DANTROLENE
ACTION
A hydantoin derivative. It is a direct-acting skeletal muscle relaxant, affecting the contractile response of the muscle at a site beyond the myoneural junction.
Dantrolene depresses excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor 1, and decreasing intracellular calcium concentration. Ryanodine receptors mediate the release of calcium from the sarcoplasmic reticulum, an essential step in muscle contraction, thus helping to re-establish a normal level of ionised calcium.
METABOLISM
The biological half life in plasma in most human subjects is between 5 and 9 hours, although half lives as long as 12.1 ± 1.9 hours have been reported after a single intravenous dose. Inactivation is by hepatic metabolism in the first instance.
INDICATIONS
- Fulminant hypermetabolism of skeletal muscle
- A characteristic of malignant hyperthermia crisis
COMES AS
- IV/PO
- 20mg powder for solution for injection vials.
- 25mg capsules.
DOSAGE
- For malignant hyperthermia
-
- By rapid IV injection. Initially 2-3mg/kg repeated if necessary. Maximum 10mg/kg per course.
- For chronic severe spasticity of voluntary muscle
- Initially 25 mg daily, then increased to up to 100mg 4 times a day. Dose increased at weekly intervals; usual dose 75mg 3 times a day.
WARNINGS AND PRECAUTIONS
- Hepatotoxocity – potentially life-threatening. Discontinue if abnormal LFTs or symptoms of liver disorder.
- WITH IV USE
- Dizziness, erythema, hepatotoxicity, injection site reactions, pulmonary oedema, rash, swelling, thrombophlebitis, weakness
DESMOPRESSIN
ACTION
Desmopressin is a synthetic analogue of ADH. ADH is produced by the hypothalamus and stored in the posterior pituitary gland. ADH stimulates water reabsorption in the kidneys by causing the insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. It also causes vasoconstriction through its action on vascular smooth muscle cells of the collecting tubules. Compared to natural ADH, desmopressin elicits a great antidiuretic response on weight basis.
INDICATIONS
- Central diabetes insipidus
- Haemorrhage
- Polyuria
- Primary nocturnal enuresis
COMES AS
- IV/PO/SL/Intranasal
- 100/200 microgram tablets
- 4 micrograms/1mL solution for injection
- For IV administration give intermittently in 0.9% NaCl. Dilute with 50mL and give over 20 minutes.
DOSAGE
- For diabetes insipidus
- Initially 100 micrograms 3 times a day
- Maintenance 100-200 3 times a day. Usual dose 0.2-1.2 mg daily
- Primary nocturnal enuresis
- 200 micrograms once daily, only increased to 400 micrograms if lower dose ineffective. Withdraw for at least one week for reassessment after 3 months.
WARNINGS AND PRECAUTIONS
Caution in asthma. Avoid fluid overload. Cardiovascular disease – not indicated for nocturnal enuresis or nocturia. Epilepsy, heart failure, hypertension.
- Elderly
- Elderly patients are at increased risk of hyponatraemia and renal impairment – measure baseline serum sodium and monitor regularly.
DEXAMETHASONE
ACTION
A synthetic glucocorticoid agonist. Unbound dexamethasone crosses cell membranes and binds with high affinity to specific cytoplasmic glucocorticoid receptors. This complex binds to DNA elements (glucocorticoid response elements) which results in a modification of protein synthesis in order to achieve inhibition of leukocyte infiltration at the site of inflammation. As an antiemetic it may involve prostaglandin antagonism or the release of endorphins.
INDICATIONS
- Suppression of inflammatory and allergic disorders. Croup. Congenital adrenal hyperplasia
- Overnight dexamethasone suppression test
- Nausea
COMES AS
- IV/IM/PO/eye drops
- 3mg/mL vials for injection vials
- 2mg tablets
DOSAGE
- Suppression of inflammatory and allergic disorders
- 0.5-10 mg daily PO
- Croup in child
- Mild – 150 micrograms/kg for 1 dose PO
- Severe – initially 150 micrograms/kg for 1 dose PO/IV prior to hospital admission then 150 micrograms/kg PO/IV then 150 micrograms/kg after 12 hours if required.
- Overnight dexamethasone suppression test
- 1mg for 1 dose to be given at night PO
- Nausea
- Used in anaesthesia IV 3.3-6.6mg
WARNINGS AND PRECAUTIONS
- Avoid alcohol.
- Avoid taking with grapefruit juice. Take with food to reduce irritation.
- Pregnancy – readily crosses the placenta and may pass into breast milk.
- May cause affective/psychotic reactions
- Endocrine and metabolic disturbances
- Intravitreal use – ocular herpes simplex
DEXMEDETOMIDINE
ACTION
Alpha2-adrenergic agonist sedative.
INDICATIONS AND USAGE
Precedex is a relatively selective alpha2-adrenergic agonist indicated for:
- Sedation of initially intubated and mechanically ventilated patients
- Sedation of non-intubated patients prior to and/or during surgical and other procedures.
DOSAGE
- Dilute the 200 mcg/2 mL (100 mcg/mL) vial contents in 0.9% sodium chloride solution to achieve required concentration (4 mcg/mL) prior to administration.
- Neat 200 mcg/50mL and 400 mcg/100 mL
- General Sedation
- Load 1 mcg/kg over 10 minutes, followed by a maintenance infusion of 0.2 to 1mcg/kg/hour.
WARNINGS AND PRECAUTIONS:
- Bradycardia and Sinus Arrest: Have occurred in young healthy volunteers with high vagal tone or with different routes of administration, e.g., rapid intravenous or bolus administration.
- Hypotension and Bradycardia: May necessitate medical intervention. May be more pronounced in patients with hypovolemia, diabetes mellitus, or chronic hypertension, and in the elderly.
- Use with caution in patients with advanced heart block or severe ventricular dysfunction.
- Co-administration with Other Vasodilators or Negative Chronotropic Agents: Use with caution due to additive pharmacodynamic effects.
- Transient Hypertension: Observed primarily during the loading dose. Consider reduction in loading infusion rate.
- Arousability: Patients can become aroused/alert with stimulation; this alone should not be considered as lack of efficacy.
- Prolonged exposure to dexmedetomidine beyond 24 hours may be associated with tolerance and tachyphylaxis and a dose-related increase in adverse events
DOBUTAMINE
ACTION
Synthetic catecholamine with strong β1 and weak β2 effects
Consists of racemic mixture of two isomers: L-isomer (α-agonist) and D-isomer (β1 and β2 agonist).
The α1 and β2 effects largely cancel each other out, resulting in an agent which is near to a pure intotrope in its actions, increasing contractility, cardiac output, stroke volume and (at higher doses) heart rate.
INDICATIONS AND USAGE
Used to increase cardiac output in the short-term treatment of patients with cardiac decompensation caused by depressed contractility from organic heart disease, cardiac surgical procedures, cardiac arrest or acute myocardial infarction.
Dobutamine can also be used in septic shock, in combination with volume replacement.
COMES AS
IV
20ml vial contains 250mg of dobutamine
Add 250mg of dobutamine (20ml) to 80ml of compatible IV fluid (i.e. 250mg in 100ml)
DOSAGE
- IV
- 2.5-20 mcg/kg/min
Warnings
- CVS
- Tachycardia and marked increase in systolic blood pressure indicate overdosage.
- Nausea and vomiting, headache, angina, palpitations are common
- Peripheral administration can cause peripheral vasoconstriction and necrosis. If peripheral administration is required a more dilute solution should be used- 250mg dobutamine in 500mL sodium chloride 0.9% (500micrograms/mL).
