Block 12 Pharmacology DONE Flashcards
(211 cards)
1
Q
azathioprine is an (a____)
A
antagonist
2
Q
azathioprine antagonises
A
purine metabolism
3
Q
azathioprine inhibits
A
purine synthesis
4
Q
because azathioprine inhibits purine synthesis it also inhibits…
A
DNA and RNA synthesis and so cell proliferation
5
Q
azathioprine is used to treat
A
autoimmune diseases, transplant recipients
6
Q
azathioprine MOA (2 steps)
A
- incorporates thiopurine analogues into DNA structure
2. causes chain termination and cytotoxicity
7
Q
azathioprine’s most severe side effect is
A
bone marrow suppression
8
Q
azathioprine should not be given in conjunction with
A
purine analogues, e.g. allopurinol
9
Q
people with the enzyme _____ are most at risk of bone marrow deficiency side effect of azathioprine
A
TPMT (thiopurine s-methyltransferase)
10
Q
(azathioprine) genetic polymorphisms of TPMT (thiopurine s-methyltransferase) can lead to
A
excessive drug toxicity
11
Q
to avoid excessive azathioprine drug toxicity due to genetic polymorphisms of TPMT we can do an…
A
assay of serum TPMT
12
Q
in long-term azathioprine treatment we must do…
A
blood tests and monitoring for signs of myelosuppression
13
Q
diclofenac class
A
NSAID, COX inhibitor
14
Q
diclofenac has an ______ effect (2)
A
analgesic and anti-pyretic
15
Q
diclofenac’s analgesic effect is due to
A
inhibition of COX-1 and COX-2 enzymes
16
Q
diclofenac’s anti-pyretic effect is due to (4 steps)
A
- effects hypothalamus
- peripheral dilation
- increased cutaneous blood flow
- heat dissipation
17
Q
diclofenac is prescribed for (3 examples)
A
pain, dysmenorrhea, ocular inflammation
18
Q
diclofenac is the least favoured non-COX specific NSAID because it…
A
targets COX-2 more than others
19
Q
a better choice than diclofenac if we want a non-cos specific NSAID is…
A
naproxen
20
Q
celecoxib class
A
NSAID, COX-2 specific inhibitor
21
Q
celecoxib inhibits
A
COX-2
22
Q
by inhibiting COX-2 celecoxib reduces
A
production of prostaglandins
23
Q
celecoxib MOA (1 step)
A
- uses its polar sulfonamide side chain to bind to hydrophilic side region close to active COX-2 binding site
24
Q
celecoxib only targets COX-2 so does not give _______ effects
A
anti-platelet
25
as celecoxib does not give anti-platelet effects it is not a substitute for...
aspirin for cardiovascular prophylaxis
26
celecoxib's inhibition of prostaglandin synthesis can cause.... due to....
sodium and water retention in ascending loop of henle due to increased fluid reabsorption
27
in collecting duct, PGE2 (prostaglandin) inhibits..
water reabsorption by counteracting antidiuretic hormone
28
celecoxib is used to treat (3)
rheumatoid arthritis, osteoarthritis, familial adenomatous polyposis (FAP)
29
celecoxib is used sparingly due to it's possible effects on the...
cardiovascular system
30
cyclophosphamide class
alkylating agent
31
cyclophosphamide is an _________ and ________ agent
antineoplastic, antiimmunosuppressive
32
cyclophosphamide is activated by the
cytochrome P450 isoforms (CYP2A6, 2B6, 3A4, 3A5, 2C9, 2C18, 2C19) in the liver
33
cyclophosphamide is used to treat (3)
multiple cancers including myelomas and leukaemias
34
cyclophosphamide has 3 MOAs, give them (3)
- attaches alkyl group to DNA bases, so DNA is fragmented by repair enzymes, stopping DNA synthesis and RNA transcription
- cross-linking of DNA to prevent DNA transcription
- induction of DNA mispairing leading to mutations
35
alkylating agents are not specific to a certain part of the....
