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pharmacology/toxicology > pharma/toxicology > Flashcards

pharma/toxicology Flashcards

1
Q

drugs that might precipitate an attack of acute intermittent porphyria

A

barbiturates
halothane
benzos
alcohol
ocp
sulfonamides

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2
Q

mx of accidental adrenaline injection

A

phentolamine

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3
Q

actions of adrenaline on alpha receptors

A

inhibits insulin secretion
stimulates glycogenolysis in liver and muscle
stimulates glycolysis in muscle

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4
Q

adrenaline actions on beta receptors

A

stimulates glucagon secretion
stimulates ACTH
stimulates lipolysis

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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

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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

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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

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8
Q

adrenoreceptor pathways

A

g protein coupled
alpha 1- activates phospholipase C, IP3, DAG
alpha 2- inhibits adenylate cyclase
beta- stimulates adenylate cyclase

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9
Q

disulfiram contraindications

A

IHD
psychosis

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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

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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

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12
Q

wolff chaikoff effect

A

amiodarone induced hypothyroidism
thyroxine formation is inhibited due to high levels of circulating iodide

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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

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14
Q

propofol mechanism

A

GABA agonist

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15
Q

sodium thiopentone

A

extremely rapid onset
used for rapid sequence induction
marked myocardial depression
metabolites build up quickly

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16
Q

ketamine mechanism

A

NMDA receptor antagonist
can be used for induction
little myocardial depression

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17
Q

etomidate

A

v little haemodynamic instability
no analgesia
may result in adrenal suppression
post op vomiting common

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18
Q

1a anti arrhythmics

A

quinidine, procainamide, dispyramide
blocks sodium channels
increases AP duration

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19
Q

quinidine side effects

A

cinchonism (headache, tinnitus, thrombocytopenia)

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20
Q

procainamide side effect

A

drug induced lupus

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21
Q

1b anti arrhythmics

A

blocks sodium channels
decreases AP duration
lidocaine, mexiletine, tocainide

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22
Q

1c anti arrythmics

A

blocks sodium channels
no effect on AP duration
flecainide, encainide, propafenone

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23
Q

type 2 anti arrythmics

A

beta adrenoreceptor antag
propranolol, atenolol, bisoprolol, metoprolol

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24
Q

type 3 anti arrythmics

A

blocks potassium channels
amiodarone, sotalol, ibutilide, bretylium

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25
Q

type 4 anti arrythmics

A

calcium channel blockers
verapamil, diltiazem

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26
Q

antibiotics inhibiting cell wall formation

A

peptidoglycan cross linking: penicillins, cephalosporins, carbopenems
peptidoglycan synthesis: glycopeptides (vanc)

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27
Q

abx inhibiting protein synthesis

A

50S: macrolides, chloramphenicol, clinda, linezolid, streptogrammins
30S: aminoglycosides, tetracyclines

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28
Q

abx inhibiting DNA synthesis

A

quinolones e.g. ciproflox

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29
Q

abx damaging DNA

A

metro

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30
Q

abx inhibiting RNA synthesis

A

rifampicin

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31
Q

abx inhibiting folic acid formation

A

sulfonamides
trimethoprim

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32
Q

what drugs potentiate aspirin?

A

PO hypoglycaemics
warfarin
steroids

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33
Q

aspirin and children

A

do not use due to risk of Reye’s
exception is kawasaki

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34
Q

managing beta blocker overdose

A

atropine if bradycardic
glucagon if resistant

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35
Q

verapamil side effects and cautions

A

s/e: HF, constipation, hypotension, bradycardia, flushing
c/i: do not give with beta blockers due to risk of HB

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36
Q

diltiazem side effects and cautions

A

use caution with HF or beta blockers

s/e: hypotension, bradycardia, HF, ankle swelling

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37
Q

which CCBs may cause ankle swelling?

