High Risk Drugs Flashcards
1
Q
Therapeutic range for for Gentamicin and Amikacin
A
One-hour (peak) serum concentration should be 5 to 10 mg/L, pre-dose trough level should be < 2mg/L.
2
Q
Indication for Gentamicin and Amikacin
A
Endocarditis.
Meningitis
Severe diabetic foot infection
3
Q
Activity against gram (-)/gram (+) for Gentamicin and Amikacin
A
Very good gram negative coverage.
P.aeruginosa + K.pneumonia.
4
Q
Mechanism of action for Gentamicin and Amikacin
A
Irreversible 30s ribosome inhibitor.
5
Q
Elimination route for Gentamicin and Amikacin
A
70% renal excreted.
6
Q
Monitoring for for Gentamicin and Amikacin: safety and efficacy.
A
Serum concentration: taken at trough level.
Renal function.
Auditory and vestibular function.
{ treatment efficacy: temperature, CRP, WBC).
7
Q
Caution/Contraindication for Gentamicin and Amikacin
A
Renal failure.
8
Q
Renal/Liver for Gentamicin and Amikacin
A
Creatinine clearance <20 mL/min.
9
Q
Adverse effects for for Gentamicin and Amikacin + why.
A
Ototoxicity: generates free radicals within the ear causing permanent damage to sensory cells and neurons.
Nephrotoxicity: Direct damage tissue. 70% is cleared here so accumulation can lead to this.
10
Q
Lithium indication.
A
Treatment and prophylaxis bipolar disorder.
11
Q
Therapeutic range for Lithium
A
0.6-1 mmol/L.
12
Q
Lithium main route of elimination.
A
Renal; 80% reabsorbed.
13
Q
When do you not prescribe lithium
A
Cardiac disease associate with rhythm disorders.
Significant renal impairment.
Untreatable hypothyroidism + Addisons disease.
14
Q
How does lithium cause hypo/hyperthyroidism.
A
Lithium concentrates by the thyroid and inhibits thyroidal iodine up-take.
15
Q
How does lithium cause hypercalcaemia and what are the potential clinical implications.
A
Increase circulation of calcium due to increase reabsorption at the loop of Henle —> Increase circulation parathyroid hormone (PTH) which can lead to bone thinning and kidney stones.
16
Q
How does lithium cause hyponatremia
A
Competitively taken up by sodium re-uptake (more than Na+) via the Na+/H+ co-transporters in the proximal tubules and then accumulates in the renal tubules. Also competitively taken up by the Na+ channels located in the loop of Henle.
17
Q
Fill in the diagram.
A
18
Q
How does lithium cause Nephrogenic diabetes insipidus.
A
By inhibiting arginine vasopressin from increase the reabsorption of water through the AQ2 channel.
19
Q
What are the formulation considerations that need to take place when using lithium.
A
Lithium available in two salts: lithium carbonate and lithium citrate. They are not dose equivalent.
Always prescribe by brand name.
20
Q
Increase lithium concentration is more likely with
(a) Thiazide diuretics
(b) Loop diuretics
(c) Spironolactone
A
(a) More likely with thiazide diuretics, loop diuretics are less likely to result in lithium toxicity.
21
Q
Which agent when combined with lithium is likely to cause neurotoxicity.
(a) Ibuprofen
(b) ACE-inhibitor
(c) Dapagliflozin
(d) Duloxetine
(e) Carbamazepine
A
(e) Carbamazepine, SSRI/duloxetine have been linked rarely to CNS toxicity.
22
Q
Which agent when combined with lithium is likely to decrease lithium levels due to increase lithium renal clearance.
(a) Ibuprofen
(b) ACE-inhibitor
(c) Dapagliflozin
(d) Duloxetine
(e) Carbamazepine
A
(c) SGLT-2 inhibitor because sodium is not being reabsorbed via the SGLT2 pump.
23
Q
Monitoring for lithium
A
One week after treatment lithium levels are taken 12 hours post-dose.
BMI, U&E, TFT, eGFR, Ca2+ then every 6 months.
24
Q
What are the signs of lithium toxicity
A
CNS disturbances: Lethargy, dizziness, lack of coordination, tinnitus
GI: diarrhoea, vomiting, anorexia
PNS: Muscle hyper irritability.
25
Lithium toxicity occurs at:
(a) 1.2 mmol/L
(b) 1.5 mmol/L
(c) 0.8 mmol/L
(d) 1.0 mmol/L
(b) 1.5 mmol/L
26
What advise should people taking lithium be given.
Carry lithium card.
Regular blood test.
