Pharmacology Flashcards
1
Q
What are the three categories of drug interactions?
A
- Physiochemical
- Pharmacodynamic
- Pharmacokinetic
2
Q
What are physiochemical interactions?
A
Where the drugs directly react with each other independent of being in the body.
3
Q
What are the four types of physiochemical interactions?
A
- Adsorption
- Precipitation
- Chelation
- Neutralisation
4
Q
What are pharmacodynamics?
A
The effect that the drug has on the body.
5
Q
What are the four types of pharmacodynamic drug interactions?
A
- Summative (1+1=2)
- Synergistic (1+1>2)
- Antagonistic (1+1<2)
- Potentiation (1+1=1+1.5)
6
Q
What are pharmacokinetics?
A
What the body does with a drug.
7
Q
What four actions does the body take on a drug?
A
- Absorption
- Distribution
- Metabolism
- Excretion
8
Q
What physiological processes/features effect absorption of drugs?
A
- Gut motility
- Acidity
9
Q
What is bioavailability?
A
The fraction of an administered dose of unchanged drug that reaches the systemic circulation.
10
Q
Where are the three places a drug in a blood vessel can travel?
A
- Attach to a protein
- Site of intended administration
- Other sites/tissue
11
Q
What enzyme is morphine metabolised by?
A
Cytochrome p450
12
Q
What is a Cp450 inhibitory drug? Give an example.
A
A drug which inhibits cytochrome p450 decreasing its metabolic potential. Metronidazole.
13
Q
What is a Cp450 inducing drug? Give an example.
A
A drug which induces cytochrome p450 increasing its metabolic potential. Phenytoin.
14
Q
Define drugs
A
A medicine or other substance which has physiological effect when ingested or otherwise introduced into the body
15
Q
Define pharmacology
A
A branch of medicine concerned with the uses, effects and modes of action of drugs
16
Q
What is an issue with patients who have co-morbidities being on multiple drugs at once?
A
Complex pharmacological reactions
17
Q
Define druggability
A
The ability of a protein target to bind to a small molecule with high affinity (also known as ligandability)
18
Q
What percentage of the human genome is druggable?
A
10-15%
19
Q
What is a receptor?
A
A component of a cell that interacts with a specific ligand and initiates a change of biochemical events leading to the ligands observed effects.
20
Q
An example of an exogenous ligand?
A
Drugs
21
Q
An example of an endogenous ligand?
A
Hormones, neurotransmitters
22
Q
What are the four types of receptor?
A
- Ligand-gated ion channels
- G-protein coupled receptor
- Kinase-linked receptors
- Cytosolic/nuclear receptors
23
Q
Which receptor type is non-membrane-bound
A
Cytosolic/nuclear receptors
24
Q
How do ligand-gated ion channels work?
A
- Protein integrated into a cell membrane which acts as a conduit for molecules to travel through
- Interaction of ligand with protein leads to conformational change allowing molecule through the formed pore in the membrane
- Absence of ligand leads to conformational change to shut the channel
25
What is an example of a ligand-gated ion channel?
Nicotinic acetylcholine receptor
26
How does a g-protein coupled receptor work?
- 7 transmembrane spanning proteins which form a pore
- G proteins are enzymes which act by changing GDP to GTP making it an energy dependent process
- Switched on when bound to GDP and off when bound to GTP
27
What is an example of a g protein coupled receptor?
Beta-adrenoreceptor
28
What is a kinase linked receptor?
- Homo or heterodimeric which are ligand activated
- Activation of the receptor leads to phosphorylation of the receptor molecule
- Phosphorylation leads to recruitment of scaffolding proteins which in turn initiates an intracellular response
29
What is an example of a kinase-linked receptor?
Receptors for growth factors?
30
What is a cytosolic/nuclear receptor?
- Exists within the cytoplasm of cells rather than being membrane spanning receptors
- Interact with ligands which have already been transported intracellularly
- Undergo a conformational change upon interaction with ligand becoming nucleus targeting
- They transfer to the nucleus and exert their effects directly onto DNA
- Transcriptional activators
31
What is myasthenia gravis caused by?
Loss of acetylcholine receptors
32
What is mastocytosis caused by?
Increased c-kit receptor (mast cell growth factor receptor)
33
What is an agonist response curve?
The effect that agonist dose has on receptor response
34
Are agonist response curves shown as logarithmic graphs or linear graphs?
Logarithmic
35
What is drug potency in relation to an agonist response curve?
