class of medication specifically used to treat viral and retroviral infections caused by viruses like HIV, herpes viruses and hepatitis B and C.
- Antivirals
- A class of drugs used to treat viral infections. They work by inhibiting the ability of viruses to multiply and spread within the body. Antiviral drugs target a diverse group of viruses such as herpes, hepatitis and influenza viruses.
- Antiretrovirals
- A subset of antivirals especially used to fight retrovirus infections, which mainly include HIV (Human Immunodeficiency Virus). Different classes of antiretroviral drugs act on different stages of the HIV life cycle.
- Retroviruses
- A type of virus that uses RNA as its genetic material and reverse transcriptase to replicate.
Antiretrovirals inhibit the replication of retroviruses, helping to control HIV infection and reduce the risk of progression to AIDS.
| Feature | Antivirals | Antiretrovirals |
|---|---|---|
| Scope | The whole class of drugs used against viral infections | A subset of antivirals |
| Viruses treated | A diverse group, such as herpes, hepatitis and influenza viruses | Retroviruses, mainly HIV |
| Action | Inhibit the ability of viruses to multiply and spread within the body | Inhibit replication of retroviruses, acting on different stages of the HIV life cycle, to control HIV infection and reduce the risk of progression to AIDS |
| Infection | Cause | Right class | Reason |
|---|---|---|---|
| (a) Influenza | Virus | Antiviral | Antivirals inhibit the ability of viruses to multiply and spread; antibiotics do not work for flu |
| (b) HIV infection | Retrovirus (RNA, reverse transcriptase) | Antiretroviral | Antiretrovirals inhibit replication of retroviruses and control HIV infection |
| (c) Urinary tract infection | Bacteria | Antibiotic | Antibiotics kill bacteria or stop them multiplying |
| (d) Hepatitis B | Virus | Antiviral | Hepatitis viruses are among those targeted by antivirals |
Method: first decide whether the cause is a bacterium or a virus, then whether the virus is a retrovirus. Remember that an antiretroviral is also an antiviral, but the more exact name is chosen for HIV.
15.4Advantages of monoclonal antibodiesOften examined
Monoclonal antibodies (also called moAbs or mAbs) are proteins. They are made in laboratories and act like proteins called antibodies in our bodies. Antibodies are parts of our immune system. They seek out the antigens (foreign materials) and stick to them in order to destroy them. Laboratory-made monoclonal antibodies help stimulate our own immune system. The word "monoclonal" refers to the fact that the antibodies created in the laboratory are clones: they are exact copies of one antibody. Monoclonal antibodies are used for diagnosis, disease treatment and research.
- Monoclonal antibodies
- Laboratory-made proteins that act like the body's antibodies. They are clones, exact copies of one antibody, and bind to one antigen only.
- Antibodies
- Proteins that are parts of our immune system. They seek out antigens and stick to them in order to destroy them.
- Antigens
- Foreign materials that antibodies seek out.
Advantages of using monoclonal antibodies
Monoclonal antibodies offer several advantages over traditional antibody therapies, including high specificity, consistent quality, and the ability to be produced in large quantities. They can be engineered to target specific antigens, making them effective for various applications like cancer diagnosis, therapy and diagnostics.
- High specificity: monoclonal antibodies are engineered to bind to a single, specific antigen or epitope, allowing for precise targeting and reducing off-target effects.
- Consistent quality: monoclonal antibodies can be produced in large quantities with consistent quality across different batches, ensuring reproducibility and reliability.
- Renewable production: once a hybridoma or recombinant cell line is established, monoclonal antibodies can be produced indefinitely.
- Versatile applications: used in diagnostics, therapy and research (see the table below).
- Engineering possibilities: monoclonal antibodies can be engineered in the lab to enhance their binding affinity or target specific molecules, allowing for tailored applications.
- Humanization: monoclonal antibodies can be humanized, minimizing the risk of immune reactions in patients.
