High Risk Drugs Flashcards
1
Q
Therapeutic Drug Monitoring: Digoxin - Target ? Level Taken ?
A
Target Level: 1-2 mcg/L
Levels Take: 6 hours post-dose
2
Q
Digoxin Indications
A
cardiac glycoside - controls rate
- AF: loading dose required
- HF: no loading dose required
can control rate at REST so is good for pts with sedentary lifestyle (elderly etc)
3
Q
Digoxin Contraindications
A
Heart Block
Ventricular arrhythmias
4
Q
Digoxin Cautions
A
Renal Failure - potassium management + drug metabolism
Hypokalaemia
Thyroid Disease
Recent Mi
5
Q
Digoxin Interactions
A
Drugs that cause hyPOkalaemia
- loops & thiazides, salbutamol, steroids, theophylline
Drugs that INCREASE concentrations:
- Amiodarone, Dronedarone, Quinine (1/2 dose)
- Rate Limiting CCBs
- Macrolides (e.g. enzyme inhibitors)
- Ciclosporin
Enzyme Inhibitors/Inducers
Drugs that REDUCE renal excretion/impair kidneys
- NSAIDs
- ACE/ARBs
6
Q
What electrolytes can increase the risk of digoxin toxicity?
A
Hypokalaemia
Hypomagnesia
Hypercalcaemia
7
Q
Digoxin Toxicity symptoms ?
A
- Bradycardia/Heart Block
- Nausea, Vomiting, Diarrhoea
- Confusion, Delerium
- Rash
KEY SYMPTOM: blurred vision, YELLOW vision
Also:
- Hypokalaemia
- Arrythmias/ECG changes
8
Q
Digoxin Monitoring
A
RENAL FUNCTION
Potassium Levels
levels - only when toxicity suspected/renal impairment
9
Q
Digoxin Toxicity Management
A
withdraw treatment + correct electrolytes
severe + life-threatening: Digoxin-Specific Antibody
10
Q
Amiodarone - Indications + Doses
A
Treatment of Arrhythmias
loading doses:
- 200 mg TDS for 1 week
- 200 mg BD for 1 week
- 200 mg OD for 1 week
11
Q
Amiodarone - Contraindications
A
- Conduction Issues
- Bradycardia
- Severe Hypotension
- Iodine Sensitivity/Hyper-Hypothyroidism
12
Q
Amiodarone - Interactions
A
interactions can happen for MONTHS after stopping because of 50 day half-life
Amiodarone = is an enzyme INHIBITOR
- NTI drugs - increased concs of Warfarin, Digoxin etc.
- Grapefruit Juice
- Statins = myopathy
- B Blockers/Other Anti-arrhythmic = cardio depression + bradycardia
- Drugs that prolong the QT
13
Q
Amiodarone - what drugs do you have to reduce the dose of if given alongside?