A

nifedipine, amlodipine, felodipine (dihydropiridines)
shorter acting dihydropyridines may cause peripheral vasodilation which may result in reflex tachy

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38
Q

CO poisoning and oxygen dissoc curve

A

CO binds to Hb and forms carboxyHb
oxygen saturation of Hb decreases
> early plateau in O2 dissociation curve
curve shifts to left

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39
Q

carboxyHb levels

A

< 3 & in non smokers
< 10% in smokers
10-30% in symptomatic poisoning
> 30% in severe toxicity

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40
Q

managing CO poisoning

A

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)

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41
Q

types of caustic subtances

A

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

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42
Q

managing poisoning with caustic substances

A

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

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43
Q

chronic complications of caustic substance ingestion

A

strictures
fistulae
gastric outlet obstruction
upper GI carcinoma

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44
Q

ciclosporin mechanism

A

binds to cyclophilin and inhibits calcineurin
> reduces IL2
> decreases clonal proliferation of T cells

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45
Q

side effects of ciclosporin

A

nephrotoxic, hepatotoxic
fluid retention
HTN
hyperK
hypertrichosis
gingival hyperplasia
tremor
impaired glucose tolerance
hyperlopidaemia
increased susceptibility to severe infection
cannabidiol may increase concentration

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46
Q

ciclosporin indications

A

organ translpant
RA
psoriasis
UC
pure red cell aplasia

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47
Q

cocaine mechanism

A

blocks uptake of DA, NA, serotonin

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48
Q

CVS effects of cocaine

A

coronary artery spasm
tachy or brady
HTN
wide QRS
long QT
aortic dissection

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49
Q

managing cocaine OD

A

chest pain: benzos + GTN
HTN: benzos + sodium nitroprusside

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50
Q

cancers and COCP

A

reduces risk of: ovarian, endometrial, colorectal
increases risk of: breast and cervical ca

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51
Q

UKMEC criteria

A

1: no restriction for use
2: advantages outweigh disadvantages
3: disadvantages outweigh advantages
4: unacceptable health risk

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52
Q

UKMEC 3 and 4 for COCP

A

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

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53
Q

how to take COCP and protection against pregnancy

A

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

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54
Q

switching combined COCP

A

miss the pill free interval if the progesterone is changing

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55
Q

cyanide action

A

inhibits cytochrome c oxidase
stops mitochondrial electron transfer chain

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56
Q

cyanide poisoning presentation and management

A

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

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57
Q

digoxin mechanism

A

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

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58
Q

digoxin toxicity

A

may occur even when plasma concentration is in therapeutic range
yellow green vision
AV block. brady
gynaecomastia

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59
Q

digoxin toxicity precipitators

A

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

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60
Q

managing digoxin toxicity

A

digibind
correct arrhythmias
monitor potassium

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61
Q

indications for DA receptor agonists

A

parkinsons
prolactinoma/galactorrhoea
cyclical breast disease
acromegaly

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62
Q

side effects of DA receptor agonists

A

nausea/vomiting
postural hypotension
hallucinations
daytime somnolence

ergot derived: pulmonary, retroperitoneal and cardiac fibrosis

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63
Q

DRESS syndrome

A

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

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64
Q

DRESS syndrome criteria

A

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

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65
Q

DRESS diagnostic tests

A

skin biopsy: inflam infiltrate (eosinophils, erythrocytes, oedema)
FBC, coag, LFTs, U&Es, CK, viral screen, glucose, TFTs
ECG, CXR, echo, urinalysis for complications

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66
Q

drug causes of agranulocytosis

A

antithyroid (carbimazole, propylthiouracil)
antipsychotics- atypical e.g. clozapine
antiepileptics- carbamazepine
abx- penicillin, chloramphenicol, cotrimox
antidepressants- mirtazepine
cytotoxic- MTX

