pharmacology Flashcards
(296 cards)
1
Q
what are the 4 drug targets
A
enzyme
receptor
ion channel
transport protein
2
Q
what are the 4 ways drug can react with receptors through chemical reactions
A
electrostatic interactions
hydrophobic interactions
covalent bonds
stereospecific interactions
3
Q
what do u call full affinity but 0 efficacy drug
A
antagonist
4
Q
what is the standard measure of potency
A
determine concentration or dose of a drug required to produce 50% tissue response
5
Q
which is related to dose, potency or efficacy
A
potency
6
Q
in ionised form, will the acid donate or accept protons
A
donate
7
Q
in ionised form, will the base donate or accept protons
A
accept
8
Q
what determines whether the drug is ionised or not
A
pH
pKa
9
Q
what happens when pKa of drug and pH of tissue is equal
A
drug 50% ionised 50% unionised
10
Q
for weak acid, when pH decreases which form will start to dominate
A
unionised form
11
Q
for weak base, when pH increase, which form starts to dominate
A
unionised form
12
Q
for weak base when pH decreases which form dominates
A
ionised form
13
Q
different forms of drug administration
A
oral
inhalational
dermal(percutaneous)
intra-nasal
14
Q
what affects diffusion of drug
A
lipid solubility
15
Q
what influence tissue distribution
A
regional blood flow
plasma protein binding
capillary permeability
tissue localisation
16
Q
factors affecting amount of drug that is bound
A
free drug conc
affinity of protein binding sites
plasma protein conc
17
Q
what are the different types of capillary structure
A
continuous
fenestrated
discontinuous
BBB
18
Q
which enzyme is responsible for drug metabolism
A
P450 enzymes
19
Q
what are the phases of drug metabolism
A
phase 1 – introduce a reactive grp to a drug
phase 2 – add a conjugate to reactive grp
20
Q
what are the main aims of the 2 stages in drug metabolism
A
decrease lipid solubility to aid excretion and elimination
21
Q
what are the major excretion methods for drug via kidney
A
glomerular filtration
active tubular secretion (or reabsorption)
passive diffusion across tubular epithelium
22
Q
what is the drug target of metformin
A
AMPK (5′-AMP-activated protein kinase (AMPK)
23
Q
where is the primary site of metformin action
A
hepatocyte mitochondria
24
Q
mechanism of action of metformin
A
inhibits gluconeogenesis and hence glucose output
metformin activates AMPK to inhibit ATP production to block gluconeogenesis, block adenylate cyclase to promote fat oxidation to restore insulin sensitivity
25
side effects of metformin
GI (abdominal pain, reduced appetite, diarrhoea, vomit)
26
why metformin can accumulate in liver and GIT
it's high polar and need organic cation transporter-1 (OCT-1) to access tissue
27
when is metformin most effective in a patient
with presence of endogenous insulin / functioning pancreatic islet cells
28
example of DPP-4 inhibitors
sitagliptin
29
what is the primary site of DPP-4 inhibitors
vascular endothelium
30
main action of DPP-4 inhibitors
reduce break down of insulin / increase insulin production
31
mechanism of action of DPP-4 inhibitors
DPP-4 metabolise incretins in plasma which incretins help to stimulate production of insulin and reduce production of glucagon by liver
by inhibiting DPP-4, can let incretin remain to stimulate insulin production
32
side effects of DPP-4
upper respiratory tract infections (flu like symptoms)
allergic reaction
33
which patients shd avoid DPP-4 inhibitors
patients with pancreatitis
34
main benefit of DPP-4 inhibitors compared to other anti-diabetic drug
no weight gain
35
when is DPP-4 inhibitors effective
when residual pancreatic beta-cell activity is present
36
examples of sulphonylurea
gliclazide
37
target of sulphonylurea
ATP sensitive K+ channel
38
primary site of sulphonylurea
pancreatic Beta cells
39
main action of sulphonylurea
stimulate insulin production
40
mechanism of action of sulphonylurea
inhibit K+ ATP channel on pancreatic beta cell
cause depolarisation and stimulate Ca2+ influx and hence insulin vesicle exocytosis
41
side effects of sulphonylurea
wight gain
hypoglycaemia
42
when is sulphonylurea most effective
when residual pancreatic beta cell activity is present
43
risk of sulphonylurea
hypoglycaemia
44
examples of SGLT-2 transporter inhibitors
dapaglifozin
45
target site of SGLT-2 inhibitors
PCT
46
mechanism of action of SGLT-2 inhibitors
inhibit SGLT-2 in PCT to reduce glucose reabsorption and increase urinary glucose excretion
47
side effects of SGLT-2 inhibitors
uro-genital infections due to increase glucose load
decrease in bone formation
worsen diabetic ketoacidosis
48
physiological changes of SGLT-2 inhibitors
reduce weight
reduce BP
49
in which patients are SGLT-2 inhibitors less effective
renal impairment
50
what to administer when HbA1c > 48
standard release metformin
51
what to administer when HbA1c > 58
metformin + one of below
DPP-4 inhibitors
Pioglitazone
Sulphonylurea
SGLT-2 inhibitor
52
which transporter does metformin use
organic cation transporter -1 (OCT-1)
53
where is OCT-1 found in body
hepatocytes (liver) allow it to be absorbed
enterocytes (Small bowel) to be distributed to site of action
PCT (kidney) help excretion
54
risk of pioglitazone
heart failure
55
mechanism of pioglitazone
reduces peripheral insulin resistance, leading to a reduction of blood-glucose concentration.
