Clinical review station

Question 1

The eGFR equation

Answer 1

(140-age) x W x Constant /serum creatine
eGFR is only an estimate and confidence intervals are quite wide. It is most likely to be inaccurate at extremes of body type eg. malnourished, amputees.[m=1.23,w=1.04]

Question 2

Creatine Clearance

Answer 2

(140-age) x BW/cr x72 x0.85

Question 3

eGFR

Answer 3

A normal eGFR is 60 or more. If your eGFR is less than 60 for three months or more, your kidneys may not be working well

Question 4

CrCl

Answer 4

110 to 150mL/min in males and 100 to 130mL/min in females

Question 5

Na+

Answer 5

(135-155) - High and low sodium = Dehydration, which may be caused by not drinking enough, diarrhea, or certain medicines called diuretics (water pills) A disorder of the adrenal glands. A kidney disease

Question 6

K+

Answer 6

(3.5-5) high potassium and low a sign of Acute kidney failure

Question 7

cr

Answer 7

(60-120) high cr a sign of kidney disease

Question 8

BP

Answer 8

less than 120/80 mmHg

Question 9

Resp Rate

Answer 9

12-20 bpm

Question 10

Aminophylline what is it

Answer 10

Used to treat SOB and difficulty breathing caused by Asthma and other…
Relaxes air passage in he lungs and makes it easier to breathe, Aminophylline less potent and short acting than theophylline
- works best at constant amount of blood so same time each day
- after started, doctors need to check the level of meds in blood regularly

Question 11

Aminophyliine - Tablets

Answer 11

380mg per day, every 6-8 hrs
- Check allergies and smoking status
Interacts with Riocoguat and Viloxazine
- Contraindication- congestive heart failure
hypothyrodidm
liver and kidney disease
pulmonary disease

Question 12

Aminophylline (Theophylline) - Oral theophylline and oral or IV aminophylline

Answer 12

Aminophylline injection is used together with other medicines to treat the acute symptoms of asthma, bronchitis, emphysema, and other lung diseases in a hospital setting.
- Aminophylline belongs to a group of medicines known as bronchodilators

• Therapeutic range: 10 to 20mg/L

-levels greater than 20 mcg/ml are often associated with toxic effects.
-Loading dose: Intravenous aminophylline 5mg/kg over 20 minutes. This loading dose only applies to patients who have not received xanthine’s in the last 24 hours.
-Maintenance dose: Sustained release theophylline 175 to 500mg every 12 hours, intravenous aminophylline 500micrograms/kg/hour.–Side effects: Headache; nausea; palpitations; seizure (more common when given too rapidly by intravenous injection) -Route of elimination: liver (90%), kidney (10%)
-Toxic effects:
-Vomiting, nausea, restlessness, insomnia, serious arrhythmias, convulsions.

Question 13

Carbimazole - Tablet - 6

Answer 13

1)-Carbimazole is a medicine used to treat an overactive thyroid (hyperthyroidism)

2)Therapy should be continued for at least six months and up to 18 months.
3)Serial thyroid function monitoring is recommended, together with appropriate dosage modification to maintain a euthyroid state.

4)Typical Dose: 40–60 mg daily, therapy usually given for 18 months
5)Common side effects (usually in the first 8 weeks): nausea, headache, arthralgia, mild gastrointestinal disturbance, skin rashes and pruritus. These reactions are usually self-limiting and may not require withdrawal of the drug, Arthralgia is joint stiffness.
6)Advise patients to be aware of the symptoms of low white blood cell count. Patients should stop the drug immediately and seek advice if they experience: sore throat, bruising or bleeding, mouth ulcers, fever and malaise
-Required Baseline: Free T3, Free T4, Full blood count · including white cell count (WCC), Thyroid stimulating hormone (TSH), Liver function tests, White blood cell differential