Adverse effects to effect.
Maintain fluid intake.
Avoid OTC NSAIDs.
27
Valproate mechanism of action.
Inhibition of sodium gated channels.
28
MHRA warning concerning Valproate.
Valproate should not be prescribed in girls, female adolescents, women who are pregnant or of childbearing age.
29
What supplementation is added during valproate regime.
Folic acid supplementation 5 mg daily
30
What is the most effective primary pregnancy prevention intervention when patient is on valproate.
(a)Levonorgestrel-releasing intrauterine system.
(b)Combined hormal contraceptive
(c) Progesterone only pill
(d) progestogen implant
(d) and (a) most effective with a failure rate less than 1%.
Others recommend with barrier protection.
31
What are the adverse effects associated with valproate (vALPROate).
Anemia
Liver dysfunction
Pancreatitis
Spino bifida
Weight gain
Thrombocytopenia
32
What % protein binding seen with valproate.
33
Which drug when co- administered with valproate is displaced.
(A) Aspirin
(B) Simvastatin
(C) Warfarin
(D) Nifidipine
(C) Warfarin is less bound to protein and valproate can displace it easily.
34
Which drug when co- administered with valproate is able to DISPLACE valproate.
(A) Aspirin
(B) Simvastatin
(C) Warfarin
(D) Nifidipine
(A) Aspirin
35
What are the key monitoring for someone who is taking valproate.
36
Indication for methotrexate.
2nd line: Maintenance of Crohn’s disease or inducing remission for CD.
Rheumatoid arthritis.
37
Mechanism of action for Methotrexate
Inhibit dihydrofolate reductase, which catalase the conversion of dihydrofolate into tetrahydrofolate, the active form folic acid. Cause increase adenosine which has anti-inflammatory effect —> repress T-cell activation, down-regulation B cells.
38
Dosing and Prescribing practice for Methotrexate
Orally or SC once WEEKLY. 25 mg for 16/52 weeks.
Prescribe 5 mg Folic acid taken on a separate day.
39
Adverse drug reaction with Methotrexate
Nausea + vomiting.
Mouth ulcers
Rash
Bone marrow suppression.
Liver disease: jaundice.
40
What should patients avoid during flu season. ( who are on methotrexate)
Live vaccines.
41
Warning signs when on Methotrexate
GI toxicity.
Sore throat—> infection.
Pulmonary toxicity—> cough, dyspnoea —> methotrexate can induce hypersensitivity pneumonitis.
Renal injury—> direct tubular damage
42
Patient comes to your pharmacy and tells you that they have had a sore throat so they would like to have some lozenges. You ask them about their medication history and you find out the following:
- Methotrexate SC 25 mg
- Diltiazem 5 mg OD for AF
- Folic acid 5 mg once a week
What are you concerned about.
Patient may be have blood disorder due to bone marrow suppression therefore stop methotrexate and advise them to go urgently go hospital.
43
Monitoring for Methotrexate
FBC, renal and LFTs: every 1-2 weeks until therapy stabilised then every 2-3 months.
Warn Tx about symptoms sore throat.
44
Why would you advise patient on Methotrexate to avoid buying OTC NSAIDs or be cautious of penicillin.
NSAIDs (ACE-I) and penicillin all reduce renal perfusion and subsequently excretion of methotrexate which could increase risk of methotrexate toxicity.
45
What agent when combined with Methotrexate increase risk of haematological toxicity
Co-trimoxazole due to additive bone marrow suppression. Both of these drugs are antimetabolite which cause suppression of DNA nucleotides.
Thymines and purines
46
Indication for Ciclosprin
Acute steroid resistance sever UC including toxic megacolon.
47
Form Cyclosporin is given in.
IV infusion
48
Cyclosporin main metabolism pathway.
CYP3A4
49
Cyclosporin monitoring
U&E (magnesium, K+), blood lipids, renal function, liver function, blood pressure, dermatological and physical examination.
Cyclosporine concentration at trough level.
50
What are the warning signs associated with cyclosporine
Neurotoxicity: tremor, headache, encephalopathy.
Blood disorders: fever, sore throat.
Liver toxicity: jaundice
Hypertension.
51
Cyclosporin affects on electrolytes and why.
In distal consulted tubule. Cyclosporin inhabits Mg2+ channels reabsorbing magnesium: hypomagnesia. It inhibits the RAAS system causing retention of K+ hyperkalemia and reduction in sodium and water reabsorption.
52
In sever liver impairment how would you manage the dosing of ciclosporin.
Dose reduction.
53
Which agent is likely to reduce cyclosporin levels.
