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?
<span>1 - 2 mcg / L</span>
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)
<u><strong>Gastro:</strong></u>Nausea and vomittingAbdominal painAnorexia (weight loss)<u><strong>Cardiac:</strong></u>Bradycardia- (HR under 60 bpm) heart slowed down too much by digoxinArrythmias (irregular heart beat)<u><strong>Mental:</strong></u>Delirium (confusion)<u><strong>Visual </strong></u>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 <span>below 60 BPM </span>(i.e. becomes bradycardic)
We need to monitor the plasma concentration of Digoxin closely. When should levels be taken?
<span>at least </span><span>6 HOURS after a dose given</span>
Digoxin toxicity can be fatal. What electrolyte imbalance can precipitate digoxin toxicity?
<span>HYPOKALEAMIA </span>is a big one. We manage this by giving K+ sparing diuretics (e.g. spironolactone) and K+ supplements.HypomagnesaemiaHypocalcaemia
How is digoxin excreted? Therefore what do we need to monitor and decrease dose if impaired?
<span>Renally</span>decrease dose if patient has renal impairment
What is digoxin used in?
Most use in <span>persistent & permanent Atrial Fibrilation</span> as <span>RATE </span>controlHas a role in Heart FailureRole in Atrial flutters
Amiodarone is used in the <strong>rhythm </strong>control of AF.Digoxin is used as<strong> rate </strong>control.interaction between these 2 drugs?
Amiodarone INCREASES plasma concentration of digoxinIt is an <strong>ENZYME inhibitor </strong>but <strong>not one of the P450’s </strong><span>(so not part of SICKFACES)</span><span>Digoxin dose needs to be <strong>decreased by 50%</strong> if given with Amiodarone</span>
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:<strong>Furosemide, Bumetanide</strong><strong>Bendroflumethiazide, indapamide, chlortolidone </strong>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 <u><strong>decrease kidney function </strong></u>and precipitate digoxin toxicity
What happens if a CCB is administered to someone on Digoxin?
Plasma conc of digoxin <strong>increased </strong>by:<u>Diltiazem</u><u>Nicardepine</u><u>Nifedipine</u><u>Verapamil</u><strong><u> </u>(also increases risk of AV BLOCK & bradycardia [slows rate])</strong>
What are the signs of Lithium toxicity?
<strong>GI disturbance warning signs:</strong>Vomitting, Diarrohea<strong>Then Mostly CNS effects:</strong>Fine Tremor to start then coarse tremorInvoluntary movement (ataxia)Involuntary eye movement (Nystagmus)Blurred visionThirst- due to hypernatreamia?<strong>Severe toxicity (level over 2 mmol/L):</strong>ConvulsionsComaRenal failuire
Lithium can cause problems in some of our organs. What are these, what would be the signs if their function had altered?
<u>Kidney</u>- monitor renal function<strong>Sign of decline: Polyuria, Polydipsia</strong><u>Thyroid</u>- usually hypothyroidism<strong>Signs: unexplained fatigue </strong>Benign intracranial hypertension (high BP in brain)<strong>Signs: persistent headache, visual disturbance</strong>
You know the target range for lithium is 0.4 - 1.0 mmol/L.What is the target in acute episodes of mania?
<u><strong>0.8 - 1.0 mmol/ L- upper end of the range!</strong></u>
What three drugs do you legally have to provide a patient alert card with?
LithiumSteroidsAnticoagulant
Lithium interacts with<u>ACE inhibitors/ ARB's</u><u>NSAIDS</u>What is this interaction?
Ace inhibitors / ARB’s and NSAIDs can decrease renal perfusionLithium excreted by KidneysLithium levels risk= lithium toxicity
Why does Lithium interact with the Diuretics (loop, thiazide AND potassium-sparing)?
Diuretics can cause electrolyte disturbanceHyponatreamia may be a resultLithium 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 neurotoxicity when Lithium is given with things like methyldopa, phenytoin, carbamazepine<strong>& the rate limiting CCB’s diltiazem and verapamil</strong>
There is increased risk of EPSE’s when Lithium is given with antipsychotics
What type of seizures can phenytoin be used in?
FocalTonic- clonicMyoclonicBut 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?
<span>10 - 20 mg/ L</span><u><strong><span>= 40- 80 micromol/L</span></strong></u>Non-linear relationship between dose and plasma conc: small change in dose=<strong> big change in conc</strong>
What are the symptoms of Phenytoin toxicity?
