Adrenergic transmission Flashcards
Components of “fight or flight” response
- Pupil dilation
- Bronchodilation
- Increased heart rate and blood pressure
- Vasoconstriction in the skin and organs
- Glycogenolysis and increased blood sugar
Alfa 1 receptor
- 7 TM pathway
- Effects
- Location of effect
- Gq
- Vasoconstriction. Constriction of visceral smooth muscles and vascular smooth muscle. Pupil dilation.
- Smooth muscle in vessels, eye, bronchi and viscera.
Alfa 2 receptor
- 7 TM pathway
- Effects
- Location of effect
- Gi
- Decreased insulin release. Negative feedback (inhibits noradrenaline release).
- smooth muscle in vessels.
Beta 1 receptor
- 7 TM pathway
- Effects
- Location of effect
- Gs
- increased inotropy, chronotropy, dromotropy, bathmotropy, renin release.
- Muscle cells in heart. Kidneys.
Beta 2 receptor
- 7 TM pathway
- Effects
- Location of effect
- Gs
- Vasodilation. Bronchodilation. Relaxation of visceral smooth muscle. Glycogenolysis.
- Smooth muscle in vessels, bronchi, and viscera.
Beta 3 receptor
- 7 TM pathway
- Effects
- Location of effect
- Gs
- Lipolysis. Thermogenesis.
- Adipose tissue, skeletal muscle tissue.
Adrenaline (non-selective adrenergic agonists)
- MOA
- Indication
- Side-effects
MOA: stimulates sympathetic by stimulating all alfa and beta adrenergic receptors.
Indication:
- cardiac arrest (stimulates the heart by increasing HR and contractility by beta1 receptor).
- anaphylactic shock (act on beta1 receptors in the heart to increase blood pressure and oxygen supply), act on alfa receptors to stimulate vasoconstriction, act on beta2 receptors to stimulate bronchodilation.
Side-effects: palpitations, tachycardia, hypertension.
Noradrenaline (non-selective adrenergic agonists)
- MOA
- Indication
- Side-effects
MOA: in opposition to adrenaline, binds mostly to alfa receptors -> peripheral vasoconstriction, in addition to increased heart rate, contractility and blood pressure.
Indication: hypotensive shock. The drug stimulates alfa1 receptors in smooth muscle cells in vessels and hereby increases TPR and blood pressure. Also increases contractility and heart rate due to beta1 receptors.
Side-effects: palpitations, tachycardia, hypertension.
Beta1-adrenergic agonist - dobutamine
- MOA
- Indication
- Side-effects
MOA: binds to beta1 receptor in heart increase L-type Ca2+ channels activity -> increase contractility, inotrophy, dromotrophy and heart rate.
Indication: cardiogenic shock.
Side-effects: palpitations (fast breathing of heart), angina (hjertekrampe).
Beta2-adrenergic agonist - salbutamol
- MOA
- Indication
- Side-effects
MOA: binds beta2 receptor in smooth muscle cells in bronchi and induce bronchodilation. Also binds the same receptor in smooth muscle cells in the uterus.
Indication: asthma and to inhibit premature labor (stimulates relaxation of the uterus).
Side-effects: bronchodilators are inhaled, so the effect is local, and therefor there are not many side-effects. But tachycardia (beta1), tremor (beta2), flushing (beta2 in skin blood vessels).
Alfa1-adrenergic antagonists - prazosin
- MOA
- Indication
- Side-effects
MOA: binds and block alfa1 receptor in smooth muscle cells in vessel walls + urine bladder. Blocks vasoconstrictive effect of adrenaline and noradrenaline -> smooth muscle cells relax -> vasodilation -> decreased blood pressure.
Indication: hypertension and urinary retention. (relaxes smooth muscle cells in the bladder).
Side-effects: postural hypotension, flushing, tachycardia, nasal congestion, impotence.
Alfa2-adrenergic agonists - clonidine
- MOA
- Indication
- Side-effects
MOA: binds and activates the presynaptic inhibitory receptors in CNS -> release of noradrenaline is inhibited -> sympathetic effects such as increased blood pressure is reduced.
Indication: migraine and hypertension.
Side-effects: drowsiness, postural hypotension, edema and weight gain, rebound hypertension (following abrupt cessation of treatment).
Beta-blockers
- MOA
- Indication
- Side-effects
MOA:
- Antagonist for beta1 receptor (metoprolol) -> blocks sympathetic tones by inhibiting noradrenaline’s effect on the receptors -> reduced blood pressure and heart workload.
- Inverse agonist for beta1 and beta2 receptors (propranolol) -> down regulate the basal activity of these receptors -> reduces sympathetic tone centrally, and reduces workload on heart (decreases CO). Blocking beta2 in the kidney reduces renin release from juxtaglomerular cells.
Indication:
- Metropolol is used in treatment of hypertension and cardiac insufficiency.
- Propranolol for exam anxiety, tremor and thyrotoxicosis.
Side-effects: life-threatening bronchoconstriction, bradycardia, cold extremities, fatigue, hypoglycemia.
False transmitter precursor - methyldopa
- MOA
- Indication
MOA: is taken up by noradrenergic neurons and converted to alpha-methyl-noradrenaline (false neurotransmitter, alfa2 receptor agonist), which cannot be degraded by MAO -> accumulation -> binds and stimulates the inhibitory presynaptic alfa2 receptor -> inhibits the release of noradrenaline to the synapse -> reduction of sympathetic stimulus.
Indication: hypertensive pregnant patients.
Amphetamine
- MOA
- Indication
MOA: act as competitive inhibitors, reducing the reuptake of DA and noradrenaline. They can also inhibit MAO, which normally break down DA and noradrenaline. Amphetamine also expels DA/NE from vesicles.
Indication: ADHD
