CICMWrecks Tables (Click to Open)
Adrenaline
Pharmacopeia - Adrenergic and Non-Adrenergic Drugs
| ADRENALINE EPINEPHRINE | |
|---|---|
| GROUP | ADRENERGIC |
| CICM Level of Understanding | Level 1 |
| INTRODUCTION | Is a naturally occurring catecholamine released in the adrenal medulla |
| USES | 1. Anaphylaxis 2. Cardiac arrest 3. Low cardiac output states (including complete heart block) 4. Severe asthma 5. Glaucoma 6. Local vasoconstriction 7. Adjunct to local anaesthetic to prolong duration of action |
| PHARMACEUTICS (PC) | |
| PC: Chemical | |
| PC: Presentation | IV,Neb. in clear sol, Vials 1mg/mL in 5 and 50 mL, Minijets with 1mg in 10mL(1:10000). With Lignocaine (1:80000-200000). In acidic sol as turns pink in alk(oxid to Adrenochrome) |
| PHARMACODYNAMICS (PD) | |
| PD: Main Action | It is a non selective adrenergic agonist. Mast cell stabilizer (anaphylaxis) |
| PD: Mode of Action | - Adrenaline is a natural catecholamine with alpha and beta effects. At low doses, beta 1 and beta 2 effects predominate. At high doses alpha 1 effect predominate. - Alpha1- GqPCR → stimulates phospholipase C → increased IP3/DAG → increased intracellular calcium and smooth muscle constriction - Beta1 and 2 → GsPCR → increased adenylate cyclase → increased cAMP → increased phosphorylation |
| PD: Route & Doses | 1. 1mg in PEA arrest IV 2. Infusion of 0.01-0.1micrograms/kg/min 3. 10mcg/kg (up to 500mcg) IM 4. Nebulizer or MDI |
| PD: Metrics (Onset/ Peak/ Duration) | |
| PD: Effects | lower doses: β2 - vasodilatory, bronchodilation Higher doses β1 agonism: ↑ino+chronotropy Highest doses: primarily a vasoconstrictor. Detail: CVS: - At low dose infusions (beta predominates), beta 2 effects lead to skeletal muscle vasculature vasodilation, leading to a decrease in DBP and SVR. It also causes coronary artery vasodilation. - Beta-1 leads to increased inotropy, increased chronotropy (increases phase 4 gradient), and increased dromotropy. It increases myocardial oxygen consumption and lowers arrhythmia threshold - At higher doses, alpha 1 effects predominate. This causes arteriolar vasoconstriction, which may increase aortic diastolic BP and therefore increase coronary perfusion pressure (e.g. arrest). At these doses it also increases coronary artery vasoconstriction. Venous return may be enhanced as capacitance vessels constrict - Extravasation may cause tissue necrosis and injection into end arteries may lead to digital ischaemia CNS: - May cause anxiety, tremor and raises pain threshold. Causes mydriasis Resp: - Small increase in MV. Potent bronchodilator - PVR increased Renal: - Decreased renal blood flow. Renin stimulation → increased aldosterone and potassium secretion - Decreases plasma volume - Increased bladder sphincter tone, may lead to difficulty of micturition GIT: - Decreased hepatosplanchnic flow. May lead to decreased lactate clearance - Relaxation of gastrointestinal smooth muscle, leading to increased transit times Haem: Coagulation is accelerated by adrenaline. Induces platelet aggregation and increases factor V activity Metabolic - Increases BMR - Increases glycolysis (liver and skeletal muscle) and gluconeogenesis. Alpha1 effects suppress insulin secretion. Causes hyperglycaemia and lactic acidosis. - Lipase activity is augmented, leading to increased lipolysis and keto-acidosis - B2 stimulates Na/K/ATPase, lowering K+. B1 activates RAAS, which leads to aldosterone increasing K+ secretion |
| PD: Side Effects / Toxicity | High doses: HTN+++, tachyarrhythmias, deranged metabolic States: ↑ glucogenolysis, lipolysis, gluconogenesi Insulin Prodxn: initial ↑ (β2) → ↓ (α) limiting use in DM. Can worsen PHTN. Avoid in glaucoma. Peripheral necrosis. |
| PHARMACOKINETICS (PK) | |
| PK: Absorption | IV, IM, SC, Inhaled, ETT 1mg arrest, 0.1mg anaph. Inf: β effects: 0.1-0.3mcg/kg/min α: >0.3 (vasocon). on/dur imm/1-2min |
| PK: Distribution | doesn’t cross the BBB |
| Protein binding (PK: Distribution) | |
| Volume of distribution (PK: Distribution) | |
| PK: Metabolism | Taken up into adrenergic neuron – Metabolized by MAO and COMT Circulating drug hepatically metabolized |
| PK: Excretion | Urine as inactive metabolites |
| - Clearance (PK: Excretion) | |
| - Half Life (PK: Excretion) | 2 minutes |
| SPECIAL POINTS |
Search bar: To search for something particular within the table.
Noradrenaline
Pharmacopeia - Adrenergic and Non-Adrenergic Drugs
| NORADRENALINE NOREPINEPHRINE | |
|---|---|
| GROUP | ADRENERGIC |
| CICM Level of Understanding | Level 1 |
| INTRODUCTION | Is a naturally occurring catecholamine released in post ganglionic SNS, medulla (20:80 Adr) |
| USES | Used to treat hypotension due to decreased SVR |
| PHARMACEUTICS (PC) | |
| PC: Chemical | |
| PC: Presentation | injectable solution only, 1mg/mL in 2 mL vials diluted in 5D or NS. CVC only due to risk of extravasation associated necrosis |
| PHARMACODYNAMICS (PD) | |
| PD: Main Action | Alpha and beta adrenergic receptor activity |
| PD: Mode of Action | - Acts primarily directly at alpha-1-adrenoreceptors (phospholipase C → IP3 → increased calcium) - To a lesser extent acts on beta 1>beta 2 effects |
| PD: Route & Doses | IV infusion- 0.05-0.5mcg/kg. Through a central line diluted with glucose or saline. |
| PD: Metrics (Onset/ Peak/ Duration) | |
| PD: Effects | Low doses: β - ↑ino+chronotropy increased MVO2 Higher doses: 1 - peripheral vasocontriction. ↑systolic/diastolic pressures may cause reflex bradycardia Detail: CVS - Increased SVR leading to increased SBP/DBP/MAP - Increased afterload - leading to increased myocardial oxygen consumption, slight decrease in cardiac output and may lead to reflex bradycardia (through beta-1 effects limit this) - Coronary artery vasodilation increased coronary O2 delivery - Pulmonary vascular resistance is increased - Excessive doses may lead to limb or organ ischaemia - Extravasation may lead to tissue necrosis CNS - Generally improves cerebral blood flow by way of improved CPP more than it decreases CBF by cerebral vasoconstriction Renal/GU - Decreases renal blood flow - Causes uterine constriction (may lead to fetal asphyxia) GIT: - Decreased splanchnic blood flow Metabolic - Less hyperglycaemia/acidosis, although it may decrease insulin secretion |
| PD: Side Effects / Toxicity | Excessive doses cause severe hypertension Reduced flow to organs splanchnic renal Issues with increased MVO2 and IHD |
| PHARMACOKINETICS (PK) | |
| PK: Absorption | IV only Clear Solution 1:1000 8-12 mcg/min uptitrated to effect onset / duration immediate / 1-2 minutes |
| PK: Distribution | doesn’t cross the BBB |
| Protein binding (PK: Distribution) | |
| Volume of distribution (PK: Distribution) | |
| PK: Metabolism | Rapidly metabolised into adrenaline by MAO (Uptake 1, Nv terminal) COMT (Uptake 2 circulation) 25% removed in the lungs |
| PK: Excretion | urine as inactive metabolites (84-96%) |
| - Clearance (PK: Excretion) | |
| - Half Life (PK: Excretion) | 2 minutes |
| SPECIAL POINTS |
Search bar: To search for something particular within the table.
