pharma/toxicology Flashcards
1
Q
drugs that might precipitate an attack of acute intermittent porphyria
A
barbiturates
halothane
benzos
alcohol
ocp
sulfonamides
2
Q
mx of accidental adrenaline injection
A
phentolamine
3
Q
actions of adrenaline on alpha receptors
A
inhibits insulin secretion
stimulates glycogenolysis in liver and muscle
stimulates glycolysis in muscle
4
Q
adrenaline actions on beta receptors
A
stimulates glucagon secretion
stimulates ACTH
stimulates lipolysis
5
Q
adrenoreceptor agonists
A
alpha1- phenylephrine
alpha 2- clonidine
beta 1- dobutamine
beta 2- salbutamol
beta 3- may have a role in preventing obesity
6
Q
adrenoreceptor antagonists
A
alpha 1- doxazosin
alpha 1a- tamsulosin
alpha 2- yohimbine
non selective- phenoxybenzamine
beta 1- atenolol
non selective- propranolol
mixed alpha and beta- carvedilol and labetalol
7
Q
adernoreceptor functions
A
alpha1- vasoconstriction, relax GI smooth muscle, saliva secretion, hepatic glycogenolysis
alpha 2- mainly presynaptic, inhibits insulin, platelet aggregation
beta1- mainly increase heart rate and force
beta2- vasodilation, bronchodilation, relax GI smooth muscle
beta 3- lipolysis
8
Q
adrenoreceptor pathways
A
g protein coupled
alpha 1- activates phospholipase C, IP3, DAG
alpha 2- inhibits adenylate cyclase
beta- stimulates adenylate cyclase
9
Q
disulfiram contraindications
A
IHD
psychosis
10
Q
allopurinol adverse effects
A
severe cutaneous adverse reaction
drug reaction w/ eosinophilia and systemic symptoms
SJS
screen for HLAB5801 if high risk of SCAR
11
Q
allopurinol interactions
A
azathioprine- allopurinol can lead to high levels of 6 mercaptopurine therefore need to reduce dose
cyclophosphamide- allopurinol reduces renal excretion
theophylline- allopurinol causes increase in plasma concentration by inhibiting its breakdown
12
Q
wolff chaikoff effect
A
amiodarone induced hypothyroidism
thyroxine formation is inhibited due to high levels of circulating iodide
13
Q
amiodarone induced thyrotoxicosis
A
type 1: excess iodine induced thyroid hormone, goitre, mx with carbimazole or potassium perchlorate
type 2: destructive thyroiditis, no goitre, mx w/ corticosteroids
14
Q
propofol mechanism
A
GABA agonist
15
Q
sodium thiopentone
A
extremely rapid onset
used for rapid sequence induction
marked myocardial depression
metabolites build up quickly
16
Q
ketamine mechanism
A
NMDA receptor antagonist
can be used for induction
little myocardial depression
17
Q
etomidate
A
v little haemodynamic instability
no analgesia
may result in adrenal suppression
post op vomiting common
18
Q
1a anti arrhythmics
A
quinidine, procainamide, dispyramide
blocks sodium channels
increases AP duration
19
Q
quinidine side effects
A
cinchonism (headache, tinnitus, thrombocytopenia)
20
Q
procainamide side effect
A
drug induced lupus
21
Q
1b anti arrhythmics
A
blocks sodium channels
decreases AP duration
lidocaine, mexiletine, tocainide
22
Q
1c anti arrythmics
A
blocks sodium channels
no effect on AP duration
flecainide, encainide, propafenone
23
Q
type 2 anti arrythmics
A
beta adrenoreceptor antag
propranolol, atenolol, bisoprolol, metoprolol
24
Q
type 3 anti arrythmics
A
blocks potassium channels
amiodarone, sotalol, ibutilide, bretylium
25
type 4 anti arrythmics
calcium channel blockers
verapamil, diltiazem
26
antibiotics inhibiting cell wall formation
peptidoglycan cross linking: penicillins, cephalosporins, carbopenems
peptidoglycan synthesis: glycopeptides (vanc)
27
abx inhibiting protein synthesis
50S: macrolides, chloramphenicol, clinda, linezolid, streptogrammins
30S: aminoglycosides, tetracyclines
28
abx inhibiting DNA synthesis
quinolones e.g. ciproflox
29
abx damaging DNA
metro
30
abx inhibiting RNA synthesis
rifampicin
31
abx inhibiting folic acid formation
sulfonamides
trimethoprim
32
what drugs potentiate aspirin?
