pharmacology Flashcards
1
Q
name 3 types of drug interactions
A
physiochemical
pharmacodynamic
pharmacokinetic
2
Q
what is pharmacodynamics
A
effect of a drug on the body (think D for dynamics D for drug)
3
Q
what is pharmacokinetics
A
what the body does with the drug
The study of absorption, distribution, metabolism & excretion of drugs
4
Q
name 3 types of pharmacodynamic reactions
A
Summatism - 1 + 1 = 2
Synergism 1 + 1 > 2
Antagonism 1 + 1 = 0
5
Q
there is a 4th variation of pharmacodynamic reactions, explain it
A
Potentiation - where one drug makes another drug more powerful but NOT vice versa 1+1=1+1.5
6
Q
define bioavailability (F). which administration has a bioavailability of F=1 and why
A
proportion of a drug or other substance that enters the circulation and actually has an effect. IV has a F = 1, as the complete drug is injected straight into systemic circulation
7
Q
why is the standardised bioavailability IV drugs at 1
A
IV drugs go straight into the system
8
Q
what things may affect the rate of absorption
A
motility, acidity (ionised vs unionised drugs), (physiochemical)
- note: ionised large molecules cannot pass through membrane
9
Q
why may IV/IA drugs have the fastest rate of absorption
A
they are injected straight into drug circulation and do not need to pass though any further membranes
10
Q
what is the easiest drug route interns of reaching general/systemic blood circulation
A
oral - there is a large surface area and good blood supply, high blood flow.
11
Q
name 3 possible locations a drug may distribute to
A
proteins (disease-linked in the blood)
effect site (direct to site)
other tissue - including tissue
12
Q
How may protein binding affect drugs effectiveness
A
if 4 moles of blue drug binds to protein, then orange drug is added which has an equal bonding strength 2 moles of orange drug would bind to protein instead – leaving 2 moles of blue drug free again to be redistributed to target location
13
Q
Define druggability
A
ability of a protein target to bind to small molecules with high affinity (small molecules referring to drugs)
14
Q
what are the 2 features of a drug target (protein) that are important when creating a drug
A
it is disease linked
it is druggable
15
Q
name 4 drug targets (proteins)
A
ion channel
enzyme
receptor
transporter
16
Q
define receptor
A
a component of a cell that interacts with a specific ligand, and initiates a change of biochemical events, leading to the ligand observed effect
17
Q
name 4. types of receptors
A
Ligand-gated ion channels
G protein coupled receptors
kinase linked receptors
Cytosolic/nuclear receptors
18
Q
what is an agonist
A
a compound that bounds and activates a receptor
19
Q
what is an antagonist
A
a compound that reduces the effect of an agonist and therefore reduces the overall effect of a receptor - (like a competitive molecule)
20
Q
what is the EC50 of a log concentration response curve
A
the concentration of agonist of a drug that gives half the maximal response
21
Q
what makes an agonist more potent
A
a lower concentration is needed to reach the same effect
22
Q
what makes an agonist more efficacious
A
a higher (more maximal) response is achieved from the same dosage (generally partial agonists are not efficacious as large dose won’t reach as high as full agonist)
23
Q
what happens to a graph when a competitive antagonist is added
A
graph shifts to the right
24
Q
what happens to a graph when a non-competitive antagonist is added
A
graph no longer reaches highest response (also shifts and not as steep)
25
what are receptor related factors that govern drug action
efficacy
| affinity
26
what are tissue related factors that govern drug action
receptor number
| signal amplification
27
true or false: antagonist have weak efficacy
False. antagonist have no efficacy at all, but have affinity. Agonists have both
28
what is the difference between an inverse agonist and an antagonist
an inverse agonist reduces the response of a receptor, whilst an antagonist simply blocks the binding site for the agonist with no effect
29
what is tolerance
reduction in drug effect overtime (as body is able to tolerate higher doses - becomes more "used to")
Down regulation of the receptors with prolonged use Need higher doses to achieve the same effect (gets more than normal)
30
what is desensitization
alters immune response to drug, allowing temporary tolerance to drugs, particularly for those who are hypersensitive to drugs
(adapts body to take normal than less)
31
what are the 3 mains of ports in active transport
```
Uniport (1 molecule)
cotransporter symport (2 molecules in same direction)
cotransporter antiport (2 molecules in opposite directions)
```
32
how do cotransporters generally work
they use one molecule moving down its gradient to pull the other molecule against its gradient
33
name 4 examples of ion channels and conditions they are associated with
Epithelial (Sodium) – heart failure
Voltage-gated (Calcium, Sodium) – nerve, arrhythmia
Metabolic (Potassium) – diabetes
Receptor Activated (Chloride) - epilepsy
34
what are cytochrome p450
these are a superfamily of membrane bound isoenzymes. an enzyme essential in the metabolism of many drugs
35
what are the 4 parts of drug interaction
Absorption
Distribution
Metabolism
Excretion
36
define absorption
A process of transfer from site of administration into general or systemic stimulation (generally blood circulation)
37
Pinocytosis is a process of absorption in the cell - how does it work?
the ingestion of liquid into a cell by the budding of small vesicles from the cell membrane
38
what is an ATP-binding cassette (ABC)
it is a superfamily of carriers that use ATP during transportation?