cell cycle so induce cell death
36
vitamin d class
coenzyme
37
vitamin d itself has little
biological activity
38
vitamin d is metabolised to
1,25-dihydroxycholecalciferol
39
1,25-dihydroxycholecalciferol is
hormonally active
40
vitamin d to 1,25-dihydroxycholecalciferol is 2 steps, the first step is in the
liver
41
the first step of vitamin d to 1,25-dihydroxycholecalciferol (in the liver) is...
cholecalciferal is hydroxylated to 25-hydroxycholecalciferol by 25-hydroxylase
42
vitamin d to 1,25-dihydroxycholecalciferol is 2 steps, the second step is in the
kidney
43
the second step of vitamin d to 1,25-dihydroxycholecalciferol( in the kidney) is...
25-hydroxycholecalciferol is metabolised to 1,25-dihydroxycholecalciferol,
due to action of 1-hydroxylase
44
25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol are
hydrophobic
45
as 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol are hydrophobic, they are transported in the blood bound to
vitamin-D binding protein
46
25-hydroxycholecalciferol half life
several weeks
47
1,25-dihydroxycholecalciferol half life
few hours
48
1,25- dihydroxycholecalciferol has a much ______ ______ for the vitamin D receptor than 25- hydroxycholecalciferol.
higher affinity
49
ciclosporin class
immunosuppressant, cyclophilin binder
50
ciclosporin use
prophylaxis of graft rejection in organ and tissue transplantation
51
ciclosporin MOA (4 steps)
1. binds to cyclophilin
2. inhibits calcineurin
3. stops transcription of IL-2
4. reversible inhibits immunocompetent lymphocytes in G0 or G1 phase of cell cycle
52
ciclosporin preferentially inhibits...
T-lymphocytes, T-1 helper and T1-suppressor
53
ciclosporin's main target is
T1-helper lymphocyte
54
aurothiomalate class
gold based anti-inflammatory, cytokine inhibitor
55
MOA of sodium aurothiomalate
unknown, free thiols play a role
56
aurothiomalate is given as an
IM injection
57
aurothiomalate benefit is not expected till...
300-500mg given
58
important to avoid ______ _____ of aurothiomalate as....
complete relapse, as second gold course not effective
59
aurothiomalate is not
widely used
60
aurothiomalate has been superceded by
other DMARDs
61
chloroquine class
anti-inflammatory, DNA/RNA synthesis inhibitor
62
chloroquine is more widely known as an
anti-malarial
63
chloroquine MOA for malaria (2 steps)
1. inhibit parasitic enzyme heme polymerase
| 2. toxic build up of heme in parasite
64
chloroquine MOA for rheumatoid arthritis
unknown, reduces levels of inflammatory agents (IL-6, IL-1b, TNF-alpha) by blocking release or reducing transcription
65
methotrexate class
folate antagonist, anti-metabolite
66
anti-metabolites are...
synthetic versions of purine or pyrimidines
67
purines/pyrimidines are the
building blocks of DNA
68
anti-metabolites prevent purines or pyrimidines becoming incorporated into DNA during...