PO hypoglycaemics
warfarin
steroids
33
aspirin and children
do not use due to risk of Reye's
exception is kawasaki
34
managing beta blocker overdose
atropine if bradycardic
glucagon if resistant
35
verapamil side effects and cautions
s/e: HF, constipation, hypotension, bradycardia, flushing
c/i: do not give with beta blockers due to risk of HB
36
diltiazem side effects and cautions
use caution with HF or beta blockers
s/e: hypotension, bradycardia, HF, ankle swelling
37
which CCBs may cause ankle swelling?
nifedipine, amlodipine, felodipine (dihydropiridines)
shorter acting dihydropyridines may cause peripheral vasodilation which may result in reflex tachy
38
CO poisoning and oxygen dissoc curve
CO binds to Hb and forms carboxyHb
oxygen saturation of Hb decreases
> early plateau in O2 dissociation curve
curve shifts to left
39
carboxyHb levels
< 3 & in non smokers
< 10% in smokers
10-30% in symptomatic poisoning
> 30% in severe toxicity
40
managing CO poisoning
high flow O2 via NRB (decreases half life of COHb) min 6 hours
consider hyperbaric oxygen for more severe cases (COHb > 25%, LOC, neuro signs, myocardial ischaemia, arrhythmia, pregnancy)
41
types of caustic subtances
oxidising agents: hydrogen peroxide, sodium hypochlorite (bleach)
strong alkali: sodium hydroxide, potassium hydroxide (dishwasher cleaner) > liquefactive necrosis, oesophageal injury
strong acid: hydrochloric, nitric (car batteries, toilet cleaner) > coagulative necrosis, gastric injury
42
managing poisoning with caustic substances
urgent upper GI referral if signs of perforation
avoid neutralisation (exothermic reaction)
high dose IV PPI
urgent OGD if drooling, vomiting, dysphagia, odynophagia, chest pain to assess degree of ulceration
discharge asymptomatic ingestion after a trial of PO fluids and observation
43
chronic complications of caustic substance ingestion
strictures
fistulae
gastric outlet obstruction
upper GI carcinoma
44
ciclosporin mechanism
binds to cyclophilin and inhibits calcineurin
> reduces IL2
> decreases clonal proliferation of T cells
45
side effects of ciclosporin
nephrotoxic, hepatotoxic
fluid retention
HTN
hyperK
hypertrichosis
gingival hyperplasia
tremor
impaired glucose tolerance
hyperlopidaemia
increased susceptibility to severe infection
cannabidiol may increase concentration
46
ciclosporin indications
organ translpant
RA
psoriasis
UC
pure red cell aplasia
47
cocaine mechanism
blocks uptake of DA, NA, serotonin
48
CVS effects of cocaine
coronary artery spasm
tachy or brady
HTN
wide QRS
long QT
aortic dissection
49
managing cocaine OD
chest pain: benzos + GTN
HTN: benzos + sodium nitroprusside
50
cancers and COCP
reduces risk of: ovarian, endometrial, colorectal
increases risk of: breast and cervical ca
51
UKMEC criteria
1: no restriction for use
2: advantages outweigh disadvantages
3: disadvantages outweigh advantages
4: unacceptable health risk
52
UKMEC 3 and 4 for COCP
3:
> 35 and < 15 cigs per day
BMI > 35
FH VTE < 45y
immonbility
BRCA carrier
gallbladder disease
4:
> 35y and > 15 cigs per day
migraine with aura
hx VTE or thrombogenic
hx IHD or CVA
breast feeding < 6w post partum
uncontrolled HTN
current breast ca
major surgery with immobilisation
positive antiphospholipid
DM diagnosed 20y ago
53
how to take COCP and protection against pregnancy
start within 5 days of cycle: no need for additional contraception
start at any other point: need additional contraception for 7 days
use additional contraception if on enzyme inducing abc e.g. rifampicin and for 7 days thereafter
54
switching combined COCP
miss the pill free interval if the progesterone is changing
