Renal sedation

Gabapentin Modulate calcium channels and enhance GABA activity Loading dose Not recommended due to short half-life Maintenance dose 900-3600 mg/day in 3-4 divided doses (doses up to 1 0,000 mg/day have been tolerated) Half-life Not established 5-7 hours (proportional to creatinine clearance) Apparent volume of distribution 0.6-0.8 L/kg Protein binding less than 10% Primary elimination route Renal Drowsiness, sedation Peripheral edema, weight gain... 

In addition to treating insomnia, gabapentin has been used to treat epilepsy, anxiety disorders, and bipolar disorder. It is generally well tolerated with sedation and headaches being the only prominent side effects. Because gabapentin is excreted unchanged in urine, it does not require metabolism by the liver. It is therefore easily eliminated by elderly patients and those with liver disease, although it should be used with caution in those with poor renal (kidney) function. 

In animal studies, the oral LDso typically ranges between 800 and 1200mg/kg. Acute signs of intoxication include sedation, flaccid muscle tone, ataxia, and prostration death is due to CNS depression. In cases in which death does not occur until several days after acute exposure, hepatic and renal injury may be the cause of death. 

Buspirone (BuSpar) [Anxiolytic] WARNING Closely monitor for worsening depression or emergence of suicidality Uses Short-term relief of anxiety Action Antianxiety antagonizes CNS serotonin receptors Dose Initial 7.5 mg PO bid T by 5 mg q2-3d to effect usual 20-30 mg/d max 60 mg/d Contra w/ MAOI Caution [B, /-] Avoid w/ severe hepatic/renal insuff Disp Tabs SE Drowsiness, dizziness, HA, N, EPS, serotonin synd, hostility, depression Notes No abuse potential or physical/psychologic d endence Interactions T Effects W/ erythromycin, clarithromycin, itraconazole, ketoconazole, diltiazem, verapamil, grapefruit juice effects W/ carbamazepine, rifampin, phenytoin, dexamethasone, phenobarbital, fluoxetine EMS T Sedation w/ concurrent EtOH use grapefruit juice may T risk of adverse effects OD May cause dizziness, miosis, N/V symptomatic and supportive... 

HydroNarcotic Analgesic/NSAID] Uses Mod-severe pain (<10 d) Action Narcotic w/ NSAID Dose 1—2 tabs q4-6h PRN Caution [C, M] Renal insuff -1- effect w/ ACE inhibitors diuretics t effect w/ CNS d ressants, EtOH, MAOI, ASA, TCA, anticoagulants Contra Component sensitivity Disp Tabs SE Sedation, fatigue, GI upset see Hydrocodone Acetaminophen Interactions -1- Effects OF ACEIs, diuretics EMS See Hydrocodone Acetaminophen T risk of bleeding w/ heparin use OD See individual agents... 

Deaths, cardiac and resp have been reported during initiation and conversion of pain pts to methadone Tx from Tx w/ other opioids Uses Severe pain detox w/ maint of narcotic addiction Action Narcotic analgesic Dose Adults. 2.5-10 mg IM q3-8h or 5-15 mg PO q8h titrate as needed Feds. 0.7 mg/kg/24 h PO or IM -s- q8h T slowly to avoid resp depression X in renal impair Caution [B/D (prolonged use/high doses at term), + (w/ doses =/> 20 mg/24 h)], severe liver Dz Disp Tabs, inj SE Resp depression, sedation, constipation, urinary retention, T QT interval, arrhythmias Interactions T Effects W/ cimetidine, CNS depressants, protease inhibitors EtOH T effects OF anticoagulants, antihistamines, barbiturates, glutethimide, methocarbamol ... 

Antiadrenergic] Uses HTN Action Centrally acting antihypCTtensive Dose Adults. 250-500 mg PO bid-tid (max 2-3 g/d) or 250 mg-1 g IV q6-8h Peds. 10 mg/kg/24 h PO in 2-3 doses (max 40 mg/kg/24 h q6-12h) or 5-10 mg/kg/dose IV q6-8h to total dose of 20 0 mg/kg/24 h X in renal insuff/elderly Caution [B (PO), C (IV), +] Contra Liver Dz MAOIs Disp Tabs, inj SE Discolors urine initial transient sedation/drowsiness frequent, edema, hemolytic anemia, hepatic disorders Interactions T Effects W/ anesthetics, diuretics, levodopa, Li, methotrimeprazine, thioxanthenes, vasodilators, verapamil T effects OF haloperidol, Li, tolbutamide effects W/amphetamines, Fe, phenothiazine, TCAs ... 

Uses Acute migraine Action S otonin 5-HTi rec tor antagonist Dose 1—2.5 mg PO once r eat PRN in 4 h 5 mg/24 h max -1- in mild renal/hepatic insuff, take w/ fluids Caution [C, M] Contra Sev e renal/hepatic impair, avoid w/ angina, ischemic heart Dz, uncontrolled HTN, cerebrovascular synds, CTgot use Disp Tabs SE Dizziness, sedation, GI upset, paresthesias, ECG changes, coronary vasospasm, arrhythmias Interactions T Effects W/ MAOIs, SSRIs T effects OF CTgot drugs X effects W7 nicotine EMS May T PR or CyT int val, monitor ECG OD May cause profound HTN and cardiac ischemia symptomatic and supportive... 

For severely hypertensive patients, clonidine has been used in combination with a diuretic, a vasodilator, and a -blocker. Some care must be taken, however, because the coadministration of clonidine and a p-blocker may cause excessive sedation. Clonidine is especially useful in patients with renal failure, since its duration of... 

The clearance of morphine and its active metabolite, morphine-6-glucuronide depends on adequate renal function. The elderly are particularly susceptible to accumulation of the drugs, hence respiratory depression and sedation. Morphine, like all opioids, passes through the placenta rapidly and has been associated with prolongation of labor in pregnant women and respiratory depression in the newborn. 

Geriatric Considerations - Summary One of the least likely antihistamines to cause CNS effects. No dose adjustments required in older adults with decreased renal function. Slow metabolizers likely to experience increased side effects and anticholinergic effects. Increased risk of sedation at higher doses. 

Of particular importance in the geriatric patient Delirium, confusion, cognitive impairment, drowsiness, sedation, altered thinking, ataxia, fatigue, anorexia, increase in creatinine, renal stones... 

At equipotent doses, all benzodiazepines have similar effects. The choice of benzodiazepine is generally based on half-life, rapidity of onset, metabolism, and potency. In patients with moderate to severe hepatic dysfunction, it may be useful to avoid benzodiazepines. All benzodiazepines are metabolized at various levels by the liver, which leads to an increased risk of sedation and confusion in hepatic failure. If it is necessary to prescribe this class of medication, lorazepam and oxazepam are reasonable choices because they are predominantly eliminated by renal excretion. 

Although it is not normally feasible to include comprehensive psychological or psychophysiological testing during the first tolerability trials, because medical aspects have to be paramount at this stage, it is possible to determine with considerable reliability any pronounced central actions of a substance as well as the approximate duration of such effects. Examples are effects on vigilance, attention, concentration and potential side effects such as sedation, stimulation, euphoric effects, etc. Further data also will be available as to the effects of the preparation on vital functions such as ECG, respiration and circulation, as well as on biochemical laboratory tests, liver enzyme and renal functions. 

Tizanidine o -Adrenoceptor agonist in the spinal cord Presynaptic and postsynaptic inhibition of reflex motor output Spasm due to multiple sclerosis, stroke, amyotrophic lateral sclerosis Renal and hepatic elimination t duration, 3-6 h Toxicities Weakness, sedation hypotension... 

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