56
why metformin may lead to lactic acidosis
accumulate metformin in bloodstream
block pyruvate carboxylase
inhibit gluconeogenesis and pyruvate build up
cause lactic acidosis
57
what are examples of dopamine precursors
levodopa, fos-levodopa
58
main goal of dopamine precursors
This compensates for the loss of endogenous dopamine in nigrostriatal neurones.
59
mechanism of dopamine precursors eg levodopa
Levodopa is taken up in the terminals of nigrostriatal neurones.
Then decarboxylated into dopamine by dopa decarboxylase (useful to think of levodopa as a prodrug for dopamine).
60
are there any drug target for levodopa
no, once converted into dopamine then the targets will be dopamine receptors
61
side effects of dopamine precursors
N+V
dizziness
headache
GI discomfort
dyskinesias
somnolence
62
relationship between levodopa and fos-levodopa
fos-levodopa is a phosphate pro drug of levodopa
more water soluble than levodopa so more suitable for sub-cutaneous infusion
63
what can rapid withdrawal if levodopa lead to
neuroleptic malignant syndrome
64
drugs to treat diabetes
metformin
SGLT-2 inhibitors
Sulfonylurea
DPP4-inhibitors
65
examples of dopa decarboxylase inhibitors
carbidopa
benserazide
66
target of dopa decarboxylase inhibitor
dopa decarboxylase
67
main target of dopa decarboxylase inhibitor
dopa decarboxylase
68
mechanism of dopa decarboxylase inhibitor
Dopa decarboxylase inhibitors block the dopa decarboxylase enzyme and prevent the conversion of dopa to dopamine.
69
why dopa decarboxylase inhibitors only hv peripheral side effects
these drugs cannot enter brain
70
side effects of dopa decarboxylase inhibitors
dyskinesias (facial twitching, head bobbing)
vitamine deficiencies
peripheral monoamine depletion
71
why carbidopa (dopa decarboxylase inhibitor) is rarely administered alone
there will be no antiparkinsonian effect
72
examples of dopamine receptor agonists
rotigotine
ropinorole
73
target of dopamine receptor agonists
dopamine receptors (D2/D3 receptors esp in parkinson's)
74
mechanism of dopamine receptor agonist
Dopamine receptor agonists bind to post-synaptic dopamine receptors (i.e. independently of dopaminergic neurone activation).
75
side effects of dopamine receptor agonists
Nausea and vomiting
Dizziness
Headache
Gastrointestinal discomfort
Somnolence
Hallucinations
Dyskinesias
76
examples of lcoal anaethetics
lidocaine
77
target site of local anaethetics
voltage gated na+ channels
78
mechanism of local anaesthetics
Uncharged form of local anaesthetics diffuse through the neurone to bind to the sodium channel from the inside.
This locks them in the open state and prevents nerve depolarisation.
79
side effects of local anaethetics
mild: redness, swelling at site of injection, numbness
severe toxicity: fear, anxiety, anaphylaxis
80
where will lidocaine's efficacy be reduced
sites of inflammation
81
is pH higher or lower in site of inflammation
lower
82
what happen to lidocaine in site of inflammation
pH is lower at these sites, so basic lidocaine exists in a more polarised (charged) state so less can diffuse across neurones.