55
cyanide action
inhibits cytochrome c oxidase
stops mitochondrial electron transfer chain
56
cyanide poisoning presentation and management
presentation: brick red skin, bitter almond smell, hypoxia, hypotension, headache, confusion, ataxia, peripheral neuropathy, dermatitis
mx: 100% oxygen, IV hydroxycobalamin, INH amyl nitrate, IV sodium nitrate, IV sodium thiosulfate
57
digoxin mechanism
positive inotropic properties
decreases conduction through AVN, slows ventricular rate in AF and flutter
inhibits NAKATPase pump > increases force of cardiac muscle contraction
stimulates vagus nerve
58
digoxin toxicity
may occur even when plasma concentration is in therapeutic range
yellow green vision
AV block. brady
gynaecomastia
59
digoxin toxicity precipitators
hypokalaemia (dig binds more easily to ATPase pump)
increasing age
renal failure
myocardial ischaemia
hypoMg, hyperCa, hyperNa, acidosis
hypoalbuminaemia, hypothermia, hypothyroid
amiodarone, quinidine, verapamil, diltiazem, spiro, ciclosporin, thiazides and loop diuretics
60
managing digoxin toxicity
digibind
correct arrhythmias
monitor potassium
61
indications for DA receptor agonists
parkinsons
prolactinoma/galactorrhoea
cyclical breast disease
acromegaly
62
side effects of DA receptor agonists
nausea/vomiting
postural hypotension
hallucinations
daytime somnolence
ergot derived: pulmonary, retroperitoneal and cardiac fibrosis
63
DRESS syndrome
morbilliform skin rash
> exfoliative dermatitis, high fever, inflammation of organ(s)
may be vesicles/bullae
may be erythroderma or mucosal involvement
2-8 weeks after starting the drug
triad: extensive rash, high fever, organ involvement
eosinophilia and abnormal LFTs
64
DRESS syndrome criteria
3 or more:
hospitalisation
reaction suspected to be drug related
acute skin rash
38C
enlarged lymph nodes at 2 sites
at least 1 internal organ involved
blood count abnormalities
65
DRESS diagnostic tests
skin biopsy: inflam infiltrate (eosinophils, erythrocytes, oedema)
FBC, coag, LFTs, U&Es, CK, viral screen, glucose, TFTs
ECG, CXR, echo, urinalysis for complications
66
drug causes of agranulocytosis
antithyroid (carbimazole, propylthiouracil)
antipsychotics- atypical e.g. clozapine
antiepileptics- carbamazepine
abx- penicillin, chloramphenicol, cotrimox
antidepressants- mirtazepine
cytotoxic- MTX
67
common drug causes of urticaria
aspirin
NSAIDs
penicillins
opiates
68
monitoring requirements: statins, ACEi, amiodarone
statins: LFTs at baseline, 3 and 12 months
ACEi: U&Es at baseline, annually and after increasing dose
amiodarone: TFTs, LFTs, U&Es, CXR at baseline and TFT, LFT 6 monthly
69
monitoring requirements: MTX, azathioprine
MTX: FBC, LFT, U&E at baseline and weekly until stable therapy, then every 2-3months
azathioprine: FBC, LFT at baseline, FBC weekly for first month, FBC and LFT 3 monthly
70
monitoring requirements: lithium, sodium valproate
lithium: TFTs and U&Es at baseline and 6 monthly, lithium levels weekly until stable then 3 monthly
valproate: LFT and FBC at baseline, LFT periodically during first 6/12
71
monitoring requirements: glitazones
LFT at baseline and regularly throughout treatment
72
drugs causing impaired glucose tolerance
thiazides, furosemide
steroids
tacrolimus, ciclosporin
IFNalpha
nicotinic acid
antipsychotics
beta blockers slightly
73
drugs causing thrombocytopaenia
quinine
abciximab
NSAIDs
furosemide
penicillins, sulfonamides, rifampicin
carbamaz, valproate
heparin
74
drugs causing urinary retention
TCAs
anticholinergics: antipsychotics, antihistamines
opioids
NSAIDs
disopyramide
75
drugs causing lung fibrosis
amiodarone
MTX, sulfasalazine