<u><strong>CNS:</strong></u>Nystagmus (involuntary eye movement)Ataxia (involuntary body movement)Slurry speechConfusionsuicidal thoughts<strong>HYPERGLYCEAMIA</strong><strong>Double vision (diplopia), blurred vision</strong><span><strong>NB: Similar to Lithium toxicity: remember the differentials (hyperglyceamia, no convulsions)</strong></span>
Phenytoin is related to SKIN & BLOOD disordersWhat does the patient need to look out for?
<p><u><strong>Skin-</strong></u> look out for RASH</p>
<p>Phenytoin also causes:</p>
<p>HIRSUTISM (excess hair growth)</p>
<p>gingival hypertrophy (enlarged gums)</p>
<p>acne</p>
<p></p>
<p><strong>Blood disorder:</strong></p>
<p>Fever, sore throat, mouth ulcers, bruising, bleeding</p>
<p></p>
With phenytoin, we should monitor ECG & BP with IV use.Should also monitor _____ function, especially in elderly
<span>LIVER</span>Phenytoin hepatically metabolised: Caution in Hepatic impairment
What is the desired range of Theophylline levels?
<span>10 - 20 mg/ L</span><strong>55 - 110 micromol/ L</strong>(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 <strong>fluconazole and miconazole= phenytoin TOXICTY</strong>Phenytoin itself INCREASES the levels of <strong>Ketoconazole and itraconazole</strong>
What is the interaction between PHENYTOIN and AMIODARONE?
Amiodarone inhibits the metabolism of Phenytoin:<u><strong>Phenytoin concentration increases</strong></u>
Phenytoin is metabolised by CYP450 enzymes. Some of the enzyme inhibitors can therefore increase [Phenytoin]. Which ones?
I soniazidC imetidineF luconazoleC hloramphenicolE rythromycinS ulfamethoxazoleC iprofloxaxinO meprazoleM etronidazole
What electrolyte disturbance can Theophylline cause?
<span>Hypokaleamia</span>Patients may also be on <u>salbutamol (/ beta 2 agonists) </u>for their asthma- can also cause hypokaleamiaSevere asthma patients- monitor K+ as may alsobe on <u>corticosteroids</u>- can cause hypokaleamia<u>Diuretics</u>- hypokaleamia<strong>Monitor plasma Potassium in severe asthma/ with theophylline therapy</strong>
What is Theophylline? How does it work?
It is a xanthineSame 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
<ul> <li>Vomiting</li> <li>Restlessness</li> <li>Agitation</li> <li>Dilated Pupils</li> <li>Sinus tachycardia (palpitations)</li> <li>Hyperglyceamia</li> <li>Severe HYPOKALEAMIA</li> <li>Hallucinations</li></ul>
<p>Severe toxicity: convulsions, arrhythmias, throwing up blood</p>
How do we treat theophylline toxicity?
<p><strong>Treatment: </strong>Repeated activated <strong>charcoal</strong>, odansetron for vomitting, potassium chloride</p>
<p>Short acting beta-blocker <strong>(e.g. Esmolol)</strong> may reverse severe tachycardia, hypokalemaia and hyperglyceamia.</p>
The plasma concentration of theophylline is increased in ….3…. conditions?
Heart FailureHepatic impairment<strong>RespiratoryViral infections</strong>So watch out for signs of toxicity (plasma conc rising above 20mg/ L)
What two social activities can DECREASE <strong>theophylline </strong>levels?
SMOKINGAlcohol 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 <strong>reduce dose</strong> in liver impairment!
What are the three E’s that Theophylline should be used in caution with?
<strong><em>Epilepsy</em></strong>- reduced seizure threshold (Hence interaction with Quinolones!)<strong><em>Elderly-</em></strong>Increased plasma theophylline conc- maybe due to reduced Liver function?<em><strong>Elevated BP-</strong></em>Hypertension, also hyperthyroidism
Theraputic range of <strong>Carbamazepine</strong>?
<span>4 - 12 mg / L</span>
Gentamicin- multiple daily dose regimen- one hour peak serum concentration?And for endocarditis?<span>NB: For once-daily: consult local guidelines</span>
<span>5 - 10 mg / L</span><strong>Endocarditis: 3 - 5 mg/ L</strong>
Gentamicin-pre-dose trough concentration?And for endocarditis?
<span>< 2 mg/ L</span><span><strong>Endocarditis: < 1 mg/ L</strong></span>