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Renin Angiotensin Mechanism.

General Pharmacology-2 (Absorption)


Absorption:


  • The transfer of drug molecule from site of administration to systemic circulation in intact form is called as absorption.

Mechanisms of Drug Absorption:


  • Drugs gets absorbed by a variety of mechanisms, for sake of understanding, the mechanisms are categorized in two main categories depending on energy consumption during the process.

1) Passive Transfer:

A) Simple Diffusion.
B) Faciliated Transfer.
C) Pore Transfer.
D) Ion pair Transfer.

2) Active Transfer.

A) Pump Transfer.
B) Carrier Mediated transfer.
C) Phagocytosis.
D) Pinocytosis. 

1) Passive Transfer:


  • The processes included under this category does not involve energy during drug transfer.The drugs gets transferred across concentration gradient i.e. from higher concentration to lower concentration without involving energy transfer.This is the most common process adopted by most of lipid soluble drugs (Unionized drugs).

A) Simple Diffusion


  • As name itself indicates this is a simple diffusion process where lipid soluble drugs gets solubilized in lipoidal cellular membranes and get transferred from extracellular fluid to cytoplasm against concentration gradient.

B) Facilitated Transfer:


  • As name indicates this diffusion process is "facilitated", here the drug molecules are attached to specific carrier proteins on cell membrane and are diffused into cell membrane without involving energy transfer.
  • Highly polar drugs and charged ions gets absorbed by this mechanism.
  • e.g. Riboflavin, Oxygen

C) Pore Transport:


  • Cell membrane shows presence of protein pores the water soluble drugs get passed through them directly to cytoplasm irrespective of the concentration gradient.
  • e.g. Water molecule, RNA, certain ions.

D) Ion Pair Transfer:


  • Here the polar ions made non polar by salt formation and then diffused through the cell membrane.

2) Active Transfer.


  • In this process the drug molecules enters cytoplasm against concentration gradient i.e. from lower concentration to higher concentration by utilizing energy.
  • e.g. certain ions, synthetic drugs like steroids, hormones etc.

A) Pump Transfer:


  • In this process the drugs are transported to cytoplasm by attaching to the proteins called as pumps using energy in the form of ATP.
  • e.g. Sodium ions.

B) Carrier Mediated Transfer:


  • In this the drug molecules are attached to the carrier molecules located on plasma membrane to form carrier-drug complex.
  • The carrier drug complex get translocated using ATP as energy and release the drug molecules in the cytoplasm.
  • The remaining carrier molecules again using ATP as energy get relocated to their position to get ready to form another carrier-drug complex.
  • This transfer depends on concentration of carriers and follows non-linear kinetics.
  • Hence even the concentration of drug increases at absorption site the absorption is not likely to increase as carriers may not free.
  • e.g. Vit B12.

C) Phagocytosis:


  • It means eating by cell, here the foreign particles are eaten by cells by pseudopodium formation.
  • e.g. ingestion of microbes by neutophiles.

D) Pincocytosis:


  • It means drinking by cell, here cells ingest liquid drops.
  • e.g. absorption of polio vaccine.

What is Significance of Drug Absorption?

Study of drug absorption is essential to,
) Determine the dosing frequency.
) Determine the effective duration of action.
) Anticipation of desired and undesired effects of the drug.

Factors affecting drug absorption:

  • Drug absorption is affected by various factors depending on route of administration. (In I/V route as drug is introduced directly into systemic circulation provides 100% absorption.)
  • Oral route is most economical and commonly used route for drug administration poses number of hurdles and affects the drug absorption.
  • The factors affecting drug absorption are categorized and discussed as follows.

A) Drug Related Factors:
1) Physical State:


  • Drugs present in liquid form shows better absorption than those present in solid form.
  • Crystalloidal form gets better absorbed than collidal form.
  • Amorphous solids show better absorption as compared to crystalline solids.