busulphan, bleomycin
nitrofurantoin
ergot derived DA agonists
76
drugs causing cataracts
steroidss
77
drugs causing corneal opacities
amiodarone
indomethacin
78
drugs causing optic neuritis
ethambutol
amiodarone
metro
79
drugs causing retinopathy
chloroquine, quinine
80
sildenafil ophthal side effects
blue discolouration
non arteritic anterior ischaemic neuropathy
81
drugs causing photosensitivity
thiazides
tetracyclines, sulfonamides, ciproflox
amiodarone
NSAIDs
psoralens
sulfonylureas
82
drugs and serotonin action
triptans: 5HT1 agonists
pizotifen, methysergide (migraine prophylaxis): 5HT2 antagonists
cyproheptadine (diarrhoea in carcinoid syndrome): 5HT2 antagonist
ondansetron: 5HT3 antagonist
83
managing ecstasy poisoning
dantrolene for hyperthermia if simple measures fail
84
ethylene glycol toxicity stages
11: similar to alcohol (confusion, dizziness, slurred speech)
2: metabolic acidosis w high anion gap and high osmolar gap. tachycardia, HTN
3: aki
85
managing ethylene glycol poisoning
fomepizole
inhibits alcohol dehydrogenase
haemodialysis for refractory cases
86
flecainide mechanism
class 1c antiarrhythmic
blocks Nav1.5 sodium channels
slows action potential
> widened QRS and prolonged PR interval
87
flecainide contraindications
post MI
structure heart disease e.g. HF
sinus node dysfunction- second degree or greater AV block
flutter
88
flecainide side effects
negatively inotropic
bradycardia
oral paraesthesia
visual disturbances
89
gentamicin contraindications
myaesthenia gravis
90
drugs that can be cleared with haemodialysis
BLAST
Barbiturate
Lithium
Alcohol incl. ethylene glycol
Salicylates
Theophyllines
91
heparin mechanism
activate antithrombin III
unfractionated: inhibits thrombin and IXa, Xa, XIa, XIIa
LMWH: increases action of antithrombin III on Xa
92
side effects of heparins
bleeding, thrombocytopenia
osteoporosis
hyperkalaemia
93
heparin monitoring
unfractionated: APTT
LMWH: anti factor Xa
94
heparin induced thrombocytopenia
antibodies against complexes of platelet factor 4 and heparin
abs bind to PF4-heparin complexes on platelet surface
> induce platelet activation
develops after 5-10 days
> 50% reduction in platelets
thrombosis
skin allergy
95
managing heparin induced thrombocytopenia
direct thrombin inhibitor e.g. argatroban
danaparoid
96
ezetimibe mechanism and side effects
decreases cholesterol absorption small intestine
headache
97
nicotinic acid mechanism and side effects
decreases hepatic VLDL secretion
flushing, myositis
98
fibrates mechanism and side effects
agonist of PPAR alpha
> increases lipoprotein lipase
myositis, pruritus, cholestasis
99
cholestyramine mechanism and side effects
reduces bile acid reabsorption in small intestine
increases cholesterol conversion to bile acid
GI side effects
100
what metabolic disturbances can cause hypomagnesaemia?
hypokalaemia
hypercalcaemia (calcium and Mg compete for transport in thick ascending loop)
Gitelmans, Bartters
101
hypomagnesaemia features
paraesthesia
tetany
seizures
arrthymias
decreased PTH, hypocalcaemia
ECG similar to hypokalaemia
exacerbates digoxin toxicity
101
managing hypomagnesaemia
< 0.4 or tetany/arrthymias/seizures:
IV Mg replacement
> 0.4: PO Mg replacement
102
IVIG indications
primary and secondary immunodeficiency
ITP
MG
GBS
kawasaki
TEN
CMV pneumonitis after transplant
low IgG after haematopoeitic stem cell transplant for malignancy
dermatomyositis
chronic inflam demyelinating polyradiculopathy
103
lithium therapeutic range and half life
therapeutic range 0.4-1.0
toxic > 1.5
long half life
excreted by kidneys
104
what could precipitate lithium toxicity?
