Skip to content
Dr. NTR University of Health Sciences, AP
Second MBBS Examination – February 2022
Pharmacology – Paper II

ESSAY QUESTIONS (2 X 15 = 30 marks)

1. List the different groups of oral anti-diabetic agents with examples. Explain in detail the mechanism an action and adverse effects of any one group. Enumerate the insulin preparations and outline the adverse effects of insulin with its management.  Add a note on diabetic ketoacidosis.

Oral anti-diabetic agents with examples
Biguanides – Metformin
Sulfonylureas – Glimepiride, Glipizide
Meglitinides – Nateglinide
Thiazolidinediones – Pioglitazone
Gliptins – Sitagliptin, Teneligliptin
Sodium–glucose co-transporter (SGLT)2 inhibitors – Empagliflozin, Dapagliflozin
α-Glucosidase inhibitors – Acarbose, Voglibose

Metformin is the only biguanide currently in use.

Mechanism of action:
Activates AMP-kinase resulting in
• Inhibition of gluconeogenesis and lipogenesis
• Stimulation of glucose uptake and utilization (glycolysis)
• Stimulation of fatty acid oxidation
• Reduction of plasma glucagon levels

• Absorption – administered orally, good bioavailability when taken with food
• Distribution – not bound to plasma proteins
• Metabolism – not metabolized
• Excretion – excreted by kidneys as active compound

Indications – First-line therapy for type 2 diabetes as it does not increase body weight or cause hypoglycemia, which are common with the use of insulin or sulfonylureas. Metaformin can also be used in combination with other antidiabetic agents in type 2 diabetics in whom oral monotherapy is inadequate.

Adverse effects
Common – Dose-related GI disturbances (e.g. anorexia, diarrhoea, nausea). Metformin interferes with the calcium-dependent absorption of vitamin B12–intrinsic factor complex in the terminal ileum, and vitamin B12 deficiency can occur after many years of metformin use.
Rare – lactic acidosis

Contraindications – Moderate to severe chronic kidney disease.

Insulin preparations
Short-acting insulin – Regular human insulin
Rapid acting insulin – Lispor, Aspart, Glulisine
Intermediate-acting insulin – Isophane insulin (NPH)
Long-acting insulins – Detemer, Glargine
Ultra-long acting insulin – Degludec

Adverse effects of insulin and their management
• Common adverse effect of insulin is hypoglycaemia due to intensive insulin therapy – if very severe, can cause brain damage or sudden cardiac death. The treatment of hypoglycaemia is to take a sweet drink or snack or, if the patient is unconscious, to give intravenous glucose or intramuscular glucagon.
• Insulin induced hypoglycaemia can lead to rebound hyperglycaemia (‘Somogyi effect’) during sleep in the early hours of the morning, because of the release of counterregulatory hormones (e.g. adrenaline, glucagon and glucocorticoids). Reducing the evening dose of insulin counters this situation.
• Weight gain
• If insulin is injected repeatedly at the same site –  hypertrophy of subcutaneous fatty tissue occurs. This may be corrected by rotating the injection site.
• Allergy to human insulin is unusual but can occur.

Diabetic ketoacidosis
• Diabetic ketoacidosis is a life-threatening medical emergency caused by inadequate or absent insulin replacement (poor compliance). It occurs commonly in people with type 1 diabetes who are on insulin pumps and infrequently in those with type 2 diabetes having sepsis or pancreatitis or are on high-dose steroid therapy.
• Signs and symptoms include nausea, vomiting, abdominal pain, deep slow (Kussmaul) breathing, change in mental status (including coma), elevated blood and urinary ketones and glucose, an arterial blood pH lower than 7.3, and low bicarbonate (15 mmol/L).
• Treatment for DKA includes aggressive intravenous hydration (preferably with normal saline) and insulin (with regular human insulin) therapy and maintenance of potassium and other electrolyte levels.

2. Enumerate the drugs used in the treatment of pulmonary tuberculosis. Explain the mechanism of action  and  adverse effects of one of the first line antitubercular drug. Discuss the treatment of multi drug resistant tuberculosis.