Vasopressin and its analogues
Pharmacopeia - Other Hormones
| ARGIPRESSIN (VASOPRESSIN) | DESMOPRESSIN (dDAVP) | TERLIPRESSIN | |
|---|---|---|---|
| GROUP | Vasopressin Hormone | Vasopressin Analogue | Vasopressin Analogue |
| CICM Level of Understanding | Level 1 | Level 2 | Level 2 |
| INTRODUCTION | Is a naturally occurring nonapeptide-9AA | Synthetic analogue of 8-arginine vasopressin (ADH) Antidiuretic peptide drug displays enhanced antidiuretic potency, fewer pressor effects due to V2-selective actions, and a prolonged half-life and duration of action compared to endogenous ADH | analogue of vasopressin – Prodrug Peiptidases Lysine vasopressin used as a vasoactive drug in the management of hypotension. It has been found to be effective when norepinephrine does not help Longer duration of action than Vasopressin |
| USES | Catecholamine sparing drug in shock Diabetes insipidus Bleeding in vWF def / mild haemophilia | Central DI – ADH replacement (Intranasal/parenteral) Nocturnal polyuria (intranasal). Haemostasis in Haemophilia with fVIII def or Type 1 Von Willebrand disease during surgical procedures and postoperatively to maintain hemostasis (parenteral). | Commonly used to stop bleeding of varices in the food pipe (oesophagus). Hepatorenal syndrome |
| PHARMACEUTICS (PC) | |||
| PC: Chemical | Prod hypothal. released by the posterior pituitary similar to oxytocin complex molecule wt | Deamino Arginine Vasopressin | Prodrug of lysine Vasopressin |
| PC: Presentation | measured in international units 20 IU/ml vial requiring dilution for eff¬ective delivery. It cannot be given orally as it is inactivated by trypsin | sublingual tablet, intra nasal spray, IV/IM | IV |
| PHARMACODYNAMICS (PD) | |||
| PD: Main Action | Acts at the GPCR Vasopressin receptors | Acts at the GPCR Vasopressin receptors | Acts at the GPCR Vasopressin receptors |
| PD: Mode of Action | Acts at the GPCR Vasopressin receptors V1 on vascular smooth muscle Inc intracellular Ca conc, vasoconstrictive V1 on platelets increase platelet aggregation V2 on the nephron Aquaporin-2 trafficking from intracellular vesicle membrane – allowing water reabsorption V2 on endothelial cells – allow vWF release that prevents breakdown of factor VIII V3 (prev V1b) on pituitary Contribute to ACTH release | Acts at the GPCR Vasopressin receptors V1 on vascular smooth muscle – vasoconstrictive – markedly less than ADH (1500x less than ADH) V1 on platelets - increase platelet aggregation – more potent than ADH V2 on the nephron - expressed in the renal collecting duct (CD) - antidiuretic actions (10x ADH) | Acts at the GPCR Vasopressin receptors V1 on vascular smooth muscle - vasoconstrictive V1 on platelets - increase platelet aggregation V2 on the nephron - antidiuretic actions |
| PD: Route & Doses | IV infusion 0.01–0.04 units/min | sublingual tablet, intra nasal spray, IV/IM 0.1 to 1.2 mg divided into 2 or 3 doses | IV 1-2mg terlipressin acetate (0.85-1.7mg Terlipressin) Q6 hourly |
| PD: Metrics (Onset/ Peak/ Duration) | Rapid onset | ||
| PD: Effects | Vasoconstriction – increased MAP Pulmonary vasodilation Increased vWF, factor VIII Antidiuretic: reduced urine output, resolution of polydypsia | Vasoconstriction (less) Increased platelet aggregation Antidiuretic (more) | Vasoconstriction Increased platelet aggregation Antidiuretic |
| PD: Side Effects / Toxicity | Hyponatraemia with H2O retention May cause severe vasoconstriction -CVC only Arrhythmias at higher doses GIT smooth muscle constriction cramping, nausea, diarrhoea | OD – Hyponatremia (Seizure, altered mental state, arrythmias, edema) | Hyponatraemia with H2O retention May cause severe vasoconstriction -CVC only Arrhythmias at higher doses GIT smooth muscle constriction cramping, nausea, diarrhoea |
| PHARMACOKINETICS (PK) | |||
| PK: Absorption | IV only | BA SL: 0.25% PO: 0.08-0.16% Intranasal: 10% | IV only |
| PK: Distribution | limited data | ||
| Protein binding (PK: Distribution) | No PB | 20% | 30% |
| Volume of distribution (PK: Distribution) | 0.14 L/kg | 0.2-0.32 L/kg | 0.5 L/kg Biphasic plasma curve |
| PK: Metabolism | Metabolised by peptidases (Vasopressinases) to amino acids | Minimal hepatic metabolism | minimal |
| PK: Excretion | 65% unchanged in urine | 65% unchanged in urine | urine |
| - Clearance (PK: Excretion) | |||
| - Half Life (PK: Excretion) | 10-35 mins | 2-3hrs | 50-70min |
| SPECIAL POINTS |
Search bar: To search for something particular within the table.
Adrenaline | Vasopressin
Pharmacopeia - Adrenergic and Non-Adrenergic Drugs
| ADRENALINE EPINEPHRINE | ARGIPRESSIN VASOPRESSIN | |
|---|---|---|
| GROUP | ADRENERGIC | NON-ADRENERGIC |
| CICM Level of Understanding | Level 1 | Level 1 |
| INTRODUCTION | Is a naturally occurring catecholamine released in the adrenal medulla | Is a naturally occurring nonapeptide-9AA. Produced hypothal. released by the posterior pituitary. similar to oxytocin complex molecule wt |
| USES | 1. Anaphylaxis 2. Cardiac arrest 3. Low cardiac output states (including complete heart block) 4. Severe asthma 5. Glaucoma 6. Local vasoconstriction 7. Adjunct to local anaesthetic to prolong duration of action | Catecholamine sparing drug in shock Diabetes insipidus Bleeding in vWF def / mild haemophilia |
| PHARMACEUTICS (PC) | ||
| PC: Chemical | ||
| PC: Presentation | IV,Neb. in clear sol, Vials 1mg/mL in 5 and 50 mL, Minijets with 1mg in 10mL(1:10000). With Lignocaine (1:80000-200000). In acidic sol as turns pink in alk(oxid to Adrenochrome) | measured in international units 20 IU/ml vial requiring dilution for eff¬ective delivery. It cannot be given orally as it is inactivated by trypsin |
| PHARMACODYNAMICS (PD) | ||
| PD: Main Action | It is a non selective adrenergic agonist. Mast cell stabilizer (anaphylaxis) | Acts at the GPCR Vasopressin receptors |
| PD: Mode of Action | - Adrenaline is a natural catecholamine with alpha and beta effects. At low doses, beta 1 and beta 2 effects predominate. At high doses alpha 1 effect predominate. - Alpha1- GqPCR → stimulates phospholipase C → increased IP3/DAG → increased intracellular calcium and smooth muscle constriction - Beta1 and 2 → GsPCR → increased adenylate cyclase → increased cAMP → increased phosphorylation | Acts at the GPCR Vasopressin receptors V1 on vascular smooth muscle Inc intracellular Ca conc, vasoconstrictive V1 on platelets increase platelet aggregation V2 on the nephron Aquaporin-2 trafficking from intracellular vesicle membrane – allowing water reabsorption V2 on endothelial cells – allow vWF release that prevents breakdown of factor VIII V3 (prev V1b) on pituitary Contribute to ACTH release |
| PD: Route & Doses | 1. 1mg in PEA arrest IV 2. Infusion of 0.01-0.1micrograms/kg/min 3. 10mcg/kg (up to 500mcg) IM 4. Nebulizer or MDI | IV infusion 0.01–0.04 units/min |
| PD: Metrics (Onset/ Peak/ Duration) | ||