dehydration
renal failure
diuretics (esp thiazides), ACEi/ARBs, NSAIDs, metronidazole
105
features and management of lithium toxicity
coarse tremor
hyperreflexia
acute confusion
polyuria
seizure
coma
mx: volume resus with normal saline if mild/mod
haemodialysis
sodium bicarb to increase urine alkalinity and promote lithium excretion
106
lidocaine metabolism
hepatic metabolism
protein bound
renal excretion
therefore increased risk of toxicity in liver dsyfunction or low protein states
107
acidosis and lidocaine
acidosis causes lidocaine to detatch from protein binding
108
managing lidocaine toxicity
20% lipid emulsion IV
109
drug interactions with lidocaine
beta blockers
ciproflox
phenytoin
110
features of lidocaine toxicity
CNS overactivity then depression
(initially blocks inhib pathways then both inhib and activating)
cardiac arrhythmias
111
bupivacaine mechanism
binds to intracellular portion of Na channels
>blocks Na influx into nerve cells
>prevents depolarisation
longer duration than lignocaine therefore useful for topical wound infiltration at end of surgery
112
bupivacaine contraindications
cardiotoxic so c/i in regional blockage in case tourniquet fails
113
114
115
doses of local anaesthetics
lidocaine 3mg/kg
bupivacaine 2mg/kg
prilocaine 6mg/kg
116
adrenaline and local anaesthetics
adrenaline can be added to prolong duration and permits higher doses
contraindicated with MAOis or TCAs
addition of adrenaline does not permit increase dose of bupivacaine because toxicity is related to protein binding
117
macrolide mechanism
blocks translocation
> inhibits bacterial protein synthesis
118
macrolides resistance
post transcriptional methylation of 23S bacterial ribosomal RNA
119
macrolides side effects
QT prolongation
GI (more common with erythromycin)
cholestatic jaundice (lower risk with erythromycin stearate)
P450 inhib
azithromycin: hearing loss and tinnitus
120
macrolides interactions
statins
macrolides inhibit P450 isoenzyme CYP3A4 that metabolises statins
121
features of mercury poisoning
paraesthesia
visual field defects
hearing loss
irritability
renal tubular acidosis
122
metformin mechanism
activates AMPK
increases insulin sensitivity
decreases hepatic gluconeogenesis and GI absorption of carbs
123
metformin contraindications
CKD (stop if eGFR < 30/creat > 150) (review dose if eGFR < 45/creat > 130)
lactic acidosis (recent MI, sepsis, AKI, severe dehydration)
iodine contrast (increased risk of AKI) (stop on the day and for 48h after)
alcohol misuse relative contraindication
123
methanol poisoning features and management
similar to alcohol intoxication
blindness
due to accumulation of formic acid
mx: fomepizole (alcohol dehydrogenase inhibitor) or ethanol, dialysis, cofactor therapy with folinic acid to reduce ophthal complications
123
metformin side effects
GI
reduced B12 absorption
lactic acidosis (in severe liver disease or CKD)
123
infliximab indications
RA
crohns
AKA anti TNF
123
how are monoclonal antibodies made?
