Drugs Flashcards
(126 cards)
1
Q
Types of drugs acting via GPCR
A
Antidepressants Antipsychotics Antiasthma Blood Pressure Glaucoma Abuse
2
Q
The G protein Gq is coupled to
A
phospholipase
3
Q
Structure of a ligand gated ion channel subunit
e.g. nicotinic acetylcholine receptor
A
4 transmembrane domains
N terminus extracellular
Large loop between TM3 and TM4
TM2 forms lining of channel
4
Q
The most diverse receptor class
A
G protein coupled receptors
5
Q
G protein
A
Protein that links GPCRs to intracellular signalling pathways.
They are trimeric and come in different forms.
Have GTPase enzyme activity.
6
Q
3 most common forms of G protein
A
Gs
Gi
Gq
7
Q
G proteins are trimeric
A
They contain alpha, beta and gamma subunits
8
Q
IP3
A
Inositol tris-phosphate
A second messenger produced in the PLC pathway. (coupled to Gq)
9
Q
Phospholipase C
A
PLC - hydrolyses PIP2 into Diacyl glycerol and IP3
10
Q
Orphan receptor
A
Receptor for which the endogenous ligand is not known
11
Q
Adenylate cyclase is linked to which G proteins
A
Gs and Gi
12
Q
Structure of a voltage gated sodium or calcium channel
A
24 TM domains, arranged into 4 pseudosubunits.
TM4 is the voltage sensor.
There is a membrane dipping loop between TM5 and TM6.
N terminus intracellular
13
Q
G protein Gi is coupled to
A
adenylate cyclase (negatively)
14
Q
The receptor class that is most frequently targetted by drugs
A
G protein coupled receptors
15
Q
Before entering the nucleus, transactivation nuclear hormone receptors must…
A
Bind ligand, dissociate from heat shock proteins and dimerize
16
Q
G protein coupled receptor
A
Receptor for a neurotransmitter, hormone or other signalling molecule that is coupled to intracellular signalling pathways via G proteins
17
Q
G proteins
A
guanine nucleotide binding proteins
18
Q
Structure of a GPCR subunit
A
7 transmembrane domains
N terminus extracellular
Large loop between TM5 and TM6
19
Q
The G protein Gs is coupled to
A
adenylate cyclase (positively)
20
Q
What is gating
A
process by which ion channel opening and closing is controlled.
21
Q
Transrepression
A
Process by which nuclear hormone receptors decrease expression of a protein
22
Q
Ligand gated ion channel
A
Ion channel with a binding site for a ligand built into it.
The ion channel is opened by actions of the neurotransmitter.
23
Q
Nuclear hormone receptors are usually present in the
A
cytoplasm
24
Q
Phospholipase C is linked to
A
Gq
25
Transactivation
The process by which nuclear hormone receptors increase expression of a protein
26
The time to onset of a functional effect following binding of an agonist to its binding site in a ligand-gated ion channel is
less than a second
27
What is the major inhibitory neurotransmitter in the CNS
GABA
28
How many subunits do nicotonic receptors contain
five
29
Structure of nicotonic receptors in foetal tissue
2 alpha
1 beta
1 delta
1 gamma
30
Structure of nicotonic receptors in a adult tissue
2 alpha
1 beta
1 delta
1 epsilon
31
Where are GABA receptors found in the cell?
Cell surface
32
Where are glucocorticoid receptors found in the cell?
Intracellular
33
Where are muscarinic acetylcholine receptors found in the cell?
Cell surface
34
Where are nicotinic acetylcholine receptors found in the cell?
