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IUMS - نفرولوژيست9/8/1392

Anti-anxiety Medications

Claim to:Decrease anxiety and stressDecrease irritability and agitation


BenzodiazepinesSelective Serotonin Reuptake Inhibitors Tricyclic AntidepressantsMonoamine Oxidase InhibitorsSerotonin Norepinephrine Reuptake InhibitorsAntihistaminesAnticonvulsantsBeta blockersAlpha-BlockersAntipsychoticsOther


Generic NameLorazepam (benz.)Clonazepam (benz.)Propranolol (beta bl.)

Antidepressants and SSRIs

Generic NameClomipramineFluoxetineCitalopramSertraline

Brand NameAnafranilProzacCelexaZoloft

Drugs routinely monitored

• Anti-epilepticsPhenytoin, Carbamazepine, (Valproate)

• Anti-psychoticsLithium

Case 1A 29 y/o male patient with bipolar disorder has been treating lithium carbonate from 1377, also depakin,clonazepam and clozapin. Last year he referred by his psychologist for high serum urea and creatinine level (BUN= 18, Cr=1.8 from 4-6 months ago). He had history of polyuria (4 L/d) and nocturia from a few years ago. Apparently he regularly checked his serum level of lithium. 2 ms ago lithium discontinued.

Case 1…His serum BUN and Cr was normal 2 yrs ago. US and all other hormonal, vasculitis, hepatic and viral tests were normal except hyperuricemai.His GFR was 40ml/min. Dx: lithium nephrotoxicityNow he is on depakin, leponex(clozapin), lisinopril, allopurinol and metoral.After 16 months Cr=1.78 and BUN=17.

Lithium

0.4 – 1.0 mmol/LTarget range

Hyperreflexia & hyperextension of limbs, convulsions, psychoses, syncope, renal failure, circulatory failure, coma, death

Signs of toxicity

Plain tubeSampling method

Slow release brands not interchangeablePractical issues

Weekly until dose stable then at least 3-monthlyHow often to repeat

pre-doseWhen to take blood

400mg – 1,200mg od poMaintenance dose

400mg-1.2g dailyLoading dose

4-5 days after starting or change in therapy or sodium/fluid intake

Time to steady state sampling

24 hoursHalf-life

Lithium – key points

• Renal excretion– 100% filtered but 80% reabsorbed– Li+ reabsorption linked to Na+ reabsorption– Influenced by dehydration, sodium depletion,

hypotension– Diuretics (e.g. thiazides) can increase Lithium levels

dramatically

• NSAIDs and ACEi’s can increase Li+ levels toxicity

Mood Stabilizers & Anticonvulsants

Generic NameDivalproexValproic acidCarbamazepine

Brand NameDepakoteDepakeneTegretol

AnticonvulsantsCarbamazepine: related to TCAs, metabolized in liver, no need to dose adjustment in CKD.Side effects: agranulocytosis, cardiac arrhythmia, hepatitis, and renal failure. Routine drug level and erythrocyte count, liver and renal function recommended.Others: lamotrigine,valproate,topiromate,and oxcarbazepine,

AnticonvulsantsGabapentin : for peripheral neuropathy, postherpetic neuralgia, and restless leg syndrome.Adverse effect: somnolence, dizziness, ataxia, fatigue and nystagmus. In patients with CKD the dose should be adjusted. In GFR<15 dose is 300mg qod.

Antidepressants Tricyclic antidepressants :root of elimination of drug and metabolites is the kidney, may accumulate in CKD leading to tachycardia, hypotension.

Anticholinergic effects, urinary retention and bladder obstructive symptoms. In CKD TCAs should be started at minimum dose and titrated up slowly as tolerated.

Antidepressants Selective serotonin reuptake inhibitors (SSRI): better tolerated and highly effective in various mood disorders. Citalopram, fluoxetine, sertralineSafe in renal disease.