S phase (of cell cycle)
69
methotrexate inhibits
folic acid reductase
70
folic acid reductase converts
folic acid to tetrahydrofolic acid
71
tetrahydrofolic acid is needed for
purine and pyrimidine synthesis
72
methotrexate MOA (4 steps)
1. inhibits folic acid reductase
2. lack of tetrahydrofolic acid
3. purines/pyrimidines can't be made
4. DNA synthesis stops
73
methotrexate affects the
most rapidly dividing cells
74
methotrexate uses
low dose for RA
75
sulfasalazine class
immunomodulatory, anti-inflammatory
76
sulfasalazine uses
ulcerative colitis, RA
77
sulfasalazine MOA
unknown
78
sulfasalazine is broken down into
5-aminosalicyclic acid (5-ASA) and sulfapyridine (SP)
79
in ulcerative colitis, sulfasalazine action is mainly via
5-ASA
80
sulfasalazine has been replaced to an extent by
mesalazine
81
mesalazine is better than sulfasalazine as it has
same active metabolite, no sulphur, better tolerated
82
calcitonin is a
hormone
83
calcitonin is produced by the
thyroid gland
84
calcitonin is important in
control of calcium conc in blood
85
calcitonin _____ action of parathyroid hormone
antagonises
86
calcitonin antagonises the action of
parathyroid hormone
87
calcitonin MOA (7 steps)
1. binds to calcitonin receptor (osteoclasts)
2. activates cAMP and calcium signalling
3. more production of vitamin D producing enzymes
4. greater calcium retention
5. more bone density
6. more bone mass
7. reduction in plasma calcium
88
calcitonin also promotes
renal excretion of Ca, Na, Mg, K, phosphate ions by decreasing tubular reabsorption
89
calcitonin is not
commonly used as treatment
90
prednisolone class
glucocorticoid receptor agonist, corticosteroid
91
prednisone is derived from
cortisone
92
prednisone is metabolised in the (organ)
liver
93
prednisone is metabolised in the liver to (thing)
active form, prednisolone
94
prednisolone can cross
cell membrane
95
prednisolone MOA (3 steps)
1. binds to corticosteroid receptor
2. changes DNA transcription
3. reduced inflammatory proteins
96
prednisolone specific example
reduction of phospholipase A2 reduces arachidonic acid production
97
raloxifene class
selective estrogen receptor modulator
98
raloxifene effect on bone and lipid metabolism
oestrogen-like (promotes)
99
raloxifene effect on breast and uterine tissue
antagonises oestrogen (inhibits)
100
raloxifene in bone (4 steps)
1. binds to oestrogen receptors
2. reduces bone resorption
3. increases bone mineral density
4. slows rate of bone loss
101
raloxifene antagonises the effects of oestrogen on mammary and uterine tissue by (1 step)
1. prevents transcription of genes with oestrogen response
102
raloxifene use
less common as post-menopausal symptoms being treated with hormones decreases
103
alendronic acid class
nitrogen-containing, second generation bisphosphonate
104
alendronic acid used to treat
corticosteroid-induced osteoporosis, Paget's disease, prevent osteoporosis in post-menopausal women
105
nitrogen containing bisphosphonates inhibit
farnesyl pyrophosphate (FPP) synthase
106
nitrogen containing bisphosphonates inhibit farnesyl pyrophosphate (FPP) synthase by acting as
analogues of isoprenoid diphosphate lipids
107
inhibition of FPP (by nitrogen containing bisphosphonates) in osteoclasts prevents
post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins, such as Rac and Rho
108
alendronic acid basically ruins
osteoclast activity, reducing bone resorption
109
in post-menopausal women alendronic acid causes
net gain in bone mass
110
digoxin class
cardiac glycoside, sodium-potassium ATPas inhibitor
111
digoxin uses
congestive heart failure, supraventricular arrhythmias, AF
112
digoxin MOA (4 steps)
1. inhibits Na-K-ATPase pump
2. increase in intracellular sodium
3. sodium-calcium exchanger (NCX) extrudes sodium and brings in calcium
4. more Ca promotes contractile proteins, myosin and actin
113
digoxin also acts on the
electrical activity of heart
114
digoxin MOA on electrical activity of heart (4 steps)
1. increases slope of phase 4 depolarisation
2. shortens action potential duration
3. decreases maximal diastolic potential
115
digoxin is a 3rd line treatment for
AF
116
