Drug effects on other systems L19-25 Flashcards
1
Q
local hormone
A
chemical messenger formed by tissue on which it acts
2
Q
where is histamine formed
A
histaminocytes
histaminergic neurones
mast cells basophils
3
Q
histamine formation
A
histidine break down by histidine decarboxylase to histamine
4
Q
histamine breakdown
A
histamine oxidase breakdown if not stored
5
Q
acute inflam response of mast cell
A
C3a/C5a receptors (complement component)
pathogen pattern receptors (pathogen)
6
Q
hypersensitivity response of mast cell
A
immunoglobulin (Ig)E cell fixed antibody
7
Q
arousal pathway
A
histamine neurones in TMN
spontaneously active
release histamine in wakefulness
8
Q
emetic centre
A
histaminergic neurones in TMN receive vestibular input for sensory
9
Q
mismatch of inputs to medulla
A
emetic (vomiting) centre activated in medulla
10
Q
histamine receptor types
A
G-protein coupled
H1
H2
H3/4
11
Q
H1
A
phospolipase C activated
triggers Ca2+
12
Q
H2
A
adenlyl cyclase activated
triggers cAMP
13
Q
H3/4
A
triggers cAMP
14
Q
H1 functions
A
myosin phosphorylation
neuronal activation
nasal/bronchial secretions
vascular permeability
NFkB activation
sensory nerve endings
prociflam cytokine secretion
15
Q
H2 functions
A
chronotropic heart rate increase
16
Q
H1 and H2 functions
A
capillary permeability and dilation
inotropic increase of heart rate
17
Q
rhinitis
A
inflammation within nose
sensory nerve ending stimulation
increases nasal secretions
capillary permeability and dilation
18
Q
urticaria
A
sensory nerve ending stimulation
capillary dilation
19
Q
anaphylaxis
A
rapid onset
HR rapid
consciousness loss
breathing difficulties
20
Q
1st generation antihistamines
A
H1 receptor antagonists
prophylaxis
21
Q
1st generation antihistamine pros
A
cheap/ effective
cross BBB ^ sedation and stops motion sickness
extra wanted effects due to broad selectivity
22
Q
1st generation antihistamine cons
A
unwanted sedation/ adverse effects
can excacerbate other drugs anticholinergic adverse effects
23
Q
muscarinic antagonist effects reversing parasympathetic activation
A
pupil dilation (blurred vision)
^ cardiac output
decreased exocrine gland secretion
decreased bladder contraction
24
Q
a1-adrenoreceptor antagonist reversing sympathetic activation
A
vasodilation > hypertension/ dizziness
25
pros of 2nd generation antihistamines
add carbonyl groups (more polar)
less unwanted sedation
less anticholinergic effects
26
2nd generation antihistamines cons
don't cross BBB as easily
27
gastric acid secretion pathway
stomach> gastric gland> parietal cell> proton pumps/ chloride co-transporter
28
peptic ulcer
perforation in lining of small intestine/ stomach
gram neg helicobacter pylori infection
29
peptic ulcer treatment
antimicrobials rid H.pylori
H2 antagonists competitively/ reversibly block histamine-binding
30
H2 antagonists cons
reoccurrence if H.pylori present and not erradicated
less effective for NSAID-induced ulcers
45 min action onset
affects other drug metabolism
decreases drug efficacy requiring acidic environment
31
H2 antagonists pros
all 4 effective for H.Pylori ulcers
heartburn effective
cheap
safe
32
Proton Pump Inhibitors
decrease H+ secretion
prodrug
acid resistant coating (removed in duodenum)
absorbed/ transported to parietal cell
metabolised to active and bind to PP
decrease gastric acid secretion
33
PPI pros
v effective
long duration
34
PPI cons
delayed action onset
increased risk of gut infection
gut pH above physio level
35
inflammation
local accumulation of fluid containing plasma proteins and white blood cells
non-specific/ dynamic/ 2nd line of defence against infection
