Block 32 PPT Flashcards
1
Q
GI bleed with melaena?
A
- 1st: fluids via cannula - IV fluid resus
- compound sodium lactate/ Hartmann’s solution
- or sodium chloride 0.9% solution
- blood transfusion
2
Q
investigation for a GI bleed w melena?
A
- definitive: endoscopy
3
Q
management of an ulcer?
A
- Pantoprazole first IV as a bolus and then IV infusion
- PPI
4
Q
drugs to withhold in a hypotensive patient?
A
rampiril and amlodipine
5
Q
gastroduodenal mcusoal injury
A
6
Q
Gastroduodenal mucosal injury mechanism?
A
- inhibition of COX -> reduced GI protection through reduced prostanoid secretion
- prostanoids stimulate mucus secretion and mantain gastric blood flow
- promote platelet aggregation
7
Q
test for H pylori?
A
CLOtest
8
Q
drug therapy for H pylori eradication?
A
- Lansoprazole
- amoxicillin
- clarithromycin - macrolide
- metronidazole - anaerobes
- combination antibiotics used to avoid selecting for resistance
9
Q
lansoprazole in H pylori eradication therapy?
A
to raise pH, H pylori thrive in acidic environments
10
Q
H pylori eradication for penicillin allery?
A
clarith and metronidazole
11
Q
H pylori eradication when there isn’t a penicillin allergy?
A
- no allergy: amoxicillin plus either clarith or metronidazole as a first line
12
Q
clarithromycin + ? increases risk of hypotension
A
amlodepine
13
Q
clarithromycin can’t be prescribed with? due to risk of rhabdomyalysis
A
simvastatin - statins
14
Q
bulk forming laxatives?
A
isphalga husk
15
Q
osmotic laxatives?
A
lactulose and macrogols
16
Q
irritant and stimulants (constipation)?
A
bisacodyl, docusate laxatives
17
Q
(constipation) - faecal softners?
A
co-danthrusate and docusate sodium
18
Q
which laxatives are safe in pregnancy?
A
- senna (stimulant laxative)
- docusate (stimulate)
19
Q
which constipation drugs are suitable for the elderly or for the terminally ill with opioid induced constipation ?
A
- bisadocyl
- co-danthramer
- co-danthrusate
20
Q
what is lactulose good for?
A
- good for hepatic encephalopathy related constipation
- broken down into lactic acid which neutralises ammonia from bacteria
21
Q
laxative choice?
A
22
Q
anti-diarrhoeals?
A
- codeine phosphate - opiod
- diphenoxylate - binds to mu receptors without causing a central effect
- loperamide - opiod with no central affect
23
Q
pathophys of IBS?
A
- visceral hypersensitivity: common
- exaggerated resp to cholecystokinin
- altered resp to meal injection
- increased bowel motility and low grade inflammation
24
Q
RF for pathophys?
A
psychological stressors: anxiety, stress, depression
25
drug classes for IBS ?
- Antimuscarinics
- antispasmodics
26
Antimuscarinics e.g.?
* dicycloverine
* propantheline
27
IBS - other antispasmodics?
* mebeverine
* peppermint oil
28
UC drug classes?
- aminosalicyclates
- corticosteroids
- cytokine modulators
- immunosuppressants
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aminosalicyclates?
* mesalazine
* olsalazine
* sulfasalazine
30
corticosteroids?
* hydrocortisone
* predinosolone
* budenoside
* * used initiallty, to induce remission
31
cytokine modulators in IBD?
* anti TNFa antibodies
* adalimumab
* infliximab
32
Immunosuppressants in IBD?
* azathioprine
* methotrexate
33
Ab used in IBD?
metronidazole
34
Biologics for IBD - be careful of?
latent TB
35
Proctitis/ left sided IBD?
* localised therapy
* e.g.e enema
36
when giving high dose steroids, protect?
* when giving high dose steroids: protect GI using PPIs and protect bones using bisphosphonates
37
2 serious interactions of azathioprine?
allopurinol and febuxostat which slow the elimination of 6-MP by inhibiting xanthine oxidase
38
what needs to be measured before azathioprine can be prescribed?
TPMT levels
39
Infilimab mechanism?