83
what is lidocaine for another disease
Lidocaine is also classified as a class 1b anti-arrythmic – slows conduction in the heart due to decreasing permeability of sodium channel to sodium
84
how is dopamine agonsist differ from levodopa
less potent than carbidopa-levodopa
85
what are off effects when treating parkinson's
the fewer nigrostriatal dopaminergic neurones present, the less neurones present to store dopamine and maintain tonic activation
86
what drug classes are to treat depression (5)
Sertraline
Citalopram
fluoxetine
venlafaxine
mirtazapine
87
drug classes to treat parkinson's (4)
dopamine precursors
dopa decarboxylase inhibitors
dopamine receptor agonists
local anaethetics
88
drug target for sertraline
serotonin transporter
89
mechanism of sertraline
inhibition of serotonin reuptake
accumulation of serotonin in CNS to regulate mood, personality, wakefulness
90
side effects of sertraline
GI (nausea, diarrhoea) sexual dysfunction, anxiety, insomnia
91
sertraline cause mild inhibition in what
dopamine transporter
92
drug target of citalopram
serotonin transporter
93
main action of citalopram
inhibit serotonin reuptake
accumulation of serotonin in CNS to regulate mood, personality, wakefulness
94
side effects of citalopram
GI (nausea, diarrhoea)
sexual dysfunction, anxiety, insomnia
prolong QT interval
95
citalopram is mild antagonist of what
muscarinic and histamine receptors
96
what is sertraline partial inhibiting
CYP2D6 at high dose
97
what is citalopram metabolised by
CYP2C19
98
drug target of fluoxetine
serotonin transporter
99
main action of fluoxetine
inhibit serotonin reuptake
accumulation of serotonin in CNS to regulate mood, personality, wakefulness
100
side effects of fluoxetine
GI (nausea, diarrhoea)
sexual dysfunction, anxiety, insomnia
101
fluoxetine is mild antagonism of what 2 receptor
5HT2A
5HT2C
102
drug target of venlafaxine (2)
serotonin and noradrenaline receptor
103
mechanism of venlafaxine
inhibit serotonin and noradrenaline reuptake
104
does venlafaxine inhibit serotonin or noradrenaline better
serotonin
105
role of noradrenaline in CNS
regulate emotions and cognition
106
side effects of venlafaxine
GI (nausea, diarrhoea)
sexual dysfunction
anxiety
insomnia
hypertension (at higher dose)
107
when administer fluoxetine, which drug has to be used with caution
warfarin (anticoagulant)
increase GI bleeding
108
drug target of mirtazapine (2)
Histamine (H1) receptor
alpha-2 receptor
5-HT2 receptor
5-HT3 receptor
109
main action of mirtazapine
increase release of serotonin and nordrenaline
110
mechanism of mirtazapine
1. antagonises central presynaptic alpha-2-adrenergic receptors
2. increase release of serotonin and noradrenaline
3. antagonises central 5HT2 receptors which leave 5HT1 receptors unopposed causing anti-depressant effects
111
side effects of mirtazapine
weight gain
sedation
sexual dysfunction (low probability)
may exacerbate REM sleep behavior disorder
112
what are the 3 common SSRI
citalopram
sertraline
fluoxetine
113
mechanism of SSRI
target 5HT receptors in presynaptic knob
block 5HT receptors
reduce reuptake of serotonin
increase serotonin in synapse
114
Why do we slowly cut off sertraline first before starting the new anti-depressant?
Caution is required when switching from one antidepressant to another due to the risk of drug interactions, serotonin syndrome, withdrawal symptoms, or relapse.
Washout required before starting new drug
115
how does mirtazapine affect sleep
Mirtazapine modestly suppress REM sleep whilst still having a beneficial impact on sleep continuity and duration due to its anti-histaminergic effects.
116
drugs to treat Hypertension (4)
ACEi
calcium channel blockers
Thiazide / thiazide - like diuretics
angiotensin receptor blockers
117
drug target of ACEi
ACE
118
mechanism of ACEi
Inhibit the angiotensin converting
enzyme.
Prevent the conversion of
angiotensin I to angiotensin II
by ACE.
119
examples of ACEi
ramipril
lisinopril
perindopril
120
side effects of ACEi
cough
hypotension
hyperkalaemia
foetal injury (so need avoid in pregnant women)
renal failure
121
why most ACEi need hepatic activation
mostly are pro drugs
122
what has to be regularly monitored when prescribing ACEi (2)
eGFR
serum potassium
123
examples of calcium channel blockers (2)
amlodipine
felodipine
124
target of calcium channel blockers to treat HTN
L-type calcium channel
125
where do calcium channel blockers block the channel at
vascular smooth muscle
126
mechanism of calcium channel blocker
Block L-type calcium channels on vascular smooth muscle.
decrease in calcium influx, with downstream inhibition of myosin light chain kinase and prevention of cross-bridge formation. The resultant vasodilation reduces peripheral resistance.
