- 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

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

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

doesn’t cross the BBB

limited data

No PB

0.14 L/kg

Taken up into adrenergic neuron – Metabolized by MAO and COMT

Circulating drug hepatically metabolized

Metabolised by peptidases (Vasopressinases) to amino acids

Urine as inactive metabolites

65% unchanged in urine

2 minutes

10-35 mins

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

Prod hypothal.
released by the posterior pituitary
similar to oxytocin complex molecule wt

ADRENERGIC

Endogenous vasopressin hormone, clinically used as a non-adrenergic vasopressor.

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

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

Level 1

Level 1

It is a non selective adrenergic agonist.

Mast cell stabilizer (anaphylaxis)

Acts at the GPCR Vasopressin receptors

Rapid onset

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

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