digoxin is rarely involved in
heart failure
117
betaxolol class
beta-adrenergic receptor
118
betaxolol is a
competitive antagonist
119
betaxolol competitively antagonises
beta-1 selective adrenergic receptor
120
beta-1 blockers are mainly in the
heart
121
beta-1 blockers bind
epinephrine, norepinephrine
122
activation of beta-1 blockers leads to
G activation and cAMP signalling
123
cAMP signalling results in a
reduction in heart rate, cardiac output, blood pressure
124
betaxolol (beta-1 blockers) are routinely prescribed in patients with
ischaemic heart disease
125
betaxolol can also competitively block (2 steps)
1. release of renin (can cause vasoconstriction)
| 2. beta(2)-adrenergic responses in bronchial and vascular smooth muscles, causing bronchospasm
126
betaxolol is less commonly used than
bisoprolol
127
diazepam class
benzodiazepine, GABA receptor agonist
128
benzodiazepines (diazepam) bind non-specifically to
benzodiazepine receptors
129
benzodiazepine receptors mediate (5)
sleep, muscle relaxation, anticonvulsant activity, motor co-ordination, memory
130
diazepam causes GABA to bind to its receptor and open the chloride channel. causing
hyperpolarisation preventing further cell excitation
131
diazepam is still used for
anxiety, muscle relaxant
132
propofol class
anaesthetic, GABA receptor modulator
133
propofol is given
IV
134
propofol used for
induction and maintenance of general anaesthesia
135
propofol MOA (1 step)
1. makes GABA bind more to GABA-A receptors
136
propofol IV produces
hypnosis rapidly, in 40 secs
137
recovery from propofol-induced anaesthesia is generally
rapid and has less frequent side effects than thiopental, methohexital and etomidate
138
lamotrigine class
anti-convulsant, sodium channel inhibitor
139
lamotrigine uses
epilepsy, bipolar disorder
140
lamotrigine MOA
unknown, could be inhibition of Na/Ca channels, stabilises neuronal membranes, modulates release of glutamate and aspartate
141
carbamazepine class
anti-convulsant, sodium channel inhibitor
142
carbamazepine is used to control
grand mal, psychomotor or focal seizures
143
carbamazepine MOA
unknown, inhibits repetitive firing by blocking Na channels
144
carbamazepine pain relief MOA
blocks synaptic transmission in trigeminal nucleus
145
response to carbamazepine is
variable, may be resistant due to RALBP1
146
carbamazepine is less commonly used as
anti-epileptic
147
carbamazepine is still commonly used as a
mood stabiliser in bipolar, trigeminal neuralgia
148
phenytoin class
anticonvulsant, sodium channel inhibitor
149
phenytoin is an anticonvulsant that lacks the _____ effect of ______
sedation, phenobarbital
150
phenytoin MOA
unclear, but in motor cortex to prevent spread of seizure
151
phenytoin is not used a lot as it has a lot of
adverse effects and interactions with other drugs
152
phenytoin rarely used as chronic therapy as there are better
anti-epileptic drugs
153
phenytoin is still first line in
status epilepticus
154
sodium valproate class
anti-convulsant, sodium channel inhibitor, GABA receptor agonist
155
sodium valproate is a
fatty acid
156
sodium valproate use
epilepsy, mood stabiliser
157
sodium valproate possible MOA (3)
1. increase GABA levels by inhibiting enzymes that catabolise GABA
2. alter properties of voltage dependent Na channels
3. histone deacetylase inhibitor
158
sodium valproate therapeutic range in epilepsy
50-100mcg/mL of total valproate
159
donepezil class
reversible acetyl cholinesterase inhibitor
160
donepezil is relatively specific for
brain acetylcholinesterase
161
donepezil leads to an increase in
aceylcholine at cholinergic synapses, enhancing cholinergic function
162
donepezil use
dementia, alzheimer's
163
suxamethonium class
depolarising nicotinic cholinergic receptor antagonist
164
suxamethonium MOA (5 steps)
1. mimics acetylcholine at NMJ
2. hydrolysed slower than acetylcholine
3. prolonged depolarisation
4. desensitisation
5. muscle relaxation
165
suxamethonium cannot be
reversed
166
suxamethonium recovery is
spontaneous
167
suxamethonium use
after general anaesthetic as muscle relaxation can be preceded by painful muscle fasciculations
168