(a) Grapefruit
(b) John’s Wart
(c) Smoking
(d) Carbamazepine
(e) Itraconazole
(d) + (b) CYP3A4 inducers.
54
Which agent is likely to increase cyclosporin levels.
(a) Grapefruit
(b) John’s Wart
(c) Smoking
(d) Carbamazepine
(e) Itraconazole
(a) + (e) are inhibitors of CYP3A4.
55
Patient presents with new onset confusion and tremor. You are on the ward and have taken a drug history, you find that the patient is on:
- Ciclosporin 120 mg IV
- Ibuprofen OTC for headache 2 days ago.
What is the likely explanation for her presentation.
Ciclosprorin toxicity due to decreased renal perfusion owing to NSAID administration leading to accumulation of cyclosporin.
56
Warfarin MAO
Inhibits Vit K dependent epoxide reductase activity, which modifies FVII, FIX, FX, and prothrombin (FII) during synthesis in liver.
57
Warfarin: Inhibits the intrinsic coagulation cascade…
True Or False
True
58
Warfarin Pharmacokinetic parameter and cautions
99% albumin bound, taking 1-3 days to see full effect.
Metabolised by CYP2C9 and CYP3A4.
Elimination is 20-60 hours but varies due to high patient inter-variability (CYP2C9 deficient).
59
What type of PK interaction does warfarin experience.
PK interaction involves albumin displacement and CYP enzymes.
60
Which drug from this list increase the INR when on Warfarin.
(a) Alcohol
(b) Carbamazepine
(c) Phenytoin
(d) Erythromycin
(d) Macrolide are inhibitors of CYP3A4.
61
Which drug from this list decreases the INR of warfarin.
(a) Amiodarone
(b) Phenytoin
(c) Clarithromycin
(d) Vancomycin
(b) Phenytoin.
62
Which drug from this list decreases the INR of warfarin due to albumin displacement.
(a) Amiodarone
(b) Phenytoin
(c) Aspirin
(d) Vancomycin
(C) Aspirin has a high ability to displace as well as its ability to increase bleeding risk.
63
Which drug should be avoided due to Antiplatelet effect when on warfarin
(a) prednisolone
(b) methotrexate
(c) Venlafaxine
(d) Miconazole
(c) Venlafaxine: SNRI
64
Which antidepressant should be avoided when used with warfarin due to anticoagulant effect.
(a) prednisolone
(b) Mirtazapine
(c) Venlafaxine
(d) Miconazole
(b) Mirtazapine (TCA and mirtazapine enhance anticoagulant effect).
65
Which drug should be avoided due to increased bleeding risk.
(a) prednisolone
(b) methotrexate
(c) Venlafaxine
(d) Clopidogrel
66
Warfarin: What is significance of reducing INR?
Increased risk of thrombotic event.
67
Warfarin: What is the significance of increasing the INR?
Risk of hemorrhagic event.
68
What key considerations are made when dosing individual on warfarin?
Age
Ethnicity
Other disease states e.g. liver disease.
Life-style: Drinker, Smoker?
Diet: High vitamin K diet (e.g. binge brocoli).
69
Warfarin: Caution/C/I
Teratogenic: Avoid in pregnancy
Significant bleeding.
70
Warfarin adverse effect:
Bleeding: spontaneous epistaxis and retroperineal bleeding, Alopecia.
71
Warfarin: Monitoring before and during
★ Before: Baseline prothrombin time.
★ At start: daily or alternate days determine the INR , then longer intervals depending on response, then up to every 12 weeks.
72
What is the maximum time between monitoring INR for patient with good response on Warfarin.
(a) 12 weeks
(b) 6 weeks
(c) 4 weeks
(d) 2 months
(e) 3 months
(a) 12 weeks.
73
Warfarin: Key counselling to patient.
★ Discuss patient warfarin treatment is balance between benefits (preventing clots) and risk (bleeding).
★ Educate patient on food, drug, alcohol interactions and to call doctor/pharmacist if see bruises and signs of bleed (e.g. blood in stool-dark colour).
★ Mention the yellow book is essential as regular blood test are required to ensure safety whilst on treatment. Explain rat poison issue.
74
What dietary advice with warfarin
☆ Green leafy vegetables: don’t binge, but keep it consistent.
☆ Cranberry juice.
☆ Don’t take garlic supplements: Increase INR.
75
Garlic interacts with warfarin
a. True
b. False
a. True advice patient to stop taking it because it increase bleeding risk.
76
How is warfarin introduced in AF.
