‫تجويز و مصرف منطقي آرامبخش ها و‬
‫مخدر ها در بيماري كليه‬
‫دكتر شيوا صيرفيان‬
‫‪ - IUMS‬نفرولوژيست‬
‫‪9/8/1392‬‬
Anti-anxiety Medications
Claim to:
Decrease anxiety and stress
Decrease irritability and agitation
Anti-anxiety Medications
Benzodiazepines
Selective Serotonin Reuptake Inhibitors
Tricyclic Antidepressants
Monoamine Oxidase Inhibitors
Serotonin Norepinephrine Reuptake
Inhibitors
Antihistamines
Anticonvulsants
Beta blockers
Alpha-Blockers
Antipsychotics
Other
Anti-anxiety Medications
Generic Name
Lorazepam (benz.)
Clonazepam (benz.)
Propranolol (beta bl.)
Antidepressants and SSRIs
Generic Name
Clomipramine
Fluoxetine
Citalopram
Sertraline

Brand Name
Anafranil
Prozac
Celexa
Zoloft
Drugs routinely monitored
• Anti-epileptics
Phenytoin,
Carbamazepine, (Valproate)
• Anti-psychotics
Lithium
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.
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.
Lithium
Half-life
24 hours
Time to steady state sampling
4-5 days after starting or change in therapy or
sodium/fluid intake
Loading dose
400mg-1.2g daily
Maintenance dose
400mg – 1,200mg od po
When to take blood
pre-dose
How often to repeat
Weekly until dose stable then at least 3-monthly
Sampling method
Plain tube
Signs of toxicity
Hyperreflexia & hyperextension of limbs,
convulsions, psychoses, syncope, renal failure,
circulatory failure, coma, death
Target range
0.4 – 1.0 mmol/L
Practical issues
Slow release brands not interchangeable
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 Name
Divalproex
Valproic acid
Carbamazepine

Brand Name
Depakote
Depakene
Tegretol
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,and
oxcarbazepine,
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.
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, sertraline
Safe in renal disease.
% of
Sedativ Normal Renal
GFR GFR 10 GFR
es
Dosage Excretion >50 to 50
<10 Comments HD CAPD CVVH
Barbitur May cause excessive sedation, increase osteomalacia in ESRD. Charcoal
ates
hemoperfusion and hemodialysis more effective than peritoneal dialysis for
poisoning.
Pentobar 30 mg q6 Hepatic
100 100%
100%
NoneNo
Dose
bital
to 8h
%
data for GFR
10 to
50
Phenoba 50 to 100 Hepatic
q8 q8 to 12h q12 to Up to 50%
Dose 1/2
Dose
rbital
mg q8 to (renal)
to
16h unchanged after normal for GFR
12h
12h
drug excreted dialy dose 10 to
with urine
sis
50
with alkaline
diuresis
Secobar 30 to 50 Hepatic
100 100%
100%
NoneNone N/A
bital
mg q6 to
%
8h
Thiopent Anesthesi Hepatic
100 100%
100%
N/A N/A
N/A
al
a
%
induction
(individual
ized)
Benzodia Norm % of
zepines al
Renal
Dosag Excreti
e
on
Benzodiaz
epines
Alprazolam0.25 to Hepatic
5.0 mg
q8h
Clorazepat 15 to Hepatic
e
60 mg (renal)
q24h
Chlordiaze 15 to Hepatic
poxide
100
mg
q24h
Clonazepa 1.5 mg Hepatic
m
q24h
GFR
10
GFR to GFR
CA
>50 50 <10Comments
HD PD CVVH
May cause excessive sedation
and encephalopathy in ESRD
100 100 100
No No N/A
% % %
ne data
100 100 100
% % %
No No N/A
dat data
a
100 100 50%
No No Dose
% %
ne datafor
GFR 10
to 50
100 100 100 Although no dose reduction is No No N/A
% % % recommended, the drug has ne data
not been studied in patients
with renal impairment.
Recommendations are based
on known drug characteristics
not clinical trials data.
Benzodi
% of
GFR
azepines Normal Renal
GFR 10 to GFR
Dosage Excretion>50 50
<10
Diazepam 5 to 40 Hepatic 100% 100% 100%
mg
q24h
Comments
HD CAPDCVVH
Active
None No
None
metabolites,
data
desmethyldiaze
pam, and
oxazepam may
accumulate in
renal failure.
Dose should be
reduced if given
longer than a
few days.
Protein binding
decreases in
uremia.