- Large-scale production: recombinant DNA technology allows for the production of monoclonal antibodies in large quantities, making them accessible for various applications.
| Field | Uses |
|---|---|
| Diagnostics | Pregnancy tests, HIV testing and other diagnostic assays |
| Therapy | Cancer treatments, autoimmune disease therapies and other drug development applications |
| Research | Molecular biology, biochemistry and other research areas |
15.4Monoclonal antibodies compared to other drug classesOften examined
Monoclonal antibodies can be compared with four other kinds of antibody or drug.
| Compared with | Advantage of monoclonal antibodies |
|---|---|
| Polyclonal antibodies | Monoclonal antibodies are clones of just one antibody and bind to one antigen only. Polyclonal antibodies come from several different types of immune cells and bind to more than one antigen. |
| Drug and radiotherapy treatments (cancer) | The drugs specifically target the cancer cells, allowing smaller doses of chemotherapy drugs to be used. This can reduce side effects and the risk to healthy cells, and improves the immune system. |
| Antibiotics | Monoclonal antibodies have safety, high target specificity, are less susceptible to resistance mechanisms, and have longer half-lives (about 21 days for IgG). |
| Small molecule drugs | Exquisite specificity, due to the greater surface area for binding with the antigen, resulting in decreased off-target effects compared with most small molecule drugs. |
| Point | Monoclonal antibodies | Antibiotics |
|---|---|---|
| Specificity | Bind to one antigen only, with high target specificity | Act on bacteria, such as their cell wall, protein synthesis or DNA replication, not on a single antigen |
| Resistance | Less susceptible to resistance mechanisms | Bacteria can become resistant through mutations and natural selection, especially when antibiotics are overused |
| Half-life | Longer half-lives (about 21 days for IgG) | Shorter half-lives than monoclonal antibodies |
Method: use the third row of the comparison table for the pairs of points, and add the book's description of resistance from section 15.2.
Key terms
- Pharmacology
- The scientific study of the effects of drugs and chemicals on living organisms.
- Drug
- Any chemical substance, natural or synthetic, which affects a biological system; used to diagnose, cure or prevent disease.
- Drug therapy (pharmacotherapy)
- An important part of the medical field that relies on pharmacology for advancement and on pharmacy for appropriate management.
- Pharmacokinetics
- The study of the absorption, distribution, metabolism and excretion of a drug.
- Target identification
- Identifying a new target molecule, a protein or other molecule involved in the disease process.
- Target validation
- Experiments that confirm that modulating the target can produce a therapeutic effect.
- Hit identification
- Screening large libraries of compounds to find hits that interact with the target.
- Hit-to-lead optimization
- Refining the hits to improve their potency, selectivity and pharmacokinetic properties.
- Preclinical development
- Testing lead compounds before human trials: in vitro studies, in vivo studies, toxicology studies and formulation development.
- In vitro studies
- Testing the lead compounds in a laboratory setting to evaluate their effects on cells and biological systems.
- In vivo studies
- Tests in animal models to assess the safety, efficacy and pharmacokinetics of the compounds.
- Efficacy
- The ability to produce a desired or intended result.
- Toxicology studies
- Evaluating potential toxicology and side effects through rigorous testing.
- Formulation development
- Developing the drug formulation for stability, delivery and dosage.
- Investigational new drug application
- Submission of preclinical data to regulatory authorities to obtain permission to begin clinical trials.
- Phase 1 trials
- Testing the drug in a small group of healthy volunteers (20 to 100) to assess safety, dosage and pharmacokinetics.
- Phase 2 trials
- Expanding the study to a larger group (100 to 500) of patients to evaluate efficacy and further assess safety.
- Phase 3 trials
- Large-scale studies (1000 to 3000 participants) that confirm efficacy, monitor side effects and compare with standard treatment.
- Phase 4 trials
- Post-marketing surveillance that monitors drug side effects.
- New drug application
- Submitting comprehensive data from all studies to regulatory authorities for approval to market the drug.
- Review process
- Regulatory agencies evaluate the data for safety, efficacy and quality before granting approval.
- Post-marketing surveillance
- Continuous monitoring of an approved drug for long-term effects, rare side effects and overall effectiveness, with further studies on new uses, dosage adjustments or combinations.
- Antibiotics
- Medicines that help stop infections caused by bacteria, by killing them or stopping them from multiplying.
- Antibiotic resistance
- The ability of bacteria (superbugs) to survive antibiotics that would normally kill them, through genetic mutations and natural selection.
- Superbugs
- Bacteria that cannot be killed by standard antibiotics because they have developed resistance.
- Penicillins
- Antibiotics (penicillin, amoxicillin, flucloxacillin) that inhibit cell wall synthesis by binding to penicillin-binding proteins, leading to cell lysis.
- Tetracyclines
- Antibiotics (tetracycline, doxycycline, minocycline) that inhibit protein synthesis by binding to the 30S ribosomal subunit.