Sedatives

Normal Dosage

% of Renal Excretion

GFR >50

GFR 10 to 50

GFR <10 CommentsHD CAPD CVVH

Barbiturates

May cause excessive sedation, increase osteomalacia in ESRD. Charcoal hemoperfusion and hemodialysis more effective than peritoneal dialysis for poisoning.

Pentobarbital

30 mg q6 to 8h

Hepatic 100%

100% 100% None

No data

Dose for GFR 10 to 50

Phenobarbital

50 to 100 mg q8 to 12h

Hepatic (renal)

q8 to 12h

q8 to 12h

q12 to 16h

Up to 50% unchanged drug excreted with urine with alkaline diuresis

Dose after dialysis

1/2 normal dose


Secobarbital

30 to 50 mg q6 to 8h

Hepatic 100%

100% 100% None

None N/A

Thiopental

Anesthesia induction (individualized)

Hepatic 100%

100% 100% N/A N/A N/A

Benzodiazepines

Normal Dosage


GFR >50

GFR 10 to 50

GFR <10 Comments

HD

CAPD CVVH

Benzodiazepines

May cause excessive sedation and encephalopathy in ESRD

Alprazolam

0.25 to 5.0 mg q8h

Hepatic100%

100%

100%

None

No data

N/A

Clorazepate

15 to 60 mg q24h

Hepatic (renal)

100%

100%

100%

No data

No data

N/A

Chlordiazepoxide

15 to 100 mg q24h

Hepatic100%

100%

50%

None

No data


Clonazepam

1.5 mg q24h

Hepatic100%

100%

100%

Although no dose reduction is recommended, the drug has not been studied in patients with renal impairment. Recommendations are based on known drug characteristics not clinical trials data.

None

No data

N/A

Benzodiazepines

Normal Dosage


GFR >50

GFR 10 to 50

GFR <10 Comments HD

CAPD

CVVH

Diazepam

5 to 40 mg q24h

Hepatic 100%

100% 100% Active metabolites, desmethyldiazepam, and oxazepam may accumulate in renal failure. Dose should be reduced if given longer than a few days. Protein binding decreases in uremia.

None

No data

None

Benzodiazepines

Normal Dosage


GFR >50

GFR 10 to 50

GFR <10 Comments HD CAPD CVVH

Lorazepam

1 to 2 mg q8 to 12h

Hepatic 100%

100%

100%

May cause excessive sedation and encephalopathy in ESRD

NoneNo data


Midazol am

Individualized

Hepatic 100%

100%

50% N/A N/A N/A

Oxazepa m

30 to 120 mg q24h

Hepatic 100%

100%

100% NoneNo data


Antagonist

Flumazenil

0.2 mg IV over 15 sec

Hepatic 100%

100%

100% NoneNo data

N/A

Miscellaneous Sedative Agents

Normal Dosage


GFR >50

GFR 10 to 50

GFR <10 Comments HD

CAPD CVVH

Buspirone 5 mg q8h

Hepatic

100%

100%

100%

None

No data

N/A

Ethchlorvynol

500 mg qhs

Hepatic

100%

Avoid

Avoid

Removed by hemoperfusion. Excessive sedation.

Avoid

AvoidN/A

Haloperidol

1 to 2 mg q8 to 12h

Hepatic

100%

100%

100%

Hypertension, excessive sedation

None

None Dose for GFR 10 to 50

Miscellaneous Sedative Agents

Normal Dosage


GFR >50

GFR 10 to 50

GFR <10 Comments HD

CAPD CVVH

Lithium carbonate

0.9 to 1.2 g q24h

Renal

100%50% to 75%

25% to 50%

Nephrotoxic. Nephrogenic diabetes insipidus. Nephrotic syndrome. Renal tubular acidosis. Interstitial fibrosis. Acute toxicity when serum levels >1.2 mEq/L. Serum levels should be measured periodically 12 hours after dose. t1/2 does not reflect extensive tissue accumulation. Plasma levels rebound after dialysis. Toxicity enhanced by volume depletion, NSAIDs, and diuretics.