Drugs used in the treatment of pulmonary tuberculosis
First-line agents – Isoniazid, Rifampin, Pyrazinamide, Ethambutol
Second-line agents
• Aminoglycosides – Amikacin, Streptomycin, Capreomycin
• Fluoroquinolones – Levofloxacin, Moxifloxacin
• Rifampin congeners – Rifabutin, Rifapentine
• Others – Aminosalicylic acid, Clofazimine, Cycloserine, Ethionamide, Linezolid
• Newer drugs – Bedaquiline, Delamanid

Isoniazid is the most active drug for the treatment of tuberculosis caused by susceptible strains.

Mechanism of Action – Isoniazid is a prodrug that is activated by KatG, the mycobacterial catalase-peroxidase. The activated form of isoniazid blocks synthesis of mycolic acids, which are essential components of mycobacterial cell walls.

Absorption – administered orally, good bioavailability when taken on empty stomach.
Distribution – diffuses readily into all body fluids and tissues
Metabolism – metabolized by acetylation in liver using N-acetyltransferase, which is genetically determined
Excretion – metabolites are excreted in the urine

• Isoniazid is bactericidal for actively growing tubercle bacilli and is less effective against nontuberculous mycobacteria.
• Isoniazid penetrates into macrophages and is active against both extracellular and intracellular organisms.
• Usual adult dose of isoniazid is 300 mg given once daily.
• Dose adjustments not required in renal failure.

Adverse effects
• Isoniazid-induced hepatitis is the most common major toxic effect.
• Peripheral neuropathy is observed in 10–20% of patients given dosages greater than standard 300-mg adult dose.
• Isoniazid promotes excretion of pyridoxine, and this toxicity is readily reversed by administration of pyridoxine in a dosage as low as 10 mg/d.
• Gastrointestinal discomfort, fever and skin rashes are occasionally seen.

Treatment of multi-drug resistant tuberculosis
Definition of MDR-TB

• A TB patient whose biological specimen is resistant to both isoniazid and rifampcin with or without resistance to other first-line anti-TB drugs. India has the highest number of MDR­-TB cases.
• As per TB India guidelines 2021, Oral Bedaquiline-containing MDR-TB regimen is recommended over injectable containing MDR-TB regimen.
• The new regimen consists of an initial phase of 4 months that may be extended up to 6 months and a continuation phase of 5 months, giving a total duration of 9–11 months.
Initial phase / Intensive phase (4 to 6 months) – Bedaquiline, Levofloxacin, Clofazimine, Pyrazinamide, Ethambutol, High dose Isoniazid, Ethionamide
Continuation phase (5 months) – Levofloxacin, Clofazimine, Pyrazinamide, Ethambutol
• The composition or the duration of the initial or continuation phase cannot be changed. Pyridoxine 100 mg/day is given to all patients during the whole course of therapy to prevent neurotoxicity of the anti­TB drugs. Strong CYP3A4 inhibitors, e.g. azole antifungals and strong CYP3A4 inducers, e.g. phenytoin should not be co-administered with Bedaquiline during the 6 month treatment duration and up to one month after the last dose of Bedaquiline because of potential drug–drug interactions.

SHORT ANSWER QUESTIONS (10 x 5 = 50 marks)

3. Write the composition of oral rehydration salt solution and its role in diarrhea.

• Acute diarrhoeal diseases are one of the leading causes of mortality in infants and young children in many developing countries. Diarrhoea, which is frequently caused by poor sanitation and hygiene, can have serious, even deadly results, typically as a result of diarrhoea-related dehydration.

• Dehydration from diarrhoea can be prevented by giving extra fluids at home, or it can be treated simply and effectively by giving adequate glucose-electrolyte solution called Oral Rehydration Salts (ORS) solution.
• ORS and Zinc has proven to be successful in the prevention and management of acute diarrhoea and dehydration. Oral rehydration salts contain a variety of salts (electrolytes) and sugar. The combination of electrolytes and sugar stimulates water and electrolyte absorption from the gut. It therefore prevents or reverses dehydration and replaces lost salts in conditions such as diarrhoea and vomiting.
• ORS is available in the market in a powder form in sachets/readymade solutions. The WHO and UNICEF have recommended replacement of standard (310 mOsm/L) ORS formula by the new (245 mOsm/L)/formula. Its composition includes NaCl, KCl, Trisodium Citrate and Glucose.
• Zinc supplementation along with ORS and continued for the next 10–14 days shown to reduce recurrences of diarrhea.