- Fluoroquinolones
- Broad-spectrum antibiotics (ciprofloxacin, levofloxacin) that inhibit bacterial DNA replication by targeting DNA gyrase and topoisomerase IV.
- Sulfonamides
- Synthetic, bacteriostatic antibiotics that competitively inhibit the conversion of PABA to dihydropteroate, needed for folate synthesis.
- Penicillin-binding proteins
- Bacterial proteins to which penicillins bind, inhibiting cell wall synthesis.
- Cell lysis
- Bursting of the bacterial cell, the result when penicillins stop cell wall synthesis.
- Aminoacyl-tRNA
- The molecule whose attachment to the ribosome is blocked by tetracyclines.
- DNA gyrase and topoisomerase IV
- Bacterial enzymes targeted by fluoroquinolones to inhibit DNA replication.
- p-Aminobenzoic acid (PABA)
- The compound whose conversion to dihydropteroate is competitively inhibited by sulfonamides.
- Folate
- A substance bacteria need for purine and DNA synthesis; humans do not synthesize it but acquire it in their diet.
- Bacteriostatic
- Describes a drug that stops bacteria from growing and multiplying, as sulfonamides do.
- Antivirals
- A class of drugs used to treat viral infections by inhibiting the ability of viruses to multiply and spread within the body.
- Antiretrovirals
- A subset of antivirals used to fight retrovirus infections, mainly HIV; they act on different stages of the HIV life cycle.
- Retroviruses
- Viruses that use RNA as their genetic material and reverse transcriptase to replicate.
- HIV (Human Immunodeficiency Virus)
- The main retrovirus treated with antiretrovirals; infection can progress to AIDS.
- Monoclonal antibodies (mAbs)
- Laboratory-made proteins that act like antibodies; clones, exact copies of one antibody, that bind to one antigen only.
- Antibodies
- Proteins that are parts of our immune system and seek out antigens and stick to them in order to destroy them.
- Antigens
- Foreign materials that antibodies seek out and bind.
- Polyclonal antibodies
- Antibodies from several different types of immune cells that bind to more than one antigen.
- Epitope
- The specific part of an antigen to which a monoclonal antibody binds.
- Off-target effects
- Unwanted effects of a drug on molecules other than its target; reduced by the high specificity of monoclonal antibodies.
- Hybridoma
- A cell line which, once established, can produce monoclonal antibodies indefinitely.
- Humanization
- Engineering monoclonal antibodies so that the risk of immune reactions in patients is minimized.
- Intravenous (IV) infusion
- The usual way of giving monoclonal antibodies: a solution injected right into a vein.
- Half-life
- The time a drug lasts in the body; monoclonal antibodies have long half-lives (about 21 days for IgG).
Multiple choice questionsp. 276–277
Section I of the exercise. Select the correct answer.
- ATo determine the chemical composition of a drug.
- BTo identify the biological origin of a disease and potential targets for intervention.Answer
- CTo evaluate the safety and efficacy of a drug in animal models.
- DTo optimize the synthetic route for a drug's production.
Target identification is the first stage of drug discovery. It finds a new target molecule, a protein or other molecule involved in the disease process, which the drug can then act on.
The other options belong to later stages: chemical composition is a laboratory question, animal safety and efficacy belong to preclinical in vivo studies, and hit-to-lead optimization refines potency, selectivity and pharmacokinetic properties rather than the synthetic route.
- APhase IAnswer
- BPhase II
- CPhase III
- DPhase IV
Phase 1 trials test the drug in a small group of healthy volunteers (20 to 100) to assess safety, dosage and pharmacokinetics.
Phase II moves to a larger group of patients (100 to 500), Phase III is large-scale (1000 to 3000 participants) and Phase IV is post-marketing monitoring, so none of them starts with healthy volunteers.
- ASolubility in aqueous solutions
- BSize and structure
- CAbility to form hydrogen bonds
- DAll of theseAnswer
Solubility in water, size and structure, and the ability to form hydrogen bonds are all physicochemical properties of the drug. Each one affects how the drug is absorbed, distributed, metabolized and excreted.
Options A, B and C are each correct on their own but incomplete, so the complete answer is D.
Note. The book prints "it's" in the stem; it should read "its".
- ADetermine therapeutic window
- BDetermine unreported toxicityAnswer
- CDetermine variation in absorption
- DDetermine tolerability
Phase IV is post-marketing surveillance (section 15.1.5). After approval the drug is monitored for long-term effects and rare side effects, which the smaller earlier trials could not detect. These are the unreported toxicities.