A
Digoxin (half dose)
Diltiazem + Verapamil
due to serious bradycardia, AV block, heart failure
14
Q
Amiodarone - Side Effects
A
BITCH x 2
B - blue man syndrome (slate-grey skin on light-exposed areas)
B - bradycardia
I - interstitial lung disease/pulmonary fibrosis
I - impaired movement, nerves, peripheral neuropathy
T - thyroid
C - corneal micro deposits/optic neuropathy
C - cutaneous photosensitivity
H - heart block
H - hepatitis
15
Q
Amiodarone - Monitoring Requirements
A
Chest X Ray (before + 6 months) LFTs (before + 6 months) Thyroid (before + 6 months) Potassium (before) Eye Tests (before + annual)
16
Q
Amiodarone - Counselling Points
A
Lungs - report SOB + cough
Eyes - night time glares when driving, if impaired vision = STOP
Skin - shield from light + use high SPF (and months after stopping due to long half life)
Nerves - report any numbness/tingling in the hands and feet
17
Q
Warfarin INR Targets
A
2.5 (2-3) - for all except:
recurrent VTE in patients receiving anticoagulation + mechanical heart valve = 3.5 (3-4)
18
Q
Warfarin pre-operative management
A
stop Warfarin 5 days before surgery
if high risk - start LMWH 3 days after stopping Warfarin (duration of action) + then omit 24 hours before surgery
19
Q
Warfarin MHRA Alerts
A
Calciphylaxis - build up of calcium in fat + skin tissues, common in patients with renal disease
presents as a painful rash
20
Q
Key Warfarin Interactions
A
- Bleeding Drugs - DOACs, LMWHs, SSRIs, Anti-platelets, NSAIDs
- Daktarin - Miconazole OTC
- Amiodarone
- Antibiotics - affects the Vit K of the gut
- Green Leafy Veggies + Green Tea
- Pink Juices = pomegranate, cranberry
- Inducers/Inhibitors (incl. smoking)
21
Q
What to do when INR out of range for Warfarin
A
MAJOR bleeding = stop warfarin, Phytomenadione IV + prothrombin complex
INR OVER 8:
- no bleeding = stop Warfarin + PO Vit K
- minor bleeding = stop Warfarin + IV Vit K
INR 5-8:
- no bleeding = withhold 1/2 doses and reduce maintenance
- minor bleeding = stop Warfarin + IV Vit K
22
Q
How often should INR for Warfarin be monitored?
A
- initiation: daily/alternate days
- stable: every 3 months
23
Q
Warfarin - Key Counselling Points
A
- take at tea time ideally - accurate INR testing in the morning
- can take dose up to 5 hours after original time
- yellow book + anticoagulation card
- dietary changes - green veggies etc
- sickness + diarrhoea can affect the absorption
- alcohol - safe to consume 1-2 units per day
- changes in smoking can affect
24
Q
Warfarin Side Effects
A
- BLEEDING!
- Calciphylaxis - a painful rash
- Abnormal Liver Function
25
Water Soluble Β Blockers
CANS (watering cans)
- Celiprolol
- Atenolol
- Nadolol
- Sotalol
26
Long Duration of Action B Blockers
CANB (can B extremely long)
- Celiprolol
- Atenolol
- Nadolol
- Bisoprolol
27
Cardio-selective B Blockers
MANB (MEN think they're good at CARDIO)
- Metoprolol
- Atenolol
- Nebivolol
- Bisoprolol
28
Theophylline levels
10-20, but 5-15 can be effective
but side effects can still occur in this therapeutic range
take levels 4-6 hours after dose (PEAK level)
measure levels 5 days after starting treatment, 3 days after dose adjustments
29
Theophylline Toxicity
FAST
- tachycardia, agitation, restlessness, CONVULSIONS, dilated pupils, hyperglycaemia
SICK
- vomiting, GI, diarrhoea, gastric irritation
30
Theophylline Side Effects
- Hypokalaemia
- Anxiety, Palpitations, Arrhythmias, Sleep Disorders, Tremor
- GI discomfort
- Headache, Dizziness, Seizures, Nausea + Vomiting
31
Theophylline Cautions
- cardiac arrythmias - can cause
- elderly - increased concentrations
- epilepsy - can cause convulsions
- fever
- peptic ulcer
- risk of hypokalaemia
- thyroid disorder (tachycardia etc)
32
Theophylline Interactions