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67
Q

common drug causes of urticaria

A

aspirin
NSAIDs
penicillins
opiates

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68
Q

monitoring requirements: statins, ACEi, amiodarone

A

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

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69
Q

monitoring requirements: MTX, azathioprine

A

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

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70
Q

monitoring requirements: lithium, sodium valproate

A

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

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71
Q

monitoring requirements: glitazones

A

LFT at baseline and regularly throughout treatment

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72
Q

drugs causing impaired glucose tolerance

A

thiazides, furosemide
steroids
tacrolimus, ciclosporin
IFNalpha
nicotinic acid
antipsychotics
beta blockers slightly

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73
Q

drugs causing thrombocytopaenia

A

quinine
abciximab
NSAIDs
furosemide
penicillins, sulfonamides, rifampicin
carbamaz, valproate
heparin

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74
Q

drugs causing urinary retention

A

TCAs
anticholinergics: antipsychotics, antihistamines
opioids
NSAIDs
disopyramide

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75
Q

drugs causing lung fibrosis

A

amiodarone
MTX, sulfasalazine
busulphan, bleomycin
nitrofurantoin
ergot derived DA agonists

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76
Q

drugs causing cataracts

A

steroidss

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77
Q

drugs causing corneal opacities

A

amiodarone
indomethacin

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78
Q

drugs causing optic neuritis

A

ethambutol
amiodarone
metro

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79
Q

drugs causing retinopathy

A

chloroquine, quinine

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80
Q

sildenafil ophthal side effects

A

blue discolouration
non arteritic anterior ischaemic neuropathy

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81
Q

drugs causing photosensitivity

A

thiazides
tetracyclines, sulfonamides, ciproflox
amiodarone
NSAIDs
psoralens
sulfonylureas

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82
Q

drugs and serotonin action

A

triptans: 5HT1 agonists
pizotifen, methysergide (migraine prophylaxis): 5HT2 antagonists
cyproheptadine (diarrhoea in carcinoid syndrome): 5HT2 antagonist
ondansetron: 5HT3 antagonist

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83
Q

managing ecstasy poisoning

A

dantrolene for hyperthermia if simple measures fail

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84
Q

ethylene glycol toxicity stages

A

11: similar to alcohol (confusion, dizziness, slurred speech)
2: metabolic acidosis w high anion gap and high osmolar gap. tachycardia, HTN
3: aki

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85
Q

managing ethylene glycol poisoning

A

fomepizole
inhibits alcohol dehydrogenase
haemodialysis for refractory cases

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86
Q

flecainide mechanism

A

class 1c antiarrhythmic
blocks Nav1.5 sodium channels
slows action potential
> widened QRS and prolonged PR interval

87
Q

flecainide contraindications

A

post MI
structure heart disease e.g. HF
sinus node dysfunction- second degree or greater AV block
flutter

88
Q

flecainide side effects

A

negatively inotropic
bradycardia
oral paraesthesia
visual disturbances

89
Q

gentamicin contraindications

A

myaesthenia gravis

90
Q

drugs that can be cleared with haemodialysis

A

BLAST
Barbiturate
Lithium
Alcohol incl. ethylene glycol
Salicylates
Theophyllines

91
Q

heparin mechanism

A

activate antithrombin III
unfractionated: inhibits thrombin and IXa, Xa, XIa, XIIa
LMWH: increases action of antithrombin III on Xa

92
Q

side effects of heparins

A

bleeding, thrombocytopenia
osteoporosis
hyperkalaemia

93
Q

heparin monitoring

A

unfractionated: APTT
LMWH: anti factor Xa

94
Q

heparin induced thrombocytopenia

A

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
Q

managing heparin induced thrombocytopenia

A

direct thrombin inhibitor e.g. argatroban
danaparoid

96
Q

ezetimibe mechanism and side effects

A

decreases cholesterol absorption small intestine
headache

97
Q

nicotinic acid mechanism and side effects

A

decreases hepatic VLDL secretion
flushing, myositis

98
Q

fibrates mechanism and side effects

A

agonist of PPAR alpha
> increases lipoprotein lipase
myositis, pruritus, cholestasis

99
Q

cholestyramine mechanism and side effects

A

reduces bile acid reabsorption in small intestine
increases cholesterol conversion to bile acid
GI side effects

100
Q

what metabolic disturbances can cause hypomagnesaemia?

