1. a) A patient presented in emergency after taking overdose of a basic drug with pKa of 8.5.
Explain how its excretion from the kidney can be enhanced?
The excretion of a basic drug can be enhanced by acidifying the urine. When the urine is acidic, it
favors the protonated (ionized) form of the drug. The ionized form cannot easily diffuse back into
the bloodstream and is thus trapped in the renal tubules, leading to increased elimination
through urine. This principle is referred to as "ion trapping." Acidification of urine in case of basic
drug overdose i.e., amphetamine overdose can be achieved using a weak acid like Ammonium
Chloride.
RNH2 + H+ ⇌ RNH3+ (Charged is more water soluble)
b) A new drug is under developmental process. Explain briefly different phases of clinical
trials involved in this process.
Such Testing required approval from an authority i.e., DRAP in Pakistan and FDA in US.
Phase Participants Objective
20–100 Subjects To determine if it is safe pharmacokinetically.
Phase 1
(normal) To determine Dose-response relationship
100–200 patients To determine if drug works in patients with target disease.
Phase 2
with target diseases To determine if drug has desired efficacy
Does it work, Double blind.
To determine with clinical spectrum of investigational drug in
Phase 3 1000 – 6000 patients
comparison to placebo (Negative control) or with an older drug
(positive control)
Broader patient Detect rare or long-term adverse effects and gather additional data on
Phase 4
population. effectiveness after the drug reaches the market.
2. a) Explain the reason for mucosal bleeding in him (warfarin and metronidazole interaction).
Reason for Mucosal Bleeding: The patient experienced bleeding due to the interaction between
metronidazole and warfarin. Metronidazole is a potent inhibitor of 2C9 isoform of P450 leads to
inhibition of the hepatic metabolism of warfarin via cytochrome P450 enzymes, increasing
warfarin levels and thus potentiating its anticoagulant effect. This results in an elevated
International Normalized Ratio (INR), predisposing the patient to mucosal bleeding.
b) Describe suicidal inhibitors with examples.
Suicidal inhibitors are drugs that are metabolized to products that irreversibly inhibits the
metabolizing enzyme:
• Allopurinol
• Sacubitril
• Spironolactone
• Propylthiouracil
• Norethindrone
3. a) Explain the pharmacological effects of tropicamide on the eye useful in this patient.
Pharmacological Effects: Tropicamide is a muscarinic antagonist that causes mydriasis (pupil
dilation) and cycloplegia (paralysis of the ciliary muscle), preventing accommodation. These
effects facilitate retinal examination during fundoscopy
b) Enlist the adverse effects of tropicamide in this case.
The adverse effects of tropicamide may include
Ocular symptoms Systemic symptoms
• Photophobia • Headache And Dizziness
• Increased Intraocular Pressure • Dry Mouth
• Mild stinging and redness of the • Tachycardia
eye • Allergic reactions
• Blurred vision • CNS symptoms e.g hallucination,
Confusion, drowsiness etc.
4. a) Describe the role of bisoprolol in improving the hemodynamic parameters in a patient
with chronic heart failure.
Bisoprolol, a β1-selective blocker, improves hemodynamics in chronic heart failure by:
• Decreasing Heart rate and Myocardial contractility
• Lowering heart oxygen demand
• Lowering cardiac workload
• Increasing Diastolic filling time
• Decease vascular resistance and preload
• Enhancing left ventricular function
• Improving ejection fraction
b) Enlist three other beta blockers useful in chronic heart failure.
• Bisoprolol
• Carvedilol
• Metoprolol
• Nebivolol.
c) Describe pharmacologic stress test.
A pharmacologic stress test is a diagnostic procedure use to evaluate coronary artery disease
(CAD) and cardiac functionality, especially in those patients who cannot perform physical stress
test.
Procedure:
The patient is administered the selected pharmacologic agent (from dobutamine adenosine,
dipyridamole), intravenously to produce the effect of exercise either by increasing heart oxygen
demand or producing coronary vasodilators, to monitor the response of heart under stress
Contraindications:
Severe asthma or bronchospasm (for adenosine/dipyridamole).
Significant arrhythmias or severe aortic stenosis (for dobutamine).
5. a) A 25yearold woman presents with recurrent kidney stones. Her 24-hour urine shows
hypercalciuria and hyperuricosuria. Which is the most appropriate drug used to reduce stone
recurrence, also give its rationale along with its recognized adverse effects?
