MPharm BioPharm

• Peptide like drugs 


  • Renin inhibitors
  • Cephalophorins
  • ACE Inhibitors - angiotension converting enzymes
  • Penicillins

  Nucleosides and Analogues

  • Antiviral e.g. Foscarnet
  • Amino acid transporter - L-dopa and a-methyldopa
• Types of transport across gastrointestinal epithelium 


  • Paracellular
  • Transcellular
  • Simple passive diffusion
  • Carrier mediated ( active transport or facilitated diffusion)
  • Endocytosis (and phagocytosis)
• Paracellular Transport


  Passive

  Diffusional (Fick's Law)

  Driven by concentration gradient

  Small (<200Da) hydrophilic molecules - Mannitol, ions, sugars, peptides, amino acids

  Inversly related to molecular weight - the higher the molecular weight, the lower the efficiency of paracellular movement
• Transcellular Transport - materials transport through the cell itself 


  Simple Passive Diffusion

  • Small lipophilic molecules (<500 Da), most drugs
  • Rate depends - drug concentration gradient, membrane permeability, drug's physiochemical properties (logP and pKa) , drug release/dosage form

  Carrier mediated

  Active transport

  • Requires energy
  • Shows temperature dependence
  • Transmembrane electrical gradient
• Transcellular 2


  Carrier mediated

  Facilitated Diffusion

  • Needs concentration gradient
  • Faster than passive diffusion
  • Saturable process
  • Can be inhibited by competitive inhibitors (substrate analogues and metabolic inhibitors e.g. dinitrophenol)
  • Minor role in drug absorption
• Endocytosis - entry/transport of molecules into cells

  • Energy and cell type dependent
  • Invagination of plasma membrane - forming membrane bound vesicles. Complex and dynamic

  Phagocytosis

  • >0.5 micrometres
  • Macrophages, neutrophils, monocytes
• Endocytosis - Pinocytosis

  • Most cell types
  • Soluble materials and particles <0.2 micrometres
  • "Cell drinking"
  • Constitutive uptake of extracellular fluid and solutes
  • Adsorption mediated
  • Specific and non-specific mechanisms
• Specific Pinocytosis - Fluid Phase PinocytosisRate is dependent on concentration of the extracellular fluid

  • Relatively low efficiency
  • Uptake of non-diffusible molecules in extracellular environment
  • Rate is dependent on concentration of the extracellular fluid
  • Relatively low efficiency
  • Uptake of non-diffusible molecules in extracellular environment
  • Plasma membrane invagination
• Non-specific adsorptive pinocytosis 


  • Solutes binding to cell surface - ionic interactions, hydrophobic/hydrophilic contacts
  • Drugs which are/contain catonic molecules - moieties
  • Polymer therapeutics
  • Local membrane depolarisation
  • Much more efficient than fluid phase
  • Induce membrane invagination, budding amd vacuole formation
• Migrating Myoelectric Complex (MMC)

  Phase 1• 40-60 mins• Relatively inactive period with only rare contractions• Phase 2• 40-60 mins• Increased number of contractions• Phase 3• Powerful peristaltic contractions• The pylorus at the base is open• Phase 4• Short transitional period between phase III and phase I
• The Small Intestine


  pH varies locally between ~5-7• Contains secretions from the pancreas, liver (bile) and from goblet cells in intestinal wall• Intestinal cells secrete mucus, enzymes and mediate the immune response (Peyer’s patches)• Brunner’s glands, located in the duodenum, secrete bicarbonate to neutralise the contents coming from the stomach• Helps to buffer acid from the stomach• The brush-border contains membrane-bound enzymes that complete protein and fat digestion
• The Small Intestine


  Overall length is ~4-5 m, high surface area• Rich network of blood and lymphatic vessels• The duodenum is ~0.3 m in length and it is theprimary site of digestion• The jejunum is ~1-2 m in length, some digestion• The ileum is ~2-3 m in length, little digestion• Hepatic portal vein delivers material to the liver• Food movement is slow through the small intestine,typically 3 – 5 hours• 95% of chemical digestion and absorption takesplace in the small intestine
• Who stated that "All substances are poisons"?

  Paracelsus
• What differentiates a poison from a remedy according to Paracelsus?

  The right dose
• What is biopharmaceutics?

  • Relationship between drug properties and response
  • Involves dosage form and pharmacological effects
• What are the properties affecting drug efficacy?

  Physicochemical properties, dosage form, route
• What are the routes of administration?

  • Oral
  • Intravenous
  • Subcutaneous
  • Intramuscular
  • Topical

  
• What does time to onset of action refer to?

  The duration before a drug begins to work

  
• What is the first physical barrier mentioned in the study material?

  Skin
• What type of epithelial cells are simple squamous?

  Single layer of flat cells

  
• Where can simple cuboidal epithelial cells be found?

  Kidney, eye, thyroid

  
• What is the structure of simple columnar epithelial cells?

  Monolayered columnar epithelium
• What is the function of stratified squamous epithelial cells?

  Protective barrier in various locations
• Where are stratified cuboidal epithelial cells found?

  Sweat and mammary glands
• What is the function of transitional epithelial cells?

  Contract and expand in bladder
• What is pseudo-stratified columnar epithelium characterized by?

  Single layer with similar nuclei
• What is bioavailability?

  • Measure of drug in systemic circulation
  • Fraction of administered dose reaching circulation
  • Highly dependent on administration route

  
• What does bioavailability F represent?

  Fraction of drug reaching systemic circulation
• What does ADME stand for?

  Absorption, Distribution, Metabolism, Excretion
• What is pharmacokinetics?

  • Study of drug absorption, distribution, metabolism, elimination
  • Characterizes time course of drug action

  
• What must happen for a drug to be 100% bioavailable when administered orally?

  Must pass through liver unchanged
• What does the area under the curve (AUC) represent?

  Drug-plasma concentration over time

  
• What is relative bioavailability?

  • Comparison of absorption rates of two formulations
  • Calculated as AUCtest / AUCstandard
• What is absolute bioavailability?

  • Comparison of bioavailability with IV administration
  • Calculated as AUCtesting route / AUC IV route
• What factors affect drug absorption?

  Lipophilicity, ionization, molecular mass
• How does local pH affect drug absorption?

  Weak acids absorbed in stomach, bases in SI
• What is the most popular route of administration?

  Oral
• What are the functions of the GI tract?

  • Supplies nutrients and water
  • Controls lumen for digestion and absorption
  • Delivers absorbed substances to liver
• How long is the GI tract from mouth to anus?

  ~10 metres
• What is the role of mucus in the GI tract?

  Protective barrier and lubrication