127
side effect of calcium channel blocker (4)
ankle oedema
constipation
palpitations
flushing/headaches
128
which type of calcium channel blocker has a higher degree of vascular activity
Dihydropyridine
129
examples of thiazide
bendro-flumethiazide
130
example of thiazide like diuretic
indapamide
131
target of thiazide / thiazide like diuretics
sodium/chloride cotransporter
132
mechanism of thiazide
block Na+/Cl- co transporter in early DCT
reduce Na+ and Cl- reabsorption
increase osmolarity of tubular fluid
reduce osmotic gradient for water reabsorption in collecting duct
133
side effects of thiazide
hypokalaemia
hyponatremia
metabolic alkalosis (increased H+ excretion)
hypercalcemia
hyperglycaemia
hyperuricemia
134
how long does Thiazide and thiazide-like diuretics lose their diuretic effects
within 1-2 weeks of treatment.
135
target of angiotensin receptor blocker
angiotensin receptor
136
examples of angiotensin receptor blockers
losartan
irbesartan
candesartan
137
mechanism of angiotensin receptor blockers
non competitive antagonists at angiotensin I receptor
on kidney and on vasculature
138
side effects of angiotensin receptor blockers
hypotension
hyperkalaemia
foetal injury (avoid in pregnant women)
renal failure (in pt with renal artery stenosis)
139
as Losartan and candesartan are pro-drugs what do they require
They require hepatic activation to generate the active metabolites required for therapeutic effects.
140
what do we use to measure how the ability of body to eliminate of drug
clearance
141
what is elimination half-life
time required for concentration of a drug to decrease to half of its starting dose in body
142
what is time to peak plasma level:
time required for a drug to reach peak conc in plasma
faster the absorption rate, lower the time to peak plasma level
143
does ACEi cause vasodilation or constriction
vasodilation
144
does ACEi cause aldosterone secretion
no
145
does ACEi cause salt and water secretion or retention in kidney
secretion
146
which group of patient use angiotensin 2 receptor blocker instead of ACEi
african or caribbean descent
147
Why might ACE inhibitors have a negative effect on eGFR
ACE inhibitors can dilate efferent arterioles, which reduces intraglomerular pressure and potentially decreases the filtration rate in the kidneys.
148
Why might ACE inhibitors cause increase in serum potassium level
Normally, angiotensin II acts on the adrenal glands to stimulate aldosterone secretion, which promotes potassium excretion in the kidneys. ACE inhibitors block the production of angiotensin II, reducing aldosterone secretion and thereby decreasing potassium excretion.
149
effect of thiazide like diuretics
reduced blood volume
reduce venous return
reduce cardiac output
150
how to diuretic travel from blood to access sodium chloride transporters and inhibit them
from blood, to basolateral side, then to apical side of DCT facing the lumen
151
does thiazide lead to hyper or hypokalaemia
hypokalaemia
152
how thiazide cause hypokalaemia
inhibit Na+ from reabsorbed from the DCT
more sodium reaches the collecting duct, the epithelial sodium channels (ENaC) in principal cells reabsorb more sodium.
sodium enters the principal cells through ENaC, the electrical gradient favors potassium secretion into the urine via potassium channel
153
what activates raas system
there is a drop in blood pressure (reduced blood volume)
to increase water and electrolyte reabsorption in the kidney
154
what are the drugs to treat asthma (5)
salbutamol
fluticasone
mometasone
budesonide
montelukast
155
drug target for salbutamol
beta 2 adrenergic receptor
156
main target of salbutamol
prevents smooth muscle contraction
157
mechanism of salbutamol
Agonist at the β2 receptor on airway smooth muscle cells
Activation reduces Ca2+ entry
this prevents smooth muscle contraction.