Question 14

Clozapine - Tablet, Orodispersible tablet, Oral suspension

Answer 14

Clozapine is a dopamine D1, dopamine D2, 5-HT2A, alpha1-adrenoceptor, and muscarinic-receptor antagonist.
-Used for Schizophrenia in patients unresponsive to, or intolerant of, conventional antipsychotic drugs
-Typical dose for 18-59 years is 12.5 mg 1–2 times a day for day 1, then 25–50 mg for day 2, then increased, if tolerated, in steps of 25–50 mg daily, dose to be increased gradually over 14–21 days, increased to up to 300 mg daily in divided doses, larger dose to be taken at night, up to 200 mg daily may be taken as a single dose at bedtime; increased in steps of 50–100 mg 1–2 times a week if required, it is preferable to increase once a week; usual dose 200–450 mg daily, max. 900 mg per day, if restarting after interval of more than 48 hours, 12.5 mg once or twice on first day (but may be feasible to increase more quickly than on initiation)—extreme caution if previous respiratory or cardiac arrest with initial dosing.Side effects: oAgitation; amenorrhoea; arrhythmias; constipation; dizziness; drowsiness; dry mouth; erectile dysfunction; fatigue; galactorrhoea; gynaecomastia; hyperglycaemia; hyperprolactinaemia; hypotension (dose-related); insomnia; leukopenia; movement disorders; muscle rigidity; neutropenia; parkinsonism; postural hypotension (dose-related); QT interval prolongation; rash; seizure; tremor; urinary retention; vomiting; weight increasedThe reference range for clozapine is usually quoted as 0.35 – 0.6mg/L.
-When antipsychotics are initiated, baseline measurements should be taken in secondary care for the first 12 months, or until their condition has stabilised, whichever longer.
The baseline monitoring that would be required would entail monitoring baseline WCC (leucocyte and neutrophil). Neutropenia or agranulocytosis is contraindicated with clozapine use. Frequent monitoring of full blood count is required.
In the UK, WCC with differential count must be monitored at least weekly for the first 18 weeks of treatment, then at least biweekly intervals weeks 18-52. After 1 year with stable neutrophil counts, patients may be monitored at least at 4-week intervals. Monitoring must continue throughout treatment and for at least 4/52 after discontinuation.Things to monitor in clozapine:oBaseline lipid levels, weight and blood glucose should be obtained

-LFTs routinely checked. Serum U&E’s including creatinine and eGFR monitored every 12months. oMonitor BP and HR. ECG monitored for QT prolongation or tachycardia. Pulse andBP monitored during dose titration and each dose change.Most adverse effects are related to dose or plasma concentration, which can include seizuresTherapeutic dose range: In most patients, antipsychotic efficacy can be expected with 200 to 450 mg/day given in divided doses. The total daily dose may be divided unevenly, with the larger portion at bedtime.
-Maximum dose: To obtain full therapeutic benefit, a few patients may require larger doses, in which case judicious increments (not exceeding 100 mg) are permissible up to 900 mg/day. However, the possibility of increased adverse reactions (in particular seizures) occurring at doses over 450 mg/day must be borne in mind.Blood should be collected in EDTA tube either immediately before a morning dose (if thepatient takes morning and night), or 10-12 hours post dose (‘trough’ sample). To allow for a steady state to be achieved take the blood sample only after the patient has taken the dose for 2-3 days.
-Suitable anticonvulsants are valproate (consider risks in pregnancy in women of child-bearing potential) and lamotrigine

