Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

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.

Dichlorphenamide (Keveyis)

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Carbonic anhydrase inhibitor, but the exact mechanism by which dichlorphenamide is able to treat periodic paralysis is unknown. Inhibits H+ ion excretion in renal tubule, resulting in increased sodium, potassium, bicarbonate, and water excretion and producing alkaline diuresis. It is indicated for primary hyperkalemic periodic paralysis, primary hypokalemic periodic paralysis, and related variants.

Acetazolamide (Diamox)

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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).

Follow-up

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Media Gallery

Mutations in periodic paralysis.

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Disease	Gene	Protein	Inheritance	Mutation
HyperPP	SCN4A	Nav1.4	Dominant	Gain
NormoPP				Gain (ω-pore)
Paramyotoniacongenita				Gain
HypoPP Type II				Gain (ω-pore)
HypoPP Type I	CACNA1S	Cav1.1	Dominant	Gain (ω-pore)
ThyrotoxicPP	KCNJ18	Kir2.18	Dominant	Loss
Andersen-Tawil syndrome	KCNJ2	Kir2.1	Dominant	Loss

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 Hyperaldosteronism Conn syndrome Bartter syndrome Licorice intoxication
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 Laxative abuse Severe diarrhea	Potassium-sparing diuretics

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.^[15]

Periodic Paralyses Medication

Medication Summary

Carbonic anhydrase inhibitors

Class Summary

Dichlorphenamide (Keveyis)

Dichlorphenamide (Keveyis)

Acetazolamide (Diamox)

Acetazolamide (Diamox)

References

Tables

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