Slow-loading regimen is done over 3-4 weeks with Warfarin 1 mg or 2 mg daily is generally an acceptable starting dose. The average daily maintenance dose is usually around 5 mg daily.
77
How is warfarin introduced in acute VTE
Heparin or a low molecular weight heparin is given concurrently — this is done in secondary care. Warfarin is inducted at 5 mg titrated according to patient response 2-15 mg daily.
78
Warfarin INR range: VTE and AF
79
Warfarin INR: mechanical valves
80
Antidote for warfarin: dose and onset of action
Vitamin K injection
81
Digoxin indication
Atrial fibrillation or flutter.
Heart failure
Emergency loading dose for atrial fibrillation or flutter.
82
Digoxin Therapeutic Range
0.7 to 2 ng/mL (wide inter-individual variations).
83
How do you start digoxin (dose)
Loading dose of 250 micrograms to 750 micrograms for 7 days followed by maintenance dose 125 micrograms-250 micrograms adjusted according to renal function and heart rate response.
84
What is max maintenance dose of digoxin.
(a) 250 micrograms
(b) 125 micrograms
(c) 300 micrograms
(d) 150 micrograms
(a) 250 micrograms daily
85
When would you suspect DigToxicity.
(a) 0.5 nanogram/mL
(b) 3.0 nanograms/mL
(c) 3.0 nanograms/L
(d)1.5 nanogram/mL in presence of hypokalemia
(e) 0.8 nanograms.
(f) 1.8 nanograms/L nanograms
(b) 3.0 nanograms/mL + (d) 1.5 nanogram/mL in presence of hypokalemia because dig toxicity is more pronounced in hypokalemia due to less competition to bind to sodium potassium pump.
86
What are the symptoms of DigToxicity.
Confusion, nausea, anorexia, visual colour disturbances.
87
What is the antidote for DigToxicity
DigiFab antibody
88
Monitoring for Digoxin
(a) Routine monitoring
(b) Monitoring when patient presents with confusion and visual colour disturbances
(c) Monitoring when patient is on amiodarone or diltiazem
(d) Monitoring when patient comes in for regular blood pressure and heat rate monitoring.
(b) and (c)
89
Lithium indication.
Treatment and prophylaxis bipolar disorder.
90
Therapeutic range for Lithium
0.6-1 mmol/L.
91
Lithium main route of elimination.
Renal; 80% reabsorbed.
92
When do you not prescribe lithium
Cardiac disease associate with rhythm disorders.
Significant renal impairment.
Untreatable hypothyroidism + Addisons disease.
93
How does lithium cause hypo/hyperthyroidism.
Lithium concentrates by the thyroid and inhibits thyroidal iodine up-take.
94
How does lithium cause hypercalcaemia and what are the potential clinical implications.
Increase circulation of calcium due to increase reabsorption at the loop of Henle —> Increase circulation parathyroid hormone (PTH) which can lead to bone thinning and kidney stones.
95
How does lithium cause hyponatremia
Competitively taken up by sodium re-uptake (more than Na+) via the Na+/H+ co-transporters in the proximal tubules and then accumulates in the renal tubules. Also competitively taken up by the Na+ channels located in the loop of Henle.
96
How does lithium cause Nephrogenic diabetes insipidus.
By inhibiting arginine vasopressin from increase the reabsorption of water through the AQ2 channel.
97
What are the formulation considerations that need to take place when using lithium.
Lithium available in two salts: lithium carbonate and lithium citrate. They are not dose equivalent.
Always prescribe by brand name.
98
Increase lithium concentration is more likely with
(a) Thiazide diuretics
(b) Loop diuretics
(c) Spironolactone
(a) More likely with thiazide diuretics, loop diuretics are less likely to result in lithium toxicity.
99
Which agent when combined with lithium is likely to cause neurotoxicity.
(a) Ibuprofen
(b) ACE-inhibitor
(c) Dapagliflozin
(d) Duloxetine
(e) Carbamazepine
(e) Carbamazepine, SSRI/duloxetine have been linked rarely to CNS toxicity.
100
Which agent when combined with lithium is likely to decrease lithium levels due to increase lithium renal clearance.
(a) Ibuprofen
(b) ACE-inhibitor
(c) Dapagliflozin
(d) Duloxetine
(e) Carbamazepine
(c) SGLT-2 inhibitor because sodium is not being reabsorbed via the SGLT2 pump.
101
Monitoring for lithium
One week after treatment lithium levels are taken 12 hours post-dose.
BMI, U&E, TFT, eGFR, Ca2+ then every 6 months.