Dose after dialysis

None


Miscellaneous Sedative Agents Norma

l Dosage


GFR >50

GFR 10 to 50

GFR <10

Comments HD

CAPD CVVH

Meprobamate

1.2 to 1.6 g q24h

Hepatic (renal)

q6h q9 to 12h

q12 to 18h

Excessive sedation. Excretion enhanced by forced diuresis.

NoneNo data

N/A

Antiparkinson Agents

Normal Dosage


GFR >50

GFR 10 to 50

GFR <10

Comments HD CAPDCVVH

Carbidopa

1 tab tid to 6 tabs daily

30 100%100% 100%Requires careful titration of dose according to clinical response

No data

No data

No data

Levodopa 25 to 500 mg bid to 8 g q24h

None 100%50% to 100%

50% to 100%

Active and inactive metabolites excreted in urine. Active metabolites with long t1/2 in ESRD.

No data

No data


Antipsychotics

Normal Dosage


GFR >50

GFR 10 to 50

GFR <10 CommentsHD

CAPD CVVH

Phenothiazines Orthostatic hypotension, extrapyramidal symptoms, and confusion can occur

Chlorpromazine

300 to 800 mg q24h

Hepatic 100%

100% 100% None

None Dose for GFR 10 to 50

Promethazine

20 to 100 mg q24h

Hepatic 100%

100% 100% Excessive sedation may occur in ESRD

No data

No data


Thioridazine

50 to 100 mg po tid. Increase gradually. Maximum of 800 mg/day.

Hepatic 100%

100% 100%

Antipsychotics

Normal Dosage


GFR >50

GFR 10 to 50

GFR <10

Comments

HD CAPD

CVVH

Trifluoperazine

1 to 2 mg bid. Increase to no more than 6 mg.

Hepatic 100% 100% 100%

Perphenazine

8 to 16 mg po bid, tid, or qid. Increase to 64 mg daily

Hepatic 100% 100% 100%

Thiothixene

2 mg po tid. Increase gradually to 15 mg daily

Hepatic 100% 100% 100%

Loxapine

12.5 to 50 mg IM q4 to 6h

Hepatic 100% 100% 100% Do not administer drug IV

Clozapine

12.5 mg po. 25 to 50 daily to 300 to 450 by end of 2 weeks.

Hepatic 100% 100% 100%

Antipsychotics

Normal Dosage


GFR >50

GFR 10 to 50

GFR <10 Comments

Risperidone

1 mg po bid. Increase to 3 mg bid.

Hepatic 100% 100% 100%

Olanzapine5 to 10 mg Hepatic 100% 100% 100% Potential hypotensive effects

Quetiapine 25 mg po bid. Increase in increments of 25 to 50 bid or tid. 300 to 400 mg daily by day 4

Hepatic 100% 100% 100%

Case 2 A 53 y/o female renal transplant patient with diabetes mellitus,and volume overload with serum creatinine 2.5 mg/dl and BUN= 85 admitted to hospital due to loss of consciousness and seizure and irritability. She was on mycofenolate, and low dose prednisolone.She has been taking low dose baclofen 10 mg bid, but for insomnia and weakness and some body pain, she recently increased its dose by recommendation a physician to 25 mg tid or qid.

Case 2She had no Hx of seizure or epilepsy.She underwent hemodialysis 3 and 4 hours.Soon after HD, she became conscious and her seizure and irritability recovered. Baclofen discontiued and she discharged from hospital after 3 days.

Case 3A 60-year-old male hypertensive and diabetic patient who took opium habitually for six months was sent to our hospital from a private hospital because of muscle weakness, rhabdomyolysis and acute renal failure. The laboratory tests revealed high serum creatine kinase, creatinine, myoglobin and lactate dehydrogenase. Intravenous hydration, bicarbonate and mannitol treatment were applied. During the follow-up period,

Case 3…the serum creatine kinase level and renal function tests gradually normalised. Although acute opiate drug intoxication can cause rhabdomyolysis, one of the causes of rhabdomyolysis is taking opium habitually. Thus this patient developed rhabdomyolysis and acute renal failure while using opium regularly. Physicians should keep in mind that habitual opium use can cause rhabdomyolysis and associated acute renal failure.