Tolerability is a question for the early small-group trials (Phase 1), so D is the tempting wrong answer.
- APenicillin
- BTetracyclineAnswer
- CCefotaxime
- DTrimethoprim
Tetracyclines inhibit protein synthesis by binding to the 30S ribosomal subunit, which blocks the attachment of aminoacyl-tRNA to the ribosome.
Penicillin acts on cell wall synthesis, not on ribosomes. Cefotaxime and trimethoprim are not among the four classes of antibiotics described in the book, so they cannot be the answer from the book's content.
- APhysical testing
- BChemical testing
- CBiological testingAnswer
- DCombined physical and chemical testing
Antibiotics work by killing bacteria or stopping them from multiplying, so their effectiveness is shown by the response of living bacteria. This is biological testing.
Physical and chemical tests measure properties of the drug or the sample, not whether the bacteria are killed or stop multiplying, so A, B and D do not answer the question.
- AVirus absorption
- BVirus penetration
- CVirus RNA and DNA replicationAnswer
- DExit of viruses from the cell
Antivirals inhibit the ability of viruses to multiply. The step that is blocked is the replication of the viral genetic material (RNA or DNA) inside the host cell.
Absorption and penetration are the steps by which the virus enters the cell, and exit is the release of new viruses. The book does not describe antivirals acting on those steps.
- ATo suppress the viral loadAnswer
- BTo cure HIV infection
- CTo allow the patient to have a pain-free death
- DTo prevent repeated infection with HIV
Antiretrovirals inhibit the replication of retroviruses and help control HIV infection (section 15.3). The goal is to keep the amount of virus in the body low, which is suppressing the viral load.
Curing HIV is not the current goal of antiretroviral therapy (see question 10), and the other two options are not treatment goals described in the book.
- AVirus penetration
- BNucleic acid replicationAnswer
- CVirus absorption
- DRemoval of the virus from the cell
Antivirals inhibit the ability of viruses to multiply, which means blocking the replication of nucleic acid (RNA or DNA).
Penetration and absorption are entry steps and removal is the release step. These are not the steps the book says antivirals block.
- AART is not effective in reducing the viral load.
- BHIV can hide within immune cells, forming latent reservoirs.Answer
- CART drugs are toxic and cause severe side effects.
- DHIV mutates too rapidly to be targeted by ART.
ART controls the replication of the virus but does not remove it from the body. Virus that hides inside immune cells is not reached by the drug, so the infection persists. This is the latent reservoir in option B.
Option A contradicts section 15.3, where antiretrovirals reduce the viral load. Option C is about side effects rather than cure, and D is not a reason given in the book.
Note. The book does not state this reason in words. The answer follows from its statement that antiretrovirals inhibit replication and help control HIV infection.
- ATuberculosisAnswer
- BSmallpox
- CHepatitis
- DWarts
Antiviral drugs treat viral infections. Tuberculosis is a bacterial disease, so it is treated with antibiotics rather than antivirals.
Smallpox, hepatitis (the book names hepatitis B and C) and warts are all caused by viruses, so antivirals can be used against them.
- AGreater specificity and constancyAnswer
- BLower cost production
- CLonger shelf life
- DAbility to target multiple antigens
Monoclonal antibodies are clones of one antibody that bind to one antigen only, and they are produced with consistent quality (section 15.4, advantages 1 and 2). This gives greater specificity and constancy.
Polyclonal antibodies come from several types of immune cells and bind more than one antigen, so D is the opposite of the advantage. Cost and shelf life are not given as advantages in the book.
- ATopically
- BIntravenouslyAnswer
- CBy inhalation
- DOrally
The book states that most monoclonal antibodies are given mostly as an intravenous (IV) solution, injected right into a vein.
Topical use, inhalation and oral use are not the route the book describes for monoclonal antibodies.
- APhase III tests the drug's efficacy, while phase IV focuses on long-term safety.Answer
- BPhase III studies involve a small number of patients, while phase IV studies involve a large number of patients.
- CPhase III trials are conducted in animals, while phase IV trials are conducted in humans.
- DPhase III trials are conducted in one country, while phase IV trials are conducted in multiple countries.
Phase 3 is a large-scale study (1000 to 3000 participants) that confirms efficacy and compares the drug with standard treatment. Phase 4 is post-marketing surveillance that monitors side effects over the long term.
