Therapeutic drug monitoring & High risk drugs Flashcards
What is the difference between HYPERglyceamia and HYPOglyceamia symptoms?
HYOGLYCEAMIA-Think how you feel if you have not eaten sugar for a while:Dizzy, head hurts, shaky, hungry, cannot see or think straight, sweatyHYPERGLYCEAMIA:Just think how you feel if you’re BUZZING:Dry mouth, need water, lots of weeing, wetting bed, stomach painblood glucose concentration ishigh so fluid moves out of cells into circulation due to osmosis so you get dehydration
What is an ionotrope? What is a positive and what is a negative ionotrope?
A drug that alters the force or energy of heart contractionsSo positive ionotrope (e.g. Digoxin, Amiodarone): increases force of contractions of heart, used in conditions such as decompensate Heart Failure, shock (severe hypotension)and Myocardial Infarction as they get blood pumping again!NB: these do not increase rate, digoxin actually decreases the rate, just increase force of contraction. Digoxin used as rate control in AF, Amiodarone used as Rhythm.Negative ionotropes: decrease force of contractions of the heart, used in conditions such as Hypertension to bring blood pressure down and Angina. Examples: Rate limiting CCB’s, cardio-selectivebeta blockers e.g. bisoprolol, carvedilol, metoprolol, some anti-arrhythmics such asflecainide
What is the desired serum concentration of Digoxin?
1 - 2 mcg / L
What is the difference between bradycardia and tachycardia? What is the the classified pulse rate for these?
Bradycardia: slow heart rate: pulse under 60 bpmTachycardia: fast heart rate: pulse over 100 bpm
What are the symptoms of DIGOXIN toxicity? (i.e. levels over 2 mcg/ L)
Gastro:Nausea and vomittingAbdominal painAnorexia (weight loss)
Cardiac:Bradycardia- (HR under 60 bpm) heart slowed down too much by digoxinArrythmias (irregular heart beat)
Mental:Delirium (confusion)
Visual disturbance- blurred, seeing yellow, blind spots
Digoxin needs close monitoring. It slows the heart rate, but increases the force of contraction. We need to monitor the heart rate: When should we be worried?
If it falls below 60 BPM (i.e. becomes bradycardic)
We need to monitor the plasma concentration of Digoxin closely. When should levels be taken?
at least 6 HOURS after a dose given
Digoxin toxicity can be fatal. What electrolyte imbalance can precipitate digoxin toxicity?
HYPOKALEAMIA is a big one. We manage this by giving K+ sparing diuretics (e.g. spironolactone) and K+ supplements. Hypomagnesaemia Hypocalcaemia
How is digoxin excreted? Therefore what do we need to monitor and decrease dose if impaired?
Renally decrease dose if patient has renal impairment
What is digoxin used in?
Most use in persistent & permanent Atrial Fibrilation as RATE control
Has a role in Heart FailureRole in Atrial flutters
Amiodarone is used in the rhythm control of AF.Digoxin is used as rate control.interaction between these 2 drugs?
Amiodarone INCREASES plasma concentration of digoxin It is an ENZYME inhibitor but not one of the P450’s (so not part of SICKFACES)
Digoxin dose needs to be decreased by 50% if given with Amiodarone
Digoxin is metabolised by the CYP450 enzyme system, primarily 2C19. It therefore has many interactions. Can you think of any drugs that increase its concentration?
Macrolides: ErythromycinClarythromycin, Azithromycin
Ciclosporin
Itraconazole
Amiodarone (but not through CYP)
Rifampicin and St Johns Wort are both CYP450 enzyme inhibitors. What TDM drug do they reduce the concentration of?
Digoxin
Why does Digoxin interact with Diuretics?
Diuretics (Loop and thiazide/ thiazide- like) may cause HYPOKALEAMIADigoxin toxicity is precipitated by HYPOkaleamiaTherefore be careful with:Furosemide, Bumetanide Bendroflumethiazide, indapamide, chlortolidone
Potassium sparing diuretics are Okay:Amiloride TriamtereneSpironolactone (this can increase [Digoxin]), Eplerenone
What drugs other than diuretics can interact with digoxin due to their Hypokaleamic effects?