4. Compare and contrast heparin and warfarin.

Source – Porcine intestinal mucosa
Mechanism of Action – By binding to antithrombin III, heparin rapidly inactivates thrombin (factor IIa) and factor Xa.
• Absorption – administered s.c / i.v
• Distribution – extensive
• Metabolism – heparin is taken up by reticuloendothelial cells, undergoes depolymerization and desulfation to inactive products.
• Elimination – inactive metabolites are excreted into the urine.
Half-life – 1.5 hrs
Anticoagulant effect – Within minutes of IV administration (or 1 to 2 hours after subcutaneous injection)
Treatment of acute venous thromboembolism (DVT or PE).
Prophylaxis of postoperative venous thrombosis in patients undergoing surgery (for example, hip replacement) and those with acute MI.
Heparins are anticoagulants of choice for treating pregnant women, because they do not cross the placenta, due to their large size and negative charge.
Side effects – Bleeding, hypersensitivity reactions, osteoporosis, thrombocytopenia
Monitoring – aPTT
Antidote – Protamine sulphate

Source – Coumarin anticoagulant
Mechanism of Action – Inhibits epoxide reductase, an enzyme required to convert  vitamin K epoxide to  reduced vitamin K after carboxylation of factors II, VII, IX, X, Protein S, Protein C.
• Absorption
– administered orally, high bioavailability (98%)
• Distribution – high plasma protein binding (99%)
• Metabolism – metabolized by (R) CYP1A2, and (S) 2C9 to inactive components.
• Elimination – inactive metabolites are excreted into the urine.
Half-life – 40 hrs
Anticoagulant effect – After 72 to 96 hours of oral administration

Treatment and prevention of DVT & PE.
Prevention of stroke in patients with valvular as well as nonvalvular AF.
Prevention of VTE during orthopedic or gynecologic surgery.
Warfarin is teratogenic and should never be used during pregnancy.
Side effects – Bleeding, Skin lesions.
Monitoring – PT-INR
Antidote – Vitamin K

5. Describe the therapeutic uses of corticosteroids.

The anti-inflammatory and immunosuppressive actions of endogenous glucocorticoids play a crucial counter-regulatory role in preventing excessive activation of inflammation and other powerful defence reactions in our body.

Many synthetic steroids with anti-inflammatory and immunosuppressive activity are available for clinical use.
a) Replacement therapy for patients with adrenal failure (Addison’s disease) – Hydrocortisone is used.
b) Anti-inflammatory/immunosuppressive therapy in:
• Asthma – Inhalational Budesonide, Fluticasone, Ciclesonide are used.
• Respiratory distress syndrome in infants delivered prematurely – Betamethasone is used
• Various inflammatory conditions of skin, eye, ear or nose (e.g. eczema, allergic conjunctivitis or rhinitis) – Topical Betamethasone, Dexamethasone, Mometasone, Hydrocortisone are used.
• Hypersensitivity states (e.g. severe allergic reactions) – Dexamethasone is used
• Miscellaneous diseases with autoimmune and inflammatory components (e.g. rheumatoid arthritis and other ‘connective tissue’ diseases, inflammatory bowel diseases, some forms of haemolytic anaemia, idiopathic thrombocytopenic purpura) – Methylprednisolone, Triamcinolone are used
• Preventing graft-versus-host disease following organ or bone marrow transplantation – Methylprednisolone is used
• Neoplastic disease in combination with cytotoxic drugs in treatment of specific malignancies (e.g. Hodgkin’s disease, acute lymphocytic leukaemia) – Methylprednisolone is used.