39
what is an solute carrier superfamily
second largest family of membrane proteins (after G proteins)
don't use ATP
40
what is an advantage to drug ionisation in terms of interaction
ionic forces are part of the ligand receptor interaction - this means it is essential for drugs to interact with its receptor
41
during administration of drugs, they face 4 major metabolic barriers, what are they?
Intestinal lumen
Intestinal wall
Liver
Lung
42
during IV administration, there is a initial high plasma concentration of drug. why may drug distribute into the brain, liver and lung initially and rapidly
these are highly perfumed areas, so higher concentrations of blood mover there, before continuing into less perfused areas, causing a fall in the initially highly perfumed areas
(passive diffusion to restore on equilibrium)
43
whats the difference between transcutaneous and intradermal/subcutaneous
transcutaneous is across the surface layer of skin. usually involves use of patches
whilst subcutaneous through the layer of skin, not passing the stratum corneum layer (2nd to bottom). within the subcutaneous tissue (hypodermis), usually uses injections
44
explain transcutaneous administration
surface of the skin
slow and continued absorption useful with transdermal patches - 72 hourly in chronic care
epidermis is an effective barrier to water solubles and limited rate and extent of absorption of lipid solubles. Need a potent and non irritant drug (as its skin)
45
explain intradermal/subcutaneous administration
Avoids the stratum corneum barrier (2nd deepest) before the muscle
mainly limited by blood flow
given in small volumes
can be used for local effect (local anaesthetic) or to deliberately limit rate of absorption (long term contraceptive implants)
usually injected into areas of fat
46
explain intramuscular administration
into the muscle, such as the thigh and shoulder (where muscle is near the surface)
depends on blood flow and water solubility
increase in either blood flow and water solubility enhances the removal of drug from injection site (epipen drug quickly removed to start working)
can also make a depot injection
47
what is a depot injection and how does it work
a slow releasing, slow acting form of your medication.
the drug binds to the the tissue or blood protein. this reduces the concentration of free drug in the plasma. therefore when the concentration drops (due to redistribution or elimination) drugs unbind from protein - allowing a long term effect.
48
explain intra-nasal administration
(through the nose) good surface area, but low levels of proteases and drug metabolising enzymes
can be used for local or systemic effects.
can also be used for both! (cocaine - a vasoconstrictor)
49
explain inhalation administration
(through the mouth as gas)
Large surface are and blood flow but limited but limited by risk of toxicity (to alveoli) and delivery of non volatile drugs
largely restricted to volatiles (evaporates easily)
asthma drug = non volatile - so given as aerosol or dry powder
delivery to small airways = approximately 5% delivery
50
define distribution
the process by which the drug is transferred reversibly from the general circulation to the tissues (till an equilibrium is reach due to passive diffusion in both directions)
Rate & extent of movement of a drug into (and out)of tissues from blood
51
Protein binding: what is the protein involved in the most commonest reversible binding
Albumin
52
True or false, some drugs can bind irreversibly to protein
true. some drugs cannot re-enter the circulation and is equivalent to elimination
53
define metabolism and first pass metabolism
the transformation of a molecule to another molecule. first pass metabolism is the phenomenon that drug concentration is greatly reduced before it reaching systemic circulation. this is caused by intestinal lumen, intestinal wall, liver and lungs
54
define elimination
removal of a drugs activity from the body
55
what is metabolism more essential for: lipid soluble drugs or water soluble drugs
Lipid soluble drugs as they would simply be reabsorbed in the kidneys before excretion
56
what is the most common method used during metabolism to transform drugs to a more polar metabolite
oxidation using enzyme Cytochrome P450
57
how many phases are involved in drug metabolism
2
58
where are CytP450 enzymes predominantly found
liver tissues
59
which specific enzymes are involved in drug metabolism of the CytP450 group
CYP1 - CYP4
60
What happens in phase 1 of drug metabolism
the drugs are transformed into more polar metabolites. this is through addition/unmasking of functioning groups. this occurs through oxidation via P450 enzyme
61
what happens in phase 2 of drug metabolism
covalent bonds are formed between drugs/metabolites and endogenous substrates (internal molecules) this makes them less active and ready for excretion
62
describe the importance of the 3 methods involved in excretion
Fluid - for low molecular weight polar compounds
Solids - for higher molecular weight compounds
Gases - important for volatile substances that need to evaporate
63
what 3 factors determine the total excretion of a drug
Total excretion = Glomerular filtration + tubular secretion - reabsorption
64
what is the process called that refers to circulation of drugs between the gastrointestinal tract and the liver
Enterohepatic circulation
65
which vein is significant in transporting drugs back from liver to the gastrointestinal tract
Hepatic portal vein
66
during drug distribution, when might zero order occur
this is when enzymes remove drugs. saturated conc of enzymes means drugs are removed at a constant rate.