anticholinesterases such as neostigmine given alongside suxamethonium can potentiate
NMJ block
169
levodopa class
dopamine replacement therapy
170
levodopa is a natural form of
dihydroxyphenylalanine
171
levodopa is an immediate precursor of
dopamine
172
levodopa can be taken
orally
173
levodopa can readily cross
blood brain barrier
174
levodopa within the brain is taken up by
dopaminergic neurons and converted to dopamine
175
levodopa use
replace dopamine lost in Parkinson's
176
bromocriptine class
dopamine agonist
177
bromocriptine mesylate is an
ergot alkaloid derivative
178
bromocriptine stimulates
dopamine activity
179
bromocriptine stimulates dopamine activity through the
D2 receptor
180
bromocriptine MOA
1. binds D2 receptor
2. Gi signalling cascade
3. inhibits adenyl cyclase
4. reduction in cAMPL
5. blockage of calcium release
181
bromocriptine improves
muscle activity and coordination
182
bromocriptine uses
Parkinson's, hyperprolactinaemia, acromegaly, pulmonary fibrosis
183
bromocriptine is less commonly used due to concerns about
fibrotic reactions
184
in Parkinson's, it is more common to use _____ or ______ than bromocriptine
pramipexole, ropinirole
185
gabapentin class
anticonvulsant, GABA analogue
186
gabapentin increases
synaptic conc of GABA
187
gabapentin is (3)
- high lipid solubility
- not metabolised by liver
- no protein binding
188
gabapentin MOA (2)
1. reduce mono-amine neurotransmitters
| 2. reduces axon excitability
189
gabapentin use
epilepsy, neuropathic pain, adjunct in chronic pain
190
selegiline class
dopamine therapy, monoamine oxidase B inhibitor
191
selegiline uses
Parkinson's, depression
192
selegiline MOA (3 steps)
1. irreversibly inhibit monoamine oxidase type B
2. inhibits deamination of dopamine in brain
3. enhances dopaminergic activity
193
selegiline at higher doses can also inhibit
monoamine oxidase type A (depression treatment)
194
isoflurane class
general anaesthetic, neuronal ion channel modulator
195
isoflurane induces
muscle relaxation
196
isoflurane reduces
pain sensitivity
197
isoflurane MOA (5 steps)
1. reduces gap junction channel opening times
2. increases gap junction channel closing times
3. activates calcium dependent ATPase in sarcoplasmic reticulum
4. increases fluidity of lipid membrane
5. binds to the GABA, glutamate, glycine receptors
198
atracurium class
competitive cholinergic receptor antagonist, non-depolarising skeletal muscle relaxant
199
atracurium MOA (3 steps)
1. antagonises neurostransmitter action of acetylcholine
2. by binding competitively with cholinergic receptors on motor end plate
3. muscle relaxation
200
repeat doses of atracurium can be administered at
regular intervals with predictable results
201
action of atracurium is reversed by
acetylcholinesterase inhibitors, e.g. neostigmine, edrophonium, pyridostigmine
202
repeated administration of maintenance doses of Atracurium has no cumulative effect on the duration of neuromuscular block if
recovery is allowed to begin prior to repeat dosing
203
memantine class
NMDA receptor antagonist
204
memantine use
dementia
205
memantine MOA (4 steps)
1. binds to NDMA receptor-operated cation channels
2. increased glutamate in brain of dementia patients usually allows Mg2+ to bind to NDMA channels so lots of Ca2+ comes in so neuronal degeneration
3. memantine binds better than Mg2+ so stops lots of Ca2+
4. protects against elevated gutamata
206
fentanyl class
opioid analgesic, opioid receptor agonist
207
fentanyl interacts with
opioid mu, kappa, and delta opioid receptors
208
opioid receptors are coupled with
G-protein receptors
209
opioid receptors function as
regulators of synaptic transmission
210
fentanyl MOA (3 steps)
1. binds to opioid receptor
2. stimulates exchange of GTP for GDP on G-protein complex
3. inhibition of adenylate cyclase and so less cAMP
4. decreased nociceptive neurotransmitter release
5. fentanyl converted to morphine
6. closure of N-type voltage calcium channels, opening of calcium-dependent potassium channels
7. hypopolarisation, reduced excitability
211
fentanyl use
IV analgesic, epidural, spinals (regional anaesthesia), transdermal patches (chronic pain)