Appropriate Drugs: Thiazide diuretics, such as hydrochlorothiazide, chlorthalidone
Reduction of Hypercalciuria: Thiazides decrease calcium excretion in urine by promoting
calcium reabsorption in the distal convoluted tubule, reducing the availability of calcium to form
stones.
Reduction of Hyperuricosuria: Thiazides indirectly reduce uric acid excretion by decreasing
overall urinary volume (via mild diuresis) and altering solubility dynamics.
Adverse Effects:
• Hypokalemia
• Hyperglycemia
• Hyperuricemia
• Volume depletion
• Hyponatremia
b) The direct oral anticoagulants are approved for prevention of stroke in patients with
nonvalvular atrial fibrillation. Enlist the drugs included in this group. Give two advantages of
these drugs over warfarin.
Drugs:
• Direct Thrombin (IIa) inhibitor
1. Dabigatran
• Direct Factor X inhibitor
1. Rivaroxaban, Apixaban, Edoxaban.
• Advantages over warfarin:
1. Rapid Onset (X inhibitor)
2. No need for routine INR monitoring. (both)
3. Fewer drug food interactions, making them easier to manage. (Ila Inhibitor)
6. Antihypertensive drugs are given as monotherapy. But later on, shifted to polytherapy due
to the adverse effects and compensatory responses. Enlist various compensatory responses
of antihypertensive drugs along with their groups in tabulated form.
Antihypertensive Drug Group Compensatory Response
Diuretics (e.g., Thiazides, loop) Minimal
Beta-blockers (e.g., Metoprolol) Minimal
ACE Inhibitors (e.g., Enalapril) Minimal
Angiotensin II Receptor Blockers (ARBs) (e.g., Losartan) Minimal
Calcium Channel Blockers (e.g., Amlodipine) Minor water and salt retention
Alpha-1 blockers (e.g., Doxazosin) water and salt retention
Minor tachycardia
Direct vasodilators (e.g., Hydralazine) water and salt retention
Moderate tachycardia
Central Alpha-2 Agonists (e.g., Clonidine) water and salt retention
Minoxidil Marked water and salt retention
Marked tachycardia
Nitroprusside water and salt retention
Fenoldopam water and salt retention,
tachycardia
7. a) Write down the mechanism of action of clozapine along with its major adverse effects.
Clozapine is an atypical antipsychotic that works by blocking dopamine D2 receptors and
serotonin 5HT2A receptors, which helps reduce psychotic symptoms.
Major Adverse Effects:
• Agranulocytosis (severe neutropenia)
• Diabetes
• weight gain
• sedation
• metabolic syndrome.
b) Describe combination therapy of antipsychotics with other groups useful in this patient.
In some cases of schizophrenia, clozapine can be combined with other medications like mood
stabilizers (e.g., lithium), anti-anxiety, cognitive enhancer or antidepressants to help manage
cooccurring mood disorders and aggression.
8. a) Tabulate the degrees of tolerance that may develop to some of the effects of opioids.
Degrees of Tolerance to Opioid Effects
Effect Degree of Tolerance
Analgesia High
Euphoria High
Respiratory Depression High
Sedation Moderate
Cough Suppression Minimal
Miosis Minimal
Constipation Minimal
Bradycardia Minimal
b) Define MAC Value.
Minimum alveolar concentration (MAC) is the anesthetic concentration that eliminates the
response in 50% of patients exposed to a standardized painful stimulus. Unit is percentage
c) Which anesthetic drug causes dissociative anesthesia? Give its mechanism of action.
Ketamine causes dissociative anesthesia by non-competitive inhibition of NMDA (N-Methyl D
Aspartate) receptors, which inhibits excitatory neurotransmission in the brain.
9. a) Enlist antiemetic agents which are safe and effective in chemotherapy induced nausea
and vomiting
• 5HT3 antagonists: Ondansetron, Granisetron, Palonosetron (long-acting), Dolasetron
• NK1 antagonists: Aprepitant, Fosaprepitant, Rolapitant
• Corticosteroids: Dexamethasone
• Dopamine (D2) Antagonists: Metoclopramide, Prochlorperazine
• Atypical Antipsychotics: Olanzapine
• Benzodiazepines: Lorazepam
• Cannabinoids (in refractory cases): Dronabinol, Nabilone
b) Discuss the role of corticosteroids to stop chemotherapy induced nausea and vomiting.