6. Write about the management of psoriasis.

Psoriasis is the most common inflammatory and autoimmune skin disease. Cytokines such as TNF, IL-17 and IL-23 are involved in the pathogenesis of psoriasis.
Psoriasis manifests as inflammation accompanied by hyper-proliferation of keratinocytes leading to an accumulation of scaly dead skin at the sites of the disease (palms and soles). The lesions may be painful and are sometimes itchy.
Although there is no cure for psoriasis, numerous topical and systemic therapies are available. They are often selected on the basis of disease severity.
Mild disease is treated with topical therapies alone.
Topical preparationsCorticosteroids (hydrocortisone, clobetasol), Vitamin D analogues (calcipotriene, calcitriol), Tazarotene
Moderate to-severe disease typically necessitates the use of systemic agents.
Nonbiologic systemic preparationsMethotrexate, Cyclosporine, Acitretin, Apremilast
Biologic systemic preparationsTNF-α inhibitors (adalimumab, etanercept, and infliximab), Cytokine inhibitors (secukinumab, ustekinumab)
Treatment regimens may clear the skin but recurrences are frequent and many patients require repeat treatment.

7. Enumerate the iron preparations and add a  note  on  the indications of parenteral iron therapy.

Iron is important for the synthesis of haemoglobin, myoglobin, cytochromes and other enzymes. Ferric iron (Fe3+) must be converted to ferrous iron (Fe2+) for absorption in the gastrointestinal tract.

Causes of iron deficiency
• chronic blood loss (e.g. with menorrhagia, hookworm, colon cancer);
• increased demand (e.g. in pregnancy and early infancy);
• inadequate dietary intake (common in developing countries);
• inadequate absorption (e.g. following gastrectomy, or in diseases resulting in generalized malabsorption).

Management of iron deficiency anemia
Iron preparations
Oral preparations – Ferrous sulfate / succinate / gluconate / fumarate
Parenteral preparations – Iron-dextran, Iron-sucrose

Indications of parenteral iron therapy – Parenteral administration of iron may be necessary in individuals who are
Unable to tolerate oral preparations because of GI disturbances.
Not able to absorb oral iron because of malabsorption syndromes, surgical procedures, inflammatory conditions involving the gastrointestinal tract.
Patients with chronic renal failure or with chemotherapy-induced anaemia who are receiving treatment with erythropoietin.

Adverse effects of parenteral iron therapy include mostly hypersensitivity reactions such as flushing, urticaria, bronchospasm. Other adverse effects include headache, fever, arthralgias, nausea and vomiting.

If large doses of iron is administered – acute iron poisoning occurs which can be treated with desferrioxamine, an iron chelator.

8. A 36 year old female patient had history of acid peptic disease and endoscopic biopsy was suggestive of helicobacter pylori infection. Describe the pharmacological management of this case.

Pathogenesis of peptic ulcers
• infection of the gastric mucosa with Helicobacter pylori (gram-negative bacillus);
• an imbalance between the mucosal-protecting agents (gastric mucus, bicarbonate, prostaglandins E2 and I2, and nitric oxide) and mucosal-damaging agents (gastric acid, pepsin).

Therapy of peptic ulcer aims to
decrease the secretion of gastric acid with proton pump inhibitors (PPIs)
neutralize gastric acid with antacids
eradicate H. pylori with antibacterials. PPIs also promote eradication of H pylori by raising intragastric pH which lower the minimal inhibitory concentrations of antibiotics against H pylori. Eradication of H. pylori infection promotes rapid and long-term healing of ulcers.

Most commonly recommended treatment regimen is a 14-day twice daily regimen of “triple therapy” consisting of PPI + Clarithromycin 500mg + Amoxicillin 1g / Metronidazole 500mg.

Due to increasing treatment failures with respect to rising clarithromycin resistance, “quadruple therapy” is now recommended as first-line treatment for patients who have clarithromycin resistance due to prior exposure or to those patients residing in regions with high clarithromycin resistance. Two 14-day treatment regimens currently are recommended
a) PPI + Bismuth subsalicylate + Metronidazole + Tetracycline
b) PPI + Amoxicillin + Clarithromycin + Metronidazole

After completion of antibiotic therapy, the PPI should be continued once daily for a total of 4–6 weeks to ensure complete ulcer healing.

