Drugs Avoided in Patients with Renal Failure

Drugs Avoided in Patients with Renal Failure

➧ The excretion of water-soluble drugs and their active metabolites will be impaired. For drugs that are renally excreted the half-life increases slowly with deteriorating renal function until severe nephron loss at which point the half-life increases sharply with further reductions in renal function. Dialysis can only usually replace a small part of the excretory capacity of the healthy kidney. 

Antibacterial agents:

1-Injectable penicillin G or carbenicillin: may be associated with neuromuscular toxicity, myoclonus, seizures, or coma. 

2-Vancomycin 

3-Amphotericin 

4-Tetracyclines: except doxycycline (Vibramycin), have an antianabolic effect that may significantly worsen the uremic state in patients with severe disease. 

5-Aminoglycosides 

6-Imipenem/cilastatin (Primaxin): can accumulate in patients with chronic kidney disease, causing seizures if doses are not reduced. 

7-Sulphonamides 

8-Nitrofurantoin (Furadantin): has a toxic metabolite that can accumulate in patients with chronic kidney disease, causing peripheral neuritis. 

Anesthetic drugs:

1-Muscle relaxants:

➧ Depolarizing muscle relaxant:

-Suxamethonium: should be avoided if hyperkalemia is present. 

➧ Non-depolarising muscle relaxants (NDMRs): 

-NDMRs depend on the kidney for elimination)

-Gallamine: should be avoided 

-Pancuronium, pipecuronium, alcuronium, curare, and doxacurium: should be used with caution. Potentiation of neuromuscular blockade may occur in the presence of metabolic acidosis, hypokalemia, hypermagnesemia, or hypocalcemia and with medications such as aminoglycosides. Monitor neuromuscular blockade whenever possible. 

-Vecuronium and mivacurium: are safe to use in renal failure as only small percentages are excreted renally.

2-Opioids:

-Morphine: is metabolized in the liver to morphine-6-glucuronide which has about half the sedative effect of morphine with a markedly prolonged half-life. 

-Pethidine: is partially metabolized to norpethidine which is less analgesic and has excitatory and convulsant properties. 

-Tramadol and codeine: Metabolites can accumulate in patients with chronic kidney disease, causing central nervous system and respiratory adverse effects.

3-Inhalational agents:

➧ There is decreased elimination of the fluoride ions which are significant metabolites of enflurane, sevoflurane, and methoxyflurane which can worsen renal function, so these inhalational agents should be avoided especially if used at low flows. 

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs):

➧ NSAIDs should be avoided as all decrease renal blood flow and may precipitate complete renal failure. 

➧ Adverse renal effects of NSAIDs include acute renal failure; nephrotic syndrome with interstitial nephritis; and chronic renal failure.

➧ The risk of acute renal failure is three times higher in NSAID users than in non-NSAID users.

➧ Other adverse effects of NSAIDs include decreased potassium excretion, which can cause hyperkalemia, and decreased sodium excretion, which can cause peripheral edema, elevated blood pressure, and decompensation of heart failure.

➧ NSAIDs can blunt antihypertensive treatment, especially if beta-blockers, ACE inhibitors, or ARBs are used.

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Drugs affecting IOP

Drugs affecting IOP

➧ Normal intraocular pressure (IOP) is between (10 - 20 mmHg). The average value of IOP is 15.5 mmHg with fluctuations of about 2.75 mmHg.

➧ IOP also varies with other factors such as heart rate, respiration, fluid intake, systemic medication, and topical drugs.

➧ Intraocular vascular tone is predominantly affected by CO₂; hypocarbia decreases IOP through vasoconstriction of the choroidal blood vessels and decreases the formation of aqueous humor through reduced carbonic anhydrase activity. The increased IOP associated with hypoventilation and hypercarbia occurs as a result of vasodilation of CBV and increases in central venous pressure. 

A) Drugs that ↑ IOP:

1-Steroid-induced glaucoma:

Mechanism:

Is a form of open-angle glaucoma that is usually associated with topical steroid use, but it may develop with inhaled, oral, intravenous, periocular, or intravitreal steroid administration. 

Risk factors:

-Preexisting primary open-angle glaucoma

-Family history of glaucoma

-High myopia, diabetes mellitus

-History of connective tissue disease (especially rheumatoid arthritis). 

➧ Patients on chronic corticosteroid therapy can remain undiagnosed with an elevated IOP, which can result in glaucomatous optic nerve damage. 

➧ Steroid-induced IOP elevation typically occurs within a few weeks of beginning steroid therapy. In most cases, the IOP lowers spontaneously to the baseline within a few weeks to months upon stopping the steroid. In rare instances, the IOP remains elevated.