Role of Corticosteroids in CINV: Corticosteroids like dexamethasone are commonly used as
adjunctive therapy for chemotherapy induced nausea and vomiting. They:
1. Reduce inflammation in the gastrointestinal tract.
2. Inhibit prostaglandin synthesis, decreasing vomiting center sensitivity.
3. Act centrally to suppress the chemoreceptor trigger zone (CTZ).
4. Enhance the efficacy of other antiemetics (e.g., 5-HT3 and NK1 receptor antagonists).
10. a) Tabulate the recommended and alternate anti-retroviral agents/drugs along with their
group, which are safe in pregnancy.
Group Recommended Drugs Alternate Drugs
Nucleoside/ Nucleotide reverse Didanosine, Abacavir,
Zidovudine, Lamivudine
transcriptase inhibitors (NRTIs) Stavudine, emtricitabine
Nonnucleoside/ Nucleotide reverse
Nevirapine
transcriptase inhibitors (NNRTIs)
Atazanavir, Indinavir,
Protease Inhibitors Lopinavir/Ritonavir
Nelfinavir. Saquinavir
b) Give rationale/advantage of combination of ritonavir with other protease inhibitors.
Ritonavir is used in combination with other protease inhibitors (PIs) to boost their
pharmacokinetics by inhibiting CYP3A4-mediated metabolism, which increases the plasma
levels, half-life, and bioavailability of the co-administered PI. This enhances their effectiveness,
allows for less frequent dosing, improves antiviral potency, reduces the risk of resistance and side
effects, and promotes better patient adherence, making it a central strategy in effective HIV
management.
11 a) Prevention of malaria in travelers:
Category Drugs for Prevention
i. Areas with chloroquine- • Malarone 1 Tablet Daily
resistant P. falciparum • Mefloquine 250 mg /week
ii. Areas with multidrug-
• Doxycycline 100mg Daily
resistant P. falciparum
iii. Terminal prophylaxis of P.
vivax & P. ovale infections;
• Primaquine (used for terminal prophylaxis)
alternative for primary
prevention
b) Treatment for uncomplicated infections with chloroquine resistant P. falciparum.
Coartem (artemether, 20 mg, plus lumefantrine, 120 mg), four tablets twice daily for 3 days
Alternative Malarone, four tablets daily for 3 days or Mefloquine, 15 mg/kg once or 750 mg, then
500 mg in 6–8 hours
12. a) Discuss the role of NSAIDs in rheumatoid arthritis.
NSAIDs help control pain and inflammation in rheumatoid arthritis by inhibiting cyclooxygenase
(COX) enzymes, particularly COX2, involved in the inflammatory process.
b) What are possible complications with chronic use of NSAIDs?
Chronic NSAID use can lead to:
• Gastrointestinal ulcers and bleeding
• Renal toxicity
• Cardiovascular risks, such as hypertension and heart failure.
c) Write down the principal mechanism of action of methotrexate in rheumatoid arthritis.
Methotrexate inhibits dihydrofolate reductase, leading to reduced synthesis of purines and
pyrimidines, which decreases inflammatory cytokine production and immune cell proliferation in
rheumatoid arthritis.
13. A pregnant female is diagnosed as hyperthyroid. You plan to start her on thioamides.
Which drug is preferred for her?
Propylthiouracil (PTU) is preferred in pregnancy due to its lower teratogenic risk compared to
methimazole.
Mechanism of Action: PTU inhibits thyroid peroxidase, reducing thyroid hormone synthesis.
Adverse Effects: Rash, agranulocytosis, and liver toxicity.
14. a) Signs and symptoms of acute iron intoxication and immediate treatment necessary.
Signs of acute iron intoxication include nausea, vomiting, abdominal pain, shock, and metabolic
acidosis. Immediate treatment involves
• Airway, Breathing, Circulation restoration
• Perform Gastric lavage
• Administer iron chelators, deferoxamine IV
b) Identify the three clinically useful chelators along with their indications.
• Deferoxamine: Acute iron poisoning.
• Deferasirox: Chronic iron overload.
• EDTA: Lead poisoning.