| PD: Effects | lower doses: β2 - vasodilatory, bronchodilation Higher doses β1 agonism: ↑ino+chronotropy Highest doses: primarily a vasoconstrictor. Detail: CVS: - At low dose infusions (beta predominates), beta 2 effects lead to skeletal muscle vasculature vasodilation, leading to a decrease in DBP and SVR. It also causes coronary artery vasodilation. - Beta-1 leads to increased inotropy, increased chronotropy (increases phase 4 gradient), and increased dromotropy. It increases myocardial oxygen consumption and lowers arrhythmia threshold - At higher doses, alpha 1 effects predominate. This causes arteriolar vasoconstriction, which may increase aortic diastolic BP and therefore increase coronary perfusion pressure (e.g. arrest). At these doses it also increases coronary artery vasoconstriction. Venous return may be enhanced as capacitance vessels constrict - Extravasation may cause tissue necrosis and injection into end arteries may lead to digital ischaemia CNS: - May cause anxiety, tremor and raises pain threshold. Causes mydriasis Resp: - Small increase in MV. Potent bronchodilator - PVR increased Renal: - Decreased renal blood flow. Renin stimulation → increased aldosterone and potassium secretion - Decreases plasma volume - Increased bladder sphincter tone, may lead to difficulty of micturition GIT: - Decreased hepatosplanchnic flow. May lead to decreased lactate clearance - Relaxation of gastrointestinal smooth muscle, leading to increased transit times Haem: Coagulation is accelerated by adrenaline. Induces platelet aggregation and increases factor V activity Metabolic - Increases BMR - Increases glycolysis (liver and skeletal muscle) and gluconeogenesis. Alpha1 effects suppress insulin secretion. Causes hyperglycaemia and lactic acidosis. - Lipase activity is augmented, leading to increased lipolysis and keto-acidosis - B2 stimulates Na/K/ATPase, lowering K+. B1 activates RAAS, which leads to aldosterone increasing K+ secretion | CVS: - in the presence of shock, vasopressin causes an increase in MAP and SVR via its vasoconstrictor effect. - In low doses it causes vasodilation in certain vascular beds in animal models. - It causes pulmonary vasodilation in hypoxic and physiological conditions. GU: a reduction in urine output and polydipsia is seen following administration in DI GIT: Gastric smooth muscle contraction Other: Increase in vWF and Factor 8 can be detected |
| PD: Side Effects / Toxicity | High doses: HTN+++, tachyarrhythmias, deranged metabolic States: ↑ glucogenolysis, lipolysis, gluconogenesi Insulin Prodxn: initial ↑ (β2) → ↓ (α) limiting use in DM. Can worsen PHTN. Avoid in glaucoma. Peripheral necrosis. | Hyponatraemia with H2O retention May cause severe vasoconstriction -CVC only Arrhythmias at higher doses GIT smooth muscle constriction cramping, nausea, diarrhoea |
| PHARMACOKINETICS (PK) | ||
| PK: Absorption | IV, IM, SC, Inhaled, ETT 1mg arrest, 0.1mg anaph. Inf: β effects: 0.1-0.3mcg/kg/min α: >0.3 (vasocon). on/dur imm/1-2min | IV only |
| PK: Distribution | doesn’t cross the BBB | limited data |
| Protein binding (PK: Distribution) | No PB | |
| Volume of distribution (PK: Distribution) | 0.14 L/kg | |
| PK: Metabolism | Taken up into adrenergic neuron – Metabolized by MAO and COMT Circulating drug hepatically metabolized | Metabolised by peptidases (Vasopressinases) to amino acids |
| PK: Excretion | Urine as inactive metabolites | 65% unchanged in urine |
| - Clearance (PK: Excretion) | ||
| - Half Life (PK: Excretion) | 2 minutes | 10-35 mins |
| SPECIAL POINTS |
Search bar: To search for something particular within the table.
Noradrenaline | Vasopressin
Pharmacopeia - Adrenergic and Non-Adrenergic Drugs
| NORADRENALINE NOREPINEPHRINE | ARGIPRESSIN VASOPRESSIN | |
|---|---|---|
| GROUP | ADRENERGIC | NON-ADRENERGIC |
| CICM Level of Understanding | Level 1 | Level 1 |
| INTRODUCTION | Is a naturally occurring catecholamine released in post ganglionic SNS, medulla (20:80 Adr) | Is a naturally occurring nonapeptide-9AA. Produced hypothal. released by the posterior pituitary. similar to oxytocin complex molecule wt |
| USES | Used to treat hypotension due to decreased SVR | Catecholamine sparing drug in shock Diabetes insipidus Bleeding in vWF def / mild haemophilia |
| PHARMACEUTICS (PC) | ||
| PC: Chemical | ||
| PC: Presentation | injectable solution only, 1mg/mL in 2 mL vials diluted in 5D or NS. CVC only due to risk of extravasation associated necrosis | measured in international units 20 IU/ml vial requiring dilution for eff¬ective delivery. It cannot be given orally as it is inactivated by trypsin |
| PHARMACODYNAMICS (PD) | ||
| PD: Main Action | Alpha and beta adrenergic receptor activity | Acts at the GPCR Vasopressin receptors |
| PD: Mode of Action | - Acts primarily directly at alpha-1-adrenoreceptors (phospholipase C → IP3 → increased calcium) - To a lesser extent acts on beta 1>beta 2 effects | Acts at the GPCR Vasopressin receptors V1 on vascular smooth muscle Inc intracellular Ca conc, vasoconstrictive V1 on platelets increase platelet aggregation V2 on the nephron Aquaporin-2 trafficking from intracellular vesicle membrane – allowing water reabsorption V2 on endothelial cells – allow vWF release that prevents breakdown of factor VIII V3 (prev V1b) on pituitary Contribute to ACTH release |
| PD: Route & Doses | IV infusion- 0.05-0.5mcg/kg. Through a central line diluted with glucose or saline. | IV infusion 0.01–0.04 units/min |
| PD: Metrics (Onset/ Peak/ Duration) | ||
| PD: Effects | Low doses: β - ↑ino+chronotropy increased MVO2 Higher doses: 1 - peripheral vasocontriction. ↑systolic/diastolic pressures may cause reflex bradycardia Detail: CVS - Increased SVR leading to increased SBP/DBP/MAP - Increased afterload - leading to increased myocardial oxygen consumption, slight decrease in cardiac output and may lead to reflex bradycardia (through beta-1 effects limit this) - Coronary artery vasodilation increased coronary O2 delivery - Pulmonary vascular resistance is increased - Excessive doses may lead to limb or organ ischaemia - Extravasation may lead to tissue necrosis CNS - Generally improves cerebral blood flow by way of improved CPP more than it decreases CBF by cerebral vasoconstriction Renal/GU - Decreases renal blood flow - Causes uterine constriction (may lead to fetal asphyxia) GIT: - Decreased splanchnic blood flow Metabolic - Less hyperglycaemia/acidosis, although it may decrease insulin secretion | CVS: - in the presence of shock, vasopressin causes an increase in MAP and SVR via its vasoconstrictor effect. - In low doses it causes vasodilation in certain vascular beds in animal models. - It causes pulmonary vasodilation in hypoxic and physiological conditions. GU: a reduction in urine output and polydipsia is seen following administration in DI GIT: Gastric smooth muscle contraction Other: Increase in vWF and Factor 8 can be detected |
| PD: Side Effects / Toxicity | Excessive doses cause severe hypertension Reduced flow to organs splanchnic renal Issues with increased MVO2 and IHD | Hyponatraemia with H2O retention May cause severe vasoconstriction -CVC only Arrhythmias at higher doses GIT smooth muscle constriction cramping, nausea, diarrhoea |
| PHARMACOKINETICS (PK) | ||
| PK: Absorption | IV only Clear Solution 1:1000 8-12 mcg/min uptitrated to effect onset / duration immediate / 1-2 minutes | IV only |
| PK: Distribution | doesn’t cross the BBB | limited data |
| Protein binding (PK: Distribution) | No PB | |
| Volume of distribution (PK: Distribution) | 0.14 L/kg | |
| PK: Metabolism | Rapidly metabolised into adrenaline by MAO (Uptake 1, Nv terminal) COMT (Uptake 2 circulation) 25% removed in the lungs | Metabolised by peptidases (Vasopressinases) to amino acids |
| PK: Excretion | urine as inactive metabolites (84-96%) | 65% unchanged in urine |
| - Clearance (PK: Excretion) | ||
| - Half Life (PK: Excretion) | 2 minutes | 10-35 mins |
| SPECIAL POINTS |
Search bar: To search for something particular within the table.