158
side effects of salbutamol
palpitations
agitation
tachycardia
arrythmias
hypokalaemia
159
type of drug of salbutamol
beta agonist
160
is salbutamol long or shor acting beta agonist
short acting beta agonist (SABA)
161
can salbutamol be administered with corticosteroids
no
162
why salbutamol cannot be administered with corticosteroids
will exacerbate hypokalaemia and have cardiac effect due to non absolute selectivity in beta2 agonist
163
drug target for fluticasone
glucocorticoid receptor
164
mechanism of fluticasone
directly decrease inflammatory cells eg eosinophils, dendritic cells, macrophages, mast cells, monocytes
hence reduce number of cytokines they produce
165
main target of fluticasone
anti-inflammatory
166
local side effects of fluticasone
sore thora
hoarse voice
opportunistic oral infections
167
systemic side effects of fluticasone
growth retardation in children
hyperglycaemia
reduced Bone mineral density
immunosuppression
effects on mood
168
why administer fluticasone, budesonide and mometasone through pulmonary vasculature instead of oral
oral bioavailbility only <1%
169
drug target of mometasone
glucocorticoid receptor
170
mechanism of mometasone
directly decrease inflammatory cells eg eosinophils, dendritic cells, macrophages, mast cells, monocytes
hence reduce number of cytokines they produce
171
local side effects of mometasone
sore thora
hoarse voice
opportunistic oral infections
172
systemic side effects of mometasone
growth retardation in children
hyperglycaemia
reduced Bone mineral density
immunosuppression
effects on mood
173
drug target of budesonide
glucocorticoid receptor
174
mechanism of budesonide
directly decrease inflammatory cells eg eosinophils, dendritic cells, macrophages, mast cells, monocytes
hence reduce number of cytokines they produce
175
local side effects of budesonide
sore thora
hoarse voice
opportunistic oral infections
176
systemic side effects of budesonide
growth retardation in children
hyperglycaemia
reduced Bone mineral density
immunosuppression
effects on mood
177
montelukast drug target
CysLT1 leukotriene receptor
178
mechanism of montelukast
Antagonism of CysLT1 leukotriene receptor on eosinophils, mast cells and airway smooth muscle cells decreases eosinophil migration, broncho-constriction and inflammation induced oedema
179
key goal of montelukast
inhibit broncho-constriction
180
side effects of montelukast
diarrhoea
fever
headaches
N+V
mood changes
anaphylaxis
181
when shd Montelukast be administered before initiate exercise
at least 2 hrs before
182
can we diagnose asthma in children under 5yo
no
183
B2 agonist mechanism to treat asthma
bronchodilators.
bind to receptors in your lungs. This relaxes the muscles in your airways, allowing them to open up.
184
Why nebulizer was the best method for delivering the salbutamol in the emergency situation?
can deliver many drug combinations
minimal patient cooperation required
all ages
concentration and dose can be modified
normal breathing pattern
185
why only small amount of inhaled drugs can penetrate deep enough to lung, where are the others (5)
1. exhaled
2. absorption from lungs
3. mucociliary clearance
4. oral swallowed portion
5. absorbed across mucous membrane in oral cavity and pharynx
186
how viral infection/ pollutants/ allergens exacerbates asthma conditions
they trigger IL-5, trigger IgE-mediated immune responses, eosinophil maturation, migration, recruitment leading to histamine release, airway inflammation, and bronchoconstriction.
187
Like salbutamol, a significant proportion of inhaled fluticasone is actually swallowed. Despite this, the oral bioavailability (i.e. the proportion of drug that reaches the plasma VIA the gastrointestinal tract) is less than 1%. Why is this the case?
first pass inactivation (liver metabolize and inactivate/eliminate the drug before it reaches the systemic circulation)
188
which enzyme does NSAIDs block
cyclooxygenase (COX)
189
why is montelukast particularly useful for NSAID (Non-steroidal anti-inflammatory drug)-induced asthma?
NSAIDs inhibit COX pathway, so arachidonic acid cannot convert to prostaglandin H2.
Arachidonic acid is redirected to lipoxigenase pathway to increase leukotriene synthesis, which trigger triggering severe bronchospasm, airway inflammation, and nasal congestion
as montelukast targets CysLT1 receptor,Montelukast competitively blocks the binding of leukotrienes to the CysLT1 receptor, reducing their effects eg bronchoconstriction and inflammation
190
how leukotrienes contribute to asthma symptoms
leukotrienes cause bronchoconstriction, airway inflammation, mucus secretion, and increased vascular permeability
191
drugs to treat GORD or peptic ulcer disease (4)
NSAIDS
PPIs
Histamine (H2) receptor antagonists
paracetamol
192
examples of NSAID
ibuprofen, naproxen, diclofenac
193
drug target of NSAIDs
Cyclo-oxygenase enzyme (COX)
194
main goal of NSAIDs
anti-inflammatory
195
mechanism of NSAIDs
NSAIDS inhibit the COX enzyme, which is the rate-limiting step for the production of all prostaglandins & thromboxane from the arachidonic acid.