* high spec for TNF-a, inhibits the binding of TNFa to receptors, neutralizing its activity
* infliximab can also stimulate apoptosis of activated lymphocytes in gut mucosaa
40
adalimumab mechanism?
TNF-a inhibitor
41
Tx of C diff associated diarrhoea?
vancomycin
42
pain pathways?
* tissue injury leads to release of inflammatory mediators w nonciceptor stimulation
* pain impulses transmitted to the dorsal horm of the SC where they contact 2nd order neurons that deccussate
* ascend via the spinothalamic tract to the RAS and thamus
* pain localization occurs at somatosensory cortex
43
peri-operative pain management options?
- opiods
- bupivacaine
- paracetamol
44
acute side effects of opiods?
- nausea, flushing/ sweating,
- hypotension,
- urticaria,
- myoclonus/ muscle rigidity.
- resp depression,
- visual distrubance
45
opiod antagonist?
* naloxone (competitive antagonist)
* but it has a shorter half life than most opiods so enough needs to be given to correct respiratory rate - resus dose
* IV dose, IM if IV not feasible
46
bupivacaine?
- sodium channel blocker
47
paracetamol?
acts on spinal receptors through action of its breakdown product NAPQI acting on TPRA1 receptors
48
vomiting center?
- nucleus of tractus solitarius
* H1, M1, NK1, 5-HT3
49
5-HT3 receptor antagonist?
ondansteron
50
ondansteron works on ? receptors?
* 5-HT3 antagonism peripherally and chemoreceptor trigger zone
* preventative
51
ondansteron causes?
QT interval prolongation
52
drugs for post op nausea and vomiting - steroids?
* dexamethasone
* prevantative
53
anticholinergic used in post op nausea and vomiting?
* scopolamine
* preventative
* sedating, not to be used in patients w narrow angle glaucoma
54
neurokinin receptor antagonist used in post op nausea and vomiting?
* aprepitant
* blocks neurokinins effect at receptor site
* preventative
55
metoclopramide and domperidone both cause?
QT prolongation
56
metroclopramide?
* acute dystonia espec in young women
* procyclidine hydrochloride can be given for acute dystonia
57
domperidone?
* doesn't cross BBB so doesn't cause same dystonic reactions as metroclopramide
58
co-amoxiclav?
* clavaunic acid and amoxicillin = to inhibit beta lactamase in bacteria
59
vomiting, not eating for several days, bowel cancer ->
think bowel obstruction
60
isotonic fluids?
- sodium chloride
- compound sodium lactate (Hartmann's solution)
61
mixed fluids?
* mixtures w Na + glucose e.g. glucose saline
62
glucose containing fluids?
* 5% glucose isotonic
* 10, 20,50% are hypertonic
63
50% glucose can cause ? as a side effect
if 50% glucose gets out of the cannula will cause an area of skin necrosis
64
how much hartmans solution can be given?
* up to 2L of either Hartmann (contains K+) or NaCl fluids can be given
* give 500ml fluid at a time
* fluid resus algorithm >
65
why is harmann's preferred to sodium chloride?
* Hartmanns is better than sodium chloride bc less risk of hyperchloremic metabolic acidosis bc NaCl comtains more Cl- than plasma
* Hartmanns lactate acts as a buffer & has a higher pH
66
maintenance fluids?
- 0.9% sodium chloride
- hartmanns
- 5% glucose
67
pharmacokinetics =
what the body does to the drug
68
pharmacodynamics =
what the drug does to us
69
volume of distribution =
amount of drug in the body (dose)/ plasma conc of drug
70
massive volume of distribution tells us?
* massive VoD tells u that the drug is conc somewhere usually binding to proteins or in fat reserves
* vol of 5L in circ only
71
amount in body =
volume of distrubution x plasma concentration
72
usually takes how many half lives to reach a steady state?
* usually takes 5 half lives to reach the steady state then the conc comes up and down to the steady state level
73
larger vs small VoD?