Noradenaline | Dobutamine
Pharmacopeia - Adrenergic and Non-Adrenergic Drugs
| NORADRENALINE NOREPINEPHRINE | DOBUTAMINE | |
|---|---|---|
| GROUP | ADRENERGIC | ADRENERGIC |
| CICM Level of Understanding | Level 1 | Level 3 |
| INTRODUCTION | Is a naturally occurring catecholamine released in post ganglionic SNS, medulla (20:80 Adr) | synthetic catechol derivative of isoprenaline |
| USES | Used to treat hypotension due to decreased SVR | 1. Inotropic support in low cardiac output secondary to MI, cardiac surgery, cardiomyopathy 2. Cardiac stress testing |
| PHARMACEUTICS (PC) | ||
| PC: Chemical | ||
| PC: Presentation | injectable solution only, 1mg/mL in 2 mL vials diluted in 5D or NS. CVC only due to risk of extravasation associated necrosis | Is a racemic mixture. White powder for reconstitution(250mg) or Clear fluid 12.5mg/ml in 20ml vials. Should not be mixed with alkaline solutions (HCO3) |
| PHARMACODYNAMICS (PD) | ||
| PD: Main Action | Alpha and beta adrenergic receptor activity | the + enantiomer is a potent α1 antagonist and β1 agonist, the -ve enantiomer has opposite effects on α1 causing agonism and is less potent (10%) β1 agonist. |
| PD: Mode of Action | - Acts primarily directly at alpha-1-adrenoreceptors (phospholipase C → IP3 → increased calcium) - To a lesser extent acts on beta 1>beta 2 effects | Predominant mechanism is via direct acting B1 stimulation (increased cAMP) and retains a small amount of B2 effects |
| PD: Route & Doses | IV infusion- 0.05-0.5mcg/kg. Through a central line diluted with glucose or saline. | IV Infusion Dose range 0.5-40mcg/kg/min. Response within 2 minutes |
| PD: Metrics (Onset/ Peak/ Duration) | ||
| PD: Effects | Low doses: β - ↑ino+chronotropy increased MVO2 Higher doses: 1 - peripheral vasocontriction. ↑systolic/diastolic pressures may cause reflex bradycardia Detail: CVS - Increased SVR leading to increased SBP/DBP/MAP - Increased afterload - leading to increased myocardial oxygen consumption, slight decrease in cardiac output and may lead to reflex bradycardia (through beta-1 effects limit this) - Coronary artery vasodilation increased coronary O2 delivery - Pulmonary vascular resistance is increased - Excessive doses may lead to limb or organ ischaemia - Extravasation may lead to tissue necrosis CNS - Generally improves cerebral blood flow by way of improved CPP more than it decreases CBF by cerebral vasoconstriction Renal/GU - Decreases renal blood flow - Causes uterine constriction (may lead to fetal asphyxia) GIT: - Decreased splanchnic blood flow Metabolic - Less hyperglycaemia/acidosis, although it may decrease insulin secretion | composite of α and β actions. Mostly β1 effect: ↑ ino+ chrono tropy and MVO2. Mild β2 eff¬ects. Detail: CVS - Beta1 effects lead to increased SA node activation (increased chronotropy), increased dromotropy and increased inotropy, thereby increasing cardiac output (inotropy greatest) - Coronary artery vasodilator - Beta-2 activity tends to decrease LVEDP and SVR, contributing to increased CO and cardiac index - Increased MVO2 - Increased risk of arrhythmias (especially at doses >10mcg/kg/min) - Should be avoided in patients with cardiac outflow obstruction (AS, tamponade) Resp - Modest pulmonary vasodilation - Inhibits HPV Renal- Increased RBF due to increased CO may occur |
| PD: Side Effects / Toxicity | Excessive doses cause severe hypertension Reduced flow to organs splanchnic renal Issues with increased MVO2 and IHD | 1. Arrhythmias (especially at doses >10mcg/kg/min) 2. Arrest in fixed output patients (AS, tamponade) 3. Increased MVO2 4. Eosinophilic myocarditis in prolonged infusion |
| PHARMACOKINETICS (PK) | ||
| PK: Absorption | IV only Clear Solution 1:1000 8-12 mcg/min uptitrated to effect onset / duration immediate / 1-2 minutes | IV, dose starts at 5mcg/kg/min uptitrate to e¬ffect, max 40mcg/kg/min |
| PK: Distribution | doesn’t cross the BBB | Small vd |
| Protein binding (PK: Distribution) | ||
| Volume of distribution (PK: Distribution) | 0.2L/kg | |
| PK: Metabolism | Rapidly metabolised into adrenaline by MAO (Uptake 1, Nv terminal) COMT (Uptake 2 circulation) 25% removed in the lungs | via COMT then gluruonidation hepatically |
| PK: Excretion | urine as inactive metabolites (84-96%) | urine as inactive metabolites |
| - Clearance (PK: Excretion) | ||
| - Half Life (PK: Excretion) | 2 minutes | 2 minutes |
| SPECIAL POINTS |
Search bar: To search for something particular within the table.
Dobutamine | Milrinone
Pharmacopeia - Adrenergic and Non-Adrenergic Drugs
| DOBUTAMINE | MILRINONE | |
|---|---|---|
| GROUP | ADRENERGIC | NON-ADRENERGIC |
| CICM Level of Understanding | Level 3 | Level 1 |
| INTRODUCTION | synthetic catechol derivative of isoprenaline | selective phosphodiesterase inhibitor |
| USES | 1. Inotropic support in low cardiac output secondary to MI, cardiac surgery, cardiomyopathy 2. Cardiac stress testing | used in severe refractory heart failure and for short periods post cardiac surgery |
| PHARMACEUTICS (PC) | ||
| PC: Chemical | ||
| PC: Presentation | Is a racemic mixture. White powder for reconstitution(250mg) or Clear fluid 12.5mg/ml in 20ml vials. Should not be mixed with alkaline solutions (HCO3) | is a yellow solution, stored at room temperature, should not be given with HCO3 or frusemide pKA of 9.67 and pH of 6.35 |
| PHARMACODYNAMICS (PD) | ||
| PD: Main Action | the + enantiomer is a potent α1 antagonist and β1 agonist, the -ve enantiomer has opposite effects on α1 causing agonism and is less potent (10%) β1 agonist. | PDEIII Inhibition: Improves myocardial contractility, vasodilation |
| PD: Mode of Action | Predominant mechanism is via direct acting B1 stimulation (increased cAMP) and retains a small amount of B2 effects | Via selective PDE3 inhibition which causes decreased cAMP breakdown intracellularly and hence increased Ca This improves myocardial contractility and improves cAMP-dependent protein phosphorylation leading to vascular smooth muscle relaxation. |
| PD: Route & Doses | IV Infusion Dose range 0.5-40mcg/kg/min. Response within 2 minutes | IV 50mcg/kg loading dose over 10min (optional) 0.375mcg/kg/min-0.75mcg/kg/min |
| PD: Metrics (Onset/ Peak/ Duration) | ||
| PD: Effects | composite of α and β actions. Mostly β1 effect: ↑ ino+ chrono tropy and MVO2. Mild β2 eff¬ects. Detail: CVS - Beta1 effects lead to increased SA node activation (increased chronotropy), increased dromotropy and increased inotropy, thereby increasing cardiac output (inotropy greatest) - Coronary artery vasodilator - Beta-2 activity tends to decrease LVEDP and SVR, contributing to increased CO and cardiac index - Increased MVO2 - Increased risk of arrhythmias (especially at doses >10mcg/kg/min) - Should be avoided in patients with cardiac outflow obstruction (AS, tamponade) Resp - Modest pulmonary vasodilation - Inhibits HPV Renal- Increased RBF due to increased CO may occur | CVS - Positive inotrope, leading to increased cardiac output. CI increases 30% - PCWP decreases 20%, with improved lusotropy - SVR and MAP decrease - May increase AV nodal conductance, accelerating arrhythmias in atrial fibrillation or flutter Resp: Decreased PVR GU: UO and GFR may increase in response to increased CO |
| PD: Side Effects / Toxicity | 1. Arrhythmias (especially at doses >10mcg/kg/min) 2. Arrest in fixed output patients (AS, tamponade) 3. Increased MVO2 4. Eosinophilic myocarditis in prolonged infusion | may be proarrhythmogenic causing SVT and VT. Have been shown to worsen outcomes in acute on chronic heart failure |
| PHARMACOKINETICS (PK) | ||
| PK: Absorption | IV, dose starts at 5mcg/kg/min uptitrate to e¬ffect, max 40mcg/kg/min | IV only |
| PK: Distribution | Small vd | small vd |
| Protein binding (PK: Distribution) | ||
| Volume of distribution (PK: Distribution) | 0.2L/kg | 0.4 L/kg |
| PK: Metabolism | via COMT then gluruonidation hepatically | minimally hepatic |
| PK: Excretion | urine as inactive metabolites | excretion is in the urine, mostly as unchanged drug, dose adjustment in renal failure |
| - Clearance (PK: Excretion) | ||
| - Half Life (PK: Excretion) | 2 minutes | 2 hours |
| SPECIAL POINTS |
Search bar: To search for something particular within the table.