Inhibit prostaglandin pathway (which triggers inflammation) and go along with leukotriene pathway
196
side effects of NSAIDS
Common: gastric irritation, ulceration and bleeding and, in extreme cases, perforation; reduced creatinine clearance and possible nephritis; and bronchoconstriction in susceptible individuals (contraindicated in asthma). Skin rashes & other allergies, dizziness, tinnitus.
Adverse cardiovascular effects (hypertension, stroke, MI) may occur following prolonged use or in patients with pre-existing CV risk.
Prolonged analgesic abuse over a period of years is associated with chronic renal failure.
Aspirin has been linked with a rare but serious post-viral encephalitis (Reye’s syndrome) in children.
197
main function of NSAIDs
1. analgesics
2. antipyretics (reduce fever)
3. anti-inflammatory
4. anti-aggregatory (inhibit platelet aggregation for stroke/MI pt)
198
PPIs example
omeprazole
lansoprazole
199
drug target of PPIs
H+/K+ ATPase (‘proton pump’)
200
main goal of PPIs
inhibit basal and stimulate gastric acid secretion
201
mechanism of PPIs
Irreversible inhibitors of H+/K+ ATPase in gastric parietal cells.
Proton pump inhibitors inhibit basal and stimulated gastric acid secretion by >90%.
202
are PPIs strong or weak bases
weak
203
where do PPIs accumulate in human
acid environment of canaliculi of parietal cells
204
why PPIs accumulate in acidic environment in parietal cells canaliculi
prolongs their duration of action
(omeprazole plasma half-life approx. 1 h but single daily dose affects acid secretion for 2-3 days).
205
side effects of PPIs
Unwanted effects are uncommon but may include headache, diarrhoea, bloating, abdominal pain & rashes.
206
which cancer may PPIs mask the symptoms of
gastric cancer
207
method of administration of PPI
oral
208
why PPIs given as capsules
degrade rapidly in oral so administered as capsules containing enteric-coated granules
209
drug target of Histamine (H2) receptor antagonsits
Histamine H2 receptors
210
examples of Histamine H2 receptors
antagonsits
ranitidine
211
main goal of Histamine H2 receptors
antagonists
inhibit gastric acid secretion
212
mechanism of Histamine H2 receptors
antagonists
H2 antagonists are competitive antagonists of H2 histamine receptors (structural analogues of histamine). They inhibit the stimulatory action of histamine released from enterochromaffin-like (ECL) cells on the gastric parietal cells.
hence inhibit gastric acid secretion by approximately 60%.
213
side effects of Histamine (H2) receptor antagonists
Incidence of side-effects is low. Diarrhoea, dizziness, muscle pains & transient rashes have been reported.
214
which Histamine receptor antagonsits inhibit cytochrome P450
cimetidine
will retard metabolism and potentiate effects of other drugs eg oral anticoagulants and TCA
215
example of paracetamol
acetaminophen
216
drug target of paracetamol
unclear
5HT3 receptors/Cannabinoid reuptake proteins/Peroxidase
217
mechanism of paracetamol
Still not totally clear.
At peripheral sites, may inhibit a peroxidase enzyme which is involved in the conversion of arachidonic acid to prostaglandins (1st step in this pathway involves the enzyme, cyclooxygenase). The ability of paracetamol to inhibit peroxidase can be blocked if excessive levels of peroxide build up (as is commonly seen in inflammation)
Activation of descending serotonergic pathways possibly via 5HT3 receptor activation.
Inhibits reuptake of endogenous endocannabinoids, which would increase activation of cannabinoid receptors - this may contribute to activation of descending pathways.
218
side effects of paracetamol
Relatively safe drug with few common side effects.
OVERDOSE:
Liver damage and less frequently renal damage.
Nausea and vomiting early features of poisoning (settle in 24h).
Onset of right subcostal pain after 24hindicates hepatic necrosis.