somatic cell hybridisation
fuse myeloma cells and spleen cells with a mouse that has been immunised with desired antigen
combine hybridome with human antibody to prevent rejection from formation of human anti-mouse antibodies
124
rituximab indications
AKA antiCD20
non hodgkins
RA
125
cetuximab indications
AKA epidermal growth factor receptor antagonist
metastatic colorectal and H&N cancer
126
trastuzumab indications
AKA HER2/neu receptor antagonist
metastatic breast ca
127
alemtuzumab indications
anti CD52
CLL
128
abciximab indications
glycoprotein IIb/IIIa antag
prevention of ischaemic events in pts undergoing PCI
129
OKT3 indications
anti CD3
prevent organ rejection
130
procedural uses for monoclonal antibodies
medical imaging when combined with radioisotope
identification of cell surface markers in biopsied tissue
dx viral infections
131
managing motion sickness
transdermal hyoscine most effective
non sedating antihistamines e.g. cyclizine/cinnarizine in preference to sedating antihistamines
132
suxamethonium mechanism and metabolism
depolarising NM blocker
inhibits ACh at NMJ
degraded by plasma cholinesterase and acetylcholinesterase
fastest onset and shortest duration of all muscle relaxants
133
suxamethonium side effects
hyperkalaemia
malignant hyperthermia
lack of acetylcholinesterase
134
atracurium mechanism and metabolism
non depolarising NM blocker
30-45 mins duration
not excreted by liver or kidney
broken down in tissues by hydrolysis
135
atracurium side effects and reveral
generalised histamine release > facial flushing, tachycardia, hypotension
reversal: neostigmine
136
vecuronium mechanism and metabolism
non depolarising NM blocker
duration 30-40 mins
degraded by liver and kidney
effects prolonged in organ dysfunction
reversed by neostigmine
137
pancuronium mechanism
non depolarising NM blocker
2-3 mins onset
2h duration
may be partially reversed with neostigmine
137
ocreotide mechanism and adverse effects
long acting somatostatin analogue
prevents release of GH, glucagon, insulin
s/e: gall stones from biliary stasis
138
ocreotide uses
variceal haemorrhage
acromegaly
carcinoid syndrome
pancreatic surgery
VIPomas
refractory diarrhoea
139
causes of oculogyric crisis
antipsychotics
metoclopramide
postencephalitic parkinsons disease
140
managing oculogyric crisis
cessation of causative medication
IV antimuscarinic- benztropine or procyclidine
141
organophosphate insecticide poisoning mechanism
inhibition of acetylcholinesterase
upregulation of nicotinic and muscarinic cholinergic neurotransmission
142
organophosphate insecticide poisoning features and management
SLUD
salivation
lacrimation
urination
defecation
CVS: hypotension, bradycardia
small pupils, muscle fasciculation
mx: atropine, ? pralidoxime
143
managing salicylate poisoning
urinary alkalinisation with IV bicarb
haemodialysis
144
managing TCA overdose
IV bicarb to reduce risk of seizures and arrhythmias
dialysis is not effective
145
contraindications in TCA OD
class 1a (quinidine) and class 1c (flecainide) antiarrhythmics because they prolong depolarisation
class III (amiodarone) prolong QT
146
managing lithium OD
volume resus with saline
haemodialysis
? sodium bicarb for urinary alkalinisation
147
managing beta blocker OD
atropine if bradycardic
glucagon
148
managing lead poisoning
dimercaprol
calcium edetate
149
managing cyanide poisoning
hydroxycobalamin (b12)
amyl nitrate + sodium nitrite + sodium thiosulfate
150
P450 inducers
CRAP GPS
Carbamazepine
Rifampicin
Alcohol (chronic)
Phenobarbitone
Griseofulvin
Phenytoin
Sulfonylureas, St Johns wart
smoking
151
P450 inhibitors
SICK FACESCOM
Sodium valproate, sertraline
Isoniazid
Cimetidine
Ketoconazole
Fluconazole, fluoxetine
Alcohol (acute), Amiodarone, Allopurinol
Chloramphenicol
Erythromycin
Sulfonamides
Ciproflox
Omeprazole
Metro
ritonavir
quinupristin
152
when to give NAC for paracetamol OD?
plasma concentration on or above single treatment line joining points of 100mg/L @ 4h and 15mg/L @ 15h
staggered or doubt over time of ingestion
presentation 8-24h after ingestion of > 150mg/kg
presentation > 24h if clearly jaundiced or hepatic tenderness or ALT raised
153
acetylcysteine side effects
anaphylactoid reaction from non IgE mediated mast cell release
infuse over 1h to reduce side effects
154
paracetamol liver transplant criteria
pH < 7.3 @ 24h after ingestion
or
PTT > 100
+ creat > 300
+ grade 3/4 encephalopathy
155
paracetamol metabolism and OD
liver conjugates paracetamol with glucuronic acid
once saturated, P450 mixed function oxidases oxidate and produce NAB benzoquinone imine toxin
glutathione: conjugates with toxin to form mercapturic acid as protection
if glutathione runs out, toxin bonds with cell proteins > denatures > cell death in hepatocytes and renal tubules
NAC is a glutathione precursor
156
risk factors for paracetamol toxicity
liver enzyme inducing drugs
malnourished or not eaten in a few days
157
what to avoid in penicillin allergic pts
0.5-6.5% will also be allergic to cephalosporins
if history of immediate hypersensitivity to penicillin, avoid cephalosporin
can use with caution: cefixime, cefotaxime, ceftazidime, ceftriaxone, cefuroxime
158
types of cellular drug targets
ion channels
G protein coupled receptors
tyrosine kinase receptors
nuclear receptors
159
how do tyrosine kinase receptors work?