Adrenaline | Milrinone
Pharmacopeia - Adrenergic and Non-Adrenergic Drugs
| ADRENALINE EPINEPHRINE | MILRINONE | |
|---|---|---|
| GROUP | ADRENERGIC | NON-ADRENERGIC |
| CICM Level of Understanding | Level 1 | Level 1 |
| INTRODUCTION | Is a naturally occurring catecholamine released in the adrenal medulla | selective phosphodiesterase inhibitor |
| USES | 1. Anaphylaxis 2. Cardiac arrest 3. Low cardiac output states (including complete heart block) 4. Severe asthma 5. Glaucoma 6. Local vasoconstriction 7. Adjunct to local anaesthetic to prolong duration of action | used in severe refractory heart failure and for short periods post cardiac surgery |
| PHARMACEUTICS (PC) | ||
| PC: Chemical | ||
| PC: Presentation | IV,Neb. in clear sol, Vials 1mg/mL in 5 and 50 mL, Minijets with 1mg in 10mL(1:10000). With Lignocaine (1:80000-200000). In acidic sol as turns pink in alk(oxid to Adrenochrome) | is a yellow solution, stored at room temperature, should not be given with HCO3 or frusemide pKA of 9.67 and pH of 6.35 |
| PHARMACODYNAMICS (PD) | ||
| PD: Main Action | It is a non selective adrenergic agonist. Mast cell stabilizer (anaphylaxis) | PDEIII Inhibition: Improves myocardial contractility, vasodilation |
| PD: Mode of Action | - Adrenaline is a natural catecholamine with alpha and beta effects. At low doses, beta 1 and beta 2 effects predominate. At high doses alpha 1 effect predominate. - Alpha1- GqPCR → stimulates phospholipase C → increased IP3/DAG → increased intracellular calcium and smooth muscle constriction - Beta1 and 2 → GsPCR → increased adenylate cyclase → increased cAMP → increased phosphorylation | Via selective PDE3 inhibition which causes decreased cAMP breakdown intracellularly and hence increased Ca This improves myocardial contractility and improves cAMP-dependent protein phosphorylation leading to vascular smooth muscle relaxation. |
| PD: Route & Doses | 1. 1mg in PEA arrest IV 2. Infusion of 0.01-0.1micrograms/kg/min 3. 10mcg/kg (up to 500mcg) IM 4. Nebulizer or MDI | IV 50mcg/kg loading dose over 10min (optional) 0.375mcg/kg/min-0.75mcg/kg/min |
| PD: Metrics (Onset/ Peak/ Duration) | ||
| PD: Effects | lower doses: β2 - vasodilatory, bronchodilation Higher doses β1 agonism: ↑ino+chronotropy Highest doses: primarily a vasoconstrictor. Detail: CVS: - At low dose infusions (beta predominates), beta 2 effects lead to skeletal muscle vasculature vasodilation, leading to a decrease in DBP and SVR. It also causes coronary artery vasodilation. - Beta-1 leads to increased inotropy, increased chronotropy (increases phase 4 gradient), and increased dromotropy. It increases myocardial oxygen consumption and lowers arrhythmia threshold - At higher doses, alpha 1 effects predominate. This causes arteriolar vasoconstriction, which may increase aortic diastolic BP and therefore increase coronary perfusion pressure (e.g. arrest). At these doses it also increases coronary artery vasoconstriction. Venous return may be enhanced as capacitance vessels constrict - Extravasation may cause tissue necrosis and injection into end arteries may lead to digital ischaemia CNS: - May cause anxiety, tremor and raises pain threshold. Causes mydriasis Resp: - Small increase in MV. Potent bronchodilator - PVR increased Renal: - Decreased renal blood flow. Renin stimulation → increased aldosterone and potassium secretion - Decreases plasma volume - Increased bladder sphincter tone, may lead to difficulty of micturition GIT: - Decreased hepatosplanchnic flow. May lead to decreased lactate clearance - Relaxation of gastrointestinal smooth muscle, leading to increased transit times Haem: Coagulation is accelerated by adrenaline. Induces platelet aggregation and increases factor V activity Metabolic - Increases BMR - Increases glycolysis (liver and skeletal muscle) and gluconeogenesis. Alpha1 effects suppress insulin secretion. Causes hyperglycaemia and lactic acidosis. - Lipase activity is augmented, leading to increased lipolysis and keto-acidosis - B2 stimulates Na/K/ATPase, lowering K+. B1 activates RAAS, which leads to aldosterone increasing K+ secretion | CVS - Positive inotrope, leading to increased cardiac output. CI increases 30% - PCWP decreases 20%, with improved lusotropy - SVR and MAP decrease - May increase AV nodal conductance, accelerating arrhythmias in atrial fibrillation or flutter Resp: Decreased PVR GU: UO and GFR may increase in response to increased CO |
| PD: Side Effects / Toxicity | High doses: HTN+++, tachyarrhythmias, deranged metabolic States: ↑ glucogenolysis, lipolysis, gluconogenesi Insulin Prodxn: initial ↑ (β2) → ↓ (α) limiting use in DM. Can worsen PHTN. Avoid in glaucoma. Peripheral necrosis. | may be proarrhythmogenic causing SVT and VT. Have been shown to worsen outcomes in acute on chronic heart failure |
| PHARMACOKINETICS (PK) | ||
| PK: Absorption | IV, IM, SC, Inhaled, ETT 1mg arrest, 0.1mg anaph. Inf: β effects: 0.1-0.3mcg/kg/min α: >0.3 (vasocon). on/dur imm/1-2min | IV only |
| PK: Distribution | doesn’t cross the BBB | small vd |
| Protein binding (PK: Distribution) | ||
| Volume of distribution (PK: Distribution) | 0.4 L/kg | |
| PK: Metabolism | Taken up into adrenergic neuron – Metabolized by MAO and COMT Circulating drug hepatically metabolized | minimally hepatic |
| PK: Excretion | Urine as inactive metabolites | excretion is in the urine, mostly as unchanged drug, dose adjustment in renal failure |
| - Clearance (PK: Excretion) | ||
| - Half Life (PK: Excretion) | 2 minutes | 2 hours |
| SPECIAL POINTS |
Search bar: To search for something particular within the table.