* larger volume of distribution means less peaks in conc bc it distributes out into thr wider space of the body
* small VoD (water soluble drugs) more peaks
74
Long half life generally requires a longer?
dosing interval
75
phase 1 of a clinical trial?
drug tested in healthy ppl
76
phase 2 of a clinical trial?
drug tested in healthy ppl to find the right dosing interval
77
phase 3 of a clinical trial?
drug used in intended patient group against placebo
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phase 4 of a clinical trial?
pick up rarer side effects when its being used in the population
79
drugs that require monitoring?
* gentamicin is given IV and then monitored (6-14 hours after dose blood sample is taken)
* lithium requires monitoring - above 3.5mmol/L regarded as a medial emergency
* has a narrow therapeutic index (short window between it working and it becoming toxic)
80
oral availability of drugs?
* oral availability = the fraction of drug that reaches the systemic circulation after oral ingestion
* oral availability is determined by absorption and first pass metabolism
81
first pass metabolism?
* FPM: pre-systemic drug metabolism
* occurs in the brush border of gut wall, portal vein or liver
82
ionised drugs don't ? easily?
* ionised drugs don't cross the PM easily
* ionised drugs are more water soluble so are more easily excreted
83
what can help aspirin excretion in the case of aspirin overdose?
* alkalisation of urine using sodium bicarb in the case of aspirin overdose - this favours excretion of aspirin in the urine
84
physiochemical factors affecting drug abs?
* pH partition theory
* lipid solubility
* salts
* crystal form
* drug stability and hydrolysis in GIT
* complexation - does it concrete together with other drugs
* abs
85
100% oral bioavailability would be when?
when u get the same conc when taking the drug orally as injecting the drug
86
how does cirrhosis affect drug metabolism?
* cirrhosis increases bioavailability by affecting FPM
* Avoid oral preparations in the cases of hepatic impairment
87
IM injections can cause issues due to?
* IM injections can cause issues due to coagulopatheis assoc w hepatic impairment or those on AC
88
oral drugs peak ? bc they have to be?
* Oral drugs peak slow bc they have to be abs
* giving an intial larger loading dose gets u in the TR quicker, then give smaller maintenance doses
89
hypoproteinaemia due to liver disease causes a higher ?
- proportion of free drug
90
physiological liver function?
* fenestrations in the endothelium, allows ready access to ECF
* rapid diffusion across the space of Disse
* brush border on hepatocytes allows rapid uptake
91
what happens in cirrhosis?
* fenestrations lost
* diffusion across space of Disse reduced
* brush border lost
* enzyme activity reduced
* intrahepatic vascuar shunts may reduce perfusion of hepatocytes
92
which drug is heavily renally excreted?
codeine
93
which drug is heavily hepatically metabolised?
fentanyl
94
first order kinetics?
* amount of drug that is eliminated per unit time is proportional to the drug conc - so a constant % of the drug is eliminated per unit time
95
zero order kinetics?
* amount of drug eliminated is constant per unit time and not related to conc - no matter how much drug there is, body can only eliminate a certain absolute amount
* this is saturation kinetics
96
when can drugs move from first to zero order kinetics?
* drugs can move from first to zero order kinetics when the enzyme metabolizing them becomes saturated
97
first vs 0 order kinetics
98
most drugs in the therapeutic range are in which type of kinetics?
- first order
- exceeding a certain dose can cause them to move to 0 order - small changes in dose can largely inc blood levels
99
GI side effects of chemotherapy?
* diarrhoea, sore mouth, nausea and vomiting
100
bone marrow side effects of chemo?
* myelosuppression, can lead to anemia, neutropenia and thrombocytopenia
101
tumour lysis syndrome from cancer chemo?
* rapid breakdown of malignant cells can cause
* hyperuricaemia,
* hyperkalaemia and high phosphate
* hypocalcaemia with renal damage/ arrhythmias
102
capecitabine is used for?
* CRC, gastric cancer and breast cancer
103
104
mercaptopurine?
purine antagonist
105
what makes sure that chemotherapy is prescribed safely?
* electronic prescribing helps make sure that chemotherapy is prescribed safely - keeps a record of what has been prescribed and makes it so that only certain users can prescribe it
106
Oxaliplatin drug class?
* alkylating agent - inhibits DNA synthesis
* platinum compound
107
what are the platnium compounds?