A

hypokalaemia
hypercalcaemia (calcium and Mg compete for transport in thick ascending loop)
Gitelmans, Bartters

101
Q

hypomagnesaemia features

A

paraesthesia
tetany
seizures
arrthymias
decreased PTH, hypocalcaemia
ECG similar to hypokalaemia
exacerbates digoxin toxicity

101
Q

managing hypomagnesaemia

A

< 0.4 or tetany/arrthymias/seizures:
IV Mg replacement

> 0.4: PO Mg replacement

102
Q

IVIG indications

A

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
Q

lithium therapeutic range and half life

A

therapeutic range 0.4-1.0
toxic > 1.5
long half life
excreted by kidneys

104
Q

what could precipitate lithium toxicity?

A

dehydration
renal failure
diuretics (esp thiazides), ACEi/ARBs, NSAIDs, metronidazole

105
Q

features and management of lithium toxicity

A

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
Q

lidocaine metabolism

A

hepatic metabolism
protein bound
renal excretion
therefore increased risk of toxicity in liver dsyfunction or low protein states

107
Q

acidosis and lidocaine

A

acidosis causes lidocaine to detatch from protein binding

108
Q

managing lidocaine toxicity

A

20% lipid emulsion IV

109
Q

drug interactions with lidocaine

A

beta blockers
ciproflox
phenytoin

110
Q

features of lidocaine toxicity

A

CNS overactivity then depression
(initially blocks inhib pathways then both inhib and activating)
cardiac arrhythmias

111
Q

bupivacaine mechanism

A

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
Q

bupivacaine contraindications

A

cardiotoxic so c/i in regional blockage in case tourniquet fails

113
Q
A
114
Q
A
115
Q

doses of local anaesthetics

A

lidocaine 3mg/kg
bupivacaine 2mg/kg
prilocaine 6mg/kg

116
Q

adrenaline and local anaesthetics

A

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
Q

macrolide mechanism

A

blocks translocation
> inhibits bacterial protein synthesis

118
Q

macrolides resistance

A

post transcriptional methylation of 23S bacterial ribosomal RNA

119
Q

macrolides side effects

A

QT prolongation
GI (more common with erythromycin)
cholestatic jaundice (lower risk with erythromycin stearate)
P450 inhib
azithromycin: hearing loss and tinnitus

120
Q

macrolides interactions

A

statins
macrolides inhibit P450 isoenzyme CYP3A4 that metabolises statins

121
Q

features of mercury poisoning

A

paraesthesia
visual field defects
hearing loss
irritability
renal tubular acidosis

122
Q

metformin mechanism

A

activates AMPK
increases insulin sensitivity
decreases hepatic gluconeogenesis and GI absorption of carbs

123
Q

metformin contraindications

A

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
Q

methanol poisoning features and management

A

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
Q

metformin side effects

A

GI
reduced B12 absorption
lactic acidosis (in severe liver disease or CKD)

123
Q

infliximab indications

A

RA
crohns
AKA anti TNF

123
Q

how are monoclonal antibodies made?

