Pharmacokinetics Flashcards
1
Q
What is pharmacology?
A
Origin, nature, chemistry, effects and uses of drugs
2
Q
What is toxicology?
A
Study of the adverse effect of chemical, physical or biological agents
3
Q
What is the pharmacodynamics?
A
What the drug does to the body
4
Q
What is the pharmacokinetics?
A
What the body does to the drug
5
Q
Why is pharmacokinetics important?
A
How dose recommendations in inserts are arrived at
Identify possible drug interactions
To adjust strategies such as Therapeutic Dose Monitoring
To safely administer drugs when urgency is required
Predict the influence of disease on treatment outcomes
6
Q
What are the sites of metabolism?
A
- Gut lumen
- Gut wall
- Plasma
- Lungs
- Kidneys
- Nerves
- Liver
7
Q
What is the result of metabolism?
A
- Deactivation
- Activation
- Type of pharmacological response
- No change in activity
- Change in iuptake
- Change in distribution
8
Q
What is Phase I of drug metabolism?
A
- Generally oxidation, reduction or hydrolysis
- Introduce/reveal a reactive chemical group
- Functionalisation
- Products often more reactive
9
Q
What is Phase II of drug metabolism?
A
- Synthetic conjugative reactions
- Hydrophilic, inactive compounds generated
10
Q
Where does drug metabolism occur?
A
- Mainly occurs in the liver, metabolites can be occurs
11
Q
How can metabolic enzymes induced or inhibited?
A
Genetic variability in metabolic enzymes occurs, and expression of metabolic enzymes can be induced and/or inhibited
12
Q
What can metabolism affect?
A
Bioavailability of drugs
13
Q
How can metabolic pathways be saturated?
A
Competition for metabolic enzymes occurs
14
Q
What are mixed function monooxygenases
A
- Throughout the body extensively in the liver
- 57 human genes coding for CYP P450 enzymes
15
Q
What are the function of mixed function monooxygenases?
A
- Biosynthesis of steroids, fatty acids and bile acids
- Metabolism of endogenous and exogenous
16
Q
What is the primary metabolic pathway of paracetamol?
A
- Paracetamol undergoes glucuronide conjugation and sulfate conjugation to form non-toxic metabolites that are easily excreted.
- These are the main routes of metabolism under normal conditions.
17
Q
What is the cytochrome P450 pathway?
A
- A small fraction of paracetamol is metabolised by CYP450 enzymes, producing a toxic metabolite.
- Normally, this toxic metabolite is detoxified by glutathione.
18
Q
What is toxicity mechanism?
A
- If glutathione levels are depleted (e.g., in overdose situations), the toxic metabolite accumulates.
- This can lead to liver damage and toxicity.
19
Q
What does phenobarbital induce?
A
The expression of CYP450
20
Q
What is CYP450 metabolised by?
A
Warfarin
21
Q
What happens when phenobarbital is taken with warfarin?
A
- This means that when phenobarbital is taken with warfarin, it increases the metabolism of warfarin, leading to lower warfarin levels in the blood.
- As a result, warfarin becomes less effective, potentially reducing its anticoagulant effect and increasing the risk of blood clot formation.
22
Q
What is simvastatin metabolised by?
A
CYP3A4 enzymes in the gut wall and liver.
23
Q
What happens to simvastatin in metabolism?
A
It undergoes high first-pass metabolism, meaning that only about 5% of the dose typically reaches circulation.
24
Q
How does grapefruit juice affect simvastatin?
A
Grapefruit juice inhibits CYP3A4, reducing the metabolism of simvastatin.
25
What is the onset of vecuronium?
Medium
26
What's the duration of vecuronium?
Medium
27
Describe the metabolism/elimination of vecuronium
Liver – eliminated via the urine and bile
28
What is the onset of atracurium?
Medium
29
What is the duration of atracurium?
Medium
30
Describe the elimination/metabolism of atracurium
Spontaneous degradation in plasma
31
What is the onset of mivacurium?
Fast
32
What is the duration of mivacurium?
Short
33
Describe the elimination/metabolism of mivacurium?
Plasma cholinesterase
34
What are the major routes of drug administration?
- Absorption
- Distribution
- Metabolism
- Elimination
35
What is absorption?
How the drug get into the bloodstream
36
What is distribution?
How the drug spreads throughout the body via the bloodstream.
