Drug absorption

Question 1

Pharmaceutical process

Answer 1

Get the drug into the patient

Question 2

Pharmacokinetic process

Answer 2

Get drug to the site of action

Question 3

Pharmacodynamic process

Answer 3

Produce the correct pharmacological effect

Question 4

Therapeutic effect

Answer 4

Produce the correct therapeutic effect

Question 5

4 basic factors of pharmacokinetics

Answer 5

• Absorption
• Distribution
• Metabolism
• Elimination

Question 6

ADME enables the understanding of…

Answer 6

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

Question 7

Drug deliver systems can be formulated to

Answer 7

• 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

Question 8

3 key factors of dosage regimes

Answer 8

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

Question 9

Factors in deciding dosage regime

Answer 9

• 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

Question 10

Methods of administration

Answer 10

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

Question 11

Oral administration

Answer 11

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

Question 12

Solution and suspensions

Answer 12

• 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

Question 13

Tablets and capsules

Answer 13

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

Question 14

Sublingual

Answer 14

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

Question 15

Definition of absorption

Answer 15

• 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

Question 16

Oral absorption depends on three factors:

Answer 16

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

Question 17

Tmax

Answer 17

• 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

Question 18

Cmax

Answer 18

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

Question 19

AUC

Answer 19

• 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

Question 20

Therapeutic concentration

Answer 20

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

Question 21

Factors affecting bioavilability

Answer 21

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

Question 22

Formulation effects on bioavailability

Answer 22

• Slow release preparations

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

Question 23

Ability of drug to pass physiological barriers effects on bioavailability

Answer 23

Due to

• Particle size
• Lipid solubility
• pH and ionisation

Question 24

Gastrointestinal effects on bioavailability

Answer 24

• 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

Question 25

First pass metabolism

Answer 25

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

Question 26

Administration routes that avoid first pass metabolism

Answer 26

• Suppository
• IV
• IM
• Inhaled aerosol
• Transdermal
• Sublingual

Question 27

Transport across membrane

Answer 27

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

Question 28

Passive diffusion

Answer 28

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

Question 29

Passive diffusion depends on. 1.

Answer 29

• 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

Question 30

Passive diffusion depends on. 2.

Answer 30

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

Question 31

Active absorption

Answer 31

• 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

Question 32

Facilitated diffusion

Answer 32

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

Question 33

Filtration, bulk flow and pore transport

Answer 33

• 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

Question 34

Medical importance of first pass metabolism

Answer 34

• 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

Question 35

Benefits of subcutaneous/IM

Answer 35

• 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

Question 36

Benefits of sublingual, buccal

Answer 36

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

Question 37

Benefits of rectal administration

Answer 37

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

Question 38

Benefits of inhalation/nasal

Answer 38

• Depends on delivery system, particle size and patient technique
• Better for volatile agents
• Can be metabolism in lungs
• Relatively rapid action
• 5-10% absorbed

Question 39

Transdermal

Answer 39

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

Question 40

Considerations for mode of administration

Answer 40

• 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