Drug administration and absorption

Drug administration and absorption

1. administration

   • oral
     • advantages
       • administration easy and convenient
       • no skilled personnel required
       • preparation doesn't have to be sterile
     • stomach is ph 2
       • Acidic drugs e.g. aspirin - mainly non-ionised in stomach - readily absorbed
       • Basicdrugse.g.amphetamine-mainlyionised in stomach - poorly absorbed
       • Neutraldrugs-alcohol-readilyabsorbed
     • duodenum ph 8 is alkaline
       • Basic drugs – amphetamine – mainly non-ionised - readily absorbed
       • Acidic drugs - aspirin – mainly ionised - should restrict absorption
       • however surface area is enormous
         • Duodenum is major site of absorption of acidic, basic and lipophilic drugs from gastro-intestinal tract
     • disadvantages
       • effects are very slow
       • absorbtion man be incomplete
     • some drugs cannot be given orally because
       • ionisedthroughoutpHrangeofgut(tubocurarine)
       • toolargetobeabsorbed(insulin)
       • destroyedinthegutbyacids,enzymesorbacteria
       • destroyedintheliverafterabsorption(firstpass effect)
   • sublingual
     • under the tongue
   • rectal/vaginal
   • epithelial
     • topical (skin
     • corneal
     • nasal
   • inhalation
     • large surface area of alveoli in lungs
       • good pulmonary blood supply
     • inhaled drugs can have
       • local effects on lungs
         • asthma
           • eg salbutanol
       • systemic effects
         • eg general anasthetic
           • halothane
   • injections
     • bypass didfficulties in absorption of gut
     • exact dose of drug given is known
     • drugs must be sterile
     • can only be given by skilled staff
     • intravenous route
       • advantages
         • rapid effect
         • large volumes can be used
         • irritant drugs solutions can be used
       • disadvantages
         • rapid delivery to heart, CNS- side effects
         • cannot recall drug
     • intramuscular and subcutaneous routes
       • advantages
         • control onset with drug vehicle
         • aqueous- rapid effect
         • oily- slow effect
       • disadvantages
         • damage at injection site
         • limited to small volumes

2. Most drugs are weak electrolytes, i.e. acids or bases • exist in equilibrium of charged and uncharged forms

   • Only non-ionised form can be absorbed across lipid membranes

3. route of chosen administration dependss on

   • chemical nature of the drug
   • how quickly an effect is required
   • how long the effect must be maintained
   • patient condition
   • convenience

4. Distribution of drugs

   • drug needs o get to its site of action, out of plasma and into tissues
     • capillaries are leaky, large pores, most drugs can move easily into interstitial fluid around tissues and, thus, interact with the target cells

5. plasma protein binding

   • bound fraction remains in plasma
   • many drugs bind to plasma proteins
     • e.g. extreme example, warfarin 99% bound
   • only unbound fraction can defuse into tissues
     • only unbound fraction is active

6. blood brain and blood placental barrier

   • capillaries in CNS
     • no pores - thus, only lipophilic drugs can cross capillary membrane into CNS, ionised drugs excluded
   • placenta
     • good barrier to drugs
       • only lippophillic drugs cross to foetus