Periodic Paralyses Medication
- Author: Naganand Sripathi, MD; Chief Editor: Nicholas Lorenzo, MD more...
Medication Summary
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Carbonic anhydrase inhibitors
Class Summary
Carbonic anhydrase (CA) is an enzyme found in many tissues of the body, including the eye. It catalyzes a reversible reaction whereby carbon dioxide becomes hydrated and carbonic acid dehydrated.
Acetazolamide (Diamox)
Exact mechanism of action unknown. In hypokalemic PP, may decrease potassium inflow to muscle because of metabolic acidosis. In hyperkalemic PP, kaliopenic effect of CA inhibitors may be beneficial. Recent data suggest carbonic anhydrase inhibitors activate skeletal muscle BK channel (Ca2+ -activated potassium channel).
Dichlorphenamide (Daranide)
May improve clinical condition of patients with hypokalemic PP or hyperkalemic PP. Kaliopenic effect of CA inhibitors may be beneficial.
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- Table 1. Primary Periodic Paralysis
- Table 2. Distinguishing Features Among the Common Forms of Periodic Paralyses
- Table 3. Differential Diagnosis of Secondary Periodic Paralyses
- Table 4. Differential Diagnosis of Other Entities Causing Acute Generalized Weakness
- Table 5. Medical Conditions Associated With Hypokalemia
- Table 6. Diagnostic Studies of Hypokalemic and Hyperkalemic Periodic Paralyses
- Table 7. Electrophysiological Patterns to Exercise Testing
| Sodium channel | Hyperkalemic PP (HyperPP) Hypokalemic PP (HypoPP2) Paramyotonia congenita |
| Calcium channel | Hypokalemic PP (HypoPP1) |
| Potassium channel | Andersen-Tawil syndrome Hyperkalemic PP or hypokalemic PP* |
| *The deficit was described in 2 small families and has not been substantiated by others.[1, 2] | |
| Syndrome | Age of Onset | Duration of Attack | Precipitating Factors | Severity of Attacks | Associated Features |
| Hyper-kalemic periodic paralyses | First decade of life | Few minutes to less than 2 h (mostly less than 1 h) | Low carbohydrate intake (fasting) Cold Rest following exercise Alcohol Infection Emotional stress Trauma Menstrual period | Rarely severe | Perioral and limb paresthesias Myotonia frequent Occasional pseudo-hypertrophy of muscles |
| Hypo-kalemic periodic paralyses | Variable -Childhood to third decade Majority of cases before 16 years | Few hours to almost a week Typically no longer than 72 h | Early morning attacks after previous day physical activity High-carbohydrate meal, Chinese food, alcohol Cold, change in barometric pressure or humidity Fever, upper respiratory tract infections Lack of sleep, fatigue Menstrual cycle | Severe Complete paralysis | Occasional myotonic lid lag Myotonia between attacks rare Unilateral, partial, monomelic Fixed muscle weakness late in disease |
| Potassium- associated myotonia | First decade | No weakness | Cold Rest after exercise | Attacks of stiffness can be mild to severe | Muscle hypertrophy |
| Para-myotonia congenita | First decade | 2-24 h | Cold | Rarely severe | Pseudo-hypertrophy of muscles Paradoxical myotonia Fixed weakness rare |
| Thyrotoxic periodic paralyses | Third and fourth decades | Few hours to 7 d | Same as hypokalemic PP Hyper-insulinemia | Same as hypokalemic PP | Fixed muscle weakness may develop Hypokalemia during attacks |
| Hypokalemic | Hyperkalemic |
Urinary potassium-wasting syndromes
| |
| Alcohol | Addison disease Chronic renal failure Hyporeninemic Hypoaldosteronism |
| Drugs - Amphotericin B, barium | Ileostomy with tight stoma |
| Renal tubular acidosis | Potassium load |
GI potassium-wasting syndromes
| Potassium-sparing diuretics |
| Disorder | Pattern and Distribution of Weakness |
| Transient ischemic attacks | Follow CNS distribution (ie, hemiparetic) May have sensory symptoms and signs |
| Sleep attacks | Occur at onset or termination of sleep Last only minutes |
Myelopathy
| Sensory symptoms Presence of a sensory level Sphincter involvement |
| Myasthenia gravis Lambert-Eaton myasthenic syndrome | Subacute in onset Associated autonomic symptoms in LEMS Hyporeflexia in LEMS Abnormal repetitive nerve stimulation Presence of distinct antibodies |
Peripheral neuropathy of acute onset
| Pattern of weakness Absent stretch reflexes |
Toxins
| Clinical presentation |
| Urine K/C Ratio | Acid Base Status | Other Associated Features | Medical Conditions |
| < 1.5 | Metabolic acidosis | Lower GI loss – Laxative abuse, diarrhea | |
| < 1.5 | Metabolic alkalosis | Normal BP | Surreptitious vomiting |
| >1.5 | Metabolic acidosis | DKA, type 1 or type 2 distal RTA | |
| >1.5 | Metabolic alkalosis | Normal BP | Diuretic use, Bartter syndrome, Gitelman syndrome |
| ≥1.5 | Metabolic alkalosis | Hypertension | Primary aldosteronism, Cushing syndrome, renal artery stenosis, congenital adrenal hyperplasia, apparent mineralocorticoid excess, Liddle syndrome |
| Hypokalemic PP | Hyperkalemic PP | |
| Serum potassium | Mildly depressed; may reach 1-5 mEq/L | Increases from baseline but may not increase beyond normal range |
| Serum CPK | Moderately elevated during attacks | Mildly elevated during attacks |
| ECG | Bradycardia Flat T waves, U waves, ST-segment depression | Tall T waves |
| Para- myotonia Congenita | Hyper- kalemic Periodic Paralysis | Hypo- kalemic Periodic Paralysis | |
| Electrophysiological pattern | I | IV | V |
| Channel mutations | Sodium T1313M, R1448C | Sodium T704M | Calcium R528H |
| Short Exercise Test: | |||
| Post exercise myotonic potentials | Yes | No | No |
| CMAP amplitude change after First trial | Increase or decrease | Increase | No |
| CMAP amplitude change after second and third trial | Gradual increase | Gradual increase | No |
| Long Exercise Test: | |||
| Immediate change of CMAP amplitude | Decrease | Increase | No |
| Late change of CMAP amplitude | Decrease | Decrease | Decrease |
| Modified from Fournier et al, 2004.[9] | |||
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