B reverses the sizes of the two studies, C wrongly places Phase 3 in animals (animal tests belong to preclinical development), and D is not a difference given in the book.
- ATo obtain permission to conduct clinical trials on a new drug.
- BTo request a patent for a new drug.
- CTo seek regulatory approval to market a new drug.Answer
- DTo conduct post-marketing surveillance on a new drug.
A new drug application submits comprehensive data from all studies to the regulatory authority for approval to market the drug (section 15.1.4).
Permission to begin clinical trials is requested through the investigational new drug application, which is the step in option A. A patent and post-marketing surveillance are not the purpose of the application.
- AProstaglandins
- BSteroids
- CLipoproteins
- DGlycoproteinsAnswer
Antibodies are proteins; the book describes monoclonal antibodies as proteins that act like the body's own antibodies (section 15.4). Proteins that carry carbohydrate chains are glycoproteins.
Prostaglandins and steroids are lipid-based molecules, and lipoproteins are proteins combined with lipids, not carbohydrates.
- AAntibodies produced by a single type of immune cell.Answer
- BAntibodies derived from multiple individuals.
- CAntibodies with multiple antigen-binding sites.
- DAntibodies found in the blood of newborn.
Monoclonal antibodies are clones of one antibody (section 15.4), so they all come from one cell line that descends from a single immune cell.
B describes polyclonal antibodies in a wrong way, C conflicts with the book's statement that monoclonal antibodies bind one antigen only, and D is not described in the book.
- AGreater specificity and consistencyAnswer
- BLow cost production
- CAbility to target multiple antigens simultaneously
- DLonger shelf life
Monoclonal antibodies bind one antigen only, which gives greater specificity, and they are produced with consistent quality. This is the same comparison as question 12.
Targeting several antigens at once is a property of polyclonal antibodies, so C is the tempting wrong answer. Cost and shelf life are not given in the book.
Note. This question repeats question 12 in the book.
- APhysiology
- BPathology
- CPharmacologyAnswer
- DMicrobiology
Pharmacology is the scientific study of the effects of drugs and chemicals on living organisms (chapter introduction).
Physiology studies how body functions work, pathology studies disease, and microbiology studies microorganisms, so none of them is the study of drug action.
Note. The book prints "the drug and their action"; it should read "the drug and its action".
- APharmacy
- BPharmacokineticsAnswer
- CPharmacodynamics
- DPharmacopoeia
Pharmacokinetics is the study of what the body does to a drug, namely its absorption, distribution, metabolism and excretion. The book uses this term for the pharmacokinetics of compounds (section 15.1.2).
Pharmacy is the practice of preparing and managing drugs, pharmacodynamics is the study of what a drug does to the body (the reverse direction), and pharmacopoeia is a book of drug standards.
Short answer questionsp. 278
Pharmacology is the scientific study of the effects of drugs and chemicals on living organisms.
A drug is any chemical substance, natural or synthetic, which affects a biological system. In pharmacology it is a chemical substance, typically of known structure, which produces a biological effect when administered to a living organism.
Drug therapy, or pharmacotherapy, is the treatment of disease with drugs, used to diagnose, cure, treat or prevent disease. It relies on pharmacology for its advancement and on pharmacy for appropriate management.
Antibiotics are medicines that help stop infections caused by bacteria. They kill bacteria or stop them from multiplying.
Antivirals are a class of drugs used to treat viral infections. They inhibit the ability of viruses to multiply and spread within the body.
Antiretrovirals are a subset of antivirals used to fight retrovirus infections, mainly HIV. They inhibit the replication of retroviruses, which use RNA as their genetic material and reverse transcriptase to replicate.
Monoclonal antibodies (moAbs or mAbs) are proteins made in the laboratory that act like the antibodies of the immune system. They are exact clones of one antibody and bind to one antigen only.
Note. The book prints "Antiretrovirus" for part (f); the chapter term is antiretrovirals, and the answer uses that term. Each part carries one mark.
A pharmacological drug is a chemical substance, typically of known structure, which produces a biological effect when it is administered to a living organism.
- It is a chemical substance, natural or synthetic, with a known structure.
- It is administered to a living organism.
- It produces a biological effect, for example to diagnose, cure, treat or prevent disease.
- Target identification: a new target molecule, a protein or other molecule involved in the disease process, is identified.
- Target validation: experiments confirm that modulating the target produces a therapeutic effect.