36
inflammation functions
restricts damage/ infection
removes causative agent/ damaged tissue
allows immune cell access to site for repair
37
cardinal signs of acute inflammation
calor
dolor
oedema
erythema
38
innate responses inducing acute inflammation
bacteria-triggered cytokine/ chemokine release from macrophages
vasodilation/ ^vascular permeability
inflam cell migration > inflam mediators
39
cells recruited acute inflammation
macrophages
dendritic cells
eosinophils
neutrophils
basophils
mast cells
40
4 inflammation stages
1. tissue damage (sentinel cell activation)
2. vasodilation and vascular permeability
3. cell recruitment
4. tissue repair (clotting/ annexin and fibrin release)
41
eicosanoids
physio active lipid compounds
signalling molecules via enzymatic/non-enzymatic oxidation of arachidonic acid
prostanoids (prostaglandins, thromboxane)
leukotrienes
42
prostaglandins
PGI2 > Prostacyclin (vasodilation/ stops platelet activation)
PGE2 > Prostaglandin (fever/pain and vascular permeability)
TXA2 > thromboxane (platelet activation and vasoconstriction)
43
types of anti-inflammatory drugs
NSAID's
glucocorticoids (steroidal anti-inflam)
immuno-suppressants
anti-histamines (antagonists of histamine receptors)
44
non-opioid analgesics
paracetamol
aspirin (NSAID)
ibuprofen (NSAID)
celecoxib (NSAID)
45
paracetamol pros / cons
:) analgesic/ antipyretic activity
:( no anti-inflam action/ liver damage on overdose
46
aspirin pros/cons
:) acetylates COX
irreversible inhibitor
anti-platelet activity
:( ^risk of GI bleeding/ irritation
47
ibuprofen pros/ cons
:) short-term analgesic
anti-inflam
:(gastric irritation/ ^ulceration risk
48
celecoxib pros/cons
:) COX-2 inhibitor decreases side effects
:( ^risk of stroke/ heart attack following FDA cat.d use
49
arachidonic acid on COX-1
housekeeper
many roles
50
arachidonic acid on COX-2
Inflam cell activation
anti-inflam/ analgesic/ antipyretic
51
side effects of non-opoid analgesics
immunosuppression
hyperglycaemia
growth impairment
natural corticosteroid synthesis suppression
52
gene targets of non-opioid analgesics
^tyrosine aminotransferase (immunosuppressive)
^lipocortin (eicosanoid generation inhibition)
decrease NFkB regulated genes (COX)
decrease activator protein 1 regulated genes (wound-healing/ collagenase/ vit C/D metabolism)
53
ACTH effects
adrenocorticotrophic hormone
^glucocorticoid hormones
^ cortisol proportion
^ w stress
54
manufactured glucocorticoids
beclometasone (asthma inhaler)
hydrocortisone cream
prednisolone (allergies/ skin infection)
55
glucocorticoid/ cortisol
prevents inflam mediator release
decreases TNF-a
twitches toward Th2 immune response via IgE
56
Cushing's syndrome
cortisol build up
latrogenic> long-term high dose cortisol use
endogenous> ACTH over-production in body
easy bruising/ purple striae/ muscle wastage/ atherosclerosis/ moon phase
57
common bacterial targets for antibiotics
cell membrane
cell wall (e.g. penicillins)
protein synthesis (e.g. macrolides/ tetracycline)
RNA polymerase
DNA synthesis (e.g. fluroquinolones)
folate metabolism (e.g. sulphonamides)
58
lactam
cyclic amide
59
beta-lactam
lactam w heteroatomic ring structure (3C and 1N)
60
types of penicillin
benzylpenicillin
broad spectrum
beta-lactamase resistant
extended spectrum
reversed spectrum (more g-)
61
benzylpenicillin
original form
less active against gram negatives
acid labile
oral (Less absorbed)
parenteral (slow IV/ IM/ high availability)
62
broad spectrum penicillin
amino group >penetration of outer membrane of g-
better absorption profile
63
