Drug Administration and Distribution Flashcards
what type of forms can be absorbed across lipid membranes?
Non-ionised forms
What is the ratio of ionised to non-ionised drug dependent on?
pH and pKa value of drug
What does the ratio of ionised to non-ionised drug affect?
Whether the drug is absorbed and where is the GI tract it happens
What are examples of molecules that can be absorbed across lipid membranes?
Gases (e.g. CO2, O2)
Hydrophobic molecules (e.g. benzene)
Small polar molecules (e.g. H20 and ethanol)
What are examples of molecules that cannot be absorbed across lipid membranes?
Large polar molecules (e.g. glucose) Charged molecules (e.g. Amino acids, H+ ions, Na+ ions)
What are drugs?
Weak electrolytes i.e. acids of bases
What form do drugs exist in?
Equilibrium of charged and uncharged forms
What is the equilibrium equation for bases?
RNH2 + H+ RNH3+
What is the equilibrium equation for acids?
RCOOH RCOO- + H+
What is pKa?
Dissociation consant (pH at which drug is 50% ionised and 50% unionised, i.e. ratio of 1:1)
What is pH?
pKa + log ([RCOO-]/ [RCOOH]) Since log (1/1)= log (1)= 0
What is the equation when pH and pKa are equal?
RCOO- = RCOOH
What happens to weak acids when the pH of the environment increases?
Ionisation increases
likely to be absorbed
What happens to weak bases when the pH of the environment increases?
Ionisation decreases
unlikely to be absorbed
What changes for each pH unit?
10-fold change
What is the pH of the plasma?
7.35-7.45
What is the pH of the buccal cavity?
6.2-7.2
What is the pH of the stomach?
1.0-3.0
What is the pH of the duodenum?
4.8-8.2
What is the pH of the jejunum and ileum?
7.5-8.0
What is the pH of the colon?
7.0-7.5
What happens in the stomach with a pKa of 4?
RCOOH RCOOH
Drug absorption
In the stomach, low pH, push equal towards protanation (uncharged)
In stomach weak acid, largerly protonated, largely uncharged so absorption may occur
What happens in the intestine with a pKa of 4?
H+ + RCOO-
No drug absorption
As you get into the intestine, pH rises, molecule will split into two, have charged form of drug and very little absorption
What happens for basic drugs in the intestine?
RNH2 RNH2
Drug absorption
What happens for basic drugs in the stomach?
H+ + RNH3
No drug absorption
What are acidic drugs?
E.g. aspirin- mainly non-ionised in stomach- readily absorbed
What are basic drugs?
E.g. amphetamine- mainly ionised in stomach- poorly absorbed
What are neutral drugs?
E.g. alcohol, readily abosrbed
What are the routes of drug administration?
Oral
Sublingual/buccal
Rectal- avoids first class metabolism
Epithelial- topical (skin), corneal, nasal
Inhalation
Injection- intravenous, sub-cutaneous, intramuscular, intrathecal (into CNS epidural ,for speed of onset of action)
What are the advantages of the oral route?
Administration easy and convenient
No skilled personnel required
Drug preparation need not be sterile
What are the disadvantages of the oral route?
Effects are slow
Absorption may be incomplete
Why can some drugs no be given orally?
Ionised throughout pH range of gut (tubocurarine)
Too large to be absorbed (insulin)
Destroyed in the gut by acids, enzymes or bacteria (proteins)
Destroyed in the liver after absorption (GTN)
What is the inhalation route useful for?
Large surface area of alveoli in lungs
Good pulmonary blood supply
What effects can inhalation drugs have?
Local effects on the lung (e.g. for asthma, salbutamol)
Systemic effects e.g. GAs
What do injected drugs bypass?
Difficulties of absorption in the gut
What must injected drugs be?
Sterile
Drugs can only be given by skilled staff
Exact dose of drug given is known
What are the advantages of the intravenous route?
Rapid effect
Large volumes can be used
Irritant drug solutions can be used
What are the disadvantages of the intravenous route?
Rapid delivery to heart, CNS- side effects
Cannot recall drug
What are the advantages of the intramuscular and sub-cutaneous routes?
Control onset with drug vehicle
Aqueous- rapid effect
Oily- slow effect
What are the disadvantages of the of the intramuscular and sub-cutaneous routes?
Damage at injection site
Limited to small volumes
What does distribution of drugs involve?
Drugs getting to the site of action
What do drugs need to do?
Get out of plasma and into tissues
What allows drugs to move easily into interstitial fluid?
Capillaries which are leaky (large pores), therefore drugs can move easily around tissues and interact with target cells
How do drugs travel around in the bloodstream?
Bound to plasma proteins
What does bound drug-plasma protein complex mean?
Bound fraction retained in plasma
Only unbound fraction can diffuse into tissues
Only unbound fraction is active
How are capillaries in the CNS different?
No pores
Only lipophillic drugs can cross capillary membrane into CNS ionised drugs excluded
What kind of drugs can pass across the placenta?
Only lipophilic drugs
How will effect of drugs be terminated?
Distribution of drugs away from their site of action
