Lec 2-Absorption Flashcards
1
Q
Switching formulations
A
- Morphine- terminal illness, cancer patients IV morphine
- Morphine- end of life care= oral morphine
- the dosage for the different routes can be large
2
Q
Drug absorption routes
A
- Absorption
- Oral
- Topical
- Inhaled
- IM
- SC
- Non- absorbed
- IV- no absorption due to dose being delivered directly into circulation- 100% = F
3
Q
Drug absorption- oral dose
A
- Absorption processes typically can delay the clinical effect of the drug as a result of the drug needing to go from the site of administration to the site of action
4
Q
Drug absorption- transdermal/topical
A
- Absorption processes typically can delay the clinical effect of the drug, as a result of the drug needing to go from the site of administration to the site of action
5
Q
Drug absorption- IM/SC
A
- Absorption processes typically can delay the clinical effect of the drug, as a result of the drug needing to go from the site of administration to the site of action
- Still has many absorption barriers
6
Q
Drug absorption processes
A
- Solid => Disintegration => Dissolution => Absorption
- These steps are Prerequisites to absorption and at each stage of this process we can lose large amounts of our initially dosed drug
- Bioavailability (F) means the extent to which the active moiety is absorbed from a drug product and becomes available in the systemic circulation
- Dissolution is the process which is the slowest especially if the drug is poorly soluble, to overcome this we can make the drug into the salt form (which is ionised therefore more soluble)
- Absorption is characterised by the bioavailability and the absorption rate constant
7
Q
Drug absorption- sites
A
- Epileptic drugs- the target site is in the brain, there are therefore many different absorption barriers to cross from GI => circulation => brain
- Capillaries are one of the main absorption barriers (cell membrane- lipid bilayer)
- The site of drug action typically intracellular
- Absorption is a pre-requisite for site-targeting and clinical effect
- All tissues/organs have a biological membrane/barrier which drugs must be able to transverse to reach their target sites and is highly dependant on lipophilicity of the drug
- A barrier in the capillary/blood vessels is one of the main barriers in the body (cell membrane lipobilayer)
- NB- most of the barriers in the body are lipobilayers
8
Q
Pharmacokinetic- drug properties
A
- Specific properties of the drug can have a significant effect in influencing how quickly or slowly a drug is able to partition across cell membranes
- Most drugs have to be non-ionised and lipophilic to cross membranes
- Factors involved in absorbing a chemical:
-
Physiochemical properties
- Hydrophilic/phobic
- Ionized/no-ionized/Weak acid or base
- Molecular Weight (Should be below 500)
9
Q
Pharmacokinetics- drug properties oral dose Lipophilicity
A
- Lipophillic (LogP)
- Be lipophillic meaning it will partition into the lipid bilayer
- Absorption rate is usally quicker
10
Q
Drug properties- ionisation
A
- Non-ionised drugs are absorbed far quicker
- This is because the outside of the lipid bilayer is charged meaning that ionised molecules are repelled
- Non-ionised drug are uneffected
11
Q
Drug absorption pathways
A
- Paracellular route- Between cells = Diffusion
- Transcellular route- through cells
- Passive= diffusion
- Carrier-mediated = active facilitated
- Endocytosis= receptor mediated
12
Q
Paracellular (passive diffusion)
A
- Passive process
- Very low MW drugs pass through
- Dependant on drug properties (Ionisation state, pH)
- The lipid-like membrane acts as a filter letting through only very small dissolved drug particles
- Concentration depends on and enhances the process
13
Q
Transcellular (passive diffusion)
A
- Drugs crossing cells via diffusion
- Must be hydrophobic drug particles
- Hydrophobic= dissolution issues
- Concentration dependent, pH and ionisation state of drug
- LogP (lipophilicity) is important in determeningthe extent of permeation
14
Q
Pharmacokinetics- transcellular (carrier mediated transport)
A
- Carrier-mediated system
- Like a transporter pump
- Requires ATP
- Enzyme therefore prone to Saturation
- System cane exist in Uptake (in) or in Efflux (out) state
- Drug-drug interaction can compete for the transporter
- Specific transporters exist for endogenous substances in the body
- One reason chemotherapy doesn’t work in some people is that a tumour will pump out the chemotherapy drug (efflux)
15
Q
Transcellular- receptor-mediated endocytosis
A
- Drug will bind to a receptor
- Drug is encolsed into a vesicle
- Then delivered to the other side
- Very specific
- Vaccines and other proteins- due to there size
16
Q
Pharmacokinetic- graphic
A
- The route of administration plays a role in the type of profile we get
- The profile tells us about how the clinical outcome
20
Q
Henderson-hasselbach- example
A
- Diazepam pKa = 3
- In stomach pH=1.2
- In Blood pH= 7.4
- The drug exists mainly in the Unionised state the ratio will be Bottom heavy
- If the drug exists mainly in the ionised state the ratio will be top heavy
21
Q
How does this affect absorption
A
- Excess HA (unionised) exists thus the concentration gradient sends it into the blood
- Excess A- (ionised) exists thus it cannot go back to the intestinal fluid
- Overall absorption is increased