For example: Ethanol and alcohol dehydrogenase
67
during drug distribution, when might first order occur
this is particularly during IV administration, rapid distribution by diffusion which slows down as equilibrium is reached. A constant FRACTION is removed per unit time
68
what determines the rate of distribution for water soluble drugs
rate of passage across membranes (as membranes are non polar the movement will be slower)
69
what determines the rate of distribution for lipid soluble drugs
blood flow to tissue that accumulates drug
70
what is the APPARENT volume of distribution (Vd) and why is it significant
Vd = total amount of drug in body (dose) / plasma concentration
71
what is Clearance (CL) during elimination
the volume of blood or plasma cleared of drug per unit time
72
how do you work out the rate constant of elimination (K)
K = CL/Vd
73
give an equation to work out the half life of a drug
t1/2 = 0.693Vd/CL
74
what is steady state (Css)
a balance between drug input and elimination
75
whats the equation for steady state (Css)
Css = rate of infusion/ CL
76
what are opioids and name 3 types
these are narcotics that act on opioid receptors
| Morphine, Opioids and Heroin (Class A drugs)
77
whats the difference between Morphine and Heroin
Morphine is naturally occurring whilst Heroin is chemically synthesised (a diamorphine)
78
how long does a single dose of opioid last
3-4 hours
79
what % of morphine is metabolised by first pass metabolism. what does this mean for the oral dosage in comparison to IV dosage
50%. this is why 2 times the dosage is given when oral administration compared to IV administration
80
what is the main function of medicinal opioids
they use the existing pain modulation system, binding to opioid receptors and inhibiting the release of pain transmitters at the spinal cord and mid brain. this modulates the perception of pain in higher receptors, making the pain bearable (EUPHORIA)
81
what are endorphins and how do they share similarities with medicine opioids
these are endogenous morphines - (Internal biological opioids). with enkephalins, they act on opioid receptors as a normal biological function, similar to opioids. this is important during fight or flight. only temporary effect.
82
other than the CNS, where are opioids receptors also found and what effect might this have when taking opioids?
they are also found in the gut and respiratory system. as opioids are generally taken systemically (oral) they can cause side effects such as nausea and vomiting and respiratory depression
83
name an opioid antagonist
Naloxone
84
what is the bioavailability of morphine
50%
85
name 3 features of opioid withdrawal
psychology, physical, Euphoria
86
define adverse affect
Unwanted or harmful reaction following administration of a drug or combination of drugs under normal conditions of use and is suspected to be related to the drug.
87
what are the 3 types of side affects
```
Hyper-susceptibility effect (below therapeutic range)
Side effect (therapeutic range)
Toxic effects (beyond therapeutic range)
```
88
what are the 6 types of adverse drug reactions (A-F)
```
Type A - Augmented pharmacological
Type B - Bizarre or idiosyncratic
Type C - Chronic
Type D - Delayed
Type E - End of treatment
Type F - failure of therapy
```
89
give an example of Type A adverse affect (augmented pharmacology)
extension of primary effect = secondary effect
predictable and dose dependent, common
Morphine and constipation
hypotension and antihypertensive
too much insulin can lead to hypoglycaemia
90
give an example of Type B adverse affect (bizarre and idiosyncratic)
not predictable and not dose dependent
| anaphylaxis and penicillin
91
give an example of Type C adverse affect (chronic)
osteoporosis and steroids
92
give an example of Type D adverse affect (delayed)
malignancies after immunosuppression
93
give an example of Type E adverse affect (end of treatment)
occurs after abrupt drug withdrawal - e.g. opiate withdrawal syndrome
94
give an example of Type F adverse affect (failure therapy)
Failure of OCP in presence of enzyme inducer
drugs that induce enzymes may cause Oral contraceptive pill to stop working
95
DoTS is another way of classifying risk of drug adverse affect
```
D = dose relatedness (toxic collateral or hyper susceptibility)
T = timing e.g. fast infusion of frusemide hearing loss and tinnitus
S = susceptibility of the patient
```
96
most common drugs to have ADR
```
Antibiotics
Anti-neoplastic
cardiovascular drugs
Hypoglycaemics
NSAIDS
CNS drugs
```
97
whats the most common systems to be affected
```
GI
Renal
Haemorrhagic (blood and blood vessels)
Metabolic
Endocrine
Dermatologic
Respiratory
```
98
what are common ADRs
```
Confusion
Nausea
Balance problems
Diarrhoea
constipation