Adrenaline | Levosimendan
Pharmacopeia - Adrenergic and Non-Adrenergic Drugs
| ADRENALINE EPINEPHRINE | LEVOSIMENDAN | |
|---|---|---|
| GROUP | ADRENERGIC | NON-ADRENERGIC |
| CICM Level of Understanding | Level 1 | Level 3 |
| INTRODUCTION | Is a naturally occurring catecholamine released in the adrenal medulla | Ca sensitizer and PDE-III inhibitor selectively |
| USES | 1. Anaphylaxis 2. Cardiac arrest 3. Low cardiac output states (including complete heart block) 4. Severe asthma 5. Glaucoma 6. Local vasoconstriction 7. Adjunct to local anaesthetic to prolong duration of action | short term management of severe acute heart failure |
| PHARMACEUTICS (PC) | ||
| PC: Chemical | ||
| PC: Presentation | IV,Neb. in clear sol, Vials 1mg/mL in 5 and 50 mL, Minijets with 1mg in 10mL(1:10000). With Lignocaine (1:80000-200000). In acidic sol as turns pink in alk(oxid to Adrenochrome) | in IV form only - clear yellow solution 2.5mg/mL in 5 and 10ml vials |
| PHARMACODYNAMICS (PD) | ||
| PD: Main Action | It is a non selective adrenergic agonist. Mast cell stabilizer (anaphylaxis) | Increases Myofilament Ca sensitivity, vasodilation |
| PD: Mode of Action | - Adrenaline is a natural catecholamine with alpha and beta effects. At low doses, beta 1 and beta 2 effects predominate. At high doses alpha 1 effect predominate. - Alpha1- GqPCR → stimulates phospholipase C → increased IP3/DAG → increased intracellular calcium and smooth muscle constriction - Beta1 and 2 → GsPCR → increased adenylate cyclase → increased cAMP → increased phosphorylation | i) ↑myofilament Ca sensitivity by binding to Cardiac trop C in Ca-dependent manner. ii) Vasodilation through opening of ATP-sensitive K channels iii) selective PDE-III inhibition at higher conc - inotropy |
| PD: Route & Doses | 1. 1mg in PEA arrest IV 2. Infusion of 0.01-0.1micrograms/kg/min 3. 10mcg/kg (up to 500mcg) IM 4. Nebulizer or MDI | IV, loading dose of 6 to 24 mcg/kg over 10 minutes then continuous infusion of 0.05-0.2 mcg/kg/min |
| PD: Metrics (Onset/ Peak/ Duration) | ||
| PD: Effects | lower doses: β2 - vasodilatory, bronchodilation Higher doses β1 agonism: ↑ino+chronotropy Highest doses: primarily a vasoconstrictor. Detail: CVS: - At low dose infusions (beta predominates), beta 2 effects lead to skeletal muscle vasculature vasodilation, leading to a decrease in DBP and SVR. It also causes coronary artery vasodilation. - Beta-1 leads to increased inotropy, increased chronotropy (increases phase 4 gradient), and increased dromotropy. It increases myocardial oxygen consumption and lowers arrhythmia threshold - At higher doses, alpha 1 effects predominate. This causes arteriolar vasoconstriction, which may increase aortic diastolic BP and therefore increase coronary perfusion pressure (e.g. arrest). At these doses it also increases coronary artery vasoconstriction. Venous return may be enhanced as capacitance vessels constrict - Extravasation may cause tissue necrosis and injection into end arteries may lead to digital ischaemia CNS: - May cause anxiety, tremor and raises pain threshold. Causes mydriasis Resp: - Small increase in MV. Potent bronchodilator - PVR increased Renal: - Decreased renal blood flow. Renin stimulation → increased aldosterone and potassium secretion - Decreases plasma volume - Increased bladder sphincter tone, may lead to difficulty of micturition GIT: - Decreased hepatosplanchnic flow. May lead to decreased lactate clearance - Relaxation of gastrointestinal smooth muscle, leading to increased transit times Haem: Coagulation is accelerated by adrenaline. Induces platelet aggregation and increases factor V activity Metabolic - Increases BMR - Increases glycolysis (liver and skeletal muscle) and gluconeogenesis. Alpha1 effects suppress insulin secretion. Causes hyperglycaemia and lactic acidosis. - Lipase activity is augmented, leading to increased lipolysis and keto-acidosis - B2 stimulates Na/K/ATPase, lowering K+. B1 activates RAAS, which leads to aldosterone increasing K+ secretion | CVS: - Increased cardiac output without increasing MVO2 - Causes coronary and peripheral vasodilation → anti-ischaemia and anti-stunning effects GU: Increased GFR and UO secondary to increased CO |
| PD: Side Effects / Toxicity | High doses: HTN+++, tachyarrhythmias, deranged metabolic States: ↑ glucogenolysis, lipolysis, gluconogenesi Insulin Prodxn: initial ↑ (β2) → ↓ (α) limiting use in DM. Can worsen PHTN. Avoid in glaucoma. Peripheral necrosis. | Interference with potassium channels causes an increase in the QTc- theoretical ↑risk of arrhythmias. May cause hypotension. Caution should be exercised in patients with renal or hepatic impairment. |
| PHARMACOKINETICS (PK) | ||
| PK: Absorption | IV, IM, SC, Inhaled, ETT 1mg arrest, 0.1mg anaph. Inf: β effects: 0.1-0.3mcg/kg/min α: >0.3 (vasocon). on/dur imm/1-2min | IV only |
| PK: Distribution | doesn’t cross the BBB | small vd |
| Protein binding (PK: Distribution) | 98% protein binding. Peak concentration after 48 hrs | |
| Volume of distribution (PK: Distribution) | 0.2 L/kg | |
| PK: Metabolism | Taken up into adrenergic neuron – Metabolized by MAO and COMT Circulating drug hepatically metabolized | Intestinal bacteria OR1896 active metabolite Hepatic conjugation |
| PK: Excretion | Urine as inactive metabolites | excretion renal and fecal. Cardiac Effects 2-7 days |
| - Clearance (PK: Excretion) | ||
| - Half Life (PK: Excretion) | 2 minutes | 1 hour (70hr for active metabolite) |
| SPECIAL POINTS |
Search bar: To search for something particular within the table.