Amphotericin (Antifungal!)
Can you think why ACE inhibitors and NSAID’s interact with digoxin?
Remember digoxin is excreted renally and caution in kidney impairmentACE inhibitors and NSAID’s can both decrease kidney function and precipitate digoxin toxicity
What happens if a CCB is administered to someone on Digoxin?
Plasma conc of digoxin increased by:Diltiazem Nicardepine Nifedipine Verapamil
(also increases risk of AV BLOCK & bradycardia [slows rate])
What are the signs of Lithium toxicity?
GI disturbance warning signs: Vomitting, Diarrohea
Then Mostly CNS effects: Fine Tremor to start then coarse tremor, Involuntary movement (ataxia) Involuntary eye movement (Nystagmus)
Blurred vision
Thirst- due to hypernatreamia
Severe toxicity (level over 2 mmol/L): ConvulsionsComaRenal failuire
Lithium can cause problems in some of our organs. What are these, what would be the signs if their function had altered?
Kidney- monitor renal function
Sign of decline: Polyuria, Polydipsia
Thyroid - usually hypothyroidism Signs: unexplained fatigue
Benign intracranial hypertension (high BP in brain) Signs: persistent headache, visual disturbance
You know the target range for lithium is 0.4 - 1.0 mmol/L.What is the target in acute episodes of mania?
0.8 - 1.0 mmol/ L- upper end of the range!
What three drugs do you legally have to provide a patient alert card with?
Lithium Steroids Anticoagulant
Lithium interacts with ACE inhibitors/ ARB’s NSAIDS What is this interaction?
Ace inhibitors / ARB’s and NSAIDs can decrease renal perfusionLithium excreted by Kidneys
Lithium levels risk= lithium toxicity
Why does Lithium interact with the Diuretics (loop, thiazide AND potassium-sparing)?
Diuretics can cause electrolyte disturbance Hyponatreamia may be a result Lithium levels influenced by sodium levels- lithium toxicity
Which antibiotic could possibly cause Lithium toxcity/ levels to rise?
Metronidazole
Please note there is increased risk of _____ when Lithium is given with things like _____, _________, __________ & ______________
There is increased risk of ____ when Lithium is given with ________
Please note there is increased risk of neurotoxicity when Lithium is given with things like methyldopa, phenytoin, carbamazepine & the rate limiting CCB’s diltiazem and verapamil
There is increased risk of EPSE’s when Lithium is given with antipsychotics
What type of seizures can phenytoin be used in?
Focal Tonic- clonic Myoclonic But not first/ 2nd line in any. Its use is fizzling out.
All types of seizure but Absent!
Desired therapeutic range for Phenytoin?Why is it so important to monitor phenytoin levels?
10 - 20 mg/ L= 40- 80 micromol/L
Non-linear relationship between dose and plasma conc: small change in dose= big change in conc
What are the symptoms of Phenytoin toxicity?
CNS: Nystagmus (involuntary eye movement) Ataxia (involuntary body movement)Slurry speech
Confusion
suicidal thoughts
HYPERGLYCEAMIA
Double vision (diplopia), blurred vision
NB: Similar to Lithium toxicity: remember the differentials (hyperglyceamia, no convulsions)
Phenytoin is related to SKIN & BLOOD disordersWhat does the patient need to look out for?
Skin- look out for RASH
Phenytoin also causes: HIRSUTISM (excess hair growth)
gingival hypertrophy (enlarged gums)
acne
Blood disorder: Fever, sore throat, mouth ulcers, bruising, bleeding
With phenytoin, we should monitor ________ &______ with IV use. Should also monitor _____ function, especially in elderly
ECG & BP with IV use
LIVER Phenytoin hepatically metabolised: Caution in Hepatic impairment
What is the desired range of Theophylline levels?