- Hit identification: large libraries of compounds are screened to find hits that interact with the target.
- Hit-to-lead optimization: the hits are refined to improve their potency, selectivity and pharmacokinetic properties.
- In vitro studies: the lead compounds are tested in the laboratory on cells and biological systems.
- In vivo studies: tests in animal models assess the safety, efficacy and pharmacokinetics of the compound.
- Toxicology studies: the potential toxicity and side effects are evaluated through rigorous testing.
- Formulation development: the drug is formulated for stability, delivery and dosage.
Clinical development begins once the data from preclinical studies are submitted to a regulatory authority, such as the FDA, in an investigational new drug application. The permission it obtains allows the clinical trials to begin.
| Phase | Participants | Purpose |
|---|---|---|
| Phase 1 | Healthy volunteers (20 to 100) | Safety, dosage and pharmacokinetics |
| Phase 2 | Patients (100 to 500) | Efficacy and further safety assessment |
| Phase 3 | Large-scale study (1000 to 3000) | Confirm efficacy, monitor side effects, compare with standard treatment |
Phase 4 is post-marketing surveillance, which continues after approval to monitor drug side effects.
- Discovery and development
- Preclinical research
- Clinical research
- FDA review (regulatory review)
- FDA post-market safety monitoring (post-marketing surveillance, phase 4)
These are the five phases shown in Fig. 15.1.
Note. Fig. 15.1 labels the fourth phase "FDA review" and the fifth "FDA post-market safety monitoring"; the text calls them regulatory review and post-marketing surveillance (phase 4).
- Antibiotics kill bacteria by destroying parts they need to survive, such as the cell wall or DNA, or they stop bacteria from multiplying by preventing them from making the proteins they need.
- Each class has its own target: penicillins inhibit cell wall synthesis, tetracyclines block protein synthesis at the 30S ribosomal subunit, fluoroquinolones inhibit DNA replication, and sulfonamides block folate synthesis.
- Antibiotics act only on bacteria, so they do not work on viral infections such as cold and flu.
- Every monoclonal antibody is an exact clone of one antibody, produced from one cell line (a hybridoma or recombinant cell line), so all the molecules are identical.
- Each antibody binds to a single antigen or epitope, so it is precisely targeted. Polyclonal antibodies, by contrast, bind more than one antigen.
- Because the binding is precise, off-target effects are reduced and the quality is consistent from batch to batch.
Extensive answer questionsp. 278
Overview
Drug discovery and development is a complex, multiphase process. It can take several years, or even up to a decade, and it passes through five stages: drug discovery, preclinical development, clinical development, regulatory review and post-marketing surveillance. A high rate of failure occurs at each stage, but the process aims to bring safe and effective medicines to patients.
1. Drug discovery
- Target identification: a new target molecule, a protein or other molecule involved in the disease process, is identified.
- Target validation: experiments confirm that modulating the target can produce a therapeutic effect.
- Hit identification: large libraries of compounds are screened to find hits that interact with the target.
- Hit-to-lead optimization: the hits are refined to improve their potency, selectivity and pharmacokinetic properties.
2. Preclinical development
- In vitro studies: the lead compounds are tested in the laboratory on cells and biological systems.
- In vivo studies: tests in animal models assess safety, efficacy and pharmacokinetics.
- Toxicology studies: potential toxicity and side effects are evaluated through rigorous testing.
- Formulation development: the drug is formulated for stability, delivery and dosage.
3. Clinical development
The data from the preclinical studies are submitted to a regulatory authority, such as the FDA, in an investigational new drug application. Permission to begin clinical trials is then given, and the trials run in phases:
| Phase | Participants | Purpose |
|---|---|---|
| Phase 1 | Healthy volunteers (20 to 100) | Safety, dosage and pharmacokinetics |
| Phase 2 | Patients (100 to 500) | Efficacy and further safety assessment |
| Phase 3 | Large-scale study (1000 to 3000) | Confirm efficacy, monitor side effects, compare with standard treatment |
4. Regulatory review
The new drug application submits comprehensive data from all the studies to the regulatory authority for approval to market the drug. The regulatory agency evaluates the data for safety, efficacy and quality before it grants approval.
5. Post-marketing surveillance (phase 4)
After approval the drug is monitored continuously for long-term effects, rare side effects and overall effectiveness in the general population. Further studies explore new uses, dosage adjustments or combinations with other drugs.