SMOKING
- drugs that increase risk of hypokalaemia
- β blockers - risk of bronchospasm
- drugs that increase the risk of convulsions e.g. quinolones
- enzyme inducers
needs to be prescribed by BRAND
33
Carbamazepine Levels
4-12mg - measure after 1-2 weeks
34
Carbamazepine Toxicity
- incoordination
- hyponatraemia
- ataxia - involuntary movement
- nystagmus - eye rolling
- drowsiness
- blurred vision + diplopia (double vision)
- arrhythmias
- GI disturbance
think - exerting effects in the BRAIN so too much starts causing some symptoms that relate - movements + eye rolling
antidote: activated charcoal
35
Carbamazepine Contraindications/Cautions
C/I
- AV conduction abnormalities
- Hx of BONE MARROW SUPPRESSION
Cautions
- Cardiac Disease
- Hx of Haematological Reactions
- Skin Reactions
- Angle-Closure Glaucoma
36
Carbamazepine Prescribing
HAS to be by brand
cross-allergy with phenytoin, primidone, phenobarbital = all the CP3 branded drugs
also test for allele in Han Chinese/Thai origin !!!!! due to risk of Steven Johnson's Syndrome
37
Carbamazepine Side Effects
LIVER DYSFUNCTION = withdraw immediately due to hepatotoxicity
SEVERE LEUCOPENIA - blood dyscrasia withdraw immediately
HYPERSENSITIVITY + SKIN RASHES - report immediately, particularly Han Chinese/Thai patients
- Hyponatraemia = can lead to water intoxication
- Major Congenital Malformations
38
Carbamazepine Interactions
Carbamazepine = ENZYME INDUCER, reduces efficacy of drugs e.g. Warfarin, Contraceptives, DOACs
Drugs that also cause bone marrow suppression
Enzyme inhibitors that increase concentrations = toxicity
Drugs that increase the risk of seizures (quinolones, mefloquine, SSRIs, antipsychotics, TCAs)
Drugs that increase risk of HYPOnatraemia
Drugs that increase risk of HEPATOTOXICITY
39
Carbamazepine Monitoring
- Therapeutic Drug Monitoring - 1-2 weeks after
- Blood Counts
- Hepatic Function
- Renal Function
40
Carbamazepine Counselling
BLOOD DYCRASIAS - report immediately fever, sore throat, mouth ulcers, unexplained bruising/bleeding
HEPATOTOXICITY - report signs of jaundice, dark urine etc.
RASHES - risk of SJS
CONTRACEPTION = reduced efficacy
41
Phenytoin Contraindications/Cautions
Contraindications:
- Heart Block, Sinus Bradycardia when used IV - if too rapid infusion risk of death/severe harm due to bradycardia, CV collapse etc.
Cautions:
- enteral feeds - due to protein content + binding of drug
- EXACERBATES ABSENCE/MYOCLONIC SEIZURES
- IV = heart issues/resp depression
42
Phenytoin Prescribing
HAS to be by brand
have to screen Han Chinese/Thai patients prior to treatment for the allele that pre-disposes them to SJS/hypersensitivity
phenytoin liquid is NOT same as tablets
IM - not to be used (fosphenyotoin instead )because absorption is erratic
supplement Vitamin D
43
Phenytoin Interactions
Phenytoin is an enzyme INDUCER - so will reduce efficacy of contraceptives, warfarin, DOACs, levothyroxine
- enzyme inhibitors = risk of phenytoin toxicity
- enzyme inducers = low phenytoin level
- seizure-threshold lowering drugs = quinolones, tramadol, mefloquine, SSRIs, antipsychotics, TCAs
- increased risk of blood dyscrasias = antifolates, immunosuppressants, DMARDs etc, but phenytoin is an ANTIFOLATE so particularly the folates
44
Phenytoin Side Effects
- RASH = discontinue !!!!!! - Han Chinese/Thai at higher risk
- appearance changes = coarsening of facial features, acne, hirsutism, GINGIVAL hypertrophy
- blood dycrasias - antifolaxe
- hypersensitivity syndrome
- LOW VITAMIN D - induces the metabolism
- HEPATOTOXIC - discontinue immediately
- Congenital Malformations
45
Phenytoin Levels
10-20 - TROUGH level
kinetics are NON-LINEAR (0 order kinetics) which means doubling dose DOESN'T mean double the concentration, unpredictable concentrations