Cell surface
35
Where does adrenaline act in the cell
G protein coupled receptors
36
Agonist
Activating substances.
| Bind to receptors and activate by mimicking the effects of a transmitter at receptors, due to structural similarities
37
Drug binding domain
a. Point on receptor protein where drug interaction is most favourable
38
Antagonist
bind the receptor but does not transduce a response
39
Amiodarone
Class III antidysrhythmic drug which targets K+ channels
40
Verapamil
Class IV antidysrhytmic drug which targets Ca2+ channels
41
Unclassified antidysrhythmic drugs
adenosine
atropine
digoxine
42
Lidocaine
Class Ib antidysrhythmic drug which targets Na+ channels
43
Atenolol
Class II antidysrhythmic drug which targets Beta 1 adrenoreceptors
44
Drug X has a Kd of 5nm
Drug Y has a Kd of 50nm
Which has a higher affintiy
Drug X has 10x higher affinity than drug Y.
45
Kd / dissociation constant
Concentration that gives 50% of maximal occupancy
46
EC50
Concentration giving 50% maximum effect
47
Potency
The concentration of drug required to give a specified response. Often enough is given to achieve the EC50.
48
Ligand
A molecule that binds to something
49
Receptor
Binds a ligand and transduces information
50
Is a enzyme a receptor?
NO
51
Orthosteric antagonism
Reversible binding of antagonist to the same site on the receptor as the agonist. Not activating receptor.
52
IC50
Concentration of antagonist giving 50% of control response
53
Issue with IC50
Changes with agonist concentration. Doesn't only measure antagonist.
54
Selectivity
The relative potency or affinity at one receptor compared with another
55
efficacy
Ability of a drug to produce desired result
56
What kind of response does a partial agonist give?
A submaximal response
57
Constitutive activity
Model explaining an agonist has a higher affinity for its receptor when in its active state
58
Tone or Basal activity
Occurs due to ongoing underlying neurotransmitter release
59
Non-competitive inhibitor
Binds at site other than agonist site (allosteric)
Reduces maximum effect
Not affected by agonist concentration
60
Un-competitive inhibitor
Use-dependent - more effective at higher agonist concentrations.
61
Heart failure
Failure of the heart to meet the body's oxygen demands. Often due to failures of contractile mechanisms.
62
A small EC50 tells you what about a drugs potency/affinity?
It is high
63
Role of calcium in cholinergic transmission
Stimulates vesicle fusion with the presynaptic membrane - thus exocytosis of ACh.
64
Device used to measure polarised light
polarimeter
65
d- / (+) enantiomer
Rotates polarised light clockwise
66
If an enantiomer rotates polarised light anticlockwise, it is...
i- / (-)
67
What's a method of classifying the stereochemistry of a molecule, that can determine structure of amino acids?
D/L
68
(+)/(-) is a method of identification in stereochemistry which classifies based on...
direction a molecule rotates polarised light when in solution
69
Give a type of isomer that can be readily interconverted
Chair/boat
70
Why are doses expressed in mg/kg?
Patients may differ in body weight and size. Using this type of dose means the plasma conc. of the drug should be about the same no matter how big or small the subject.
71
Rectangular hyperbola
Curve that rises and then smoothly reaches a plateau. Characteristic of conc.-response/binding relationships. Predicted by Hill-Langmuir
72
Competitive antagonist
Drug that binds to the same site as an agonist, but doesnt activate the receptor. Presence of competitive antagonist will reduce occupancy by agonist. In a functional assay, it will cause a parallel rightward shift in the agonist conc. response curve.
73
Ki
Term used to define the affinity of a competitive antagonist, or to define the affinity of a ligand derived from a competitive binding assay.
74
Sigmoid curve
S shaped curve
| Seen with conc.response relationships
75
A large EC50 tells you what about a drugs potency/affinity?
it is low
76
A low kd for a drug
high potency/affinity
77
A high pkd for a drug means
high potency/affinity
78
A high EC50 means
high potency/affinity
79
A low pA2 means
A low drug potency
80
How does adrenaline differ from how NA interacts
Acts as hormone, released by adrenal medulla into bloodstream
81
Monoamine oxidase
Enzyme responsible for metabolism of various neurotransmitters - adrenaline and serotonin
82
Paravertebral ganglia
sympathetic ganglia lying close to the spinal cord
83
Amlodipine
Calcium antagonist used to treat hypertension
84
Perindorpil
ACE inhibitor used to treat hypertension, alongside calcium blockers.
