Drug absorption Flashcards
1
Q
Pharmaceutical process
A
Get the drug into the patient
2
Q
Pharmacokinetic process
A
Get drug to the site of action
3
Q
Pharmacodynamic process
A
Produce the correct pharmacological effect
4
Q
Therapeutic effect
A
Produce the correct therapeutic effect
5
Q
4 basic factors of pharmacokinetics
A
- Absorption
- Distribution
- Metabolism
- Elimination
6
Q
ADME enables the understanding of…
A
- Dosage
- Drug administration
- Drug handling
- Patient variability
- Potential for harm
7
Q
Drug deliver systems can be formulated to
A
- allow selective targeting of a tissue site
- Avoid pre- or systemic metabolism
- Allow a 24 hour action
- Means you can tailor to patient’s needs, pharmacological characteristic and disease state
8
Q
3 key factors of dosage regimes
A
- Dose of the drug to be given
- Frequency of administration (as frequency increases, compliance decreases)
- Timing of administration
9
Q
Factors in deciding dosage regime
A
- Recommended dose
- Renal function
- Hepatic function
- Age and weight
- Disease to be treated
- Drug toxicity
- You give a starting dose and increase until you achieve the desired effect
10
Q
Methods of administration
A
- Oral
- IV
- Subcutaneous
- IM
- Sublingual
- Rectal
- Inhalation
- Nasal
- Transdermal
11
Q
Oral administration
A
- Solutions and suspensions
- Capsules
- Tablets
- Modified release tablets
12
Q
Solution and suspensions
A
- Useful for swallowing difficulties, can be given via NG or PEG tube
- Suspensions: can be useful if the insoluble variety is unpalatable as it can be contained in a small volume
13
Q
Tablets and capsules
A
- Convenient
- Accurate dose
- Reproducibility
- Drug stability
- Ease of mass production
14
Q
Sublingual
A
- Under the tongue
- It bypasses the liver, first pass metabolism
- e.g. GTN spray
15
Q
Definition of absorption
A
- Process of movement of unchanged drug from the site of administration to the systemic circulation
- Correlation between plasma concentration of a drug and the therapeutic response
16
Q
Oral absorption depends on three factors:
A
- Time to peak concentration: Tmax
- Peak concentration: Cmax
- Bioavailability: area under drug concentration-time curve - AUC
17
Q
Tmax
A
- Time to peak concentration
- The more rapid the rate of absorption, the earlier the drug concentration peak
- Quicker in liquid form or in solution or certain tablets that break down quickly
18
Q
Cmax
A
- Peak concentration
- Increasing the dose does not affect the time at which the peak concentration is reached but it does increase the peak concentration
19
Q
AUC
A
- Bioavailability, area under the drug concentration-time curve
- Amount of drug which reaches the systemic circulation
- IV bioavailability is 100%, could be as low as 50% orally
20
Q
Therapeutic concentration
A
- Drug is active over a range of concentrations
- Below there is no pharmacological action
- Above and toxicity occurs
- In between is therapeutic index
21
Q
Factors affecting bioavilability
A
- Formulation
- Ability of drugs to pass physiological barriers
- Gastrointestinal effects
- First pass metabolism
- Route of administration
22
Q
Formulation effects on bioavailability
A
- Slow release preparations
- How quickly it breaks up: modified release formulations could be slow release so break up slowly in gut
23
Q
Ability of drug to pass physiological barriers effects on bioavailability
A
Due to
- Particle size
- Lipid solubility
- pH and ionisation
24
Q
Gastrointestinal effects on bioavailability
A
- Gastric absorption will affect speed at which drug reaches site of action, most drugs absorbed in small intestine
- Gut motility: diarrhoea/constipation
- Food: can enhance/impair rate of absorption
- Illness: malabsorption -> coeliac can increase or decrease rate of absorption
- Migraine reduces rate of stomach emptying and thus analgesic drugs
25
First pass metabolism
- Phenomenon where concentration of a drug is greatly reduced before it reaches systemic circulation
- Need a significantly higher oral dose
26
Administration routes that avoid first pass metabolism
- Suppository
- IV
- IM
- Inhaled aerosol
- Transdermal
- Sublingual
27
Transport across membrane
- Passive diffusion
- Active absorption
- Facilitated diffusion
- Filtration, bulk flow, pore transport
28
Passive diffusion
- Occurs along conc. gradient
- Non selective
- Not saturable
- Requires no energy
- No carrier needed
29
Passive diffusion depends on. 1.
- Ionisation: most drugs are weak acids or bases so their degree of ionisation depends on the pH of the environment
- Only un-ionised drug crosses the membrane
- Un-ionised should distribute across the membrane until equilibrium is reached
- An acidic drug will be more concentrated in the compartment with high pH
30
Passive diffusion depends on. 2.
Lipid solubility:
- To pass across a lipid layer a drug must be in solution and be lipid soluble
- Ability of a drug to diffuse across a lipid barrier is expressed as a lipid-water partition coefficient
- some might not be lipid soluble at all e.g. gentamicin
31
Active absorption
- Relatively unusual
- Requires carrier and energy: against concentration gradient, drugs are reversibly bound to a carrier system
- Specific: must resemble naturally occurring compounds
- Saturable
- Iron, K, Na, Ca
- Uptake of levodopa by brain
32
Facilitated diffusion
- Along concentration gradient
- Requires carriers
- Saturable
- Structure specific
- No energy required
- Monosaccharides, amino acids, vitamins
33
Filtration, bulk flow and pore transport
- Filtration normally occurs through channels in the cell membrane
- Low molecular size
- Driving force is hydrostatic or osmotic pressure difference across membrane
- Generally in water soluble drugs -> urea, water & sugars, renal excretion, removal of drug from CSF and entry of drug into the liver
34
Medical importance of first pass metabolism
- Can be a limit on oral route for some drugs e.g. insulin
4 systems effect first pass:
- Gut lumen (acid, enzymes)
- Gut wall (acid, enzymes)
- Liver (hepatic enzymes)
- Bacterial enzymes
- Can all be changed by drugs and disease
35
Benefits of subcutaneous/IM
- Can change the rate of absorption from these sites with different physical properties of formulation
- Depends on blood flow to site
- Needs small volume
- Avoids first pass metabolism
- Some drugs are not well absorbed from this route
- Can split muscle if on anticoagulants
36
Benefits of sublingual, buccal
- Bypasses first pass metabolism which will inactivate the drug
- Enters circulation directly
- GTN for angina
37
Benefits of rectal administration
- Bypasses first pass metabolism
- Absorption tends to be slow
- Often used for drugs which irritate stomach
38
Benefits of inhalation/nasal
- Depends on delivery system, particle size and patient technique
- Better for volatile agents
- Can be metabolism in lungs
- Relatively rapid action
- 5-10% absorbed
39
Transdermal
- Avoids first pass metabolism
- Controlled release
- Few substances well absorbed
- Need to be non-irritant
40
Considerations for mode of administration
- Purpose and site of drug action: local absorption, avoid first pass metabolism
- Disease effects
- Ability to take meds
- Speed of action: immediate (IV) or slow/doesn't really matter (oral)
- Reliability of absorption
