Pharmacology Flashcards
1
Q
What is pharmacodynamics?
A
how the drug affects the body
2
Q
What is pharmacokinetics?
A
how the body affects the drug: disposition of the compound
absorption > distribution > metabolism > excretion
3
Q
What is druggability?
A
ability of a protein target to bind small molecules with high affinity
4
Q
What are the 4 main drug targets?
A
receptors
enzymes
transporters
ion channels
5
Q
How do receptors work as drug targets?
A
interact with a ligand = initiates a change
ligands are exogenous (drugs) or endogenous (hormones, NTs)
6
Q
Receptors facilitate communication between chemicals via what?
A
neurotransmitters eg ACh, serotonin
autacoids (locally produced) eg cytokines, hormones
hormones eg testosterone, hydrocortisone
7
Q
What are the 4 types of receptor?
A
ligand-gated ion channels
g-protein coupled
kinase-linked receptors
nuclear receptors
8
Q
Give an example of a ligand-gated ion channel?
A
nicotinic ACh receptor
9
Q
Give an example of a g-protein coupled receptor?
A
beta-adrenoceptors
10
Q
What ligands can interact with g protein coupled receptors?
A
light energy, peptides, lipids, sugars, proteins
11
Q
How do g protein coupled receptors work?
A
g proteins transmit signals from GPCRs
g proteins = GTPases are molecular switches
ON = bound to GDP
OFF = bound to GTP
12
Q
How does the muscarinic ACh receptor (M3R) work?
A
g protein coupled
couples with Gq and PLC
produces 2nd messengers: IP3 or DAG
13
Q
How do beta-2-adrenoceptors work?
A
g protein coupled
couples with Gs and AC
produces 2nd messenger cyclic-AMP
14
Q
How do kinase-linked receptors work?
A
ligand binds to receptor on tyrosine kinas
kinase activity is stimulated (enzymatic)
tyrosines are phosphorylated
intracellular proteins bind to phospho-tyrosine docking sites
15
Q
How do nuclear receptors work?
A
steroid receptors
modify gene transcription
have zinc fingers which bind to DNA
16
Q
Give 2 examples for how chemical imbalances can lead to pathology?
A
allergy = increase in histamine Parkinson's = decrease in dopamine
17
Q
Give 2 examples of how receptor imbalances can lead to pathology.
A
myasthenia gravis = loss of ACh receptors
mastocytosis = increase in c-kit receptor
18
Q
What is potency?
A
measure of how well a drug works
highly potent = low concentrations illicit a great response
19
Q
What is the EC50 of a drug?
A
the concentration that gives half the maximal response
20
Q
What is the efficacy/intrinsic activity of a drug?
A
the maximum response achievable from a dose (the Emax of a drug)
the higher the Emax, the higher the efficacy
21
Q
How is intrinsic activity calculated?
A
Emax of partial agonist/Emax of full agonist
22
Q
What is a full agonist compared to a partial agonist?
A
full agonist can reach a 100% response - their Emax is 100
a partial agonist cannot get a full response and has an Emax below 100
23
Q
What are antagonists?
A
decrease the effect of agonists
DON’T activate receptors
24
Q
What is a competitive antagonist?
A
compete with agonist to bind so the agonist has no effect
bind to the same active site
25
How does a competitive antagonist affect a response graph?
shifts right
| must increase amount of agonist to illicit same response
26
What is a non-competitive antagonist?
binds to an allosteric site on receptor to prevent it's activation by an agonist
27
How does a non-competitive antagonist affect a response graph?
shifts right and down
| even more agonist needed for the same response
28
What are the 2 main cholinergic receptor agonists?
muscarine (mACh receptor)
| nicotine (nACh receptor)
29
What is the antagonist of muscarine?
atropine
30
What is the antagonist of nicotine?
curare
31
What type of receptor are all histamine receptors?