drug actives receptor
steps within cell incl phosphorylation of targets
effects including cell growth and differentiation
e.g. insulin works on tyrosine kinase receptors
160
how do nuclear receptors work?
activation or inhibition by drug
> increased or decreased gene transcription
drugs interacting with these must be lipid soluble to penetrate cell membrane
> forms complex with receptor protein
e.g. prednisolone, Lthyroxine
161
zero order elimination kinetics
rate of excretion is constant despite changes in plasma concentration
due to saturation of metabolic process
e.g. phenytoin, salicylates
162
phase I and phase II drug metabolism reaction
1: oxidation, reduction, hydrolysis
mainly by P450
products are typically more active and toxic
2: conjugation
products are typically inactive and excreted in urine or bile
e.g. glucoronyl, acetyl, methyl, sulfate
163
first pass metabolism is seen in what drugs?
aspirin
isosorbide dinitrate, GTN
lidocaine
propranolol
verapamil
isoprenaline, testosterone, hydrocortisone
164
zero order kinetics
metabolism independent of concentration of reactant
due to metabolic pathways becoming saturated
> constant amount of drug eliminated per unit time
e.g. alcohol, heparin, salicylates, phenytoin
165
acetylator status
50% of UK population are deficient in hepatic N acetyltransferase
Procainamide
Sulfasalazine
Hydralazine
Isoniazid
Dapsone
166
phosphodiesterase type V inhibitors mechanism
increase cGMP
> smooth muscle relaxation
> vasodilation
167
PDE5 inhibitors contraindications and side effects
c/i: patients on nitrates or nicorandil, hypotension, recent stroke or MI (6 months)
s/e: visual disturbances (blue)
non arteritic anterior ischaemic neuropathy
nasal congestion
flushing
GI side effects
headache
priapism
168
how to manage oedematous patient post op?
treat hypovolaemia first
then negative balance of sodium and water
monitor using urine Na levels
169
types of potassium sparing diuretics
epithelial Na channel blockers- amiloride, triamterene
aldosterone antag- spiro, eplerenone
use with caution with ACEi (may precipitate hyperkalaemia)
170
amiloride mechanism
blocks epithelial Na channel in DCT
weak diuretic
usually given with a thiazide or loop as an alternative to K supplementation
171
mechanism and indication of aldosterone antagonist
acts in cortical collecting duct
ascites
heart failure
nephrotic syndrome
conn's
172
what drugs may exacerbate heart failure?
thiazoladinediones (fluid retention)
verapamil (negative inotropic)
NSAIDs/glucocorticoids (fluid retention)
class 1 antiarrthymics e.g. flecainide (negative inotropic and proarrhythmic)
173
drugs to avoid in renal failure
tetracycline, nitrofurantoin
NSAIDs
lithium
metformin
likely to accumulate:
most abx
digoxin, atenolol
MTX
sulfonylureas
furosemide
opioids
174
harmful abx in pregnancy
tetracyclines
aminoglycosides
sulfonamides, trimethoprim
quinolones (arthropathy)
175
drugs to avoid in pregnancy
ACEi, ARBs
statins
warfarin
sulfonylureas
retinoids
cytotoxics
176
POP adverse effects
increased incidence of functional ovarian cysts
breast tenderness, weight gain, acne, headaches generally subside after a few months
177
cinchonism
quinine toxicity
cardiac arrhythmia (blockade of Na and K channels)
hypoglycaemia (pancreatic insulin secretion)
flash pulm oedema
renal failure long term
tinnitus, visual blurring, dry skin, abdo pain
178
managing cinchonism
difficult to distinguish from aspirin poisoning so measure serum salicylate levels
largely supportive- fluids, inotropes, bicarb, positive pressure ventilation for pulm oedema
179
quinolones mechanism of action and resistance
e.g. ciproflox, levoflox
inhibit topoisomerase II (DNA gyrase) and topoisomerase IV