A means of measuring how much of a drug is required to elicit a certain response.
EC50 = the concentration of a drug which gives half of the maximal receptor response
36
What is drug efficacy in relation to an agonist response curve?
How effective the drug is at eliciting a receptor response. You can have highly efficacious drugs which have a low potency - the two are not mutually inclusive.
37
What is selective agonism?
Certain signalling molecules have different activities on the same receptor
38
What is a receptor subtype?
Different types of the same receptor which may interact with different agonists and antagonists e.g. histamine receptor subtypes are all agonised by histamine but differentially antagonised producing receptor subtypes.
39
What are muscarinic acetylcholine receptors agonised by?
Muscarine
40
What are nicotinic acetylcholine receptors agonised by?
Nicotine
41
What are muscarinic acetylcholine receptors antagonised by?
Atropine
42
What are nicotinic acetylcholine receptors antagonised by?
Curare
43
What factors govern drug actions?
1. Affinity
2. Efficacy
3. Numbers of receptors
4. Signal transduction or amplification
44
What is inverse agonism?
When a molecule down-regulates a response rather than just blocking a response.
45
Are drugs specific or selective?
Selective - no drug can ever be truly specific however can be exquisitely selective on what receptors it interacts with reducing collateral damage/effects.
46
How do enzyme inhibitors work?
Prevent a substrate from entering the enzymes active site and prevents the enzyme from catalysing the reaction.
47
What are the two types of enzyme inhibitors?
1. Reversible inhibitors - bind non-covalently
| 2. Irreversible inhibitors - react covalently with the enzyme and change it chemically.
48
How do statins work?
Block the rate limiting step in cholesterol biosynthesis - block the activity of the enzyme HMG-CoA reductase. This in turn prevents cholesterol biosynthesis.
49
How do ACE inhibitors lower blood pressure?
ACE inhibitors inhibit the action of angiotensin converting enzyme which prevents the conversion of angiotensin 1->2. This prevents tubular ion reabsorption, vasoconstriction and ADH secretion all lowering retention of water and thereby lowering blood pressure.
50
How do peripheral DDC inhibitors help treat parkinson's disease?
DDC inhibitors block activity of the DDC enzyme whjich acts by breaking down L-dopa to dopamine in the peripheral nervous system. This means more L-dopa is available to cross the BBB as dopamine is unable to cross the BBB. This increases reserve of dopamine available for the CNS to utilise.
51
How do peripheral COMT inhibitors help treat parkinson's disease?
Prevent breakdown of L-dopa in the peripheral nervous system so more is available to cross BBB.
52
How do central COMT inhibitors help treat parkinson's disease?
Prevent breakdown of dopamine -> 3MT to keep dopamine levels high in the CNS.
53
What is a uniporter?
Uses energy from ATP to pull molecules in.
54
What is a symporter?
Uses movement in of one molecule to pull in another molecule.
55
What is a antiporter?
One substance moves against its gradient using energy from the second substance moving down its gradient.
56
How many deaths occur in the UK a year due to medication errors?
712
57
Name 5 routes of drug administration and the time taken for them to elicit their pharmaceutical effects
```
Oral 30-90m
Intravenous 30-60s
Intraarterial
Intraosseous 30-60s
Intramuscular 10-20m
Subcutaneous 15-30m
Inhalation 2-3m
Topical m-h
Sublingual 3-5m
Rectal 5-30m
Intrathecal
```
58
What methods do drugs use to cross body membranes?
1. Passive diffusion - lipid soluble molecules
2. Diffusion through ion channels - small water-soluble molecules
3. Carrier mediated process
4. Pinocytosis - large molecules
59
What is drug ionisation?
Ionisation is a property of drugs that are weak acids or weak bases. Drugs with ionisable groups on exist in an equilibrium between the ionised and non-ionised form.
60
What is the PKa of a drug?
The dissociation/ionisation constant. The pH at which half of the substance is ionised and half is unionised.
61
Where in the GI tract are weak acids best absorbed?
Stomach
62
Where in the GI tract are weak bases best absorbed?
Intestine
63
What are obstacles which inhibit drugs from being administered orally?
1. Drug structure - needs to be lipid soluble, highly polarised drugs will only be partially absorbed
2. Drug formulation - capsule around drug must disintegrate/dissolve
3. Gastric emptying
4. First pass metabolism
64
What are the four metabolic barriers to reach circulation?