219
main function of paracetamol
analgesic
anti-pyretic
220
is paracetamol anti-inflammatory
No
221
is naproxen (NSAIDs) selective
no, inhibit both COX 1 and COX 2
222
what are COX 1 and COX 2 pathway for respectively
COX-1: platelet function
COX-2: pain relief and anti-pyretics
223
do COX 2 directly cause pain
no
they sensitise peripheral nociceptors mediators (eg bradykinin and histamine) which cause pain
224
what is the unintended effect of naproxen
target to inhibit COX-2 but inhibits COX-1 as well, causing side effects
225
where is side effects of naproxen to treat joint pain
gastric mucosal cells that cause stomach injury
226
why naproxen cause gastric injury side effects
inhibit Prostaglandin production and hence inhibit prostaglandin mediated protection of gastric mucosa
227
how prostaglandin protect gastric mucosal cells from acid (3)
increase bicarbonate release
increase mucus protection
increase blood flow
228
why cannot take both oral naproxen and topical diclofenac together
increase risk risk of stomach injury
229
what to do if administered both oral naproxen and topical diclofenac together accidentally
stop gel
switch to ibuprofen
stop NSAIDs completely
230
for pt with OA and RA, what should administer with naproxen
PPIs with NSAIDs
231
for pt with low back pain, psoriatic arthritis, axial spondyloarthritis, what to administer with naproxen
gastroprotection with NSAIDs
232
for pt with high risk of GI side effects, which NSAID to administer
COX-2 selective NSAID
co prescribe PPI
233
for pt with moderate risk of GI side effects, which NSAID to administer
COX-2 inhibitor
or NSAID + PPI
234
for pt with low risk of GI side effects, which NSAID to administer
non selective NSAID
235
why need coprescribe NSAID + PPI
NSAID leave stomach wall exposed to effect of acid which causes pain
PPI help reduce acid production
236
why in osteoporosis/OA patient, GP will prescribe Histamine receptor antagonist instead of PPI
PPI increase risk of fracture (cause change in pH and reduce calcium absorption available for bone, reduce bone turnover, adverse to bone)
237
drug target of statin
Hydroxymethylglutaryl-CoA (HMG-CoA) reductase
238
main goal of statin
reduce cholesterol level
239
mechanism of statin
selective, competitive inhibitor of hydroxymethylglutaryl-CoA (HMG-CoA) reductase, which is the enzyme responsible for converting HMG-CoA to mevalonate in the cholesterol synthesis pathway
By reducing hepatic cholesterol synthesis, an upregulation of LDL-receptors and increased hepatic uptake of LDL-cholesterol from the circulation occurs.
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side effects of statin
muscle toxicity
constipation
diarrhoea
GI symptoms
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what should be regularly checked for using statin
hyperkalaemia
acute renal failure
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drug target of aspirin
Cyclo-oxygenase
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mechanism of aspirin
Irreversible inactivation of COX enzyme. Prevents oxidation of arachidonic acid to produce prostaglandins.
Reduction of thromboxane A2 in platelets reduces aggregation.
Reduction of PGE2 (i) at sensory pain neurones reduces pain and sensation and (ii) in the brain decreases fever
(iii) antiplatelet
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main goal of aspirin
pain relief
anti-inflammatory
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side effects of aspirin
dyspepsia
haemorrhage
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what does aspirin need to administer in patients with peptic ulcer
PPIs
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drug target of trimethoprim
Dihydrofolate reductase
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mechanism of trimethoprim
Direct competitor of the enzyme dihydrofolate reductase. Inhibits the reduction of dihydrofolic cid to tetrahydrofolic acid (active form) – a necessary component for synthesising purines required for DNA and protein production.
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main goal of Trimethoprim
antibiotic
manage UTI in CKD
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side effects of Trimethoprim (2)
diarrhoea
skin infection
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what is Trimethoprim co-administered with
sulfamethoxazole (co-trimoxazole)
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why Trimethoprim need to administer with sulfamethoxazole
they block two steps in bacterial biosynthesis of essential nucleic acids and proteins.
treat a variety of infections of the urinary tract, respiratory system, and gastrointestinal tract
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drug target of gentamicin
30s ribosomal subunit
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mechanism of gentamicin
target gram negative cell membrane
Binds to the bacterial 30s ribosomal subunit disturbing the translation of mRNA leading to the formation of dysfunctional proteins.
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main goal of gentamicin
antibiotic
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side effects of gentamicin
Ototoxicity (hearing/balance problems)
nephrotoxicity
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is gentamicin administered orally or IV
IV
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which disease are gentamicin used to treat in hospital
More likely to be administered intravenously (in hospital) for endocarditis, septicaemia, meningitis, pneumonia or surgical prophylaxis.
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what is proteinuria a marker of
glomerular dysfunction
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drugs to treat proteinuria
ACEi
SGLT-2 inhibitor
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how trimethoprim affects creatinine secretion
inhibits active secretion of creatinine making GFR equation invalid
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how ibuprofen affects prostaglandin
inhibits PG synthesis, reduce PG-induced vasodilation and hence reduce renal blood flow, damage kidney
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how ACEi affects perfusion in glomerulus
reduces perfusion pressure in glomerulus
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what to consider when prescribe drugs for a patient with reduced renal function
1. will drug damage kidney (eg ibuprofen)
2. is the drug elimated by kidney (we dun wna let drug accumulate in blood) (eg metformin, morphine)
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drug to treat pain (2)
paracetamol
opioids
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drug target of paracetamol
Unclear.