- * oxiplatin, cisplatin, carboplatin - drugs ending in platin
* used for solid malignancy
108
side effects of chemo?
* severe nausea and vomiting
* nephrotoxicity (hydration is esssential)
* ototoxicity
* peripheral neuropathy
* myelosuppression
109
if chemo is given via cannula, what can happen?
extravasation
110
anastrazole?
* aromatase inhibitor
- given to post menopausal women
* aromatase converts test produced by the ovaries into oestradiol
111
why is anastrazole only given to post menopausal women?
* giving anastrazole to a pre-menoposal woman would trigger release of more FSH meaning more oestrogen production - pointless
* post-menopausal women have generally stopped producing oestrogen but still some test and oestrodiol (conversion in peripheral tissues)
* androgens -> estradiol by aromatase in the breast tissue
* this conversion is enough to stimulate an oestrogen responsive BC
112
general side effects of anastrazole?
* drowsiness - affects ability to drive or operate machinery
* asthenia
* hot flushes
* hair thinning
113
steven jonson syndrome?
* severe skin reaction, mucous membranes freq involved
* blisters. fever, flu like syndromes
* can progress to sepsis and multi organ failure untreated
114
tamoxifen?
* SERM - selective estrogen receptor modulator
* completitively binds at the oestrogen receptor inhibiting transcription of oestrogen receptive genes
* strongly antiestrogenic on mammary epithelium, used in prevention and Tx of BC
115
who can tamoxifen be used in?
* Effective in pre and post menopausal women w ER+ breast cancer
* once a day for 5 yrs
116
tamoxifen interacts with?
* WARFARIN through inhibition of CYP3A4 increasing risk of bleeding
* SSRIs e.g. fluoxetine possibly inhibit metaboism of tamoxifen
117
signs of leukemia?
* sig raised leucocytes - raised in 40-50s rarely occurs w infection
* marked leukoblastosis
118
stages of leukemia treatment?
1. induction
2. consolidation
3. maintenance
119
1. induction (leukemia treatment)
* intestive therapy aimed at destroying as many leukemia cells as possible and achieving remission (no leukemia cells on bone marrow biopsy)
* lasts 4-6 weeks
120
2. consolidation (leukemia treatment)
* aimed at remission and preventing spread
* often involves intra-spinal injections then tablets (looks for cancer cells hiden behind BBB)
* usually a month and a half
121
3. maintenance in the treatment in leukemia?
* lasts 2 years (girls) or 3 yrs (boys) from the start of interim treatment
* regular tablets +/- injections
122
Chemotherapy combination of drugs ?
* reduced development of drug resis
* rapidly dividing so can undergo new mutations which are advantageous
123
cyclophosphamide mechanism?
* alkylating agent causing cross linking between DNA strands leading to cell apoptosis
* binds to DNA preventing synthesis
* binds to proteins blocking DNA repair processes
124
side effects of cyclophosphamide?
* impaired fertility in the future
* bone marrow suppression and neutropenia
* can develop other malignancies like AML or bladder cancer
125
reducing risk of bladder cancer from cyclophoshamide?
* bladder cancer risk reduced by giving mesna (mercaptoethane sulphonic acid) prior to treatment
* causes haemorrhagic cystitis - mesna
126
vincristine mechanism?
* vinca alkaloids
* miotic inhibitors
* binds to tubulin molecules preventing formation of microtubules preventing chromosome separation
* eventually leads to cell death
127
? vincristine is fatal
* intrathecal vincristine is fatal
128
vincristine is used for?
leukemias
129
doxorobucin drug class?
* cytotoxic antibiotic
* anthracycline
* prevention of DNA double helix from being resealed
130
side effect of doxorubicin?
dilated cardiomyopathy - can happen many yrs later
131
methotrexate mechanism?
* folic acid antagonist
* immunosuppressant
132
uses of methotrexate?
* DMARD used in RA and psoriasis
* used in abortion and molar pregnancy
133
methotrexate toxicties?
* nephrotoxic, hepatotoxic, bone marrow toxic
* requires reg monitoring
134
oral mucositis ?
* sore mouth is mostly associated with fluorouracil, methotrexate and anthracyclines
* saline mouthwashes
135
hyperuricaemi may be present in?