G-protein coupled receptors
32
What is the agonist for a histamine receptor?
histamine
33
What does histamine do in the gut when it binds to a histamine receptor?
contraction fo ileum
| acid secretion from parietal cells
34
What is the antagonist to histamine?
mepryamine
35
What effect foes mepryamine have on the gut when it binds to a histamine receptor?
reversed contraction of ileum
| no effect on acid secretion
36
What are the main 4 factors governing drug action?
1. affinity
2. efficacy
3. number of receptors
4. signal amplification
37
What is the affinity of a drug?
how well a ligand binds to the receptor
38
What is the efficacy of a drug?
how well a ligand activates the receptor
39
Do antagonists show affinity and efficacy?
does show affinity
| has 0 efficacy
40
What happens when the number of receptors is reduced?
more drug is required to illicit the same response
| max response can usually still be achieved
41
What is the receptor reserve?
where agonists need to activate only a small number of receptors to reach max response
= spare receptors
holds for full agonist in many tissues but no reserve for partial agonists
42
How can receptors be inactivated? Give an example.
by irreversible antagonists
| eg bromoacetyl alprenolol menthane (BAAM) = irreversible B-adrenoceptor antagonist
43
What is signal amplification in drug action?
determines how powerful a response will be depending on the type of tissue the receptor is in
tissues with the same receptor and agonist may have completely different responses
44
What is allosteric modulation?
binding of an allosteric ligand to a receptor can effect an agonist's effect
45
What are the 2 types of allosteric modulation?
affinity modulation: change in EC50 value
| efficacy modulation: change in Emax
46
What is positive and negative allosteric modulation called?
```
positive = allosteric
negative = orthosteric (binds to actual active site)
```
47
What is inverse agonism?
drug binds to the same receptor as the agonist but induces the opposite response
48
What is tolerance to a drug?
a decrease in the effect of an agonist over time
49
How does tolerance to a drug increase?
with continuous, repeated high concentrations
50
What is desensitisation of receptors to drugs?
decreased responsiveness with chronic or repeated exposure
51
What are the 3 main ways a receptor becomes desensitised?
1. uncoupled: receptor can't interact with g-proteins
2. receptor is internalised in a vesicle
3. receptor is degraded
52
What is specificity?
the ability of a drug to produce an action at a specific site
53
What is selectivity?
the degree to which a drug acts on a given site relative to other sites
54
What is the drug most commonly used for overdoses in the UK?
paracetamol
55
How is a paracetamol overdose treated?
activated charcoal
| paracetamol binds to it and both leave the body = adsorption
56
What are the 4 categories of physiochemical reactions?
adsorption
precipitation
chelation
neutralisation
57
In terms of pharmacodynamics, what is summation? What equation represents this?
1 + 1 = 2
different drugs have a proportional effect
e.g. 2 half anaesthetic doses of different drugs will add up to a whole anaesthetic dose
58
In terms of pharmacodynamics, what is synergism? What equation represents this?
1 + 1 > 2
| the sum of 2 drugs is more than you would expect of them individually
59
Give 2 examples of 2 drugs that have a synergistic effect?
paracetamol and morphine: increase effect
| propofol and midazolam: lower doses of both below what you would expect
60
How could the synergistic effect of 2 drugs be measured?
compare pain score before and after the medication (in the same person)
pain score will decrease more than you would expect
61
In terms of pharmacodynamics, what is anatagonism? What equation represents this?
1 + 1 = 0
| the opposite of a drug is given to cancel out it's effect
62
Give 2 examples of 2 antagonist drugs.
1. doxazosin: alpha blocker in peripheral vasculature = decreases BP by vasodilation, very potent so with anaesthetic drugs = no vasoconstriction = decreased BP
need alpha agonist to bring BP back up
2. opioids and naloxone: both target opioid receptors
63
In terms of pharmacodynamics, what is potentiation? What equation represents this?
