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, AzithromycinCiclosporinItraconazoleAmiodarone (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
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
- Vomiting
- Restlessness
- Agitation
- Dilated Pupils
- Sinus tachycardia (palpitations)
- Hyperglyceamia
- Severe HYPOKALEAMIA
- Hallucinations
Severe toxicity: convulsions, arrhythmias, throwing up blood
Treatment: Repeated activated charcoal, odansetron for vomitting, potassium chloride
Short acting beta-blocker (e.g. Esmolol) may reverse severe tachycardia, hypokalemaia and hyperglyceamia.
Vomiting
Malaise
JaundiceAlso colours urine/ body fluids/ soft contact lenses red/ orange
Reduce methotrexate excretion in kidney As do penicillins!
Full blood count: can cause both LOW PLATELETS and LOW NEUTROPHILS (Neutropenia)
Renal function- Nephrotoxic- Urinalysis, CrCl used for dosing
Hearing function in the elderly
Plasma concentration
Renal function
Hearing function
Plasma concentration
NB: differs to vancomycin as do not need to monitor FBC- does not cause neutropenia/ low platelets
Diuretics– clears excess fluid out of body but the remaining fluid is more concentrated; increases the risk of developing the crystals that cause gout
Beta-blockers and ACE inhibitors
low-dose aspirin – used to reduce the risk of blood clots
niacin – used to treat high cholesterol
ciclosporin – used to treat conditions such as psoriasis
Build up of uric acid causing:
sudden attack of severe pain in one or more joints, typically big toe.
joint feeling hot and very tender, swelling in and around the affected joint
Dietary risk factors: high in meat and seafood and high in beverages sweetened with fructose promotes higher levels of uric acid, also alcohol.
Phospohorus can help cure gout: Banana is a rich source of phosphorus.
Must be given by slow infusionMonitor ECG- rapid infusion would be toxic to heart and arrhythmias occur Need to the patient is weeing enough- contraindicated in anuria (absence of urination) as potassium would build up
What are the following indicative of with NSAID therapy?
Unexplained weight loss
difficulty swallowing
nausea or vomiting
bloating
burping or acid reflux- recent onset dyspepsia
Start with an immediate release solution such as Oramorph Then once optimal dose found- switch to modified release (MST Continus- administered BD [12 hourly])For breakthrough pain, immediate release (Oramorph) morphine at a dose of 1/6 the usual.
What should a patient do if they miss a warfarin dose?
Loop diureticsDue to hyperglyceamia side effect!
Na +K +Mg +Renal functionUric acid levels (risk of gout)Hyperglyceamia- can exacerbate diabetesHypotension- BP lowering effects
What is the max daily dose of Codeine?
How long must intervals between doses be?
,Max number of days OTC?