Question 15

Digoxin

Answer 15

Mode of action is Inhibition of sodium-potassium ATPase
-Therapeutic range: 0.8 – 2 µg/L
-Optimal sampling time: Pre-dose (trough sample) of > 6 hours post-dose
-Plasma digoxin and potassium should be monitored.
-Effective plasma concentration (0.5 – 2.0 μg/L; 0.6 – 2.6 nmol/L)
-Toxic effects observed at >2.3 μg/L (3.0 nmol/L)We also know that potassium has an inverse proportionality effect on the digoxin and therefore can induce toxicity at incredibly low levels
-So in hypokalaemia (low potassium levels), toxicity can be observed at 1.2 μg/L (1.5 nmol/L)
-most common trigger of digoxin toxicity is hypokalaemia, which can occur as a result of diuretic therapy
-Factors that increase the risk of digoxin toxicity include :oHypothyroidism/hyperthyroidism, Advanced age, MI, Renal insufficiency, Hypercalcemia, Alkalosis, Hypoxemia and Acidosis
-Medications associated with digoxin toxicity include : oDiuretics, Amiodarone, Beta-blockers, Benzodiazepines, Calcium channel blockers, Macrolide antibiotics, Propylthiouracil and Amphotericin Digoxin toxicity can cause problems with the nervous system, the heart rate, and electrolytes. This includes symptoms such as irregular heartbeat (rapid HR), nausea/vomiting/diarrhoea, fatigue, weakness, weight loss, confusion, vision problem (blurred vision, flashing lights/spots, changes in colour appearance)
Key Drug interactions with digoxin include: Antidepressants oavoid tricyclic antidepressants (proarrhythmic), venlafaxine (arrythmias), trazodone (increases digoxin concertation)oconsider selective serotonin reuptake inhibitors (SSRIs) or mirtazapine insteadBeta-blockers – can reduce heart rate/bradycardia, increase risk of AV block NOTE: Atrioventricular (AV) block is partial or complete interruption of impulse transmission from the atria to the ventricles, causing <3 to beat with abnormal rhythm oincreased digoxin concentration can occur with carvedilol (Monitor for signs of digoxin toxicity (confusion, anorexia, nausea, and disturbance of colour vision) when starting, adjusting, or stopping carvedilol)
-Bupropion – may increase digoxin levels
- Digoxin levels may rise on discontinuation
-Diuretics, Acetazolamide, and Amphotericin  Increased cardiac toxicity with digoxin ifhypokalaemia occurs with these drugs
-St John’s wort – plasma concentration may be reduced -Advise people taking digoxin that they should not use St John’s wort
-Proton pump inhibitors – increased plasma levels of digoxin
-Monitor for signs and symptoms of digoxin toxicity (and adjust doses accordingly) if digoxin is given with the following drugs, which may increase plasma concentration of digoxin:oAmiodaroneoAntimicrobials (itraconazole, macrolide antibiotics, tetracycline, and trimethoprim), oCalcium-channel blockers (diltiazem, verapamil, and possibly nifedipine). There is also an increased risk of AV block and bradycardia with verapamil. oChloroquine and hydroxychloroquineoSpironolactone.

Question 16

Gentamicin

Answer 16

Gentamicin has a therapeutic range in serum of 5 to 10 mg/L for peak levels and 1 to 2 mg/L for trough levels
Gentamicin Toxicity is known to cause any of the following: Kidney damage and renal failure. Nerve damage. Ototoxicity (damage to the ear, such as hearing loss, vertigo or ringing in the ears (tinnitus), Balance problems, Problems with memory/concentration and fatigue, Oscillopsia (bouncing vision)Gentamicin is an aminoglycoside used to treat serious infections

Question 17

Lithium

Answer 17

A serum lithium level of 0.6–0.8 mmol/L is suitable for people who are being prescribed lithium for the first time.
-Higher serum lithium levels (0.8–1.0 mmol/L) are suitable for people who have relapsed previously while taking lithium
-Signs of lithium toxicity include increasing diarrhoea, vomiting, anorexia, muscle weakness, lethargy, dizziness, ataxia, lack of coordination, tinnitus, blurred vision, coarse
tremor of the extremities and lower jaw, muscle hyper-irritability, choreoathetoid movements, dysarthria, and drowsiness.
-Lithium broken down by kidneys so important to check renal function
-Tests for lithium should be taken 12 hours after the dose to achieve level of 0.4-1.0 mmol/L but optimal range differs based on the patient
-Lithium half-life is 18 to 36 hours
-Tests can be done every week to monitor plasma lithium levels, after each change in dose and then every 3 months once the dose is stable.
-Prolonged vomiting/diarrhoea can decrease Na+ levels causing retention of Lithium and can cause toxicity but if only for a couple of hours, is unlikely to have affected Lithium levels yet.
-Interactions with Lithium: oDiuretics  can cause a rapid increase in serum lithium levelsoNonsteroidal anti-inflammatory drugs (NSAIDs)  may increase serum lithium levelsoHaloperidol  severe neurotoxicity oCarbamazepine  neurotoxic reactions with co-administered with lithiumoAntidepressants  ones with serotonergic activity (SSRIs, TCAs, serotonin and noradrenaline reuptake inhibitors (SNRI) like venlafaxine or duloxetine) oACE inhibitors  decrease lithium excretion oDrugs that prolong the QT-interval (ie. Haloperidol, Quetiapine, Olanzapine) oDrugs that cause hypokalaemia  can increase risk of torsade de pointsMonitor: BMI, Urea and electrolytes, eGFR (kidney function), calcium and thyroid function tests every 6 months (more often if there is evidence of impaired renal function).It is not recommended to take lithium when pregnant, especially in the first trimester as it can be harmful for the baby  strongly recommended to stop lithium therapy if planned pregnancySpeak with GP and require medical assistant if you experience:severe hand shaking (tremor), stomach ache with nausea or diarrhoea, muscle weakness, unsteady on feet/feeling lightheaded, muscle twitches, slurring words, blurred vision, confusion or unusually sleepy  this may indicate LITHIUM TOXICITY (when blood levels are too high) What can trigger lithium toxicity (high Li levels):oGetting dehydrated (ie. Diarrhoea, vomiting)oBig changes in salt levels in your diet oOther medications (NSAIDs, ACE inhibitor, etc)