A

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
Q

rituximab indications

A

AKA antiCD20
non hodgkins
RA

125
Q

cetuximab indications

A

AKA epidermal growth factor receptor antagonist
metastatic colorectal and H&N cancer

126
Q

trastuzumab indications

A

AKA HER2/neu receptor antagonist
metastatic breast ca

127
Q

alemtuzumab indications

A

anti CD52
CLL

128
Q

abciximab indications

A

glycoprotein IIb/IIIa antag
prevention of ischaemic events in pts undergoing PCI

129
Q

OKT3 indications

A

anti CD3
prevent organ rejection

130
Q

procedural uses for monoclonal antibodies

A

medical imaging when combined with radioisotope
identification of cell surface markers in biopsied tissue
dx viral infections

131
Q

managing motion sickness

A

transdermal hyoscine most effective
non sedating antihistamines e.g. cyclizine/cinnarizine in preference to sedating antihistamines

132
Q

suxamethonium mechanism and metabolism

A

depolarising NM blocker
inhibits ACh at NMJ

degraded by plasma cholinesterase and acetylcholinesterase
fastest onset and shortest duration of all muscle relaxants

133
Q

suxamethonium side effects

A

hyperkalaemia
malignant hyperthermia
lack of acetylcholinesterase

134
Q

atracurium mechanism and metabolism

A

non depolarising NM blocker
30-45 mins duration
not excreted by liver or kidney
broken down in tissues by hydrolysis

135
Q

atracurium side effects and reveral

A

generalised histamine release > facial flushing, tachycardia, hypotension
reversal: neostigmine

136
Q

vecuronium mechanism and metabolism

A

non depolarising NM blocker
duration 30-40 mins
degraded by liver and kidney
effects prolonged in organ dysfunction

reversed by neostigmine

137
Q

pancuronium mechanism

A

non depolarising NM blocker
2-3 mins onset
2h duration
may be partially reversed with neostigmine

137
Q

ocreotide mechanism and adverse effects

A

long acting somatostatin analogue
prevents release of GH, glucagon, insulin
s/e: gall stones from biliary stasis

138
Q

ocreotide uses

A

variceal haemorrhage
acromegaly
carcinoid syndrome
pancreatic surgery
VIPomas
refractory diarrhoea

139
Q

causes of oculogyric crisis

A

antipsychotics
metoclopramide
postencephalitic parkinsons disease

140
Q

managing oculogyric crisis

A

cessation of causative medication
IV antimuscarinic- benztropine or procyclidine

141
Q

organophosphate insecticide poisoning mechanism

A

inhibition of acetylcholinesterase
upregulation of nicotinic and muscarinic cholinergic neurotransmission

142
Q

organophosphate insecticide poisoning features and management

A

SLUD
salivation
lacrimation
urination
defecation
CVS: hypotension, bradycardia
small pupils, muscle fasciculation

mx: atropine, ? pralidoxime

143
Q

managing salicylate poisoning

A

urinary alkalinisation with IV bicarb
haemodialysis

144
Q

managing TCA overdose

A

IV bicarb to reduce risk of seizures and arrhythmias
dialysis is not effective

145
Q

contraindications in TCA OD

A

class 1a (quinidine) and class 1c (flecainide) antiarrhythmics because they prolong depolarisation
class III (amiodarone) prolong QT

146
Q

managing lithium OD

A

volume resus with saline
haemodialysis
? sodium bicarb for urinary alkalinisation

147
Q

managing beta blocker OD

A

atropine if bradycardic
glucagon

148
Q

managing lead poisoning

A

dimercaprol
calcium edetate

149
Q

managing cyanide poisoning

A

hydroxycobalamin (b12)
amyl nitrate + sodium nitrite + sodium thiosulfate

150
Q

P450 inducers

A

CRAP GPS
Carbamazepine
Rifampicin
Alcohol (chronic)
Phenobarbitone

Griseofulvin
Phenytoin
Sulfonylureas, St Johns wart
smoking

151
Q

P450 inhibitors

A

SICK FACESCOM
Sodium valproate, sertraline
Isoniazid
Cimetidine
Ketoconazole
Fluconazole, fluoxetine
Alcohol (acute), Amiodarone, Allopurinol
Chloramphenicol
Erythromycin
Sulfonamides
Ciproflox
Omeprazole
Metro

ritonavir
quinupristin

152
Q

when to give NAC for paracetamol OD?