Benzodi
azepine Normal% of
Dosag Renal
s
e
Excretion
Lorazepa 1 to 2 Hepatic
m
mg q8
to 12h
Midazol Individu Hepatic
am
alized
Oxazepa 30 to Hepatic
m
120 mg
q24h
Antagonist
Flumaz 0.2 mg Hepatic
enil
IV over
15 sec
GFR
GFR 10 to GFR
>50 50 <10 Comments
100 100%100%
%
HD CAPD CVVH
None No data Dose for
GFR 10
to 50
100 100%50%
N/A N/A
N/A
%
May cause
100 100%100% excessive
None No data Dose for
sedation and
%
GFR 10
encephalopathy
to 50
in ESRD
100 100%100%
%
None No data N/A
Miscellane
ous
Norm % of
Sedative al
Renal
Agents
Dosa Excre
ge
tion
Buspirone 5 mg Hepati
q8h c
Ethchlorvyn 500
ol
mg
qhs
GFR
10
GFR to
>50 50
100 100
%
%
GFR
<10 Comments
100
%
HD CAPD CVVH
None No
N/A
data
Hepati 100 Avoid Avoid Removed by
Avoid Avoid N/A
c
%
hemoperfusion.
Excessive
sedation.
Haloperidol 1 to 2 Hepati 100 100 100 Hypertension,
mg q8 c
%
%
%
excessive
to 12h
sedation
None None Dose for
GFR 10 to
50
Miscellan
% of
eous
Nor Rena
Sedative mal l
Agents Dosa Excr GFR
ge etion >50
Lithium 0.9 to Renal 100%
carbonate 1.2 g
q24h
GFR
10 to
50
50%
to
75%
GFR
<10
25%
to
50%
CA
Comments
HD
PD CVVH
Nephrotoxic. Nephrogenic Dose Non Dose
diabetes insipidus.
after e for GFR
Nephrotic syndrome. Renal dialysis
10 to
tubular acidosis. Interstitial
50
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.
Miscellaneou
s Sedative
Agents
% of
Normal Renal
GFR
Dosage Excretion >50
Meprobamate 1.2 to Hepatic
q6h
1.6 g
(renal)
q24h
GFR
10 to
50
q9 to
12h
GFR
<10
q12
to
18h
Comments HD CAPDCVVH
Excessive
None No
N/A
sedation.
data
Excretion
enhanced by
forced
diuresis.
% of
Antiparkin Normal Renal
GFR GFR 10 GFR
son Agents Dosage Excretion >50 to 50 <10 Comments HD CAPD CVVH
Carbidopa 1 tab tid 30
100% 100% 100% Requires
No
No
No data
to 6 tabs
careful
data data
daily
titration of
dose
according to
clinical
response
Levodopa 25 to 500 None
mg bid to
8 g q24h
100% 50% to 50% Active and No
No
100% to
inactive
data data
100% metabolites
excreted in
urine. Active
metabolites
with long t1/2
in ESRD.
Dose
for GFR
10 to
50
% of
Antipsych Normal Renal
GFR GFR 10 GFR
otics
Dosage Excretion >50 to 50 <10 Comments HD CAPD CVVH
Phenothiazines
Orthostatic hypotension,
extrapyramidal symptoms,
and confusion can occur
Chlorproma 300 to
Hepatic
100%100% 100%
Non None Dose for
zine
800 mg
e
GFR 10
q24h
to 50
Promethazi 20 to 100 Hepatic
100%100% 100% Excessive
No No
Dose for
ne
mg q24h
sedation may data data GFR 10
occur in
to 50
ESRD
Thioridazin 50 to 100 Hepatic
100%100% 100%
e
mg po tid.
Increase
gradually.
Maximum
of 800
mg/day.
% of
Antipsy Normal
Renal
GFR
chotics Dosage
Excretion >50
Trifluope1 to 2 mg bid. Hepatic
100%
razine Increase to no
more than 6
mg.
Perphen 8 to 16 mg po Hepatic
100%
azine
bid, tid, or qid.
Increase to 64
mg daily
Thiothix 2 mg po tid.
Hepatic
100%
ene
Increase
gradually to 15
mg daily
Loxapin 12.5 to 50 mg Hepatic
100%
e
IM q4 to 6h
Clozapin 12.5 mg po. 25 Hepatic
e
to 50 daily to
300 to 450 by
end of 2
weeks.
GFR
10 to GFR
50
<10
100% 100%
Comm
ents HDCAPD CVVH
100% 100%
100% 100%
100% 100%
100% 100% 100%
Do not
adminis
ter
drug IV
Antipsycho Normal
% of RenalGFR
tics
Dosage
Excretion >50
Risperidone 1 mg po bid.
Hepatic
100%
Increase to 3 mg
bid.
Olanzapine 5 to 10 mg
Hepatic
100%
Quetiapine 25 mg po bid.