85
ACE inhibitor
Reduce activity of ACE in blood, preventing formation of AGII, reducing high BP
86
Three main classes of diuretics...
Thiazide
Loop
K+ sparing
87
Spirinolactone
Potassium sparing diuretic works by blocking aldosterone receptors
88
Amiloride
Potassium sparing diuretic works by inhibiting Na+ channels in luminal membrane
89
How does aldosterone increase Na+ absorption in principal cells?
- Increases Na+/K+ ATPases
- Increase Na+ channels
- Stimulate Na+ channels via protein mediator
90
Examples of ACE inhibitors
Captopril
| Lisinopril
91
AGII receptor types
type 1 - vascular effects and aldosterone release
| type 2 - growth and development
92
Propranolol
Non-selective competitive antagonist at β-adrenoreceptors
| lipid soluble, penetrates CNS causing vivid dreams
93
Atenolol and Bisopropol
Competitive β1-adrenoreceptor antagonists.
| Water soluble.
94
What pain mediators might cardiac muscle cells release when they become ischaemic?
adenosine
bradykinin
K+
95
Features of LDL and VLDL making them bad?
- fatty streak formation
- inhibit fibrinolysis
- activate platelets
96
Dietary changes to treat hyperlipidaemia
- Reduce saturated fat
- Increase unsaturated fat
- Increase fibre
- Avoid trans-fats
- Avoid hydrogenated fats
97
Lipid lowering drugs to treat hyperlipidaemia's
Statins
| ezetimibe
98
Statins
Inhibit HMG-CoA reductase.
Interfere body's ability to produce cholesterol.
Causes more LDL receptors.
99
salbutamol interacts with what receptor
Agonist at beta 2 adrenoreceptors
100
Atropine
mAChR antagonist
101
beta1 adrenoreceptors
control heart rate and force of contraction
102
chronotropic drugs
Affect heart rate
103
Ionotropic drugs
affect strength of heart contractions
104
Thrombin
Enzyme which converts soluble fibrinogen to insoluble fibrin. produced from prothrombin.
105
according to VW system, class I drugs are:
sodium channel blockers
106
According to VW system, class II drugs are:
beta-adrenoceptor antagonists
107
According to VW system, class III drugs are:
amiodarone
| sotalol
108
According to VW system, class IV drugs are:
Calcium channel blockers
109
Statins
Lipid lowering drugs
| Cause muscle inflammation and damage.
110
Plasmin
Enzyme which breaks down fibrin into soluble products. Precursor is plasminogen.
111
ECG showing ST elevation suggests...
STEMI
112
Blood markes in ACS suggests
NSTEMI
113
No blood markers in ACS suggests
Unstable angina
114
Drugs to prevent thrombosis
Aspirin
Ticagrelor/clopidogrel
Heparins
Atorvastatin
115
What type of drugs would be prescribed to someone with arterial thrombosis?
Drugs which modify platelet aggregation
116
What drugs would be prescribed to some with venous thrombosis?
Ones which modify coagulation
| e.g. heparins
117
What does antithrombin act on?
Factor X
| and thrombin
118
PLATO trial
Showed ticagrelor more effective than clopidogrel
119
Re-entry dysrhythmia
A disorder of impulse generation, e.g. atrial fibrillation
120
Disorders of impulse conduction
WPW syndrome
| Atrio-ventricular block.
121
Ectopic focus
Abnormal impulse generation
122
Ventricular fibrillation
Abnormal impulse generation in ventricles
123
Class IV drugs
Block L-type VSCC
Slow SA & AV node conduction
Suppress ectopic pacemaker
124
forward symptoms of congestive heart failure
inability of heart to pump blood efficiently.
| Low output symptoms
125
backward symptoms of congestive heart failure
inability of heart to fill with blood efficiently.
| Congestive symptoms
126
glucocorticoid receptor
GPCR involved in gene regulation.