1. Intestinal lumen - enzymes which split peptides, esters and glycosidic bonds
2. Intestinal wall - wall is rich in cellular enzymes and efflux transporters
3. Liver
4. Lung
65
How would you give a drug which undergoes hepatic first pass metabolism?
Sublingual or rectal administration to bypass the splanchnic circulation to the liver
66
What drugs can be given transcutaneously?
- Lipid soluble
- Non-irritant
- When slow-release treatment is needed
67
What drugs can be given subcutaneously?
- Drugs given in small volume
- Local effect drugs
- Slow release drugs e.g. contraceptives
68
What drugs can be given intramuscularly?
- Slow release e.g. depot contraceptives or antipsychotics
69
What drugs can be given as an aerosol?
- Non-volatile
| - Drugs of limited toxicity risk
70
What does "distribution" refer to in the context of pharmacology?
The rate and extent by which a drug is transferred reversibly from the general circulation to the tissues. This occurs following an increase in drug concentration in the blood, when blood drug concentration declines, the reverse happens.
71
What tissues/organs are IV drugs distributed to first?
Well perfused areas e.g. brain, liver, lungs
72
How can a "depot" effect be created through protein binding of a drug?
Protein binding (when reversible) creates an equilibrium between bound and unbound drug. Binding lowers the free concentration and can act as a depot releasing the bound drug when the plasma concentration drops through redistribution or elimination
73
What is the blood brain barrier formed from?
- Small number and size of pores in endothelium
- Astrocyte feet surrounding vessels
- Tight junctions
74
What are efflux transporters?
Cell surface transporters which transport drug molecules which enter the cells, out of the cells and back into the circulation. This is used to protect the brain.
75
Why are drugs removed from the brain via diffusion into plasma, active transport in the choroid plexus or elimination through the CSF?
The brain does limited metabolising.
76
Why is it important to consider whether a female is pregnant before giving some drugs?
Drugs may cross the placenta into the foetal circulation.
77
What types of drugs cross the placenta?
- Lipid soluble
| - Small molecules
78
How are drugs eliminated from the body?
Metabolism or excretion
79
Why do xenobiotics need to be converted from lipophilic into hydrophilic metabolites before excretion in urine?
The kidneys can only excrete water soluble materials.
80
What happens in the first phase of drug metabolism?
- Reactive functional groups are added to the drug or exposed (-OH, -SH, amine, -carboxyl) through oxidation, hydroxylation, reduction or hydrolysis
- Oxidation is the most common reaction, cytochrome p450 catalyses this
81
What happens in the second phase of drug metabolism?
- Primary conjugation with endogenous molecules (glucuronic acid, sulphate) forming covalent bonds and hydrophilic metabolites
82
Where does drug metabolism occur in a cell?
Smooth endoplasmic reticulum
83
What molecules are excreted as fluids?
- Low molecular weight
| - Polar molecules
84
What is the equation for total excretion of a drug through urine?
Total excretion = glomerular filtration + tubular secretion - tubular reabsorption
85
What molecules are excreted in solids?
- High molecular weight compounds
86
What molecules are excreted as gasses?
Volatile compounds
87
What is first order kinetics
Where a constant fraction of drug is eliminated from the body per unit time
88
What is zero order kinetics
The rate of the removal of the drug is constant and unaffected by an increase in the concentration
89
What shape is a concentration-time graph for a first order reaction?
Logarithmic
90
What shape is a concentration-time graph for a first order reaction?
Linear
91
Define half life
The time taken for a concentration of a drug to reduce by half
92
What is bioavailability?
The fraction of an administered drug that reaches the systemic circulation unaltered.
93
What is the bioavailability of intravenously administered drugs?
1
94
What is the equation for volume of distribution?
Vd = total amount of drug in a body/plasma concentration
95
Why is the volume of distribution important clinically?
Enables us to determine how much of a drug needs to be administered to produce a particular plasma concentration.
96
What factor controls the Vd of water soluble drugs?
Rate of passage across membranes
97
What factor controls the Vd of lipid soluble drugs?
Distribution of blood flow to the tissues that accumulate the drug
98
What is drug clearance (CL)?
The volume of blood or plasma cleared of a drug per unit time.
99
Why are repeat drug doses given?
To maintain a constant drug concentration in the blood at the site of action for therapeutic effect.
100
What is steady state (Css)?
A balance between drug input and elimination.
101
How will a high Vd effect the Css and CL?
Css - delay in reaching Css
| CL - slower rate of elimination
102
What is a loading dose?
An initial high dose that loads the system and shortens the time taken to reach steady state.
