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

1. تجويز و مصرف منطقي آرامبخش ها و مخدر ها در بيماري كليه دكتر شيوا صيرفيان نفرولوژيست - IUMS 9/8/1392

2. Anti-anxiety Medications Claim to: • Decrease anxiety and stress • Decrease irritability and agitation

3. Anti-anxiety Medications • Benzodiazepines • Selective Serotonin Reuptake Inhibitors • Tricyclic Antidepressants • Monoamine OxidaseInhibitors • Serotonin Norepinephrine Reuptake Inhibitors • Antihistamines • Anticonvulsants • Beta blockers • Alpha-Blockers • Antipsychotics • Other

4. Anti-anxiety Medications Generic Name • Lorazepam (benz.) • Clonazepam (benz.) • Propranolol (beta bl.)

5. Antidepressants and SSRIs • Generic Name • Clomipramine • Fluoxetine • Citalopram • Sertraline • Brand Name • Anafranil • Prozac • Celexa • Zoloft

6. Drugs routinely monitored • Anti-epileptics • Phenytoin, • Carbamazepine, (Valproate) • Anti-psychotics • Lithium

7. Case 1 • A 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.

8. 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 nephrotoxicity • Now he is on depakin, leponex(clozapin), lisinopril, allopurinol and metoral. • After 16 months Cr=1.78 and BUN=17.

11. Mood Stabilizers & Anticonvulsants • Generic Name • Divalproex • Valproic acid • Carbamazepine • Brand Name • Depakote • Depakene • Tegretol

12. Anticonvulsants • Carbamazepine: 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,andoxcarbazepine,

13. Anticonvulsants • Gabapentin: 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.

14. 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.

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

27. 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.

28. Case 2 • She 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. • Baclofendiscontiued and she discharged from hospital after 3 days.

29. Case 3 • A 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 creatinekinase, creatinine, myoglobin and lactate dehydrogenase. Intravenous hydration, bicarbonate and mannitol treatment were applied. During the follow-up period,

30. Case 3… • the serum creatinekinase 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.

31. 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.

32. Opioids • Metabolite 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.

33. Opioids • Other opioids: codein, oxycodone, and hydromorphone. Seizures,myoclonus,orofacialdyskinesias, 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.

39. 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)

43. 3,4-methylenedioxy-methamphetamine (MDMA, Ecstasy) • Presentation– following typical of amphetamines but not features of usual recreational doses of E • Sympathomimetic 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].