L5: Sympathomimtics Flashcards
(62 cards)
What are adrenergic agonists?
These drugs act either directly or indirectly (by the release of norepinephrine stored), to activate adrenergic receptors and mimic the effects of endogenous catecholamines (sympathetic stimulation)
Do all Sympathomimetics activate adrenergic receptors by the Same degree?
- Not all sympathomimetic drugs activate the adrenergic receptors to the same degree.
- some drugs have a higher affinity towards certain receptor classes (selectivity) depending on the ultrastructure of these receptors; however, in large doses, this selectivity is lost.
What is the classification of adrenergic receptors?
❖ According to the chemical structure
❖ According to the mechanism of action
❖ According to selectivity
What are adrenergic agonists classified into according to chemical structure?
I. Catecholamines (contain catechol nucleus)
Natural: adrenaline, noradrenaline, dopamine
Synthetic e.g Isoprenaline
II. Non-Catecholamines
phenylephrine amphetamine
What are adrenergic agonists classified into according to MOA?
A. Direct acting: e.g. E, NE, and dopamine
B. Indirect acting: e.g. amphetamine
C. Both direct and indirect: e.g. ephedrine
What are adrenergic agonists classified into according to selectivity?
A. Drugs acting mainly on α1 receptors: e.g. NE, phenylephrine
B. Drugs acting mainly on β receptors:
On β1 mainly: e.g. dobutamine
On β2 mainly: e.g. salbutamol and terbutaline
On both β1 and β2: e.g. isoprenaline
C. Drugs acting on α and β receptors: e.g. adrenaline, ephedrine
D. Drugs acting on α, β, and dopamine receptors: dopamine
What is the nature of epinephrine?
Natural alkaloid synthesized by the adrenal medulla.
What is the pharmacokinetics of adrenaline?
It is ineffective when given orally. It should be given IM or SC.
IV injection is highly dangerous and is likely to precipitate ventricular fibrillation (tachyarrhythmia)
It does not cross BBB(highly polar)
Because of the extensive metabolism (MAO, COMT) of the drug, little is excreted unchanged in the urine.
What is the pharmacodynamics of adrenaline?
Mechanism of action:
Epinephrine Stimulates all α1,α2,β1,β2,β3 receptors.
α1-adrenoceptors activation leads to an increase in intracellular IP3& DAG(Gq).
β-adrenoceptors activation leads to an increase in intracellular cAMP (Gs).
α2-adrenoceptors activation leads to decrease intracellular cAMP (Gi).
what are the pharmacological effects of epinephrine on the eyes?
Local adrenaline: no effects (destroyed by the alkalinity of the tears).
Local dibivalyl adrenaline (pro-drug):↓ IOP (due to VC of ciliary BV → ↓ aqueous humor secretion) by a different mechanism from physostigmine
what are the pharmacological effects of epinephrine at CVS?
Heart: Increase rate (chronotropic effect) and force (inotropic effect) of the cardiac muscle (β1)
BP: (small dose = VD)
Increases systolic pressure due to positive inotropic and chronotropic effects (β1),
decreases diastolic pressure (because VD of skeletal muscle blood vessels (β2) overcomes the VC produced by α1 receptors in the skin and splanchnic vascular beds).
Blood vessels : (Large (therapeutic) dose = VC)
At high doses, VC (α1) of all vascular beds predominates leading to an increase in both systolic and diastolic BP.
Increase coronary blood flow due to increased cardiac work (accumulation of metabolites), and β2 stimulation (VD).
what are the pharmacological effects of epinephrine on the respiratory system?
Relaxation of bronchial smooth muscle (β2). = Bronchodilation
Decrease bronchial secretions (due to VC)(α1). =bronchial decongestion.
What are the pharmacological effects of epinephrine on the GIT and urinary system?
Wall: relaxation (β2).
Sphincters: contraction (α1).
What are the pharmacological effects of epinephrine on the exocrine glands?
Sweat glands: sympathetic sweating (forehead and palms) (α1).
What is the metabolic action of epinephrine?
Liver → ↑ glycogenolysis (β2). (Even though insulin secretion is increased by beta two but the net effect is in favor of glycogenesis)
Kidney → ↑ renin secretion (β1)
Fat cells → ↑ lipolysis ( β3)
What are the local effects of epinephrine?
Decongestant (hemostatic), Delay absorption of drugs given SC (Toprolongs the action of anesthetics and it is due to vasoconstriction)
Which one causes higher VC?
Adrenaline or noradrenaline
Noradrenaline does, because it only affects alpha receptors and has no effect on beta receptors
What are the therapeutic uses of adrenaline?
Anaphylactic shock
Acute bronchial asthma
Cardiac arrest
Local uses
What are anaphylactic shocks?
It is a life-threatening condition (acute hypersensitivity reaction) resulting from the massive release of histamine from inflammatory cells in response to exposure to an allergic substance (e.g. penicillin). Histamine causes severe hypotension and bronchoconstriction by its effect on histamine (H1) receptors.
How are anaphylactic shocks treated?
Injection of epinephrine immediately dilates the bronchi (β2), decreases bronchial secretions (α1), and elevates BP (VC); so, epinephrine is considered the “physiological antidote” of histamine as it can reverse all its effects by actions on different receptors.
Use of adrenaline for acute bronchial asthma
within minutes after s.c. administration, epinephrine:
induces bronchodilation (β2)
decrease airway edema (α1 )
Use of adrenaline for cardiac arrest
early i.v. epinephrine administration, during cardiopulmonary resuscitation (CPR), can restore cardiac activity (β1) and improve vascular tone collapse (α1).
Local uses of adrenaline
- In acute epistaxis (nasal bleeding) to produce VC of nasal BV.
- Injected locally with local anesthetics: To prolong the duration of local anesthetics due to local VC…
What are the adverse effects of adrenaline?
- Severe hypertension and cerebral hemorrhage.
- Tachycardia, palpitations, and ventricular fibrillation.
- Acute heart failure.
- Gangrene of fingers when used with local anesthetics in high concentrations (due to VC).