Digoxin | Levosimendan
Pharmacopeia - Digoxin vs Levosimendan
| DIGOXIN | LEVOSIMENDAN | |
|---|---|---|
| GROUP | Antiarrhythmic – Vaughan Williams Class V Other | NON-ADRENERGIC |
| CICM Level of Understanding | Level 1 | Level 1 |
| INTRODUCTION | glycoside derived from the dried leaves of the foxglove Block Na-K-ATPase pump | Ca sensitizer and PDE-III inhibitor selectively |
| USES | used in AF and atrial flutter, SVT and in heart failure | short term management of severe acute heart failure |
| PHARMACEUTICS (PC) | ||
| PC: Chemical | ||
| PC: Presentation | PO: tablets 62.5mcg or 250mcg. IV:25-250mcg/ml. Narrow therapeutic window. Monitoring necessary - 0.5-2mcg/L(~1) | in IV form only - clear yellow solution 2.5mg/mL in 5 and 10ml vials |
| PHARMACODYNAMICS (PD) | ||
| PD: Main Action | Increases Myofilament Ca sensitivity, vasodilation | |
| PD: Mode of Action | i) Na/K ATPase inhibition → ↑ intracell Na → ↓ Na-Ca pump → ↑ intracell Ca → inotropy ii) direct: ↑ AV node ERP, ↓ V ERP iii) Indirect: Via Vagus – bradycardia, ↓ A refr. Augmentn of direct ↑ AV node ERP | i) ↑myofilament Ca sensitivity by binding to Cardiac trop C in Ca-dependent manner. ii) Vasodilation through opening of ATP-sensitive K channels iii) selective PDE-III inhibition at higher conc - inotropy |
| PD: Route & Doses | IV/PO. loading 250-500mcg QID then 62.5-125mcg daily | IV, loading dose of 6 to 24 mcg/kg over 10 minutes then continuous infusion of 0.05-0.2 mcg/kg/min |
| PD: Metrics (Onset/ Peak/ Duration) | onset / duration Oral: 1-2 hours; I.V.: 5-60 mins / 3-4 days | |
| PD: Effects | Effects: Inotropy Direct and indirect effects on refractory period + bradycardia -> treat AF&flutter | CVS: - Increased cardiac output without increasing MVO2 - Causes coronary and peripheral vasodilation → anti-ischaemia and anti-stunning effects GU: Increased GFR and UO secondary to increased CO |
| PD: Side Effects / Toxicity | Thyroid-Vd Narrow therapeutic window -monitoring - 0.5-2mcg/L(~1) Toxic > 2.5- arrhythmias, AV block. anorexia,N/V/D, lethargy. Altered Red green colour perception. ECG: ↑ PR, ST dep, T fl-attening, ↓QT. (may not indicate toxicity) | Interference with potassium channels causes an increase in the QTc- theoretical ↑risk of arrhythmias. May cause hypotension. Caution should be exercised in patients with renal or hepatic impairment. |
| PHARMACOKINETICS (PK) | ||
| PK: Absorption | IV, PO BA 60-80% | IV only |
| PK: Distribution | small vd | |
| Protein binding (PK: Distribution) | prot bind ~25%; uremia- displaced fm pl prot bind sites | 98% protein binding. Peak concentration after 48 hrs |
| Volume of distribution (PK: Distribution) | 6-7 L/kg thyroid (↑ in hyper, ↓ hypo). | 0.2 L/kg |
| PK: Metabolism | Stomach:Sequential sugar hydrolysis+ redn of lactone ring by intestinal bacteria min hepatic, most excr unchanged | Intestinal bacteria OR1896 active metabolite Hepatic conjugation |
| PK: Excretion | Urine (50% to 70% unchanged) | excretion renal and fecal. Cardiac Effects 2-7 days |
| - Clearance (PK: Excretion) | ||
| - Half Life (PK: Excretion) | 36-48 hours | 1 hour (70hr for active metabolite) |
| SPECIAL POINTS |
Search bar: To search for something particular within the table.
Dobutamine | Levosimendan
Pharmacopeia - Adrenergic and Non-Adrenergic Drugs
| DOBUTAMINE | LEVOSIMENDAN | |
|---|---|---|
| GROUP | ADRENERGIC | NON-ADRENERGIC |
| CICM Level of Understanding | Level 3 | Level 3 |
| INTRODUCTION | synthetic catechol derivative of isoprenaline | Ca sensitizer and PDE-III inhibitor selectively |
| USES | 1. Inotropic support in low cardiac output secondary to MI, cardiac surgery, cardiomyopathy 2. Cardiac stress testing | short term management of severe acute heart failure |
| PHARMACEUTICS (PC) | ||
| PC: Chemical | ||
| PC: Presentation | Is a racemic mixture. White powder for reconstitution(250mg) or Clear fluid 12.5mg/ml in 20ml vials. Should not be mixed with alkaline solutions (HCO3) | in IV form only - clear yellow solution 2.5mg/mL in 5 and 10ml vials |
| PHARMACODYNAMICS (PD) | ||
| PD: Main Action | the + enantiomer is a potent α1 antagonist and β1 agonist, the -ve enantiomer has opposite effects on α1 causing agonism and is less potent (10%) β1 agonist. | Increases Myofilament Ca sensitivity, vasodilation |
| PD: Mode of Action | Predominant mechanism is via direct acting B1 stimulation (increased cAMP) and retains a small amount of B2 effects | i) ↑myofilament Ca sensitivity by binding to Cardiac trop C in Ca-dependent manner. ii) Vasodilation through opening of ATP-sensitive K channels iii) selective PDE-III inhibition at higher conc - inotropy |
| PD: Route & Doses | IV Infusion Dose range 0.5-40mcg/kg/min. Response within 2 minutes | IV, loading dose of 6 to 24 mcg/kg over 10 minutes then continuous infusion of 0.05-0.2 mcg/kg/min |
| PD: Metrics (Onset/ Peak/ Duration) | ||
| PD: Effects | composite of α and β actions. Mostly β1 effect: ↑ ino+ chrono tropy and MVO2. Mild β2 eff¬ects. Detail: CVS - Beta1 effects lead to increased SA node activation (increased chronotropy), increased dromotropy and increased inotropy, thereby increasing cardiac output (inotropy greatest) - Coronary artery vasodilator - Beta-2 activity tends to decrease LVEDP and SVR, contributing to increased CO and cardiac index - Increased MVO2 - Increased risk of arrhythmias (especially at doses >10mcg/kg/min) - Should be avoided in patients with cardiac outflow obstruction (AS, tamponade) Resp - Modest pulmonary vasodilation - Inhibits HPV Renal- Increased RBF due to increased CO may occur | CVS: - Increased cardiac output without increasing MVO2 - Causes coronary and peripheral vasodilation → anti-ischaemia and anti-stunning effects GU: Increased GFR and UO secondary to increased CO |
| PD: Side Effects / Toxicity | 1. Arrhythmias (especially at doses >10mcg/kg/min) 2. Arrest in fixed output patients (AS, tamponade) 3. Increased MVO2 4. Eosinophilic myocarditis in prolonged infusion | Interference with potassium channels causes an increase in the QTc- theoretical ↑risk of arrhythmias. May cause hypotension. Caution should be exercised in patients with renal or hepatic impairment. |
| PHARMACOKINETICS (PK) | ||
| PK: Absorption | IV, dose starts at 5mcg/kg/min uptitrate to e¬ffect, max 40mcg/kg/min | IV only |
| PK: Distribution | Small vd | small vd |
| Protein binding (PK: Distribution) | 98% protein binding. Peak concentration after 48 hrs | |
| Volume of distribution (PK: Distribution) | 0.2L/kg | 0.2 L/kg |
| PK: Metabolism | via COMT then gluruonidation hepatically | Intestinal bacteria OR1896 active metabolite Hepatic conjugation |
| PK: Excretion | urine as inactive metabolites | excretion renal and fecal. Cardiac Effects 2-7 days |
| - Clearance (PK: Excretion) | ||
| - Half Life (PK: Excretion) | 2 minutes | 1 hour (70hr for active metabolite) |
| SPECIAL POINTS |
Search bar: To search for something particular within the table.