Hypotension
```
99
what are the 4 types of hypersensitivity reactions
immediate (IgE mediated)
cytotoxic reactions (antibody mediated)
Immune complex reaction
Delated Hypersensitivity/lymphocyte mediated
100
features of Type 1 hypersensitivity
involves prior exposure to the antigen/drug (anaphylaxis on second exposure)
immediate reaction
igE mediated - formed after exposure to molecule
IgE becomes attached to mast cells/leucocytes, in preperation for second exposure (mast cell degranulation)
101
explain key characteristics of anaphylaxis
occurs within minutes (during digestion - could be up to hour) and last 1-2 hours
vasodilation
increased vascular permeability
bronchoconstriction
these features can lead to difficulty breathing, urticaria and angio-oedema
102
what are the 3 key biological changes that occurs in anaphylaxis
vasodilation
increased vascular permeability
bronchoconstriction
103
features of Type 2 hypersensitivity
drug/metabolite combines with protein - which is then treated as a foreign protein
antibodies IgG and IgM formed
antibodies combine with 'antigen' and complements activated - induces cell lyses
occurs during Rh incompatibility in
104
features of type 3 hypersensitivity
antigen and antibody form large complex which cause a complement cascade
small blood vessels are damaged/blocked
this causes leucocytes to e attracted to the site of reaction = inflammatory response
105
features of type 4 hypersensitivity
antigen specific receptors develop on t-lymphocytes (which may cause delayed response)
subsequent administration leads to local/tissue allergic reaction
106
what is anaphylactoid
non-immune anaphylaxis
due to direct mast cell degranulation --> no white blood cells or antibodies involved
no prior exposure needed (as it isn't immune centred)
clinically identical symptoms
107
main clinical features of anaphylaxis
```
Exposure to drug, immediate rapid onset
rash
swelling of lips, face, oedema, centra cyanosis (discolouration of body)
wheeze/ shortness of breath
Hypotension = Anaphylactic shock
Cardiac arrest
```
108
how would you manage anaphylaxis (6 things)
Commence basic life support (ABC)
stop drug if infusion
adrenaline!!! IM - 500mcg
high flow oxygen (due to lack of oxygen in brain from shock)
IV fluids (to raise bp)
IV antihistamine (as this causes inflammation)
IV hydrocortisone 100-200mg- reduce risk of reoccurrence
if shock - may need IV adrenaline (not IM)
109
what is the affect of adrenaline in anaphylaxis
triggers the stimulation of 3 main adrenoceptors that have various affects on the body to reduce reaction caused by anaphylaxis
110
where are alpha adrenoceptors found and what does their activation lead to
blood vessels - vasoconstriction
111
where are beta - 1 - adrenoceptors found and what does their activation lead to
heart - increase force of contraction (+ ionotropic) and speed up heart rate (+ chronotropic)
112
where are beta 2 adrenoceptors found and what does their activation lead to
bronchioles of the long - reduce oedema and brochodilation
113
where are beta 2 adrenoceptors found and what does their activation lead to
bronchioles of the long - reduce oedema and bronchodilation
114
how is the release of inflammatory mediators reduced
intracellular c-AMP Is a messenger that stops the release of mediators of the mast cells and basophils from releasing mediators
115
name 3 categories of risk factors for hypersensitivty
MEDICINAL factors: drugs with proteins or polysaccharides (like biological molecule you find in the body) are more likely to cause hypersensitivity
HOST factors: Women > men, and immunosuppressed
GENETIC factors: people with a certain HLA group (human leukocyte antigen)
116
what are the clinical criteria used to determine whether a patient is allergic to a drug
symptoms dont correlate with pharmacological properties of the drug (not normal side effect)
No linear relation with dose
Reaction - small amount can cause severe effect
reaction similar to those produced by allergens
disappearance on cessation
reappears on re-exposure
only in minority of patients on the drug (if its majority, more likely to be down to the drug than the host)
117
in the case a patient undergoes an abnormal adverse drug reaction that may react in hospitalisation, as a doctor what would be the next step after stopping the drug and informing the patient?
report the adverse drug affect on a YELLOW CARD
118
what is the half life of a drug
the time taken for the plasma drug concentration to fall to half its original value
119
define a 'narrow therapeutic index' and name a drug that is not classified as one
this defines those drugs where small change in dose can lead to serious therapeutic adverse effects.
Simvastatin does not have a narrow therapeutic index