* may be present in high-grade lymphoma and leukaemia, can be markedly worsened by chemotherapy and is associated with acute renal failure
136
treatment of hyperuricaemia?
* allopurinol
* or febuxostat
* rasburicase
137
which chemotherapy agents cause bone marrow suppression?
* All cytotoxic drugs except vincristine sulfate and bleomycin cause bone-marrow suppression.
* This commonly occurs 7 to 10 days after administration
138
drugs used for low risk of emesis from chemo?
dexamethasone or lorzepam
139
high risk of emesis from chemo Tx?
- serotonin antagonist with dexamethasone
* neurokinin receptorantagonist aprepitant is effective
140
treatment of methotrexate induce mucositis or myelosuppression?
* Folinic acid
* (given as calcium folinate) is used to counteract the folate-antagonist effects- methotrexate-induced mucositis or myelosuppression (‘folinic acid rescue’).
141
urethral toxicity from chemo?
* from cyclophosphamide and ifosfamide
* mesna used to treat
142
acute pain Mx ladder?
* step 1: paracetamol
* step 2: swap paracetamol for ibuprofen
* if the person can't take NSAIDs, use weak opioids like coedine phosphate
* step 3: add paracetamol to the ibuprofen or weak opiod
* step 4: continue with paracetamol and replace ibuprofen with other NSAID like naproxen
* step 5: add weak opiod to the paracetamol and/or nSAID
143
WHO analgesic ladder
Step 1: non opiods - NSAIDs, paracetamol
Step 2: weak opiods - codeine
Step 3: strong opiods
144
chronic pain management?
* Acceptance and commitment therapy
* CBT
* acupuncture or dry needling
145
antidepressants used in chronic pain management?
* antidepressants: amitriptyline, citalopram, duloxetine, fluoxetine, paroxetine, sertraline
146
lifestyle advice for chronic pain?
* diet, weight, alcohol use, smoking, exercise for improving health
147
neuropathic pain Mx?
* trycyclic antidepressant or with antiepileptic drugs
* amitriptyline and pregabalin are effective for neuropathic pain
* can be used in combination if there's an inadequate response to either drug
148
what else can be used for neuropathic pain>
* nortriptyline
* gabapentin
* opiod analgesics: tramadol, morphine, oxycodone
149
management of drug induced especially opiate induced vomiting ?
* anti-emetics e.g. cyclizine, ondansteron, prochlorperazine
* ondansteron has the advantage of not producing sedation
150
management of motion sickness?
* hycosine hydrobromide
* anti-histamines
151
what are the less sedating antihistamines?
cinnarizine and cyclizine
152
more sedating antihistamines?
include promethazine hydrochloride and promethazine teoclate.
153
management of post op nausea and vomiting
* 5-HT3 receptor antagonists e.g. ondansteron
* dexamethasone
* droperidol
* cyclizine
* prochlorperazine
154
cytotoxic drug induced vomiting?
* 5-HT3 antagoist
* dexamethasone may also be needed
* delayed symptoms: dexamethasone is the drug of choice, used alone with metoclopramide hydrochloride - high risk of neuro side effects
155
drugs used for pregnancy induced nausea and vomiting?
* cyclizine
* prochlorperazine
* promethazine hydrochloride
* ondansteron
156
# Supplementation
hyperemesis gravidrarum management?
* severe/ persistent hyperemesis gravidrarum -> supplementation of thiamine to reduce risk of Wernicke's encephalopathy
157
indications for IV fluids?
- management of adult patient requiring IV fluid resus - including treatment of hypovolaemia
- * patient NBM e.g. bowel obstruction, ileus, post op
* vomiting or severe diarrhoea
* hypovolaemic as a result of blood loss
158
Types of fluids/
* crystalloids: solutions of molecules in water (e.g. solutions of small molecules in water, Hartmann's, dextrose)
* colloids: solutions of larger organic molecules e.g. albumin, gelofusine
* crystalloids superior for initial resusicitation
159
hartman's solution?
* sodium chloride 0.9%
* used for resus/ maintenance
160
sodium chloride 0.18%
* dextrose
* for maintenance
161
Resus - fluids?