beta lactam antibiotic mechanism
inhibit enzyme (transpeptidases) > no links in peptidoglycan cell wall
swell and rupture of cell wall
multiplying organisms
64
peptidoglycan monomer
N-acetylmuramic acid with N-acetylglucosamine and tetrapeptide connecting
65
penicillin pharmacokinetics
A > varies
D> wide dist no CSF entrance
M> short half-lives (30-80mins)
E> kidney w 90% tubular secretion/ clearance reduction in neonates
66
probenecid
inhibits tubular secretion
67
penicillin adverse reactions
hypersensitivity
GIT disturbance
haemostatic effects
68
folate biosynthesis
pABA>(dihydropteroate)>folate>(dihydrofolate reductase)>tetrahydrofolate>thymidylate synthesis> DNA
69
Sulphonamide mechanism
blocks dihydropteroate synthetase
bacteriostatic
70
sulphonamide pharmacokinetics
A> oral/ absorbed from stomach and intestines
D> wide inc. CNS
M>n-acetylation metabolism in liver
E>urine ~30mins
71
sulphonamide adverse reactions
photosensitivity
stevens-johnson syndrome
hemopoietic disturbances
72
fluoroquinolones
broad spectrum
gram+/g-
target DNA replication via TII topoisomerases
absorbed in upper GI tract/ excreted in tubular
CYP182 inhibition
73
quinolone inhibition
DNA gyrase > supercoiling regulation and packaging (inhibited in gram negatives)
DNA topoisomerase IV > gyrase homologue (inhibited in g+)
74
euk vs pro ribosomes
euk> 80S
pro> 70S
50S (23S/5S) and 30S sub-units
75
macrolide mechanism of action
block peptide translocation
bind near RNA exit tunnel
peptidyl transferase RNA drop off
76
macrolide ADME
A > capsules protect from gastric juices
D> crosses placenta not BBB
M>demethylation
E> excreted in bile
77
macrolides adverse reactions
cholestatic hepatitis
GIT
transitory auditory impairments
78
tetracycline mechanism of action
interrupts elongation phase of synthesis
sterically inhibits tRNA binding
unbinds/ rebinds/ futile loop
79
tetracycline ADME
A> fasting state
M> long half-lives due to enterohepatic recirculation
E> bile / glomerular filtration
80
hallmarks of cancer
resisting cell death
sustaining proliferative signalling
evading growth supressors
activating invasion/ metastasis
inducing angiogenesis
enabling replicative immortality
81
cancer treatment options
surgery
biological
radiation
chemotherapy
82
drugs affecting G1 phase
protein depleting
83
asparagine + asparaginase
aspartic acid/ ammonia
84
tamoxifen
S requires activation of hormone regulated genes and so replaces oestrogen in cancer cell to stop growth and proliferation
85
Alkylating agents
ciplatin
nitrogen mustard
cyclophosphamide
daunorubicin
86
antimetabolites
methotrexate
5-fluoruracil
6-mercaptopurine-A
87
topoisomerase inhibitors
T1-irinotecan
T2-etoposide
88
anthracyclines
inhibitx txn/replication
e.g. dauxorubicin
89
BCR-ABL1 fusion protein function
tyrosine kinase ability
90
PARP inhibitors
PARP (DNA damage repair) inhibition leads to double strand break
BRCA mutation in cancer cells die while normal cells survive
91
distributional selectivity
useful for drugs equally toxic to host and parasite > selective parasite accumulation/ limited compartment/
92
plasmodium life cycle
asexual reproduction
gametocyte development
RBC penetration
93
4-aminoquinolones
accumulates in parasitic lysozomes, inhibiting digestion of host Hb
resistance in efflux of drugs from cells
94
quinine methanols
binds to malarial pigment haemozoin >intercalates into DNA
erythrocytic
:)chloroquine resistance treatment
95
8-aminoquinolones
radical cure
metabolised in liver
cytotoxic derivatives
haemolytic anaemia
96
anti-folates
prophylactic
DNA synthesis inhibition
activated by CYP2C19/ cycloguanil