10 - 20 mg/ L = 55 - 110 micromol/ L
(mg/ L= same as phenyotin!
and digoxin is 1 - 2 mcg/ L so similar! and you know Lithium!)
Phenytoin is an interesting drug when it comes to interactions as it itself is an enzyme inducer, but its levels are effected by other enzyme inducers/ inhibitors. It can (effectively) induce its own metabolism.This weird effect is displayed by its varied interactions with the anti-fungals. Ketoconazole and Fluconazole are both Part of SICKFACES and are enzyme inhibitors…
However,Phenytoins own levels are INCREASED by fluconazole and miconazole= phenytoin TOXICTY
Phenytoin itself INCREASES the levels of Ketoconazole and itraconazole
What is the interaction between PHENYTOIN and AMIODARONE?
Amiodarone inhibits the metabolism of Phenytoin:Phenytoin concentration increases
Phenytoin is metabolised by CYP450 enzymes. Some of the enzyme inhibitors can therefore increase [Phenytoin]. Which ones?
Isoniazid Cimetidine Fluconazole Chloramphenicol ErythromycinSulfamethoxazole Ciprofloxaxin Omeprazole Metronidazole
What electrolyte disturbance can Theophylline cause?
HypokaleamiaPatients may also be on salbutamol (/ beta 2 agonists) for their asthma- can also cause hypokaleamia
Severe asthma patients- monitor K+ as may alsobe on corticosteroids- can cause hypokaleamia
Diuretics- hypokaleamia
Monitor plasma Potassium in severe asthma/ with theophylline therapy.
What is Theophylline? How does it work?
It is a xanthine Same family as CaffeineIt is a broncho dilator
Theophylline is used in Chronic Asthma Therapy only, usually orally as an MR prep.When is Theophylline used in Asthma therapy?
Can be used at step 3 or 4 of the asthma pathwayStep 3: as an add-on therapy to ICS/ LABAStep 4: As a regular bronchodilator (6 week trial)
Signs of Theophylline toxicity?Hint: same family as caffeine
- Vomiting
- Restlessness
- Agitation
- Dilated Pupils
- Sinus tachycardia (palpitations)
- Hyperglyceamia
- Severe HYPOKALEAMIA
- Hallucinations
Severe toxicity: convulsions, arrhythmias, throwing up blood
How do we treat theophylline toxicity?
Treatment: Repeated activated charcoal, ondansetron for vomitting, potassium chloride
Short acting beta-blocker (e.g. Esmolol) may reverse severe tachycardia, hypokalemaia and hyperglyceamia.
The plasma concentration of theophylline is increased in ….3…. conditions?
Heart Failure
Hepatic impairment
RespiratoryViral infections
So watch out for signs of toxicity (plasma conc rising above 20mg/ L)
What two social activities can DECREASE theophylline levels?
SMOKING
Alcohol consumption
Why is it important to ensure the same BRAND of theophylline is maintained?
Rate of absorption from different modified release preparations can change between brandsThe brands have different dosing regimesBrands: Uniphyllin Continus®, Slo-phyllin®, Nuelin SA®
How can Slo-phyllin (theophylline) capsules be taken?
Swallow whole with water OR granules can be sprinkled onto yoghurt/ soft food and swallowed without chewing
How is theophylline metabolised?
HEPATICALLYtherefore reduce dose in liver impairment!
What are the three E’s that Theophylline should be used in caution with?
Epilepsy- reduced seizure threshold (Hence interaction with Quinolones!) Elderly-Increased plasma theophylline conc- maybe due to reduced Liver function
Elevated BP- Hypertension, also hyperthyroidism
Theraputic range of Carbamazepine?
4 - 12 mg / L
Gentamicin- multiple daily dose regimen- one hour peak serum concentration?And for endocarditis?
NB: For once-daily: consult local guidelines
5 - 10 mg / L
Endocarditis: 3 - 5 mg/ L
Gentamicin-pre-dose trough concentration?And for endocarditis?
< 2 mg/ L
Endocarditis: < 1 mg/ L