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Flashcards in Drug absorption Deck (40):

Pharmaceutical process

Get the drug into the patient


Pharmacokinetic process

Get drug to the site of action


Pharmacodynamic process

Produce the correct pharmacological effect


Therapeutic effect

Produce the correct therapeutic effect


4 basic factors of pharmacokinetics

- Absorption
- Distribution
- Metabolism
- Elimination


ADME enables the understanding of...

- Dosage
- Drug administration
- Drug handling
- Patient variability
- Potential for harm


Drug deliver systems can be formulated to

- 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


3 key factors of dosage regimes

- Dose of the drug to be given
- Frequency of administration (as frequency increases, compliance decreases)
- Timing of administration


Factors in deciding dosage regime

- 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


Methods of administration

- Oral
- IV
- Subcutaneous
- IM
- Sublingual
- Rectal
- Inhalation
- Nasal
- Transdermal


Oral administration

- Solutions and suspensions
- Capsules
- Tablets
- Modified release tablets


Solution and suspensions

- 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


Tablets and capsules

- Convenient
- Accurate dose
- Reproducibility
- Drug stability
- Ease of mass production



- Under the tongue
- It bypasses the liver, first pass metabolism
- e.g. GTN spray


Definition of absorption

- 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


Oral absorption depends on three factors:

- Time to peak concentration: Tmax
- Peak concentration: Cmax
- Bioavailability: area under drug concentration-time curve - AUC



- 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



- Peak concentration
- Increasing the dose does not affect the time at which the peak concentration is reached but it does increase the peak concentration



- 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


Therapeutic concentration

- Drug is active over a range of concentrations
- Below there is no pharmacological action
- Above and toxicity occurs
- In between is therapeutic index


Factors affecting bioavilability

- Formulation
- Ability of drugs to pass physiological barriers
- Gastrointestinal effects
- First pass metabolism
- Route of administration


Formulation effects on bioavailability

- Slow release preparations
- How quickly it breaks up: modified release formulations could be slow release so break up slowly in gut


Ability of drug to pass physiological barriers effects on bioavailability

Due to
- Particle size
- Lipid solubility
- pH and ionisation


Gastrointestinal effects on bioavailability

- 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


First pass metabolism

- Phenomenon where concentration of a drug is greatly reduced before it reaches systemic circulation
- Need a significantly higher oral dose


Administration routes that avoid first pass metabolism

- Suppository
- IV
- IM
- Inhaled aerosol
- Transdermal
- Sublingual


Transport across membrane

- Passive diffusion
- Active absorption
- Facilitated diffusion
- Filtration, bulk flow, pore transport


Passive diffusion

- Occurs along conc. gradient
- Non selective
- Not saturable
- Requires no energy
- No carrier needed


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


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


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


Facilitated diffusion

- Along concentration gradient
- Requires carriers
- Saturable
- Structure specific
- No energy required
- Monosaccharides, amino acids, vitamins


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


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


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


Benefits of sublingual, buccal

- Bypasses first pass metabolism which will inactivate the drug
- Enters circulation directly
- GTN for angina


Benefits of rectal administration

- Bypasses first pass metabolism
- Absorption tends to be slow
- Often used for drugs which irritate stomach


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



- Avoids first pass metabolism
- Controlled release
- Few substances well absorbed
- Need to be non-irritant


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