Pharmacokinetics Explaination Flashcards
What is the first pass effect?
where a significant portion of the (orally administered) drug is metabolised by the liver before it reaches systemic circulation
What is bioavalibility?
- the amount of the drug that reaches systemic circulation in an unchanged form and becomes available for biological effect after administration (from any route)
What is half life?
the rate of elimination (the time for drug concentration in the blood to half)
What are the 6 routes of administration and their sites of absorption?
- oral (mouth, GI tract)
- inhalation (nasal passage or lungs)
- intravenous (IV) (directly into venous blood)
- intramuscular (directly into muscle)
- transdermal (skin)
- buccal (oral mucosa)
What is drug absorption?
the movement of the drug into the blood stream where it must cross a series of membranes
5 common modes of transport in drug absorption
- filtration through pores
- passive diffusion through the membrane
- active transport
- facilitated diffusion
- phago/pinocytosis
What is the route of absorption - oral to blood?
GI tract, liver, right heart, lungs, left heart, arterial circulation
What is the route of absorption - inhalation to blood?
lungs, left heart, arterial circulation
What is the route of absorption - buccal to blood?
oral mucosa, venous circulation, right heart, lungs, left heart, arterial circulation
What is the route of absorption - transdermal to blood?
skin absorption, venous circulation, right heart, lungs, left heart, arterial circulation
What is the route of absorption - intramuscular to blood?
muscle tissue, muscle capillaries, venous circulation, right heart, lungs, left heart, arterial circulation
What is the bioavalibility of intravenous administration?
100%
What is metabolism?
- biochemical modification or degradation through specialised enzymatic actions (2 phases)
What are the 2 phases of metabolism?
1) non-synthetic, 2) synthetic
What does phase 1 metabolism involve?
non-synthetic reactions that break down existing bonds in the drug’s molecules
What do phase 1 metabolism reactions result in?
alters the drug’s structure without creating new bonds, influencing its pharmacological activity or facilitating further metabolism
What does phase 2 metabolism involve?
synthetic bonds that form new chemical bonds to create drug metabolites
What do phase 2 metabolism reactions often result in?
the formation of more water-soluble metabolites
What is the benefit of a substance being more water-soluble?
easier to excrete, aiding in their elimination
What are the 5 types of reactions in phase 1 metabolism?
- hydrolysis
- oxidation
- reduction
- dealkylation
- deacetylation
What are the 4 types of reactions in phase 2 metabolism?
- sulphation
- glucuronidation
- acetylation
- amino acid conjugation
What is half life and clearance used for?
To quantify the rate and extent of the drug removal from the body
What are most drugs metabolised to?
water soluble substances, whhich are excreted in urine
If a drug can only be metabolised into lipid soluble compounds, where are they excreted?
in the bile, through the large intestine (in the faeces)
Where does most metabolism occur?
In the liver, often catalysed by CYP450 enzymes
What is catabolism?
the process of breaking down molecules into smaller units
what are the steps of the first pass effect?
- dissolve in stomach’s gastric juices
- diffusion into blood stream from intestine
- delivery to liver by hepatic portal vein
- processing by the liver (may involve metabolism)
- delivery to systemic circulation
What result does the first pass effect have?
the oral bioavailability of the drug reduced
Name 5 factors that affect the rate and extent of drug distribusion
- chemical structure of drug
- route of administration
- presence of food/drugs in GI tract
- stability of the drug in the GI tract (if oral route)
- ease of transport through membranes (like BBB)
How is the extent of distribution expressed?
the volum of distribution (total amount of drug present in the body/concentration in blood plasma)
What does a high volume of distribution value correspond to?
extensive distribution in the peripheral tissue
What factors can cause half life values to vary?
patient and drug specific values like liver or kidney failure
What is the theraputic index?
the difference between the theraputic effect and toxic effect in 50% of people
What is the time range for drug detection in blood, urine, and hair?
- blood = hours to days
- urine = days to weeks
- hair = days to months
What does urine testing show? Name 3 methods of testing
indicate the presence of the drug and common metabolites
- immunoassays
- simple colour change tests
- chromatography
What can support defence in law regarding BAC?
- witness statements
- estimate of BAC by expert witness
What can support defence in law regarding BAC - what do calculations of BAC include?
- total ethanol consumed and time of consumption
- weight, general health, and person’s drinking habits
- metabolic rate
How is the concentration (g/L) of alcohol in the body determined?
(total alcohol consumed - amount of alcohol metabolised) / volume of distribution
How is the mass (g) of alcohol in the body consumed?
(amount of alcohol consumed in ml) x (% ABV) x (density of ethanol: 0.789g/ml)
What is the average volume of distribution of ethanol?
0.54 litres/kg of body weight
What is the approximate clearance rate of ethanol?
0.12 g/kg of body weight per hour
What would increase the clearance of ethanol by 20% and why?
if the person is an experienced drinker, in order to account for induction of the liver enzymes which metabolise alcohol
What enzymes does ketamine use for metabolism, and what metabolite does that produce?
CYP450 and CYP3A4, and norketamine
Where is ketamine metabolised, eliminated, and excreted?
liver, kidneys, urine