37
What is distribution?
How the drug spreads throughout the body via the bloodstream.
38
What is metabolism?
How the body chemically alters the drug, usually in the liver.
39
What is elimination?
How the drug leaves the body
40
What are the routes of drug administration?
- Oral
- Sublingual
- Inhalation
- Topical
- Transdermal
- Intramuscular
- Subcutaneous
- Intravenous
41
What is sublingual administration?
Placed under the tongue where it dissolves and is absorbed directly into the bloodstream via oral mucosa.
42
What is topical administration?
Applied directly to skin or mucous membranes for local effect.
43
What is Transdermal administration?
Drug is delivered across the skin for systemic effect, often via a patch.
44
What is subcutaneous administration?
Injected into the fatty layer under the skin.
45
What are the advantages of oral administration?
- Convenient
46
What is the disadvantage of oral administration?
First-pass effect, many variables and barriers.
47
What are the advantages of sublingual administration?
No first pass effect
48
What are the disadvantages of sublingual administration?
- Inconvenient
- Small dose limit
- Taste
49
What are the advantages of topical administration?
- Convenient
- Localised
50
What are the disadvantage of topical administration?
Only local
51
What are the advantages of inhalation?
- Fast
- Rapid delivery to blood
52
What are the disadvantages of inhalation?
Requires special properites of drug (e.g. atomised, vapourised)
53
What are the advantages of transdermal administration?
Prolonged release
54
What are the disadvantages of transdermal administration?
Skin very effective barrier
55
What are the advantages of an intramuscular administration?
Rapid
56
What are the disadvantages of Intramuscular administration?
Painful, requires trained personnel
57
What are the advantages of subcutaneous administration?
Slower absorption
58
What are the disadvantage of subcutaneous administration?
Easier to train self-administration
59
What are the advantages of intravenous?
- Direct
- Total dose
- Rapid
60
What are the disadvantages of intravenous administration?
- Requires professional
- Infection risk
- Rapid response
61
What is bioavailability in absorption?
- Fraction of unchanged drug that reaches the systemic circulation
- IV injection gives 100% bioavailibility - used as a reference
- Oral bioavailibility is a lot lower
62
What are the properties of ionised drugs?
- Ionised drugs have low solubility - less likely to be absorbed unless a specific carrier protein is present
63
What are the pH of gastric acid
1.0-3.0
64
What is the pH of the large intestine
6.0-7.0
65
What is the pH of the small intestine?
5.0-6.0
66
What is the pH of plasma
7.4
67
What is the choice of route of administration affected by
drug and patient factors
68
What are the main drug properties that affect absorption?
lipophilicity and ionisation
69
What factors affect distribution?
- Degree of drug ionisation
- Lipid solubility
- pH of compartments
- Cardiac output and blood flow
- Capillary permeability
- Plasma protein binding
70
What are the factors affecting the compartment model?
- Tissue permeability
- Binding within compartments
- pH partitioning
- Fat:water partitioning
71
What is tissue permeability in the compartment model?
Determines how easily drugs cross tissue barriers.
72
How does binding within compartments affect the compartment model?
Drug binding to proteins or tissues can affect distribution.
73
How can pH partitioning affect the compartment model?
The pH differences between compartments influence drug ionisation and distribution.
74
How can fat: water partitioning affect the compartment model?
Determines how much drug accumulates in fat versus water-rich tissues.
75
How are bisphosphonates groups distributed?
- phosphonate groups have a high affinity for calcium
- Quickly distributed to the skeleton
- Oral alendronate - daily/ weekly
- IV zoledronate - yearly
76
What plasma proteins do drugs bind to?
- Albumin
- α-1 acid glycoprotein
- Lipoproteins
- Globulins
77
What does warfarin bind to in the plasma?
Albumin
78
How does aspirin affect warfarin?
Aspirin has a high affinity for albumin and can displace warfarin from its binding sites.
79
What can the displacement of warfarin cause?
- This displacement increases the concentration of free (active) warfarin in the blood.
- The result can be a significant increase in anticoagulant effects, leading to a higher risk of bleeding.
80
How are drugs eliminated?
unchanged or as metabolites
81
What are the sources of excretion?
- Breath
- Urine
- Saliva
- Perspiration
- Feces
- Milk
- Bile
- Hair
82
What are the most Important organs involved in elimination?
Kidneys
