Pharmacokinetics Flashcards
Pharmacokinetics
The effect of the drug on the body
Define drug
- single chemical entity
- which is one of the constituents of a medicine
Define medicine
- Contains one or more active contituents together
- With additives to facilitate administration
Individual variation of Drugs
- Age
- Genetic factors
- Physiological status
- Altered pathology
- Drug interactions
Administration routes: Enteral (via gut)
- Oral
- Rectal
Parenteral (avoid gut)
- Buccal
- Sublingual
- Topical
- Transdermal
- Intranasal
- Intradermal
- Subcutaneous
- Intraocular
- Epidermal
- Intarvenous
Enteral routes
- Slow and unpredictable absorption
- Safe
- Non-invasive
Parenteral routes
- Used for drugs that are destroyed by gut or first pass metabolism
- Allows access to otherwise protected or hard to access areas
- Enables lower dose of drug to be used
Difference between lipid soluble and water soluble drug
Lipid-soluble compounds can dissolve through a membrane, while water soluble compounds can not.
Gastrointestinal Factors which influence absoption
Oesophageal passage
The pH of the gastrointestinal tract
Gastric motility
Presence of food and drink
Drug Efflux
These proteins use energy to push drugs back into the intestine, limiting the absorption of fat soluble drug via the intestinal wall
Absorption in paediatrics
(be cautious of this one ddont make sense)
- Smaller size
- Infants have a proportionally larger body fluid content than adults
- Thus larger dose per body weight
How does respiratory affect absorption
Less mucous in the respiratory tract
Less well developed immune response
How does the brain and the BBB affect absoption
The BBB(blood brain barrier) is not fully developed until the brain matures.
Normally takes a year
SO care to be taken with compounds that may cause cerebral irritation.
How Does skin affect absorption
- Neonates Larger Surface
- Skin is thinner and more permeable than adults
- Steroidal creams should be avoided
How does stomach affect the absorption of drugs
- Less stomach acid
- Some drugs more permeable than normal in stomach
Distribution
The amount of drug in body tissues fluids or spaces
Other factors that affect drug distribution
- Blood flow in the tissue
- Binding to plasma proteins
- Cellular binding
- Adipose store in the tissue
Plasma Binding
(also referred to as Protein binding)
- Drug binding varies widely. For example the presence of plasma albumin in cells cause drugs to bind to it.
- Therefore only the drug that is unbound or free is able to distribute to target tissues.
Effects of plasma binding
- Highly bound drugs require larger loading doses
- Highly bound drugs have limited tissue distribution
- Changes in available plasma protein, may have a profound effect on free drug availability
What is volume of distribution
Hypothetical proportion of how much drug the body can absorb
Calculation:
V/D
V=volume
D=Distribution
Example Question for Volume Distribution :
What’s the volume distribution of a drug confined to blood stream of a 70kg Person with 3 litres of blood?
Hint: formula V/D
3/70=
0.042 Lt/kg
Drug Metabolism
- Primarily takes place in the liver
- Phase 1 Metabolism
- Phase 2 Metabolism
Drugs may go through
* Phase 1 Metabolism alone
* Phase 2 metabolism alone
* Phase 1 metabolism then phase 2 metabolism
Phase 1 Metabolism
causes breaking down of the molecule to more water soluble components
Phase II Metabolism
Adds on water soluble conjugate molecules to make the whole complex more water soluble
got to slide 34 on pharmacokinetics for paracetamol metabolism
Whats cytochrome P450
- Phase 1 metabolic enzyme
- Responsible for metabolising >60% of all therapeutic drugs
- Cytochrome P450 inhibited by a number of substances found in grapefruit juice
Drugs that are metabolised by CYP 3A4 (cytochrome)
More on PPT
- fentanyl
- Ketoconazole
- Oxycodone
- Diazepam
- Midazolam
- Metoprolol
- Amlodipine
Inhibitors of CYP 3A4
More on PPT
- Protease inhibitors
- Grapefruit
- Black pepper
- Conazoles
Inducers of CYP 3A4
- Phenytoin
- Dexamethasone
- Rifampicin
Metabolism of drugs in liver of infants
- Infant Livers have fewer metabolic enzyme systems
- Slower elimination
- Longer half lives
- Less frequent dosing for some medication
- Protein levels lower in paediatric patient especially in premature babies
- Higher concentration of un-protein bound drug in the blood
Drug elimination
The final phase of drug cycle is elmination. Drugs are eliminated in three ways:
* Redistribution
* Liver metabolism
* Renal Excretion
Drug Excretion
In bile from the liver
In urine from the kidney
Drugs can also be excreted via lungs, faeces, saliva, sweat, breast milk, hair
Role of kidneys in drug elimination
- Glomerulus
* Filtration occurs
2.Proximal Tubule
* Drug re-absorption
* Drug efflux
3.Collecting Duct
* Drug re-absorption
* Drug efflux
Water soluble drugs are largely voided in the urine without being reabso
GI/liver clearance
- Liver eliminates drug into the kidney.
- While in the kidney some drugs get reabsorbed into the liver
- liver metabolises frug into the gall bladder.
- Bile
- Small intestine then digests so this drug is then cleared out from the faeces.
- Sometimes the intestinal flora de-conjugates metabolised drug to liberate the parent drug back to the liver.