Opioids Adverse effects: constipation (80%),sedation (20-60%), myoclonus (60%), nausea, vomiting(15-30%), pruritis(2-10%). Opioids can exacerbate the effects of uremia such as pruritus, nausea, myoclonus; following acute opioid administration.Morphine, propoxyphene, and meperidine effects heavily related to kidney function,metabolites are source of toxicity.

OpioidsMetabolite of propoxyphene (norpropoxyphene) is not dialyzable and or reversed by noloxone, has risk of hypoglycemia and cardiotoxicity.Long-term morphine use is associated with accumulation of its metabolites in CSF, interaction with other drugs.Short-term use of morphine is safe but dose should be decreased by 30-50%, interval increased by 6-8 hrs.

OpioidsOther opioids: codein, oxycodone, and hydromorphone. Seizures,myoclonus,orofacial dyskinesias, and central nervous system depression with greater frequency in CKD patients.Opioids can promote renal impairment (rhabdomyolysis) and fibrillary GN.Opioids metabolized by the liver, fentanyl and methadone, which are not highly dependent on GFR.

Analgesics(Narcotics and Narcotic Antagonists)

Normal Dosage


GFR >50

GFR 10 to 50

GFR 10

Comments HD CAPD

CVVH

Alfentanil Anesthetic induction 8 to 40 µg/kg

Hepatic 100%

100% 100%

Titrate the dose regimen

N/A N/A N/A

Butorphanol 2 mg q3 to 4h

Hepatic 100%

75% 50% No data

No data

N/A

Codein 30 to 60 mg q4 to 6h

Hepatic 100%

75% 50% No data

No data


Fentanyl Anesthetic induction (individualized)

Hepatic 100%

75% 50%CRRT-titrate

N/A N/A N/A

Narcotics and Narcotic Antagonists

Normal Dosage


GFR >50

GFR 10 to 50

GFR <10

Comments HD

CAPD

CVVH

Meperidine 50 to 100 mg q3 to 4h

Hepatic 100%

75% 50% Avoid

Avoid Avoid

Normeperidine, an active metabolite, accumulates in ESRD and may cause seizures. Protein binding is reduced in ESRD; 20% to 25% excreted unchanged in acidic urine.

Methadone

2.5 to 5 mg q6 to 8h

Hepatic 100%

100% 50% to 75%

NoneNone N/A

Morphine 20 to 25 mg q4h

Hepatic 100%

75% 50% Increased sensitivity to drug effect in ESRD

NoneNo data


Narcotics and Narcotic Antagonists

Normal Dosage


GFR >50

GFR 10 to 50

GFR< 10

Comments HD CAPD CVVH

Naloxone 0.4 to 2 mg IV

Hepatic 100%

100%

100%

N/A N/A Dose for GFR 10 to 50

Pentazocine 50 mg q4h

Hepatic 100%

75% 75% None

No data Dose for GFR 10 to 50

Propoxyphene

65 mg po q6 to 8h

Hepatic 100%

100%

Avoid

Active metabolite norpropoxyphene accumulates in ESRD

Avoid

Avoid N/A

Sufentanil Anesthetic induction

Hepatic 100%

100%

100%

CRRT-titrate

N/A N/A N/A

Anticonvulsants

Starting Dose

Maximum Dose


GFR >50

GFR 10 to 50

GFR <10

Comments HD CAPD

CVVH

Carbamazepine

2 to 8 mg/kg/day; adjust for side effect and TDM

2% 100%

100%

100%

Plasma concentration: 4 to 12, double vision, fluid retention, myelosuppression

None

None None

Clonazepam

0.5 mg tid

2 mg tid

1% 100%

100%

100%

Although no dose reduction is recommended, the drug has not been studied in patients with renal impairment. Recommendations are based on known drug characteristics, not clinical trials data.