* 500ml bolus of crystalloid soidum - NaCl/ Hartmannls over less than 15 mins
* if patient still has evidence of hypovolaemia - give further 250-500ml bolus
* repeat until you've given 2L then seek expert help
162
fluid resus in more complex patients?
If patients have complex medical comorbidities (e.g. heart failure, renal failure) and/or are elderly then you should apply a more cautious approach to fluid resuscitation (e.g. giving fluid boluses of 250 ml rather than 500 ml and seeking expert help
163
IV fluids indicated for the management of an adult patient with hypokalaemia.
* potassium chloride with sodium chloride IV infusion is the initial treatment for correction of severe hypokalaemia when enough potassium can't be taken by mouth
* initial potassium replacement shouldn't involve glucose transfusions bc glucose can cause a further decrease in plasma potassium conc
164
relationship between drug dose and resp?
* describes the magnitude of the response of an organism, as a function of exposure (or doses) to a stimulus or stressor (usually a chemical) after a certain exposure time
165
changes in receptor sensitivity?
* when receptor sensitivity changes, the same conc of a drug will produce a greater or lesser physiological response
* changes in sensitivity occur e.g. after prolonged stimulation of cells by agonists, the cell becomes refractory to further stimulation - desensitisation
166
TI?
* measurement of the relative safety of a drug
* The therapeutic index (TI) is the range of doses at which a medication is effective without unacceptable adverse events.
167
Explain receptor desensitisation?
* underlying mechanisms may involve receptor changes like phosphorylation or the receptor may be concealed within the cell so that it's no longer exposed to the ligand
168
tolerance?
* tolerance - e.g. accelerated metabolism
* tolerance leads to increasing doses of a drug being needed to produce the same effect
* Other possible mechanisms are a decrease in binding affinity between a drug and receptor and a decrease in the number of receptors
169
impact of pharmacokinetics on drug dosing schedule?
* drug half life can be used to determine dosing schedule and the time to attain a steady state concentration
* short half life requires more frequent dosing
170
common medicines that are likely to cause harm to patients with impaired liver function ?
* rifampicin and fusidic acid are excreted in bile unchanged
* hypoproteinaemia - increased toxicity of highly protein bound drugs like phenytoin and prednisolone
* reduced clotting - warfarin
171
drugs that can cause harm to ppl w impaired liver function - hepatic encephalopathy?
* hepatic encephalopathy - all sedative drugs, opioid analgesics, those diuretics that produce hypokalaemia, and drugs that cause constipation.
172
drugs that can harm ppl w impaired liver cuntion - fluid overload
* fluid overload - oedema and ascites exacerbated by drugs that cause fluid retention like NSAIDs and corticosterouds
173
First and second line in constipation?
- first-line laxative: bulk-forming laxative first-line, such as ispaghula
- second-line: osmotic laxative, such as a macrogol
174
inducing remission in crohns?
- glucocorticoids first line
- mesalazine second line
- azathioprine or mercaptopurine can be added on
175
infliximab in CD?
infliximab is useful in refractory disease and fistulating Crohn's. Patients typically continue on azathioprine or methotrexate
176
maintaining remission in crohns?
- azathioprine or mercaptopurine first line
- stop smoking
177
Inducing vs remaining remission in CD?
- Inducing - steroids
- maintaining - azathioprine/ mercaptopurine
178
inducing remission in UC - procitis?
- topical (rectal) aminosalicyclate
- add oral amino if this doesn't work
- add topical/ oral steroid if this doesn't work
179
Left sided colitis - inducing remission?
- topical aminosalicyclate
- 2: high dose oral amino
- 3: add steroid
180
inducing remission in extensive UC?
- topical amino and a high dose aminosalicyclate
181
severe colitis?
- should be treated in hospital
- IV steroids are usually given first-line
182
maintaining remission in UC?
- proctitis: topical amino
- left sided/ extensive: oral amino
182
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UC - Following a severe relapse or >=2 exacerbations in the past year
oral azathioprine or oral mercaptopurine
182
Methotrexate in UC?>
methotrexate is not recommended for the management of UC (in contrast to Crohn's disease)
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