Hepatic
Increase in
increments of 25
to 50 bid or tid.
300 to 400 mg
daily by day 4
GFR 10
to 50
100%
GFR
<10
100%
100%
100%
100% 100%
100%
Comments
Potential
hypotensive
effects
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 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.
Baclofen discontiued and she
discharged from hospital after 3 days.
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 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.
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 3050%, interval increased by 6-8 hrs.
Opioids
Other 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(N
% of
arcotics and
Renal
Narcotic
Normal Excretio GFR GFR 10 GFR
Antagonists) Dosage n
>50 to 50 10 Comments HD CAPD CVVH
Alfentanil
Anesthetic Hepatic 100%100% 100 Titrate the N/A N/A
N/A
induction
% dose
8 to 40
regimen
µg/kg
Butorphanol
Codein
Fentanyl
2 mg q3 Hepatic
to 4h
30 to 60 Hepatic
mg q4 to
6h
100%75%
Anesthetic Hepatic
induction
(individual
ized)
100%75%
100%75%
50%
No No data N/A
data
50%
No No data Dose
data
for
GFR
10 to
50
50% CRRT-titrate N/A N/A
N/A
% of
Narcotics
Renal
and Narcotic Normal Excretio GFR GFR 10 GFR Commen
Antagonists Dosage n
>50 to 50 <10 ts
HD CAPD CVVH
Meperidine
50 to
Hepatic 100%75%
50%
Avoid Avoid Avoid
100 mg
q3 to 4h
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 Hepatic
q6 to 8h
Morphine 20 to 25 mg Hepatic
q4h
100%100%
100%75%
50% to
None None
75%
50%
Increased None No
sensitivity
data
to drug
effect in
ESRD
N/A
Dose
for
GFR
10 to
50
Narcotics
and Narcotic Normal
Antagonists Dosage
Naloxone
0.4 to 2
mg IV
Pentazocine
% of
GFR
Renal
>50
Excretion
Hepatic
100
%
50 mg q4hHepatic
Propoxyphene 65 mg po Hepatic
q6 to 8h
Sufentanil
Anesthetic Hepatic
induction
GFR
10 toGFR
50 < 10Comments HD CAPD CVVH
100 100
N/A N/A
Dose
%
%
for
GFR 10
to 50
100 75% 75%
Non No
%
e data
Dose
for
GFR 10
to 50
100 100 AvoidActive
Avoi Avoid N/A
%
%
metabolite d
norpropoxy
phene
accumulate
s in ESRD
100 100 100 CRRT-titrate N/A N/A
N/A
%
%
%
Anticon
Maxi % of
vulsant Starting mum Renal
GFR
s
Dose
Dose Excretion >50
Carbam 2 to 8
2%
100
azepine mg/kg/d
%
ay;
adjust
for side
effect
and TDM
Clonaze 0.5 mg 2 mg 1%
100
pam
tid
tid
%
GFR
Comments
HD CAPD CVV
10 to GFR
H
50 <10
100%100 Plasma
Non None None
% concentration: 4 e
to 12, double
vision, fluid
retention,
myelosuppression
100%100 Although no dose Non No
N/A
% reduction is
e
data
recommended,
the drug has not
been studied in
patients with renal
impairment.
Recommendations
are based on
known drug
characteristics,
not clinical trials
data.
Normal Doses
Antico
Maxi
nvulsa Startin mum
nts
g Dose Dose
Gabape 150 mg 900
ntin
tid
mg tid
Dosage Adjustment in
Renal Failure
% of
GFR
Renal
GFR 10 to GFR
Excretion >50 50
<10
77%
100 50% 25%
%
Lamotri 25 to 150
1%
gine
50
mg/da
mg/day y
Commen HD
ts
Fewer
CNS side
effects
compared
to other
agents
CAPD CVVH
300 mg 300 mg Dose
load, qod
for GFR
then
10 to
200 to
50
300
after
hemodi
alysis
100 100% 100% Autoinduc No dataNo dataDose
%
tion,
for GFR
major
10 to
drug-drug
50
interaction
with
valproate
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)
COCAINE
Users, Carriers & Routes of
Administration
• In 1999, an estimated 1.5m Americans
were current users and 3.7m had taken it
in the past 12 months. Hair analysis for
metabolites suggests a 4-5 fold larger
problem.
• Its subjective and sympathomimetic
actions are often indistinguishable from
amphetamine even for experienced users.
• Onset can be very rapid when snorted or
smoked (freebasing 'crack').
• Occasionally massive overdose in drug
smugglers presents after
swallowed/secreted packets rupture.
Traub, S. J. et. al. N Engl J Med 2003;349:2519-2526
OPIATES
Papaver Somniferum
Presentation
• 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 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].