None

No data

N/A

Normal Doses

Dosage Adjustment in Renal Failure

Anticonvulsants

Starting Dose

Maximum Dose


GFR >50

GFR 10 to 50

GFR <10

Comments

HD CAPD CVVH

Gabapentin

150 mg tid

900 mg tid

77% 100%

50% 25% Fewer CNS side effects compared to other agents

300 mg load, then 200 to 300 after hemodialysis

300 mg qod


Lamotrigine

25 to 50 mg/day

150 mg/day

1% 100%

100%100%Autoinduction, major drug-drug interaction with valproate

No data

No data


World Health Organization 3-Step Pain Relief Ladder

Step 1: mild pain (rating of 1–4 on 0–10 scale)Non-narcotic analgesics (eg, acetylsalicylic acid, acetaminophen,nonsteroidal anti-inflammatory drugs)± Adjuvant therapy*

Step 2: mild to moderate pain (rating of 5–6 on 0–10 scale)Opioids (eg, codeine, oxycodone, hydrocodone, tramadol)± Nonopioid± Adjuvant therapy*

Step 3: moderate to severe pain (rating 7–10 on 0–10 scale)Opioids (eg, morphine, hydromorphone, methadone, fentanyl, oxycodone)± Nonopioid± Adjuvant therapy*

Adapted from WHO’s pain relief ladder. Available at www.who.int/ cancer/palliative/painladder/en. Accessed 21 Mar 2005. *Medications to counteract opioid side effects or provide additional

analgesia (eg, anticonvulsants, antiepileptics, corticosteroids, and/or step 1 medications)

http://www.who.int/

Traub, S. J. et. al. N Engl J Med 2003;349:2519-2526

COCAINE

Users, Carriers & Routes of Users, Carriers & Routes of AdministrationAdministration

•• In 1999, an estimated 1.5m Americans In 1999, an estimated 1.5m Americans were current users and 3.7m had taken it were current users and 3.7m had taken it in the past 12 months. Hair analysis for in the past 12 months. Hair analysis for metabolites suggests a 4metabolites suggests a 4--5 fold larger 5 fold larger problem.problem.

•• Its subjective and Its subjective and sympathomimeticsympathomimeticactions are often indistinguishable from actions are often indistinguishable from amphetamine even for experienced users.amphetamine even for experienced users.

•• Onset can be very rapid when snorted or Onset can be very rapid when snorted or smoked (freebasing 'crack').smoked (freebasing 'crack').

•• Occasionally massive overdose in drug Occasionally massive overdose in drug smugglers presents after smugglers presents after swallowed/secreted packets rupture. swallowed/secreted packets rupture.

PapaverPapaver SomniferumSomniferumOPIATESPresentation• Pin-point pupils & Coma• Severe respiratory depression/cyanosis • BP may be low but often well maintained

- NB pentazocine overdose actually BP• Hypotonia often marked

- dextropropoxyphene and pethidine muscle tone and cause fits

Complications•All opiates can cause non-cardiogenic pulmonary oedema

- but most frequent with IV heroin. • Rhabdomyolysis is common in opiate-induced coma

- it should be looked for in all cases. • Substances used to dilute ('cut') illicit opiates may be toxic

e.g. talc and quinine.

3,4-methylenedioxy-methamphetamine (MDMA, Ecstasy)Presentation – following typical of amphetamines but not features of usual recreational doses of ESympathomimetic effects - mydriasis, BP, HR, skin pallor. Central effects - hyperexcitability, talkativeness and agitation. [Paranoid features may be obvious especially in chronic users – not applicable to E]. Complications A 'heat-stroke' like syndrome: rhabdomyolysis, hyperpyrexia (>42 C), DIC and acute renal failure. It carries a poor prognosis (see cocaine).[Intracranial (and subarachnoid) haemorrhage (? 2ary to hypertensive effect but can occur after single therapeutic doses and vasospasm reported at angiography 'string-of-beads' sign) – not applicable to E].

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تجويز و مصرف منطقي آرامبخش ها و مخدر ها در بيماري كليه