Question 18

Vancomycin

Answer 18

Vancomycin is an antibiotic drug used to treat serious, life-threatening infections by gram-positive bacteria that are resistant to less-toxic agents. The reference range for vancomycin trough levels is 5-15 mcg/mL. The reference range for vancomycin peak levels is 20-40 mcg/mLWhat drug interactions are associated with vancomycin?
oOtotoxic medication - concurrent and/or sequential systemic or topical use of other potentially ototoxic requires careful monitoring.oNephrotoxic medication - concurrent and/or sequential systemic or topical use ofother potentially nephrotoxic requires careful monitoring. What are the adverse effects of vancomycin?oBlood disorders - agranulocytosis, neutropenia and thrombocytopeniaoImmune disorders - hypersensitivity and anaphylactic reactionsoEar disorders - transient loss of hearing, vertigo, tinnitus, dizzinessoVascular disorders - decrease in blood pressure, vasculitisoRespiratory disorders - dyspnoea, stridoroGastrointestinal disorders - nausea, vomiting, diarrhoeaoSkin disorders - flushing of the upper body, pruritus, urticariaoRenal disorders - renal insufficiency, increase in serum creatinine and urea, interstitial nephritis, renal failure

Question 19

Warfarin

Answer 19

Vitamin K antagonistThe time in the therapeutic range (an international normalized ratio [INR] between 2.0 and 3.0) (TTR) has been used as a measure of warfarin (W) therapy quality.The typical induction dose of warfarin is 10 mg daily for 2 days, but this should be tailored to individual requirements. A low starting dose (5 mg) is often more suitable for frail or elderly people, people with alow body weight, people with liver disease or cardiac failure, and people at high risk of bleeding. Subsequent doses depend on the prothrombin time, reported as an international normalized ratio (INR). The daily maintenance dose of warfarin is usually 3–9 mg, taken at the same time each day.Optimal sampling time: 24 to 36 hours post-doseHalf-life: 20 – 72 hours High protein binding so in this case, any fluctuations on plasma proteins will have a dramatic effect on the concentration of warfarinThe following factors may exaggerate the effect of warfarin and necessitate a dose reduction:oWeight loss.oAcute illnessoSmoking cessation.The following factors may reduce the effect of warfarin and necessitate a dose increase:oWeight gain.oDiarrhoea.oVomiting.

Question 20

WARFARRRRIN

Answer 20

The following interactions may enhance the effect of warfarin and are likely to need close monitoring and clinical intervention, especially when initiating, changing, and stopping concurrent treatment.oAlcohol — the person should avoid binge drinking. Heavy drinkers or people with liver disease should avoid alcohol or should not take warfarin.oAmiodarone — during the loading phase, check the INR once a week and adjust the dose according to the INR. When the loading phase has been completed, check the INR every 2–4 weeks for 1–2 months. Similarly, when stopping amiodarone, the INR should be checked frequently and the dose adjusted as needed. The interaction between warfarin and amiodarone persists for a month or more after amiodarone is withdrawn.oAntibiotics — measure the INR 4–7 days after any antibiotic has been started. It is difficult to predict if the INR will increase or decrease (this will also depend on how illthe person is). For example:oCo-trimoxazole — consider whether trimethoprim can be used instead or reduce warfarin dose.oMetronidazole, erythromycin, and clarithromycin — reduce the warfarin dose as necessary.oAntidepressants — selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) should be avoided where possible because of their antiplatelet effect. Some tricyclic antidepressants (TCAs) and mirtazapine should also be avoided due to an enhanced anticoagulant effect. Consider offering trazodone instead.oAspirin or aspirin-containing products (for example, cold and influenza preparations, and topical salicylates) — avoid concurrent use unless clinically indicated.oAzoles (in particular fluconazole, miconazole, and voriconazole) — measure the INR 4–7 days after an oral azole has been started, and adjust the dose based on the INR. Monitoring is also recommended in people using intravaginal or topical miconazole.oIf miconazole and warfarin are used concurrently, the anticoagulant effect should be carefully monitored and, if necessary, the dose of warfarin reduced.oCranberry juice or cranberry-containing products — advise the person to avoid concurrent use; INRs greater than 8 have occurred.oClopidogrel or dipyridamole — concurrent use should be avoided unless clinically indicated.oCorticosteroids — recheck the INR 4–7 days after starting an oral corticosteroid, and adjust the dose of warfarin as needed based on the INR.oDirect-acting antiviral medications for treatment of chronic hepatitis C — monitor INR closely, and adjust warfarin treatment if necessary. Changes in liver function, secondary to hepatitis C treatment with direct-acting antivirals, may affect the efficacy of warfarin because of possible changes in liver function during treatment. Direct-acting antiviral medications include boceprevir (Victrelis®), daclatasvir (Daklinza®), dasabuvir (Exviera®), ombitasvir/paritaprevir/ritonavir (Viekirax®), sofosbuvir (Sovaldi®), ledipasvir with sofosbuvir (Harvoni®), and simeprevir (Olysio®).