5HT3 receptors/Cannabinoid reuptake proteins/Peroxidase
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mechanism of paracetamol
Still not totally clear.
At peripheral sites, may inhibit a peroxidase enzyme which is involved in the conversion of arachidonic acid to prostaglandins (1st step in this pathway involves the enzyme, COX). The ability of paracetamol to inhibit peroxidase can be blocked if excessive levels of peroxide build up (as is commonly seen in inflammation)
Activation of descending serotonergic pathways possibly via 5HT3 receptor activation.
Inhibits reuptake of endogenous endocannabinoids, which would increase activation of cannabinoid receptors - this may contribute to activation of descending pathways.
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side effects of paracetamol
Relatively safe drug with few common side effects.
OVERDOSE:
Liver damage and less frequently renal damage.
Nausea and vomiting early features of poisoning (settle in 24h).
Onset of right subcostal pain after 24h indicates hepatic necrosis.
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drug target of opioids
opioid receptor
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examples of opioids (both weak and strong)
Weak – codeine, tramadol
Strong – morphine, fentanyl, (heroin)
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mechanism of opioids
depressant effect
on cellular activity
Multiple sites within pain pathway, where activation of the opioid receptor leads to decreased perception or increased tolerance to pain.
Anti-tussive (cough suppressants) effect due to decreased activation of afferent nerves relaying cough stimulus from airways to brain
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side effects of opioids
Mild – nausea & vomiting (increase activity in chemoreceptor trigger zone) and constipation (opioid receptors in GIT can reduce gut motility)
OVERDOSE - respiratory depression (direct and indirect inhibition of respiratory control centre.)
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drug target of co-amoxiclav
Amoxicillin = penicillin binding proteins
Clavulanate = beta lactamase
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mechanism of co-amoxiclav
amoxicillin: binds to bacterial penicillin binding proteins to prevent transpeptidation
clavulanate: inhibit beta lactamase (Beta lactamase is a bacterial enzyme that degrades beta lactam Abx and confer resistance to these Abx)
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side effects of co-amoxiclav
Amoxicillin is well tolerated. Most common side effects are nausea and diarrhoea.
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is amoxicillin broad or narrow spectrum Abx and bactericidal or bacteriostatic
bactericidal
broad spectrum
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drug target of lactulose
no drug target
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mechanism of lactulose
Lactulose is a non-absorbable disaccharide.
It reaches the large bowel unchanged. This causes water retention via osmosis and an easier to pass stool. It can also be metabolised by colonic bacteria. The colonic metabolism of sugars has an additional laxative effect.
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side effects of lactulose
Abdominal pain, diarrhoea, flatulence, nausea.
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how long does lactulose take to have effect
begins working in 8-12 hrs but may take up to 2 days to improve constipation
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main goal of lactulose
improve constipation
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difference in effects between NSAIDs and paracetamol
NSAIDs: anti-inflammatory, anti-pyretic, analgesia
paracetamol: anti-pyretic, analgesia
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compare and contrast in terms of mechanism of paracetamol and NSAIDS
both inhibit production of prostaglandins from arachidonic acid
difference: NSAIDs inhibits COX(first step); paracetamol inhibits peroxidase activity (2nd step)
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surgical treatment for acute appendicitis
surgery: open laparoscopy and appendectomy
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medical treatment for appendicitis
analgesia
antibiotics
hydration (IV crstalloids)
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in periaqueductal gray (PAG), how GABAergic neurone make us feel pain
GABA is inhibitory, it inhibits descending pain-inhibitory neurons
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how opioid has analgesia effetcs
opioids inhibit adenyl cyclase and calcium channels, open K+ channel for hyperpolarisation of GABAergic neurones, reduce GABA neurones cause less inhibition of descending pain-inhibitory pathway
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why opioid may cause shallower breathing
they act on respiratory control centre on brain, cause reduce stimulus to lungs and reduce respiratory rate --> hypoxia -> suffocate/die
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is naloxone opioid receptor agonist or antagonist
antagonist
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pro-drug of morphine
codeine
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what will codeine metabolised into (2)
norcodeine (inactove metabolite) and morphine (active)
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which enzyme helps to metabolise codeine to norcodeine and morphine respectively
CYP3A4 for fast metabolism to norcodeine
CYP2A6 for slow metabolism to morphine
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