2. Drug Absorption Flashcards
What is generic substitution?
Generic substitution occurs when a different formulation of the same drug is substituted. All generic versions of a drug are considered by the licensing authority to be equivalent to each other and to the originator drug.
What is therapeutic substitution?
Therapeutic substitution is the replacement of the originally-prescribed drug with an alternative molecule with assumed equivalent therapeutic effect. The alternative drug may be within the same class or from another class with assumed therapeutic equivalence
Name the advantages and disadvantages of drug administration via oral route?
Advantages – Cheap – Safe – Convenient Disadvantages – Patient compliance – Variation in bioavailability of drug
Particle size and formation, what is contained in a drug capsule?
Drug Excipients Binding agents Lubricants Coatings
List the advantages of the different forms of oral route: Buccal / sublingual mucosa Gastric mucosa Small intestine Large intestine / colon Rectal mucosa
Buccal / sublingual mucosa – Direct absorption into bloodstream – Avoids first pass metabolism – Not ideal surface for absorption Gastric mucosa – Enteric coating Small intestine – Main site of drug absorption – Large surface area, more neutral pH Large intestine / colon – Poor absorption, long transit times Rectal mucosa – Direct to systemic circulation
4 ways small molecules cross cell membranes
1) Diffusing directly through the lipid
-Lipid solubility highly important
2) Diffusing through aqueous pores
-More likely important for diffusion of gases
3) Transmembrane carrier protein
– e.g. solute carriers
4) Pinocytosis
– Mostly macromolecules, not drugs
What is the physicochemical factor affecting drug absorption?
Drug ionisation
What is the henderson-hasselblach equation for a weak base?
pKa - pH = Log10 [BH+]/[B]
ionised on top
What is the henderson-hasselblach equation for a weak acid?
pKa - pH = Log10 [AH]/[A-]
note ionised on bottom
weak acid are more likely to be absorbed by SI than weak bases
Weak acid are ____likely to be absorbed by SI than weak bases
Weak acid are more likely to be absorbed by SI than weak bases
Effect of food on gastric emptying?
Slows the rate
Effect of decreased absorption on drug absorption
Intestinal motility
Interactions with food, acids
Presystemic metabolism
Effect of delayed absorption on drug absorption
Gastric emptying
Clinically important
Cmas may decrease
Increased absorption effect on drug absorption
Poorly water soluble drugs
increased solubilisation
Decreased pre systemic metabolism
What is process of first pass metabolism in levodopa uptake?
Levodopa: Prodrug in treatment of Parkinson’s disease
Rapidly taken up from stomach and small intestine. Large neural amino acid transport carrier (LNAA)
DOPA decarboxylase present in gastric mucosa
Effect of intestinal disease in drug absorption?
Altered rate of drug absorption due to disease state
– E.g. Increased GI motility, compromised GI integrity
– What about reduced motility? (e.g. diabetic gastroparesis)
E.g. Crohn’s and coeliac disease
Factors that affect oral absorption?
- Particle size and formulation
- GI motility
3, First pass metabolism
– First pass metabolism by gut wall or hepatic enzymes - Physicochemical factors
– Direct drug interactions, dietary factors, varying pH - Splanchnic blood flow
– Increased flow increases drug absorption - Efflux pumps
– P-glycoprotein
Name 2 parenteral routes and their properties?
Subcutaneous:
Slow absorption due to blood flow
Intramuscular:
-Lipophilic drugs rapidly
-Polar drugs via bulk flow and endothelial cell junctions
-High MTW or very lipophilic drugs via lymphatics
What determines the rate of onset when using parenteral routes?
Extent of capillary perfusion
Drug vehicle
Affected by factors that alter perfusion
Inhalation as a method of drug administration:
Where is the drug absorbed via?
Systemic effects?
Local effects achieved by:
Where is the drug absorbed via: Alveolar epithelium and bronchial mucosa
Systemic effects:
-Lipid-soluble drugs
-Drugs of abuse
-Accidental poisoning
Local effects achieved by:
-Modifying structure e.g. ipratropium
-Changing the particle size e.g. salbutamol
-Selectivity for receptors e.g. salbutamol
-Rapid breakdown in circulation e.g. fluticasone
Intranasal drug administration:
Advantages?
Limitations?
Advantages:
- Easily accessible
- Rich vascular plexus
- Avoids hepatic first pass metabolism
- Ease, convenience, safety
Limitations:
-Limited drugs suitable as it requires concentrated drug
What are the local and systemic uses for drug administrations via the topical route?
Local uses:
- Corticosteroids for eczema e.g. hydrocortisone
- Antihistamines for insect bites e.g. mepyramine
- Local anaesthetics
Systemic uses:
- Transdural patches (HRT, GTN, nicotine)
- Accidental poisoning (AChEsterase insecticides)
What are difference in weak acid and base absorption?
Weak bases:
- Ionised in acidic pH
- Absorbed in SI
- Ionisation in plasma
Weak acids
- Unionised in acidic pH
- BUT also absorbed in small intestine due to large SA