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Flashcards in Drug absorption Deck (40):
1

Pharmaceutical process

Get the drug into the patient

2

Pharmacokinetic process

Get drug to the site of action

3

Pharmacodynamic process

Produce the correct pharmacological effect

4

Therapeutic effect

Produce the correct therapeutic effect

5

4 basic factors of pharmacokinetics

- Absorption
- Distribution
- Metabolism
- Elimination

6

ADME enables the understanding of...

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

7

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

8

3 key factors of dosage regimes

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

9

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

10

Methods of administration

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

11

Oral administration

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

12

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

13

Tablets and capsules

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

14

Sublingual

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

15

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

16

Oral absorption depends on three factors:

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

17

Tmax

- 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

Cmax

- 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

AUC

- 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

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

21

Factors affecting bioavilability

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

22

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

23

Ability of drug to pass physiological barriers effects on bioavailability

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

24

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

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