highly protein bound - so when albumin is low need to measure free-drug concentration
- proteins levels change in pregnancy, liver impairment, elderly, neonates
46
Phenytoin Monitoring
- Therapeutic Drug Monitoring (Trough - at 10 days)
- ECG + Blood Pressure
- Full Blood Counts
- Liver Function
- Folate
- Vitamin D
47
Phenytoin Toxicity
- slurred speech
- nystagmus (eye rolling)
- ataxia (lack of co-ordination)
- confusion
- hyperglycaemia
- blurred vision, double vision
difference between carbamazepine + phenytoin = carbamazepine is hypoNATRAEMIA and phenytoin in hyPERglycaemia
Carbamazepine = GI effects
48
Sodium Valproate Contraindications/Cautions
Contraindicated
- Mitochondrial Mutations = higher risk of liver failure
- Hx/Family Hx of Hepatic Dysfunction
- Urea Cycle Disorders (liver)
- PREGNANCY
Cautions
- Systemic Lupus Erythematosus
- Liver Toxicity - usually occurs within the first 6 months
MHRA = contraindicated in women/girls of child-bearing age unless terms of the PPP being met
- highly effective contraception
- annual review + re--evaluation of treatment
- sign a risk acknowledgement form yearly
49
Sodium Valproate Interactions
Sodium Valproate = INHIBITOR
- increased concentrations of OTHER AEDs
```
Lamotrigine = risk of rash due to increased exposure
Topiramate = risk of toxicity
Olanzapine = increased risk of adverse effects
```
Drugs that lower seizure threshold = quinolones, TCAs, tramadol, SSRIs, Mefloquine, Antipsychotics
Drugs that can cause blood dyscrasias
Drugs that are hepatotoxic
50
Sodium Valproate Side Effects
HEPATOTOXICITY - discontinue
BLOOD DYSCRASIAS
PANCREATITIS
MAJOR CONGENITAL MALFORMATIONS
51
Sodium Valproate Monitoring
Monitor LFTs before + 6 months
| Full Blood Counts
52
Sodium Valproate - Conditions of the PPP
have to exclude pregnancy
be on a form of HIGHLY EFFECTIVE contraception
- 1 user independent
- 2 user dependent
sign the risk acknowledgement form annually
53
Sodium Valproate - Counselling
- signs of hepatotoxicity
| - signs of bone marrow suppression
54
Sodium Valproate Prescribing
if under the PPP:
7 day prescription validity
maximum 30 days supply
emergency supply - refer to specialist prescriber if under the PPP
Category 2 - try and maintain on the same brand
1st Line in all generalised seizures
55
Lithium Contraindications/Cautions
C/I
- Addison's disease
- Cardiac Disease
- Dehydration
- Low Sodium Diets
- Untreated Hypothyroidism (can cause)
Caution:
- Epilepsy - may lower seizure threshold
- Diuretics (lowers sodium)
- Myasthenia Gravis
- Psoriasis
- QT prolongation
- N&V/Diarrhoea - due to dehydration
56
Lithium - Interactions
- drugs that lower seizure threshold
- drugs that prolong the QT
- drugs that cause hypokalaemia (and increase risk of arrhythmias)
- nephrotoxic drugs
- drugs that cause hyponatraemia/affect salt balance
- increased risk of neurotoxicity
- increased risk of serotonin syndrome
- drugs that can cause EPSEs - antipsychotics, metoclopramide
57
Lithium - Side Effects
- Thyroid Disorders long term
- RENAL impairment = nephrotoxic
- BENIGN INTRACRANIAL HYPERTENSION
- QT PROLONGATION
- LOWERS SEIZURE THRESHOLD
- tremor
- metallic taste/taste disturbances
- weight gain
- ankle swelling
- thirsty + pass more urine
58
Lithium - Toxicity
REVENGE
- Renal Disturbances
- Extrapyramidal Symptoms (tremor, muscle weakness, nystagmus)
- Visual Disturbances
- Nervous System
- GI Effects
59
Lithium Levels + Monitoring
Target: 0.4-1 - TROUGH level taken after 12 hours (take in the evening so that a blood sample can be taken in the morning)
acute = aim for higher end of 0.8-1
take levels WEEKLY, then 3 MONTHLY when stable (and some people can go to 6 monthly)