resistance: mutations to DNA gyrase, efflux pumps reduce intracellular quinolone concentration
180
quinolones side effects and c/i
lower seizure threshold
tendon damage
cartilage damage
lengthened QT
c/i: breastfeeding/pregnant, G6PD
181
features of salicylate overdose
mixed resp alkalosis and metabolic acidosis
early stimulation of resp centre > resp alkalosis
later direct acid and AKI > metab acidosis
in children, metab acidosis predominates
hyperventilation
tinnitus
lethargy
sweating, pyrexia
nausea/vomiting
hyperglycaemia, hypoglycaemia
seizures, coma
182
managing salicylate OD and indications for dialysis
sodium bicarb urinary alkalinisation
dialysis:
serum > 700mg/L
metab acidosis resistant to treatment
AKI
pulm oedema
seizures
coma
183
causes and features of serotonin syndrome
MAOi, SSRIs, ecstasy, amphetamines
St Johns Wort and tramadol can interact with SSRIs to cause SS
hyperreflexia, myoclonus, rigidity
hyperthermia, sweating
confusion
184
managing serotonin syndrome
IV fluids
benzos
more severe cases: cyproheptadine, chlorpromazine serotonin antagonists
184
NMS vs serotonin syndrome
NMS has longer onset (hours-days)
NMS reduced reflexes; SS hyperreflexia
SS dilated pupils
raised CK more associated with NMS
185
nicorandil side effects
headache
flushing
anal ulceration
186
sulfonylureas side effects
(gliclazide, glimepiride)
hypoglycaemia
increased appetite, weight gain
SIADH
cholestatic liver dysfunction
187
glitazones/thiazoladinediones side effects
weight gain
fluid retention
liver dysfunction
fractures
188
gliptins side effects
pancreatitis
189
tacrolimus mechanism
reduces IL2 release
> decreases clonal proliferation of T cells
binds to FKBP
> complex inhibits calcineurin (calcineurin activates transcription factors in T cells)
190
tamoxifen mechanism and adverse effects
oestrogen receptor antagonist and partial agonist
menstrual disturbance
hot flushes
VTE
endometrial ca
191
raloxifene mechanism
pure oestrogen receptor antagonist
lower risk of endometrial ca
192
ACEi teratogenic effects
renal dysgenesis
craniofacial abnormalities
193
carbamazepine teratogenic effects
neural tube defects
craniofacial abnormalities
194
chloramphenicol teratogenic effects
grey baby
195
diethylstilbesterol adverse effects
vaginal clear cell adenocarcinoma
196
lithium teratogenic effects
ebsteins anomaly
197
maternal diabetes mellitus teratogenic effects
macrosomia
neural tube defects
polyhydramnios
preterm labour
caudal regression
198
valproate teratogenic effects
neural tube defects
craniofacial abnormalities
199
warfarin teratogenic effects
craniofacial abnormalities
200
monitoring ciclosporin
trough levels
201
trastuzumab
monoclonal antibody against HER2/neu receptor
s/e: flu like, diarrhoea
cardiotoxicity
202
features of TCA OD
dry mouth, dilated pupils, agitation, sinus tachy, blurred vision
arrythymias
seizures
metab acidosis
coma
sinus tachy
wide QRS
prolonged QT
QRS > 100 assoc with seizures
QRS > 160 assoc with ventricular arrythmias
203
managing TCA OD
IV bicarb for hypotension/arrhthymias
avoid quinidine, flecainide, amiodarone because they prolong depolarisation
IV lipid emulsion
204
rifampicin mechanism and s/e
inhibits bacterial DNA dependent RNA polymerase
prevents DNA transcription to RNA
liver enzyme inducer
hepatitis
orange secretions
flu like
205
isoniazid mechanism and s/e
inhibits mycolic acid synthesis
peripheral neuropathy (prevent with B6 pyridoxine)
hepatitis
agranulocytosis
liver enzyme inhib
206
pyrazinamide mechanism and s/e
converted by pyrazinamidase to pyrazinoic acid
> inhibits fatty acid synthase
hyperuricaemia > gout
arthralfia, myalgia
hepatitis
207
ethambutol mechanism and s/e
inhibits arabinosyl transferase which polymerases arabinose to arabinan
optic neuritis
adjust dose if renal impairment