1 + 1 = 1 + 1.5
| drug A has the same effect but causes effect of drug B to increase
64
Give an example of 2 drugs that show potentiation.
probenecid (for malaria) and penicillin: excreted from same place in kidney so they compete
probenecid wins and is excreted, penicillin remains in the body
duration of action for penicillin increases
65
Where are drugs metabolised?
mostly liver
| also kidney and lungs (ACEi) sometimes
66
What kinds of changes are made to drugs during metabolism?
changed so they can be excreted
| changes pro-drugs to functional metabolites e.g. codeine to morphine
67
How is bioavailability of an oral drug compared to an IV drug calculated? Define it.
draw blood concentration by time graph
area under oral/area under IV
how much of oral medication makes it into the system vs how much IV drug gets into the system when given as a bonus
68
Compare the absorption of oral and IV drugs.
IV drugs reach a high blood concentration very quickly and are then excreted very quickly
Oral drugs take a longer route to reach functionality, don't reach a very high blood concentration and take longer to be excreted
69
What is the bioavailability of paracetamol?
100% - oral and IV dose is usually the same
70
What factors slow down the motility of the gut?
morphine
| anything that effects the parasympathetic NS
71
What happens to drug absorption when gut motility slows?
absorption decreases
| drugs take longer to get into system
72
Name 2 drugs that increase gut motility.
metaclopramide and erythromycin
| to increase feeding (need enteral feeling) and drug intake through nasogastric tubes
73
What is the commonest interaction of 2 drugs which cause motility changes?
oral contraceptive pill and antibiotics
74
Which part of a drug is able to cross phospholipid bilayers and which is not? Why?
drugs are split into an ionised and unionised portion
the ionised drugs can't cross phospholipid bilayers as they are lipophilic
unionised portions can cross
75
What can change the proportion of ionised drug?
changing the acidity of the environment
76
What happens to the proportion of ionised and unionised drug when an acidic drug enters an acidic environment? Or when a basic drug enters and acidic environment?
acidic in acidic = increased unionised portion
basic in acidic = increased ionised portion
or vice versa
77
Which types of drugs alter the pH of the stomach? How does the effect drug absorption?
PPIs and antacids
| alter absorption of other drugs depending on their pH
78
What kind of environment alters the effectiveness of local anaesthetics?
don't work near accesses
environment is too acidic
general anaesthetic often has to be used
79
How does the interaction between anti-retroviral drugs and PPIs effect drug absorption?
anti-retroviral drugs can cause heartburn
PPIs given to treat heartburn
also decrease amount of anti-retroviral drug absorbed as it increases the ionised portion of arv drug in the gut > less absorbed > reduced effect
80
Where does a drug go if it has a large volume of distribution? Give an example.
goes to random places in the body, binds to proteins
a low proportion goes to the effect site
e.g. propofol
81
Where does a drug go if it has a low volume of distribution? Give an example.
stays in blood and most goes to effect site
| e.g. muscle relaxants
82
How does protein binding effect the distribution of a drug?
alters drug concentration in plasma
decreases distribution
less available for effect
83
What happens when 2 highly protein bound drugs are given together? Explain with an example.
2 protein bound drugs can increase hate therapeutic level to a toxic level
warfarin and amiodarone
both highly protein bound > toxic dose of warfarin
warfarin has a narrow therapeutic range
amiodarone increases the international normalised ratio (INR) of warfarin until it is too high
warfarin is an anti-coagulant = higher risk of bleeding
84
Explain enzyme induction in terms of morphine and CYP450.
morphine is metabolised to morphine-6-glucuronide via enzymes CYP450
m-6-g is x10 more potent than morphine
m-6-g is able to be excreted quickly so potency doesn't matter until phenytoin is added
anti-epileptic drug phenytoin is added: increases effect of CYP450 = increases m-6-g = increases potency = more available before excretion
85
What happens when chronic alcoholics are given morphine?
enzymes are constantly induced
| effect of morphine likely to be potentiated
86
Explain enzyme inhibition in terms of morphine and CYP450.