Metaraminol | Noradrenaline
Pharmacopeia - Adrenergic and Non-Adrenergic Drugs
| METARAMINOL | NORADRENALINE NOREPINEPHRINE | |
|---|---|---|
| GROUP | ADRENERGIC | ADRENERGIC |
| CICM Level of Understanding | Level 2 | Level 1 |
| INTRODUCTION | synthetic noncatecholamine with both direct and indirect sympathomimetic actions. | Is a naturally occurring catecholamine released in post ganglionic SNS, medulla (20:80 Adr) |
| USES | short term correction of BP in the setting of regional anaesthesia and off label for short term BP correction | Used to treat hypotension due to decreased SVR |
| PHARMACEUTICS (PC) | ||
| PC: Chemical | ||
| PC: Presentation | clear solution 10mg/mL in one mL vials and usually diluted to 10mg in 10ml or 20ml | injectable solution only, 1mg/mL in 2 mL vials diluted in 5D or NS. CVC only due to risk of extravasation associated necrosis |
| PHARMACODYNAMICS (PD) | ||
| PD: Main Action | both direct and indirect sympathomimetic actions. It acts mainly via alpha1/2 adrenoceptors to cause vasoconstriction but also has some minor beta activity. | Alpha and beta adrenergic receptor activity |
| PD: Mode of Action | through ↑TPR May be transient bradycardia due to baroreceptor feedback upon infusion initiation. ↑Pulmonary vascular resistance. ↑coronary artery flow by an indirect mechanism (stimulates NA release) | - Acts primarily directly at alpha-1-adrenoreceptors (phospholipase C → IP3 → increased calcium) - To a lesser extent acts on beta 1>beta 2 effects |
| PD: Route & Doses | IV boluses or infusion | IV infusion- 0.05-0.5mcg/kg. Through a central line diluted with glucose or saline. |
| PD: Metrics (Onset/ Peak/ Duration) | ||
| PD: Effects | CVS: - Increased SVR leading to an increase in diastolic and systolic BP - Reflex bradycardia may occur despite B1 effects - It has positive inotropic effects but cardiac output is more likely to decrease as a result of increased afterload - Coronary artery blood flow increases as an indirect mechanism - Increased PVR CNS: - Doesn’t cross BBB - Causes cerebral vasoconstriction but increases CPP Renal/GU - Renal vasoconstriction but re-established renal perfusion pressure in hypotension - Uterine contraction and reduces uterine blood flow Metabolic - Inhibits insulin release and increases lipolysis - May increase VO2 | Low doses: β - ↑ino+chronotropy increased MVO2 Higher doses: 1 - peripheral vasocontriction. ↑systolic/diastolic pressures may cause reflex bradycardia Detail: CVS - Increased SVR leading to increased SBP/DBP/MAP - Increased afterload - leading to increased myocardial oxygen consumption, slight decrease in cardiac output and may lead to reflex bradycardia (through beta-1 effects limit this) - Coronary artery vasodilation increased coronary O2 delivery - Pulmonary vascular resistance is increased - Excessive doses may lead to limb or organ ischaemia - Extravasation may lead to tissue necrosis CNS - Generally improves cerebral blood flow by way of improved CPP more than it decreases CBF by cerebral vasoconstriction Renal/GU - Decreases renal blood flow - Causes uterine constriction (may lead to fetal asphyxia) GIT: - Decreased splanchnic blood flow Metabolic - Less hyperglycaemia/acidosis, although it may decrease insulin secretion |
| PD: Side Effects / Toxicity | Caution should be exercised in patients with pulmonary hypertension. May cause severe hypertension in some patients | Excessive doses cause severe hypertension Reduced flow to organs splanchnic renal Issues with increased MVO2 and IHD |
| PHARMACOKINETICS (PK) | ||
| PK: Absorption | IV. BA 100% 0.1-0.2mg boluses titrated to BP onset / dur imm / up to 20 mins | IV only Clear Solution 1:1000 8-12 mcg/min uptitrated to effect onset / duration immediate / 1-2 minutes |
| PK: Distribution | limited data on pharmacokinetics | doesn’t cross the BBB |
| Protein binding (PK: Distribution) | ||
| Volume of distribution (PK: Distribution) | ||
| PK: Metabolism | Hepatic | Rapidly metabolised into adrenaline by MAO (Uptake 1, Nv terminal) COMT (Uptake 2 circulation) 25% removed in the lungs |
| PK: Excretion | Unknown | urine as inactive metabolites (84-96%) |
| - Clearance (PK: Excretion) | ||
| - Half Life (PK: Excretion) | short | 2 minutes |
| SPECIAL POINTS |
Search bar: To search for something particular within the table.
Ephedrine | Metaraminol
Pharmacopeia - Adrenergic and Non-Adrenergic Drugs
| EPHEDRINE | METARAMINOL | |
|---|---|---|
| GROUP | ADRENERGIC | ADRENERGIC |
| CICM Level of Understanding | Level 2 | Level 2 |
| INTRODUCTION | Synthetic direct and indirect sympathomimetic with alpha and beta activity | synthetic noncatecholamine with both direct and indirect sympathomimetic actions. |
| USES | 1. Hypotension during surgery 2.Nocturnal enureisis 3. Diabetic autonomic neuropathy 4.Hiccups 5. Nasal decongestant | short term correction of BP in the setting of regional anaesthesia and off label for short term BP correction |
| PHARMACEUTICS (PC) | ||
| PC: Chemical | ||
| PC: Presentation | - Clear colourless solution for injection (3-9mg slow injection, dose repeated ever 3-4 min) - Oral tablets - Nasal spray | clear solution 10mg/mL in one mL vials and usually diluted to 10mg in 10ml or 20ml |
| PHARMACODYNAMICS (PD) | ||
| PD: Main Action | alpha and beta activity | both direct and indirect sympathomimetic actions. It acts mainly via alpha1/2 adrenoceptors to cause vasoconstriction but also has some minor beta activity. |
| PD: Mode of Action | direct and indirect sympathomimetic with alpha and beta activity | through ↑TPR May be transient bradycardia due to baroreceptor feedback upon infusion initiation. ↑Pulmonary vascular resistance. ↑coronary artery flow by an indirect mechanism (stimulates NA release) |
| PD: Route & Doses | IV 3-6mg bolus | IV boluses or infusion |
| PD: Metrics (Onset/ Peak/ Duration) | ||
| PD: Effects | 1. CVS - Effects similar to adrenaline but longer duration as drug is not metabolized by MAO or COMT - Positive inotrope, chronotrope. Increases CO MVO2 - Increases coronary blood flow - Increased SVR and PVR 2. Resp - Respiratory stimulant - Bronchodilation 3. CNS - Stimulatory effect similar to amphetamine - Cerebral blood flow increases - Mydriasis occurs - Has local anesthetic effects 4. GIT - Relaxes GI smooth muscle - Splanchnic vasoconstriciton 5. GU - Decreased RBF - Contracts bladder sphincter and relaxes detrusor muscle- acute urinary retention - Does not cause uterine constriction 6. Metabolic - Increased hepatic glycogenolysis - Increased BMR | CVS: - Increased SVR leading to an increase in diastolic and systolic BP - Reflex bradycardia may occur despite B1 effects - It has positive inotropic effects but cardiac output is more likely to decrease as a result of increased afterload - Coronary artery blood flow increases as an indirect mechanism - Increased PVR CNS: - Doesn’t cross BBB - Causes cerebral vasoconstriction but increases CPP Renal/GU - Renal vasoconstriction but re-established renal perfusion pressure in hypotension - Uterine contraction and reduces uterine blood flow Metabolic - Inhibits insulin release and increases lipolysis - May increase VO2 |
| PD: Side Effects / Toxicity | Insomnia, anxiety, tremor, headache, dysrhythmias, nausea and vomiting, and chest pain irritant to mucous membranes Acute hypertensive crisis with: MAOIs, doxapram, beta-blockers, oxytocin, and ergot alkaloids | Caution should be exercised in patients with pulmonary hypertension. May cause severe hypertension in some patients |
| PHARMACOKINETICS (PK) | ||
| PK: Absorption | - Rapidly absorbed orally | IV. BA 100% 0.1-0.2mg boluses titrated to BP onset / dur imm / up to 20 mins |
| PK: Distribution | - Widely distributed and crosses BBB, placenta and breast milk | limited data on pharmacokinetics |
| Protein binding (PK: Distribution) | ||
| Volume of distribution (PK: Distribution) | ||
| PK: Metabolism | - Resistant to MAO and COMT. Hepatic metabolism with a major metabolite being active and may have central effects | Hepatic |
| PK: Excretion | - 50-90% excreted unchanged in urine. Urinary elimination is pH dependent (enhanced by acidic urine) - Tachyphylaxis rapidly occurs | Unknown |
| - Clearance (PK: Excretion) | ||
| - Half Life (PK: Excretion) | Elimination T1/2 is 6 hours | short |
| SPECIAL POINTS |
Search bar: To search for something particular within the table.
Recent Comments