102
What are the signs of lithium toxicity
CNS disturbances: Lethargy, dizziness, lack of coordination, tinnitus
GI: diarrhoea, vomiting, anorexia
PNS: Muscle hyper irritability.
103
Lithium toxicity occurs at:
(a) 1.2 mmol/L
(b) 1.5 mmol/L
(c) 0.8 mmol/L
(d) 1.0 mmol/L
(b) 1.5 mmol/L
104
What advise should patient receiving lithium be given.
Carry lithium card.
Regular blood test.
Adverse effects.
Maintain fluid intake.
Avoid OTC NSAIDs.
105
Indication for Ciclosprin
Acute steroid resistance sever UC including toxic megacolon.
106
Form Cyclosporin is given in.
IV infusion
107
Cyclosporin main metabolism pathway.
CYP3A4
108
Cyclosporin monitoring
U&E (magnesium, K+), blood lipids, renal function, liver function, blood pressure, dermatological and physical examination.
109
What are the warning signs associated with cyclosporine
Neurotoxicity: tremor, headache, encephalopathy.
Blood disorders: fever, sore throat.
Liver toxicity: jaundice
Hypertension.
110
Cyclosporin affects on electrolytes and why.
In distal consulted tubule. Cyclosporin inhibits Mg2+ channels reabsorbing magnesium: hypomagnesemia. It inhibits the RAAS system causing retention of K+ hyperkalemia and reduction in sodium and water reabsorption.
111
In sever liver impairment how would you manage the dosing of ciclosporin.
Dose reduction.
112
Which agents is likely to reduce cyclosporin levels.
(a) Grapefruit
(b) John’s Wart
(c) Smoking
(d) Carbamazepine
(e) Itraconazole
(d) + (b) CYP3A4 inducers.
113
Which agent is likely to increase cyclosporin levels.
(a) Grapefruit
(b) John’s Wart
(c) Smoking
(d) Carbamazepine
(e) Itraconazole
114
Patient presents with new onset confusion and tremor. You are on the ward and have taken a drug history, you find that the patient is on:
- Ciclosporin 120 mg IV
- Ibuprofen OTC for headache 2 days ago.
What is the likely explanation for her presentation.
Ciclosprorin toxicity due to decreased renal perfusion owing to NSAID administration leading to accumulation of cyclosporin.
115
Theophylline (aminophylline) therapeutic range.
10-20 mg/L
116
Theophylline mechanism of action.
Main action is through inhibition of PDE4 that results in reduced inflammatory response mediated by alveolar macrophages.
117
Theophylline undesirable side effects.
Seizure
Tachycardia
Headaches
Nausea
118
Major route of elimination for theophylline
Liver metabolism.
119
Major enzyme metabolising theophylline.
CYP1A2.
120
Major lifestyle interaction with theophylline.
Cigarette smoking induces CYP1A2 enzymes reducing theophylline concentration.
121
Major pharmacodynamic interaction with theophylline.
(a) Beta-2-agonist +theophylline
(b) Phenytoin + theophylline
(c) Allopurinol + theophylline
(d) erythromycin+ theophylline
(e) cigarette + theophylline
(a) major pharmacodynamic interaction they both increase risk of hypokalemia.
122
Drug-disease interaction where theophylline concentration increases.
(a) Asthma + theophylline
(b) Heart failure + theophylline
(c) Chronic renal disease +theophylline
(e) Hypothyroidism +theophylline.
(b) Heart failure decreases the flow of blood to the liver therefore there is increased concentration of theophylline.
123
Which drug increases the plasma concentration of theophylline.
(a) carbamazepine
(b) ritonavir
(c) erythromycin
(d)corticosteroids.
(c) Macrolide increases the plasma concentration of theophylline.
124
Which drug increases the risk of convulsions with theophylline.
(a) Ciprofloxacin
(b) Cimetidine
(c) Carbamazepine
(d)Primidone
(a) Ciprofloxacin has seizure potential.
125
Which drugs decreases the concentration of theophylline.
(a) ciprofloxacin
(b) diltiazem
(c)phenytoin
(d)oestrogen
(c) phenytoin, is an inducer therefore decreases theophylline concentration.
126
What are the monitoring requirements for initiating Theophylline.
Before starting:
LFTs
Urea and electrolytes [K+]
Smoking status
After:
Take plasma concentration of theophylline 5 days after treatment then 3 days after any dose adjustment.
Once stable: when signs toxicity, adherence issue or drug-drug interaction.
127
What are the symptoms of theophylline toxicity.
CNS/cardiac/GI
Nausea
Vomiting
Tremor
Sinus tachycardia.
Dilated pupils