metronidazole inhibits CYP450
causes CYP450 to convert morphine to m-6-g much slower
m-6-g won't work as effectively
87
How can enzyme inhibition still allow morphine to have a potent effect?
may cause morphine to stay in the body for longer
| so body still experiences an effect from morphine not just m-6-g
88
What is the drug most commonly used for overdose around the world?
aspirin
89
How can excretion of aspirin be increased?
it is an acidic drug
| if an alkali is given in the blood, excretion occurs quicker
90
What is renal excretion dependent on?
pH
91
Give 4 examples of drugs which are weak acids. How do you speed up excretion?
aspirin, ibuprofen, paracetamol, warfarin
| alkalinise urine
92
Give 3 examples of drugs which are weak bases.
less common
| amphetamine, salbutamol, atropine
93
What does warfarin do?
inhibits vitamin K factors in the coagulation cascade
| anti-coagulant
94
What are the 2 factors that effect warfarin the most?
LOTS of interactions
1. protein binding: other protein bound drugs increase its effect
2a. enzyme induction: phenytoin leads to faster warfarin breakdown = has less of an effect
b. enzyme inhibition: mentranidazole leads to slower warfarin breakdown = increased INR = increased risk of bleeding
95
What drug does grapefruit juice interact with?
warfarin
effects protein binding and CYP450
shouldn't be drank when on warfarin
96
What 4 groups of drugs contribute to acute kidney injury? What are the 2 most common?
1. NSAIDs
2. Furomeside
gentimicin
ACEi
97
How are drug effects altered in acute kidney injury?
effects are prolonged as they can't be excreted when kidneys aren't working
98
Gentimicin and furosemide increase the risk of what?
deafness: ototoxic
| especially when given together or too fast
99
What type of drug are statins? What do they do?
HMG-CoA reductase inhibitors
| block rate-limiting step in the cholesterol pathway = lower LDL = lowers risk of CVD
100
What are the 3 A benefits of NSAIDs?
analgesic, anti-pyretic, anti-inflammatory
101
What enzyme do NSAIDs inhibit? What pathway does this block?
```
inhibit cyclooxygenase (COX) by competitive inhibition
prevents arachidonic acid reaching COX active site and forming prostaglandin H2
```
102
What is special about how aspirin acts on COX?
it irreversibly inhibits COX
| non-selective so can inhibits both forms of COX
103
COX has 2 isoforms. What are they?
COX-1: normal and widespread around body
COX-2: induced, found in inflammation
some drugs are specific to one of these
104
Name 2 examples of ACE inhibitors.
captopril, enalapril
105
What do ACE inhibitors treat?
hypertension
106
How do ACE inhibitors work? What pathway do they inhibit?
ACE is required to convert angiotensin I to angiotensin II
when inhibited: less angiotensin II binds to AT1 receptors
reduces vasoconstriction and aldosterone production = REDUCES BP
107
What are the main symptoms of Parkinson's?
```
hypokinesia: reduced motor movement
tremor at rest
muscle rigidity, motor intertia
cognitive impariment
degenerative disease of basal ganglia
early degeneration of dopaminergic neutrons in nigrostriatal pathway = autonomic dysfunction and dementia
```
108
What pathway do drugs for Parkinson's have to target?
dopamine pathway
| must be able to cross blood brain barrier
109
What are the 3 different types of protein port?
1. uniporter: uses ATP to pull molecules in
2. symporter: uses movement of 1 molecule to pull in another against it's concentration gradient
3. antiporter: one substance moves down its gradient using energy from the 2nd substance moving down its gradient
110
Give an example of a symporter and a drug that inhibits it.
Na-K-Cl cotransporter (NKCC): functions in organs that secrete fluids
furosemide: loop diuretic for hypertension and oedema
inhibits luminal NKCC in thick ascending limb of loop of Henle
causes Na, Cl and K loss in urine
reduces hyperosmolarity and reduces water diffusion out of CD into blood = water loss = dehydration
