Therapeutic drug monitoring & High risk drugs Flashcards
What is the difference between HYPERglyceamia and HYPOglyceamia symptoms?
HYOGLYCEAMIA:
Dizzy, head hurts, shaky, hungry, cannot see or think straight, sweaty
HYPERGLYCEAMIA:
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?
Drug that alters force or energy of heart contractions
Positive ionotrope (e.g. Digoxin, Amiodarone): ↑ force of contractions of heart, (decompensateHF, shock (severe hypotension)+ heart attack as they get blood pumping again! NB: these do not increase rate, digoxin decreases rate, just increase force of contraction. Digoxin used as rate control in AF, Amiodarone used as Rhythm.
Negative ionotropes: ↓ force of contractions of heart, (Hypertension to bring BP down + Angina) I.e. 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 & vomiting, Abdominal pain, Anorexia (weight loss)
Cardiac: Bradycardia (HR under 60 bpm), Arrythmias (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 <60 BPM (i.e. bradycardic)
We need to monitor the plasma concentration of Digoxin closely. When should levels be taken?
> 6 HOURS after a dose given
Digoxin toxicity can be fatal. What electrolyte imbalance can precipitate digoxin toxicity?
HYPOKALEAMIA: We manage this by giving K+ sparing diuretics (e.g. spironolactone) and K+ supplements.
Hypomagnesaemia
Hypercalcaemia
How is digoxin excreted? Therefore what do we need to monitor and decrease dose if impaired?
Renally excreted, decrease dose if patient has renal impairment
What is digoxin used in?
Most use in persistent & permanent Atrial Fibrilation
RATE control
Has a role in Heart Failure
Role 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 Cp of digoxin
= ENZYME inhibitor but not one of P450’s class (so not part of SICKFACES)
Digoxin dose 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: Erythromycin, Clarythromycin, Azithromycin
Ciclosporin
Itraconazole
Amiodarone (but not through CYP)
Rifampicin and St Johns Wort are both CYP450 enzyme inducers. What TDM drug do they reduce the concentration of?
Digoxin
Why does Digoxin interact with Diuretics?
~ Diuretics (Loop & thiazide/ thiazide- like) may cause HYPOKALEAMIA
~ Digoxin toxicity precipitated by HYPOkaleamia
SO careful with these
K sparing diuretics Okay:Amiloride/ Triamterene/Spironolactone (this can increase [Digoxin]), Eplerenon
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 excreted renally + caution in kidney impairment
==> ACE inhibitors & NSAID’s can both decrease kidney function + precipitate digoxin toxicity
What happens if a CCB is administered to someone on Digoxin?
conc of digoxin ⬆ by:
Diltiazem
Nicardepine
Nifedipine
Verapamil
(also ⬆ risk of AV BLOCK & bradycardia)
What are the signs of Lithium toxicity?
GI disturbance warning signs: V, D
Mostly CNS effects:
Fine Tremor then coarse tremor
Involuntary movement (ataxia)
Involuntary eye movement (Nystagmus)
Blurred vision
Thirst- due to hypernatreamia?
Severe toxicity (level over 2 mmol/L):
Convulsions
Coma
Renal 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 range!
What three drugs do you legally have to provide a patient alert card with?
LithiumSteroidsAnticoagulant
Lithium interacts with ACE inhibitors/ ARB’s/NSAIDS
What is this interaction?
ACE inhibitors / ARB’s & NSAIDs = decrease renal perfusion
=> Lithium excreted by Kidneys => Lithium levels risk= lithium toxicity
Why does Lithium interact with the Diuretics (loop, thiazide AND potassium-sparing)?
Diuretics = cause electrolyte disturbance
=> Hyponatreamia
=> Lithium levels influenced by sodium levels- lithium toxicity
Which antibiotic could possibly cause Lithium toxcity/ levels to rise?
Metronidazole
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
What should a patient do if they miss a warfarin dose?