3 monthly people:
- all over 65
- on drugs that interact
- impaired renal/thyroid
- raised calcium
- poor symptom control/adherence
- last level 0.8 or higher
60
Lithium Monitoring
Thyroid - baseline + 6 months
BMI - baseline + 6 months
Electrolytes - baseline + 6 months
eGFR/Renal - baseline + 6 months
baseline = blood counts + cardiac parameters (arrhythmias etc)
61
Lithium Prescribing
always prescribe by BRAND
full prophylactic effect not seen for 6-12 months after initiating
taper dose over MINIMUM 4 weeks, but ideally 3 months
62
Lithium Counselling
- thyroid disorder symptoms
- renal impairment
- benign intracranial hypertension = HEADACHES
- fluid intake + dietary sodium
- always carry alert card for lithium
- DON'T take OTC Ibuprofen/soluble analgesics or antacids due to salt content
- stay hydrated in hot weather/exercising
63
Clozapine - MHRA Alerts
Risk of Intestinal Obstruction, Impaction + Paralytic Ileum which can be fatal
Blood Concentration Monitoring: carry out when
- changes to smoking habits
- when concomitant meds interact
- reduced clearance of Clozapine
- toxicity
64
Clozapine Contraindications + Cautions
Contraindications:
- Alcoholic/Toxic Psychoses/Drug Intoxication
- Bone Marrow Disorders
- Coma
- Uncontrolled Epilepsy
- Severe Cardiac Disorders
Cautions:
- over 60
- glaucoma
- prostatic hypertrophy
65
Clozapine Interactions
CHANGES to smoking !!!!
- drugs that cause bone marrow suppression
- drugs that cause hypotension
- drugs that increase risk of constipation = antimuscarinics, opioids, loperamide etc
66
Clozapine Side Effects
CARDIOMYOPATHY
BLOOD DYSCRASIAS
CONSTIPATION
Hypersalivation
Postural Hypotension
Weight Gain
Antimuscarinic = urinary disorders, blurred vision, dry eye, dry mouth, constipation
67
Clozapine Monitoring
AGRANULOCYTOSIS, monitor neutrophils
- Weekly for first 17 weeks
- then 2-weekly for 1 year
- then 4-weekly thereafter
- levels get sent to the manufacturer
MYOCARDITIS - fatal reports in the first 2 months
- stop + review
- tachycardia in the 1st two months to report
68
Clozapine Prescribing
good for treatment resistant schizophrenia - that is unresponsive to other drugs
patients can have when they've tried 1st Gen + a 2nd Gen for a sufficient period
withdraw GRADUALLY over 1-2 weeks to avoid rebound psychosis
69
Clozapine Counselling
- signs + symptoms of bone marrow suppression
- signs + symptoms of cardiomyopathy = tachycardia
- if MISSED 2 doses = will need to re-titrate
70
Vancomycin Indications
MRSA (gram positives)
C Diff (orally)
71
Vancomycin Contraindications/Cautions
C/I
- previous hearing loss
Cautions
- allergy to Teicoplanin
72
Vancomycin Interactions
- ototoxic drugs
| - nephrotoxic drugs
73
Vancomycin Side Effects
- Nephrotoxicity
- Ototoxicity
- Red Man Syndrome
- Blood Dyscrasis
- Skin Disorders
- Thrombophlebitis
- Cardiac Issues - cardiac arrest, cardiac shock
74
Vancomycin Monitoring
- periodic auditory testing
- blood counts
- urinalysis
- hepatic function
- renal function
75
Vancomycin Levels
10-20 mg/L
15-20mg for more severe/deep-seated infections
76
Gentamicin Indications
BROAD SPECTRUM - gram negative aerobes
77
Gentamicin MHRA Warnings
Ototoxicity - monitor hearing, those with mitochondrial mutations at higher risk
Nephrotoxicity - monitor renal function
Histamine-Related ADRs - some batches had higher amounts of histamine so monitor for signs of reactions
78
Gentamicin Contraindications/Cautions:
C/I
- Myasthenia Gravis
Cautions
- Auditory Disorders
- Conditions of Muscular Weakness
- Dehydration
- Vestibular Disorder
79
Gentamicin Side Effects
- Skin Reactions = Stevens Johnson's Syndrome
- Tinnitus
- Nausea/Vomiting
- Nephrotoxicity
- Impaired Neuromuscular Transmission (MG!)