9. A 25 year old male developed and infection due to Methicillin Resistant Staphylococcus Aureus (MRSA).   Describe in brief the drugs available to treat such infection.

Methicillin, the first antistaphylococcal penicillin to be developed, is no longer used clinically due to
• high incidence of resistance against Staphylococcus aureus, and
• high risk of adverse effects, mainly interstitial nephritis
MRSA develops resistance towards all β-lactam antibiotics by acquiring a very low affinity Penicillin binding protein (PBP).
MRSA is responsible for causing skin and soft tissue infections.

Drugs available to treat MRSA infections
Ceftaroline – It interferes with the synthesis of bacterial cell wall by binding to penicillin-binding protein 2a, which mediates methicillin resistance in staphylococci.
Vancomycin & Teicoplanin  – These drugs inhibit cell wall synthesis by binding firmly to the d-Ala-d-Ala terminus of nascent peptidoglycan pentapeptide. This inhibits the transglycosylase, preventing further elongation of peptidoglycan and cross-linking. The peptidoglycan is thus weakened, and the cell becomes susceptible to lysis.
Tigecycline – Binds to the 30S subunit of the bacterial ribosome and prevent binding of tRNA molecules loaded with amino acids. Addition of a glycyl amide group to the tetracycline ring prevents recognition of tigecycline by many bacterial efflux pumps.
Quinupristin / Dalfopristin – This drug combination produces a synergistic effect by inhibiting bacterial protein synthesis. Dalfopristin binds to 50S ribosome and induces a conformational change in it, which enhances binding of quinupristin. Quinupristin blocks initial attachment of t-RNA and elongation step of protein synthesis.
Linezolid – Binds to the 23S RNA component of the 50S ribosomal subunit and prevents formation of the 70S initiation complex required for bacterial protein synthesis.
Daptomycin – This drug binds to the cell membrane via calcium-dependent insertion of its lipid tail. This results in depolarization of the cell membrane with potassium efflux and rapid cell death.
Dalbavancin and other ‘vancins’ – These drugs have two mechanisms of action.
• inhibits cell wall synthesis by binding to the d-Ala-d-Ala terminus of peptidoglycan in the growing cell wall.
• disrupts the bacterial cell membrane potential and increases membrane permeability.

10. Discuss the treatment of uncomplicated malaria.

Definition of uncomplicated malariaA patient who presents with symptoms of malaria and a positive parasitological test (microscopy or RDT) but with no features of severe malaria is defined as having uncomplicated malaria. The main aim of treating uncomplicated malaria is to cure the infection as rapidly as possible and to prevent progression to severe disease.

As per WHO guidelines 2021,

a) for uncomplicated P. falciparum  malaria

Children and adults (except pregnant women in their first trimester) are treated with any one of the following options
artemether + lumefantrine
artesunate + amodiaquine
artesunate + mefloquine
dihydroartemisinin + piperaquine
artesunate + sulfadoxine–pyrimethamine (SP).

Artemisinin-based combination therapy (ACT) is a combination of a rapidly acting artemisinin derivative with a longer-acting (more slowly eliminated) partner drug. A 3-day course of the artemisinin component of ACTs rapidly clears parasites from the blood (reducing parasite asexual cycle) and is also active against the sexual stages of the gametocytes that mediate onward transmission to mosquitos. The longer- acting partner drug clears the remaining parasites and provides protection against development of resistance to the artemisinin derivative.

Pregnant women during the first trimester is treated with 7 days of quinine + clindamycin.

In high-transmission areas of P. falciparum malaria, a single dose of primaquine 0.25 mg/kg bw to be considered with ACT to patients (except for pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months) to reduce transmission. G6PD testing is not required.

b) for uncomplicated malaria due to P. vivax, P. ovale, P. malariae or P. knowlesi

Children and adults
• In areas with chloroquine-susceptible infections – either ACT (except pregnant women in their first trimester) or chloroquine.
• In areas with chloroquine-resistant infections – ACT (except pregnant women in their first trimester).

Pregnant women – treated with 7 days of quinine.

