Drug Absorbtion Flashcards
What is Pharmacodynamics?
What the drug does to the body, its mechanism of action
What is Pharmacokinetics?
What the body does to the drug, ADME
What is ADME and define all of the terms
- Absorption -the process by which unchanged drug enters the circulation
- Distribution - dispersion of a drug among fluids and tissues of the body
- Metabolism - transformation of a drug into daughter compound(s)
- Excretion - removal of drugs/metabolites from the body
- These processes all occur at different times. Some of the drugs may be absorbed whilst some of it may be distributed.
Why is monitoring ADME important?
- Key factors in determining the speed of onset of a drug’s effects, their duration of action and the potential for problems in special cases
- Essential for the safe and intelligent use of medicines by all doctors – essential for treatment
- Designing dosing regimens
- Monitoring treatment compliance
- Substance abuse monitoring
- Medicine licensing requirement
When do you take paracetamol, what are its cautions and its adverse effects?
- Indications: mild to moderate pain, pyrexia (raised body temp).
- Cautions: e.g. hepatic impairment (dose-related toxicity – avoid large doses); interactions (alcohol)
- Dose: by month, 0.5-1 g every 4-6 hours to a max of 4 g daily; by intravenous infusion, over 15 min, 1 g every 4-6 hours, max 4 g daily, max 60 mg/kg daily
- Side-effects: rare but include skin reactions
Give 6 reasons why a drug can be removed from development
Pharmacodynamics
effect on man
Animal toxicity
Commercial reasons
Lack of efficacy
Other reasons
What are the key principles of drug absorption?
Absorption - The process by which unchanged drug gets from site of delivery to the circulation
• Medicines need to be absorbed unless given directly into the circulation
• Different routes of administration present different barriers to absorption
• Different routes of administration result in different bioavailability and onset
• They are given in different locations, which impacts the speed of action.
What are the 2 routes of administration?
- Oral dose – passes through the liver (hepatic portal vein). Hepatocytes might metabolise a lot of the drug, so only a small fraction of the drug is admitted to the rest of the circulation. First pass metabolism is the name of this process.
- It can be injected using I.V injections.
Describe the key principles of absorption 2
- Choice of delivery route is a compromise
- Speed of onset
- Convenience: oral or i.v.?
- Bioavailability: proportion of administered drug reaching the systemic circulation – 100% for drugs given i.v. This is the same as fraction: F. F = 1 for I.V.
- Side effects / specificity of action
Describe the key principles of drug absorption 3 - membrane
- Absorption requires drugs to cross biological barriers (layers of cells with semi-permeable, lipophilic membranes)
- Most absorption occurs through cells, some occurs between cells
- Pass through a lipid bilayer and pass into cytosol.
- Some drugs go between cells and some through the cells. This means the drugs need to be able to dissolve in the aqueous medium, but not to a great extent.
Transcellular
Paracellular
Describe the key principles of drug absorption 4 and Ficks law
- Absorption can occur by:
- active transport through cells (very few medicines) – uses energy
- facilitated diffusion through cells (few medicines)
- passive diffusion (most medicines) – this is what most drugs do.
- If the molecules are charged they are less likely to pass through the membrane.
Describe key principles of drug absorption 5 - drugs are weak acids and bases. Ionising equations
- If the molecules are polar/charged they are less likely to pass through the plasma membrane.
- Most drugs are weak acids and bases and are thus ionisable.
- It can exist in neutral or charged version. Neutral is better for passive diffusion.
- The extent of ionisation depends on the Ph of the environment and the acid-base dissociation constant of the drug
Describe the key principles of drug absorption 6 - what state the drugs should be when they diffuse across the membrane
- To diffuse across cell membranes medicines must be uncharged
- Non-ionisable, lipophilic drugs are absorbed most effectively
- Ionised (charged) drugs absorbed least effectively
Describe the Henderson-Hasselbalch equations
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Describe the absorption of aspirin
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