A

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
Q

acetylcysteine side effects

A

anaphylactoid reaction from non IgE mediated mast cell release
infuse over 1h to reduce side effects

154
Q

paracetamol liver transplant criteria

A

pH < 7.3 @ 24h after ingestion
or
PTT > 100
+ creat > 300
+ grade 3/4 encephalopathy

155
Q

paracetamol metabolism and OD

A

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
Q

risk factors for paracetamol toxicity

A

liver enzyme inducing drugs
malnourished or not eaten in a few days

157
Q

what to avoid in penicillin allergic pts

A

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
Q

types of cellular drug targets

A

ion channels
G protein coupled receptors
tyrosine kinase receptors
nuclear receptors

159
Q

how do tyrosine kinase receptors work?

A

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
Q

how do nuclear receptors work?

A

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
Q

zero order elimination kinetics

A

rate of excretion is constant despite changes in plasma concentration
due to saturation of metabolic process
e.g. phenytoin, salicylates

162
Q

phase I and phase II drug metabolism reaction

A

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
Q

first pass metabolism is seen in what drugs?

A

aspirin
isosorbide dinitrate, GTN
lidocaine
propranolol
verapamil
isoprenaline, testosterone, hydrocortisone

164
Q

zero order kinetics

A

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
Q

acetylator status

A

50% of UK population are deficient in hepatic N acetyltransferase

Procainamide
Sulfasalazine
Hydralazine
Isoniazid
Dapsone

166
Q

phosphodiesterase type V inhibitors mechanism

A

increase cGMP
> smooth muscle relaxation
> vasodilation

167
Q

PDE5 inhibitors contraindications and side effects

A

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
Q

how to manage oedematous patient post op?

A

treat hypovolaemia first
then negative balance of sodium and water
monitor using urine Na levels

169
Q

types of potassium sparing diuretics

A

epithelial Na channel blockers- amiloride, triamterene
aldosterone antag- spiro, eplerenone

use with caution with ACEi (may precipitate hyperkalaemia)

170
Q

amiloride mechanism

A

blocks epithelial Na channel in DCT
weak diuretic
usually given with a thiazide or loop as an alternative to K supplementation

171
Q

mechanism and indication of aldosterone antagonist

A

acts in cortical collecting duct
ascites
heart failure
nephrotic syndrome
conn’s

172
Q

what drugs may exacerbate heart failure?

A

thiazoladinediones (fluid retention)
verapamil (negative inotropic)
NSAIDs/glucocorticoids (fluid retention)
class 1 antiarrthymics e.g. flecainide (negative inotropic and proarrhythmic)

173
Q

drugs to avoid in renal failure

A

tetracycline, nitrofurantoin
NSAIDs
lithium
metformin

likely to accumulate:
most abx
digoxin, atenolol
MTX
sulfonylureas
furosemide
opioids

174
Q

harmful abx in pregnancy

A

tetracyclines
aminoglycosides
sulfonamides, trimethoprim
quinolones (arthropathy)

175
Q

drugs to avoid in pregnancy

A

ACEi, ARBs
statins
warfarin
sulfonylureas
retinoids
cytotoxics

176
Q

POP adverse effects

A

increased incidence of functional ovarian cysts
breast tenderness, weight gain, acne, headaches generally subside after a few months

177
Q

cinchonism

A

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
Q

managing cinchonism

A

difficult to distinguish from aspirin poisoning so measure serum salicylate levels
largely supportive- fluids, inotropes, bicarb, positive pressure ventilation for pulm oedema

179
Q

quinolones mechanism of action and resistance

A

e.g. ciproflox, levoflox
inhibit topoisomerase II (DNA gyrase) and topoisomerase IV

resistance: mutations to DNA gyrase, efflux pumps reduce intracellular quinolone concentration