To prevent relapse, P. vivax or P. ovale malaria in children and adults (except those mentioned below) must be treated with a 14-day course of primaquine in all transmission settings.
• pregnant women
• women breastfeeding infants aged < 6 months
• people with G6PD deficiency

Women who are pregnant or breastfeeding – weekly chemoprophylaxis with chloroquine must be considered until delivery or breastfeeding are completed, then, on the basis of G6PD status, treatment with primaquine to prevent future relapse.

People with G6PD deficiency – primaquine at 0.75 mg/kg bw once a week for 8 weeks can be considered, with close medical supervision for potential primaquine-induced haemolysis.

Pregnant women should not start taking quinine on an empty stomach as the drug causes hypoglycemia and therefore should eat regularly, while on quinine treatment.

11. Write about the toxicity amelioration of anticancer agents.

Cancer treatment aimed at killing rapidly dividing cancer cells also affects normal cells undergoing rapid proliferation (for example, cells of the buccal mucosa, bone marrow, gastrointestinal mucosa, and hair follicles), contributing to the toxic effects of chemotherapy.
Some of the adverse effects are immediate (eg, nausea, vomiting, hypersensitivity reactions), whereas others are delayed (myelosuppression, alopecia, infertility, agent specific organ toxicity).
Some adverse effects are common (eg, myelosuppression) to many anticancer drugs, whereas others are agent specific (eg, bladder toxicity with cyclophosphamide, cardiotoxicity with doxorubicin, and pulmonary fibrosis with bleomycin).
Some adverse effects are reversible (eg, alopecia), whereas others (cardiac, pulmonary, and bladder toxicities) can be irreversible.
Targeted anticancer drugs have least adverse effects
Monoclonal antibodies – infusion-related reactions.
Tyrosien kinase inhibitors – diarrhea and nausea

Anticancer drugs should not be used in pregnancy, especially during the first trimester because of their potential to cause teratogenic effects.

Adverse effect Management
Neurotoxicity Amifostine
Cardiotoxicity Dexrazoxane
Myelosuppression Anemia = Epoetin alfa / Darbepoetin alfa, Lenalidomide, Leucovorin

Thrombocytopenia = Oprelvekin (IL-11), romiplostim, eltrombopag

Neutropenia = Filgrastim (G-CSF), Sargramostim (GM-CSF)

Nausea, vomiting 5HT3-antagonist, NK-1 receptor antagonist, Dexamethasone
Mucositis Palifermin
Diarrhea / Constipation Antidiarrheals / Stool softeners
Nephrotoxicity Amifostine (additionally for Methotrexate renal failure = Glucarpidase, and for Cisplatin renal failure = aggressive hydration + diuretics)
Hyperuricaemia Allopurinol, Rasburicase, Corticosteroids
Cystitis Mesna (sodium 2-mercaptoethane sulfonate) and Acetylcysteine.
Osteoporosis Bisphosphonates, SERMS, Denosumab

12. Explain the management of paracetamol poisoning.

• Paracetamol is the most commonly used analgesic and antipyretic agent. It is administered orally as well as parenterally. Paracetamol is metabolized by hepatic microsomal enzymes to the inactive sulfate and glucuronide derivatives.
Acute ingestion of more than 150–200 mg/kg (children) or 7 g total (adults) of paracetamol is considered potentially toxic. A highly toxic metabolite (N-acetyl-p-benzoquinone) is produced in the liver due to glutathione depletion. Chronic alcoholics produces the toxic metabolite even with lower doses of paracetamol.
Initially, the patient is asymptomatic or has mild gastrointestinal upset (nausea, vomiting). After 24–36 hours, evidence of liver injury appears, with elevated aminotransferase levels and hypoprothrombinemia. Fulminant liver failure may ensue, leading to metabolic acidosis, hypoglycemia, encephalopathy, and death. Renal failure may also occur.
Acetylcysteine is the specific antidote that acts as a glutathione substitute and binds to the toxic metabolite as it is produced. It is most effective when given early and should be started within 8–10 hours if possible.
Liver transplantation may be required for patients with fulminant hepatic failure.