- Hypokalaemia, Hypocalcaemia, Hypomagnaesia
- Abs associated Colitis
- Blood Disorders
80
Gentamicin Interactions
Nephrotoxic Drugs
Neuromuscular Blocking Effects
Ototoxic Drugs = Loops, Cisplatin, Vancomycin
81
Gentamicin Monitoring
MULTIPLE DAILY DOSING - need a peak (1 hr after) and trough
- peak target: 5-10
- trough target: < 2
if PEAK is too high = reduce the dose
if TROUGH is too high = extend the interval
82
Ciclosporin Indications
potent immunosuppressant - used for:
| - RA, UC, Atopic Dermatitis, Severe Psoriasis, Transplantation
83
Ciclosporin MHRA Alerts
HAS to be prescribed by brand
84
Ciclosporin Contraindications
- Malignancy
- Uncontrolled Hypertension
- Uncontrolled Infections
85
Ciclosporin Cautions
- Elderly
- Hyperuricaemia
- Active Herpes Simplex infections
- Psoriasis
- Dermatitis
86
Ciclosporin Side Effects
NEPHROTOXIC = kidneys
- Bone Marrow Suppression
- hyperglycaemia
- Hypertension (contraindication!)
- Electrolytes - hyperkalaemia + hypomagnesia
- Neurotoxicity - seizures, tremor, headache, encephalopathy
- liver toxicity
Differences to Tacrolimus:
- Gingival Hyperplasia
- Visual Disturbances = intracranial hypertension
- Hyperlipidaemia
87
Ciclosporin Interactions
Nephrotoxic Drugs: NSAIDs, lithium, diuretics, ACEs/Arbs
AVOID live vaccines
Risk of hyperkalaemia
Drugs that increase risk of hypertension
Digoxin - dose adjustments (kidneys)
Colchicine - AVOID
Statins - AVOID
Grapefruit, Pomelo, Purple Grapefruit juices
88
Ciclosporin Monitoring
- LFTs
- K
- Mg
- Lipids prior to tx + 1 month after starting
- KIDNEYS!
- Blood Pressure = DISCONTINUE if hypertension develops
89
Ciclosporin Counselling
- avoid excessive sunlight
- increased risk of blurred vision
- grapefruit
90
Tacrolimus Indications
- prevention of rejection
91
Tacrolimus MHRA alert
PRESCRIBE BY BRAND
92
Tacrolimus Contraindications
Topical Only - malignant skin lesions, eyes, mucous membranes, immunodeficiency, infection at treatment site
93
Tacrolimus Cautions
- UV Light
- Increased risk of Infection
- Malignancies
- Neurotoxicity
- QT prolongation
- ALLERGY TO MACROLIDES !!!!!
94
Tacrolimus Interactions
- nephrotoxic drugs
- tacrolimus + ciclosporin
- drugs that increase risk of hyperkalaemia
95
Tacrolimus Side Effects
same as Ciclosporin
- Kidney Impairment
- Liver Impairment
- Bone Marrow Suppression
- Neurotoxicity (tremor + headache)
- Hyperglycaemia
Differences:
- CARDIOVASCULAR - QT, arrhythmias, myopathy
- Skin Reactions
- Eye Disorders
report ANY signs + symptoms to the doctor
96
Tacrolimus Monitoring
- ECG
- Blood Pressure
- Hepatic Function
- Renal Function
- Fasting Blood Glucose
- Electrolytes
- Blood Counts