180
Q

quinolones side effects and c/i

A

lower seizure threshold
tendon damage
cartilage damage
lengthened QT

c/i: breastfeeding/pregnant, G6PD

181
Q

features of salicylate overdose

A

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
Q

managing salicylate OD and indications for dialysis

A

sodium bicarb urinary alkalinisation

dialysis:
serum > 700mg/L
metab acidosis resistant to treatment
AKI
pulm oedema
seizures
coma

183
Q

causes and features of serotonin syndrome

A

MAOi, SSRIs, ecstasy, amphetamines
St Johns Wort and tramadol can interact with SSRIs to cause SS

hyperreflexia, myoclonus, rigidity
hyperthermia, sweating
confusion

184
Q

managing serotonin syndrome

A

IV fluids
benzos
more severe cases: cyproheptadine, chlorpromazine serotonin antagonists

184
Q

NMS vs serotonin syndrome

A

NMS has longer onset (hours-days)
NMS reduced reflexes; SS hyperreflexia
SS dilated pupils
raised CK more associated with NMS

185
Q

nicorandil side effects

A

headache
flushing
anal ulceration

186
Q

sulfonylureas side effects

A

(gliclazide, glimepiride)
hypoglycaemia
increased appetite, weight gain
SIADH
cholestatic liver dysfunction

187
Q

glitazones/thiazoladinediones side effects

A

weight gain
fluid retention
liver dysfunction
fractures

188
Q

gliptins side effects

A

pancreatitis

189
Q

tacrolimus mechanism

A

reduces IL2 release
> decreases clonal proliferation of T cells
binds to FKBP
> complex inhibits calcineurin (calcineurin activates transcription factors in T cells)

190
Q

tamoxifen mechanism and adverse effects

A

oestrogen receptor antagonist and partial agonist

menstrual disturbance
hot flushes
VTE
endometrial ca

191
Q

raloxifene mechanism

A

pure oestrogen receptor antagonist
lower risk of endometrial ca

192
Q

ACEi teratogenic effects

A

renal dysgenesis
craniofacial abnormalities

193
Q

carbamazepine teratogenic effects

A

neural tube defects
craniofacial abnormalities

194
Q

chloramphenicol teratogenic effects

A

grey baby

195
Q

diethylstilbesterol adverse effects

A

vaginal clear cell adenocarcinoma

196
Q

lithium teratogenic effects

A

ebsteins anomaly

197
Q

maternal diabetes mellitus teratogenic effects

A

macrosomia
neural tube defects
polyhydramnios
preterm labour
caudal regression

198
Q

valproate teratogenic effects

A

neural tube defects
craniofacial abnormalities

199
Q

warfarin teratogenic effects

A

craniofacial abnormalities

200
Q

monitoring ciclosporin

A

trough levels

201
Q

trastuzumab

A

monoclonal antibody against HER2/neu receptor

s/e: flu like, diarrhoea
cardiotoxicity

202
Q

features of TCA OD

A

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
Q

managing TCA OD

A

IV bicarb for hypotension/arrhthymias
avoid quinidine, flecainide, amiodarone because they prolong depolarisation
IV lipid emulsion

204
Q

rifampicin mechanism and s/e

A

inhibits bacterial DNA dependent RNA polymerase
prevents DNA transcription to RNA

liver enzyme inducer
hepatitis
orange secretions
flu like

205
Q

isoniazid mechanism and s/e

A

inhibits mycolic acid synthesis

peripheral neuropathy (prevent with B6 pyridoxine)
hepatitis
agranulocytosis
liver enzyme inhib

206
Q

pyrazinamide mechanism and s/e

A

converted by pyrazinamidase to pyrazinoic acid
> inhibits fatty acid synthase

hyperuricaemia > gout
arthralfia, myalgia
hepatitis

207
Q

ethambutol mechanism and s/e

A

inhibits arabinosyl transferase which polymerases arabinose to arabinan

optic neuritis
adjust dose if renal impairment

pharmacology/toxicology (1 decks)

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