2-Topical anticholinergic or sympathomimetic dilating drops, TCA, MAOI, antihistamines, antiparkinsonian drugs, antipsychotic medications, and antispasmolytic agents:

Mechanism:

These medications produce pupillary dilation and precipitate an attack of acute angle-closure glaucoma in anatomically predisposed eyes that have narrow angles. 

3-Sulfa containing medications:

Mechanism:

Induce anterior rotation of the ciliary body causing angle-closure glaucoma. Typically, the angle closure is bilateral and occurs within the first several doses of the sulfonamide-containing medication. Patients with narrow or wide-open angles are potentially susceptible to this rare and idiosyncratic reaction.

4-Ketamine: 

The effect on IOP varies. Early studies reported an increase in IOP after IV or IM administration of ketamine. Ketamine given after premedication with diazepam and meperidine does not affect IOP and IM administered ketamine may even lower IOP in children. 

5-Depolarizing muscle relaxants (Succinylcholine):

Causes a transient (4–6 min) but significant increase in IOP of (10 - 20 mm Hg). Although the mechanism is unclear, the increase is not attributable simply to induced muscle fasciculations. 

6-Large volume Local anesthetic:

Injecting a large volume (8–10 mL) of Local anesthetic into the orbit (e.g. peribulbar block).

7-Tracheal intubation:

Sympathetic cardiovascular responses to tracheal intubation. 

8- Caffeine

B) Drugs that ↓ IOP:

In general, CNS depressants lower IOP.

1-Intravenous anesthetics and volatile agents:

Mechanism:

Relax extraocular muscle tone, depress the CNS (i.e., the diencephalon), improve the outflow of aqueous humor, and lower venous and arterial blood pressures.

➧ e.g. thiopental, propofol, etomidate, decrease in IOP by 14 - 50 % have been noted.

➧ During controlled ventilation and normocapnia, volatile inhaled anesthetics reduce IOP in proportion to the depth of anesthesia.

2-Non depolarizing neuromuscular blocking drugs:

Either do not affect IOP or produce a slight decrease.

3-Benzodiazepines:

IV administered diazepam (0.15 mg/kg) and equipotent intravenous doses of midazolam (0.03 mg/kg).

4-Narcotic premedication:

Causes no change, or only a slight decrease, in IOP. 

5-Neuroleptanalgesia:

Produced by mixtures of (fentanyl and droperidol) decreases IOP by 12 % in normocapnic patients. 

6- Alcohol consumption:

This leads to a transient decrease in IOP.

7- Several pretreatment regimens:

➧ IV lidocaine (1.5 mg/kg) or sufentanil (0.05–0.15 µg/kg) given 3 - 5 min. before induction. 

➧ Oral administration of the centrally acting antihypertensive drug clonidine (5 µg/kg) 2 hrs before induction of anesthesia blunts the IOP response to intubation. 

➧ Intranasal administration of nitroglycerin

➧ β-adrenergic receptor blocking drugs

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Drugs with Rebound Phenomenon

Drugs with Rebound Phenomenon

➧ The rebound effect, or rebound phenomenon, is the tendency of some medications, in sudden discontinuation, to cause a return of the symptoms it relieved, to a degree stronger than they were before treatment first began. Medications with a known rebound effect can be withdrawn gradually, or, in conjunction with another medication that does not exhibit a rebound effect. 

1-Sedative Hypnotics: 

-Benzodiazepine withdrawal can cause rebound anxiety and insomnia. 

-Eszopiclone and Zolpidem) can cause rebound insomnia. 

2-Stimulants:

➧ e.g. Methylphenidate or Dextroamphetamine 

➧ Rebound effects include psychosis, depression, and a return of ADHD symptoms but in a temporarily exaggerated form. 

3-Antidepressants:

➧ e.g. SSRIs

➧ Cause rebound depression and/or panic attacks and anxiety when discontinued. 

4-Alpha-2 adrenergic agents:

➧ e.g. Clonidine and Guanfacine

➧ The most notable rebound effect is rebound hypertension. 

5-Beta-adrenergic antagonists:

➧ e.g. Bisoprolol

➧ Sudden withdrawal leads to rebound tachycardia and anginal pain. 

6-Highly potent corticosteroids:

➧ e.g. Clobetasol for psoriasis

➧ Abrupt withdrawal can cause rebound psoriasis and hypoglycemia. 

7-Warfarin: 

➧ Withdrawal leads to thromboembolism 

8-Alcohol:

➧ Withdrawal leads to alcohol withdrawal syndrome: (anxiety and convulsions). 

9- Painkillers:

➧ Withdrawal can cause rebound headaches. 

10-Topical decongestants:

➧ Nasal sprays e.g. Phenylephrine

➧ Continuous usage can lead to constant nasal congestion, known as Rhinitis medicamentosa, and discontinuation to rebound nasal congestion.

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