Question 21

WARFARRRIN

Answer 21

oFibrates — avoid concurrent use if possible, or reduce the warfarin dose as necessary.oGlucosamine — avoid concurrent use.oNonsteroidal anti-inflammatory drugs (NSAIDs) — avoid concurrent use, or reduce warfarin dose as necessary. If the person must take an oral NSAID, measure the INR 4–7 days after starting treatment. In addition, the person must be counselled on the signs of gastrointestinal bleeding. oTamoxifen — avoid concurrent use, or reduce warfarin dose as necessary. Measure the person’s INR 1–2 weeks after starting treatment with tamoxifen.oThyroxine — reduce warfarin dose as necessary. Consider weekly monitoring whilst the thyroxine dose is being titrated.The following interactions may reduce the effect of warfarin and are likely to need close monitoring and clinical intervention, especially when initiating, changing, and stopping concurrent treatment.oSt John’s Wort — stop St John’s Wort, monitor the INR, and adjust warfarin dose as necessary. St John’s wort can cause a moderate clinical reduction in the anticoagulant effect.oGriseofulvin — increase warfarin dose as necessary.oRifampicin — increase warfarin dose as necessary.oCarbamazepine — increase warfarin dose as necessary.oPhenobarbital or primidone — a reduced effect may be seen within 2–4 days (maximum effect by about 3 weeks) after starting phenobarbital and persisting for upto 6 weeks after phenobarbital is stopped. Monitor INR until stable. Increase warfarin dose as necessary.oPhenytoin — increase warfarin dose as necessary. After stopping phenytoin, the INR may continue to be affected for up to 6 weeks.oVitamin K-containing vitamin complexes, including some enteral feeds (containing vitamin K), mineral supplements, and green vegetables (as well as over-the-counter chilblain products) — the warfarin dose should be increased, or the intake of vitaminK reduced. Vitamin K-rich diets should not be changed without at the same time reducing the warfarin dose, because excessive anticoagulation and bleeding may occur.In addition, it is also prudent to monitor the INR when warfarin is used concurrently withthe following drugs, especially in older people, as interactions have been documented:oAllopurinol.oAzathioprine.oGrapefruit juice (it may be easier to completely avoid this).oInfluenza vaccine.oMethylphenidate.oOrlistat (may reduce the absorption of vitamin K).oParacetamol or paracetamol-containing products (particularly if prolonged regular use).oProton pump inhibitors.oQuinolone antibiotics.
oStatins (particularly fluvastatin or rosuvastatin; not pravastatin).oStopping smoking (it takes about 1 week for enzyme induction due to smoking to wear off).oZafirlukast

Question 22

Methotrexate

Answer 22

Patients taking methotrexate should undergo monitoring of CBC, serum creatinine, transaminases is recommended weekly for the first four weeks and then at least bimonthly. A complete list of the current medications should be revised to avoid any possible drug interactions before prescribing methotrexate

Initially 2.5–10 mg once weekly, then increased in steps of 2.5–5 mg, adjusted according to response, dose to be adjusted at intervals of at least 1 week