Types of antibiotics
Antibiotics are medicines that help stop bacterial infections. There are hundreds of antibiotics, but most of them can be classified into four groups. Each group acts on a different bacterial target.
| Group | Examples | Mode of action |
|---|---|---|
| Penicillins | Penicillin, amoxicillin, flucloxacillin | Inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins, leading to cell lysis |
| Tetracyclines | Tetracycline, doxycycline, minocycline | Inhibit protein synthesis by binding to the 30S ribosomal subunit, blocking the attachment of aminoacyl-tRNA to the ribosome |
| Fluoroquinolones | Ciprofloxacin, levofloxacin | Inhibit bacterial DNA replication by targeting the enzymes DNA gyrase and topoisomerase IV |
| Sulfonamides | Mafenide, sulfacetamide, sulfadiazine, sulfanilamide | Competitively inhibit the conversion of p-aminobenzoic acid to dihydropteroate, which bacteria need for folate, purine and DNA synthesis |
Mode of action
Penicillins weaken the cell wall, so the cell bursts (lysis). Tetracyclines stop the ribosome from making proteins. Fluoroquinolones stop the bacterial DNA from being copied. Sulfonamides block the folate pathway. Humans do not make folate but obtain it in the diet, so their DNA synthesis is less affected by sulfonamides.
Fluoroquinolones were once used to treat a wide range of respiratory and urinary tract infections, but they are no longer used routinely because of the risk of serious side effects.
Note. The book prints "Discuss the types antibiotics"; it should read "the types of antibiotics".
Antivirals
Antivirals are a class of drugs used to treat viral infections. They inhibit the ability of viruses to multiply and spread within the body. They target a diverse group of viruses, including herpes, hepatitis and influenza viruses.
Antiretrovirals
Antiretrovirals are a subset of antivirals used especially to fight retroviral infections, mainly HIV. Retroviruses use RNA as their genetic material and reverse transcriptase to replicate. Antiretrovirals inhibit the replication of retroviruses, which helps to control HIV infection and reduces the risk of progression to AIDS.
All antiretrovirals are antivirals, but not all antivirals are antiretrovirals.
Where the drugs act
A virus multiplies only inside a host cell. Antivirals interfere with this cycle, and the step that is most easily blocked is the replication of the viral genetic material (RNA or DNA).
Comparison
| Feature | Antibiotics | Antivirals | Antiretrovirals |
|---|---|---|---|
| Infecting agent | Bacteria | Viruses | Retroviruses, mainly HIV |
| Action | Kill bacteria or stop them multiplying | Inhibit the ability of viruses to multiply and spread | Inhibit the replication of retroviruses and help control HIV |
| Infections named in the book | Skin, chest and urinary tract infections | Herpes, hepatitis B and C, influenza | HIV, which can progress to AIDS |
Note. The book prints "What are antivirus and antiretrovirus"; the chapter term is "antivirals", which the answer uses.
What monoclonal antibodies are
Monoclonal antibodies (moAbs or mAbs) are proteins made in the laboratory that act like the proteins called antibodies in the body. They are clones of one antibody, so every molecule is identical and binds to one antigen or epitope only. They are used for diagnosis, disease treatment and research.
Advantages
- High specificity: the antibodies are engineered to bind a single antigen or epitope, so they target precisely and reduce off-target effects.
- Consistent quality: they can be produced in large quantities with consistent quality across batches, which makes them reproducible and reliable.
- Renewable production: once a hybridoma or recombinant cell line is established, the antibodies can be produced indefinitely.
- Versatile applications: they are used in diagnostics (pregnancy tests, HIV testing and other assays), therapy (cancer treatments, autoimmune disease therapies and other drug development) and research (molecular biology and biochemistry).
- Engineering possibilities: they can be engineered in the laboratory to enhance their binding affinity or to target specific molecules.
- Humanization: they can be humanized, which minimizes the risk of immune reactions in patients.
- Large-scale production: recombinant DNA technology allows them to be produced in large quantities.
Advantages over other drug classes
Compared with antibiotics, monoclonal antibodies have high target-specificity, are less susceptible to resistance mechanisms and have longer half-lives (about 21 days for IgG). Compared with small molecule drugs, their greater surface area for binding the antigen gives exquisite specificity and decreased off-target effects.
Most monoclonal antibodies are given as an intravenous (IV) solution injected into a vein.
Monoclonal antibodies are clones of one antibody and bind to one antigen only. Polyclonal antibodies come from several types of immune cells and bind more than one antigen. Compared with other drug classes, monoclonal antibodies have the following advantages.