2) Solubility:

  • All biological membranes are lipoidal in nature and hence drug with better lipid solubility show better absorption.
  • e.g. Alcohol,
  • Contrary to above, drugs with more water solubility shows poor absorption.
  • e.g. Neostigmine.

B) Dosage Form Related Factors:

1) Particle Size:

  • Larger the particle size lesser will be surface area for absorption and hence lesser will be absorption.
  • Contrary to this, lesser the particle size more will be surface are for absorption and hence greater will be the absorption.
  • e.g. Griseofulvin (Gris OD) an oral antifungal antibiotic has shown remarkable increase in absorption after micronization (Size reduction)

2) Formulation:

  • A range of dosage forms are available which can them self affect the absorption.
  • Powders have greater surface area as compared to others and hence show good absorption.
  • Capsules takes lesser time for disintegration and hence show better absorption as compared to tablets.
  • The fast dissolving tablets disintegrate quickly and gets absorbed faster.

3) Formulation Variables and Additives:

  • We observe batch to batch variations in certain criterias for quality controls.
  • If compression force becomes high disintegration time will increase affecting absorption.
  • Certain additives like calcium, aluminium, magnesium compounds, lactose are known to retard absorption of certain drugs.

  • e.g. Absorption of Tetracycline gets hampered when calcium, aluminium, magnesium compounds are used as additives in the formulation.

C) Patient Related Factors (Physiological Factors):


1) pH of Surrounding Medium:

  • Gastrointestinal tract shows a great variation in pH from acidic to basic, stomach contains very strong acidic pH while colon shows basic pH.
  • Acidic drugs like Aspirin when comes in contact with acidic pH of stomach, they become "unionized", as we know unionized form is more lipid soluble gets better absorbed.
  • Acidic drugs when reaches intestine due to its alkaline pH remains "ionized" as we know ionized form is less lipid soluble shows very poor absorption.
  • In contrary to above, basic drugs like Neostigmine in acidic environment of stomach remain "ionized" and show poor absorption @ stomuch.
  • When basic drugs reaches intestine because of alkaline pH there they get "unionized" and gets absorbed well.

2) Presence of other substances:

  • Other substances present in GI tract like food may affect absorption.
  • Drugs when administered competes for site of absorption with other substances present in GI tract like food, hence for better absorption drugs are usually given before breakfast e.g. Macrolide Antibiotics like Azithromycin, Roxytrhromycin are advised before breakfast for better absorption. (NOTE: However drugs which cause gastric irritation like NASAIDs  MUST NOT GIVEN on empty stomach ).
  • Certain substances present in food however known to improve absorption of certain drugs e.g. Vitamin C improves absorption of Iron compounds, fatty meals promote absorption of Griseofulvin.

3) Degree of Ionization: 

  • Unionized form is more lipid soluble hence shows good absorption.
  • Ionized form is less lipid soluble and more water soluble and hence shows poor absorption. 

4) Presence of Disease: 

  • In presence of diseases like diarrhea, dysentery, achlorhydria absorption of drugs is less.

5) Other Medicines:

  • Usually two or more drugs are administered together, these two drugs may interfere with absorption of each other.
  • e.g. Antacid "Aluminium Hydroxide Gel" when given with antibiotic "Tetracycline" forms insoluble chelate of tetracycline retarding its absorption.

6) Surface Area:

  • Stomach has lesser surface area for absorption as compared to intestine and hence absorption from intestine is more as compared to than from stomach.
  • Drugs present in aggregate form disintegrate slowly, when size reduction is done effective surface area increases showing improved absorption. e.g. Griseofulvin (Gris OD), an oral antifungal antibiotic has shown remarkable increase in absorption after micronization (Size reduction).

7) GI Transit Time:

  • The time taken by food to leave stomach and travel through intestine is called as GI transit time.
  • GI transit time gets affected by many factors like food, drugs, disease, psychological stress etc.
  • More the transit time more will be the absorption, lesser the transit time lesser will be absorption.




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