EBL W2 - Pharmaceutics principles – expanded info on liquid dosage forms, basic PK in context of GI tract

Question 1

Cimetidine: class, target, mechanism, dose, physicochemical properties

Answer 1

• Class: H2-receptor antagonist (H2-blocker)
• Target: H2-receptors on basolateral membrane of gastric parietal cells
• Mechanism: Inhibits acid secretion and cytochrome P450 (CYP1A2, 2C9, 2D6)
• Doses: Varies 400–800 mg/day, 1–4x/day
  o logP: 0.4 (low lipophilicity)
  o pKa: 6.8 (partially ionised at pH 7.4)
  o Aqueous solubility: ~50 mg/mL (sparingly soluble)

Question 2

Indications for cimetidine

Answer 2

o Peptic ulcers (gastric/duodenal), NSAID-induced ulcers
o Reflux oesophagitis, stress ulcer prophylaxis
o Short bowel syndrome

Question 3

Cimetidine: formulations and routes (pros and cons)

Answer 3

📌 Oral
* Forms: Tablet, Oral solution (200 mg/5 mL), Syrup
* Pros: Convenient, cost-effective, non-invasive, prolonged action
* Cons: Lag time, enzymatic degradation risk
📌 IV
* Pros: Rapid onset, 100% bioavailability, bypasses absorption
* Cons: Infection risk, invasive

Question 4

risks of using methyl/propyl parabens and reason for the combination

Answer 4

• Risks: Allergies, endocrine disruption
• Reason for Combo: Enhanced antimicrobial spectrum (methyl → antibacterial, propyl → antifungal); synergistic → lower required doses

Question 5

risks of using propylene glycol (PG)

Answer 5

• Risks: CNS depression, lactic acidosis, hyperosmolality
• UK Child Limits:
  o 1 mo–4 yrs: 50 mg/kg/day
  o 5–11 yrs: 500 mg/kg/day

Question 6

Recommendations for ethanol consumption in children

Answer 6

• 3% v/v OK only for ages 6–12 for up to 2 weeks
• Not allowed under 6 years (Max 0.5%, use ≤1 week)
• ≥12 yrs: Adult limits apply

Question 7

methods + mechanisms of powder flow improvement

Answer 7

Method - Mechanism
Flow Aids (Glidants) - Reduce friction/cohesion (e.g. Aerosil)
Granulation - Improves shape & size (wet/dry)
Particle Size Optimization - Reduces electrostatic sticking
Particle Shape Modification - Spherical particles flow better
Moisture Control - Prevents clumping (e.g. silica gel)
Lubricants - Reduce friction (e.g. magnesium stearate)
Mechanical Vibration - Prevents clogging in hoppers

Question 8

ADME – Distribution (Oral Cimetidine)

Answer 8

1. Absorption: Mainly in small intestine
2. First-pass: Low hepatic metabolism
3. Plasma: 15–20% protein-bound
4. Target: Gastric parietal cells via bloodstream
5. Vd (Volume of Distribution): ~1 L/kg (mostly extracellular)
6. Elimination: Renal (60–70% unchanged in urine), minor liver metabolism

Question 9

name 6 GI drugs

Answer 9

Omeprazole
Famotidine
Metoclopramide
Misoprostol
Sulfasalazine
Linaclotide

Question 10

Omeprazole: target, action, use

Answer 10

H⁺/K⁺ ATPase (enzyme)
Inhibits proton pump → ↓ acid
GERD (Gastroesophageal Reflux Disease), ulcers

Question 11

Famotidine: target, action, use

Answer 11

H₂-receptors (G-Protein Coupled Receptor)
Blocks acid secretion
GERD, ulcers

Question 12

Metoclopramide: target, action, use

Answer 12

• D₂ (Dopamine) & 5-HT₄ (Serotonin) Receptors
• Prokinetic (any drug or substance that enhances gastrointestinal (GI) motility)
• GERD, gastroparesis (delayed gastric emptying w/o physical obstruction)

Question 13

Misoprostol: target, action, use

Answer 13

EP3 prostaglandin receptor
↑ gastric mucus + bicarbonate, ↓ acid
NSAID-ulcer, prophylaxis (taking steps to stop a disease or problem before it happens)

Question 14

Sulfasalazine: target, action, use

Answer 14

COX enzyme
Anti-inflammatory effect in the intestines.

IBD

Question 15

Linaclotide: target, action, use

Answer 15

activates GC-C receptor
↑ fluid secretion, ↓ pain and improves motility
IBS with Constipation

Question 16

4 Types of pharmacological targets

Answer 16

Ion channels
enzymes
receptors
transporters

Question 17

drugs that act on ion channels: function, GI example

Answer 17

Modulate ion flow across membranes
Ca²⁺ blockers reduce smooth muscle contraction in GI tract

Question 18

drugs that act on enzymes: function, GI example

Answer 18

• inhibit or activate enzymes to alter metabolic pathways
• Sulfasalazine is a prodrug that, when it reaches the colon, is broken down by bacterial enzymes into two active parts:

The 5-ASA part inhibits the COX enzyme, which reduces the production of prostaglandins — chemicals involved in inflammation.

Question 19

drugs that act on receptors: function, GI example

Answer 19

• Signal activation/block by drug binding
• Loperamide acts on μ-opioid receptor
• Agonist
• ↓ peristalsis, ↑ water absorption in intestines
• used for diarrhoea

Question 20

drugs that act on transporters: function, GI example

Answer 20

Substance movement accross membranes
PPI affects H⁺ transport in gastric parietal cells

Question 21

role of agonist

Answer 21

full activation

Question 22

role of partial agonist

Answer 22

partial activation

Question 23

role of antagonist

Answer 23

Blocks response (e.g. competitive/non-competitive) by preventing agonist binding

Question 24

role of allosteric modulators

Answer 24

+ve (↑ response), −ve (↓ response), neutral have no effect

Question 25

role of inverse agonists

Answer 25

Produces opposite response of natural ligand (agonist)

Question 26

role of inhibitors/activators

Answer 26

Modify enzyme/receptor activity

Question 27

ADME – Elimination of cimetidine

Answer 27

* Main route: Renal (glomerular filtration + tubular secretion) * 60–70% excreted unchanged (urine) in 24 hrs * Remainder: Metabolized in liver * Clearance: 500–600 mL/min * Half-life: ~2 hours

Question 28

elimination, metabolism, excretion definition

Answer 28

* Elimination = metabolism + excretion (irreversible loss) * Metabolism = chemical modification * Excretion = unchanged removal (e.g. via urine)

Question 29

Off-label Drug Use: definition, key patient points

Answer 29

* Definition: Licensed drug used for unlicensed indication/age/dose/route * Key Patient Points: o Drug is licensed, but use isn’t officially approved o Chosen based on clinical judgement and evidence o Risks/benefits are carefully considered o Patient has the right to know and ask questions * Note: Common off-label uses may not need disclosure. New/unusual uses must be discussed.

Question 31

what's an ulcer

Answer 31

a sore or open wound that forms on the inside of your body, usually when the protective lining is damaged.