Compared with antibiotics
| Feature | Monoclonal antibodies | Antibiotics |
|---|---|---|
| Target-specificity | High target-specificity, binding one antigen | Less target-specific |
| Resistance | Less susceptible to resistance mechanisms | Bacteria develop resistance through genetic mutation and natural selection |
| Half-life | Longer, about 21 days for IgG | Shorter |
Compared with drug and radiotherapy treatments
| Feature | Monoclonal antibodies | Drug and radiotherapy |
|---|---|---|
| Targeting | Specifically target cancer cells | Less specific, and healthy cells are at greater risk |
| Dose | Can allow smaller doses of chemotherapy drugs to be used | Larger doses of chemotherapy drugs |
| Side effects | Reduced side effects and reduced risk to healthy cells | Greater side effects |
Compared with small molecule drugs
| Feature | Monoclonal antibodies | Small molecule drugs |
|---|---|---|
| Binding | Greater surface area for binding the antigen, giving exquisite specificity | Smaller surface area for binding |
| Off-target effects | Decreased off-target effects | More off-target effects |
FBISE 2026 questions
Questions from the FBISE HSSC-II 2026 (1st Annual) papers that belong to this unit, answered the way an examiner expects.
a. Antivirals (1.5 marks)
Antivirals are a class of drugs used to treat viral infections. They work by inhibiting the ability of viruses to multiply and spread within the body. They target a diverse group of viruses, such as herpes, hepatitis and influenza viruses.
b. Antiretrovirals (1.5 marks)
Antiretrovirals are a subset of antivirals used especially against retrovirus infections, mainly HIV. A retrovirus uses RNA as its genetic material and reverse transcriptase to replicate. Antiretrovirals inhibit the replication of retroviruses, acting on different stages of the HIV life cycle, which helps to control HIV infection and reduces the risk of progression to AIDS.
Clinical development starts with the investigational new drug application: the preclinical data are submitted to the regulatory authorities (such as the FDA) to obtain permission to begin clinical trials. The trials then run in four phases.
| Phase | Participants | Purpose |
|---|---|---|
| Phase 1 | Small group of healthy volunteers (20 to 100) | Assess safety, dosage and pharmacokinetics |
| Phase 2 | Larger group of patients (100 to 500) | Evaluate efficacy and further assess safety |
| Phase 3 | Large-scale studies (1000 to 3000 participants) | Confirm efficacy, monitor side effects and compare with standard treatment |
| Phase 4 | The public after marketing | Post-marketing surveillance of drug side effects |
Antivirals (1.5 marks)
A virus multiplies only inside a host cell, by absorption, penetration, replication of its RNA or DNA and exit. Antivirals work by inhibiting the ability of the virus to multiply and spread in the body. The step that is blocked most easily is the replication of the viral nucleic acid inside the host cell.
Antiretrovirals (1.5 marks)
Retroviruses such as HIV use RNA as genetic material and need reverse transcriptase to replicate. Antiretrovirals are a subset of antivirals that inhibit the replication of retroviruses. Different classes of antiretrovirals act on different stages of the HIV life cycle. They control HIV infection and reduce the risk of progression to AIDS; they keep the virus down rather than cure the infection.
Exam focus
- Antivirals and antiretrovirals: what they are, how they work and how they differ. (short)Set B Q.2 (viii) and Set D Q.2 (xiv) OR; book long question 3 and MCQ 7 to 11.Go to answer
- Clinical development of a drug: the IND and the four trial phases with participants and purpose. (short)Set B Q.2 (xiv) OR; book short question 5 and MCQ 2, 4 and 14.Go to answer
- What are monoclonal antibodies, and what are their advantages over polyclonal antibodies and conventional drugs? (long)Not set from this unit in 2026 (the 2026 monoclonal antibody questions are covered in the immunity unit), but book long questions 4 and 5 and MCQ 12, 17 and 18 ask it.Go to answer
- Explain the drug discovery and development process (five phases). (long)No paper question in 2026; book long question 1 and short questions 3, 4 and 6.Go to answer
- Types of antibiotics and their mode of action. (long)No paper question in 2026; book long question 2, short question 7 and MCQ 5 and 6.Go to answer
- Define pharmacology, drug, drug therapy and pharmacokinetics. (short)No paper question in 2026; book short questions 1 and 2 and MCQ 19 and 20.Go to answer