ADRENERGIC DRUGS Flashcards
Beta-2 receptors
Receptors in the bronchial smooth muscle are largely of the beta2 subtype
NE has little effect on beta2 receptors, so has relatively little capacity to increase bronchial air flow
Epinephrine and isoproterenol, on the other hand, are potent bronchodilators
Cutaneous blood vessel receptor(s)
Expressive almost exclusively alpha1 receptors; thus NE and E cause constriction of such vessels
Smooth muscle of blood vessels that supply skeletal muscle
Has both beta2 and alpha1 receptors
Beta2 activation = vasodilation Alpha1 activation = vasoconstriction
Low conc. E = beta2 activation = vasodilation
High conc. E = alpha1 activation predominates = vasoconstriction
*physiological conc. E = primarily vasodilation
Catecholamines
Eg: Epinephrine, Norepinephrine, Isoproterenol, Dopamine
Basic chemical structure consists of a catechol = o-dihydroxy-benzene (has hydroxyl substitutions on the aromatic ring)
Properties:
- High potency
- Rapid inactivation*
- Poor CNS penetration (d/t polar property)
- by MAO intraneuronally and by COMT post-synaptically
- also metabolized in other tissues —> MAO also found in gut walk and liver, and COMT also found in gut wall
Non-catecholamines
Eg: Phenylephrine, ephedrine, and amphetamine
Compounds lacking the catechol -OH groups
Have longer half-lives (not inactivated by COMT)
More liposoluble, thus greater CNS penetration
Epinephrine
- Direct acting adrenergic agonist
- Synthesized from tyrosine in the adrenal medulla
- agonist @ alpha & beta receptors
CV Effects:
- inc contractility (+ inotropic: beta1 effect)
- inc contraction rate (+ chronotropic: beta1 effect)
- inc in CO, therefore there is an increased oxygen demand of the myocardium
- inc renin release (beta1)
- constricts arterioles in skin, mucous membranes, and viscera (alpha1)
- @ low doses, vasodilates vessels going to skeletal muscle and liver (beta2)
- systolic pressure inc. is greater than diastolic
Smooth muscle Effects:
- Powerful bronchodilation (beta2)
- Relaxes GI smooth muscle (alpha1, alpha2, beta2). Intestinal tone, frequency and spontaneous contractions are reduced. Sphincters are contracted (alpha1)
- detrusor muscle relaxes (beta2), while trigone and sphincter contract (alpha1). Contraction of smooth muscle in prostrate (alpha1). Urinary retention.
CNS Effects:
-Polar molecule, thus doesn’t enter CNS
Metabolic Effects:
-Hyperglycemia
•inc glycogenolysis in liver (beta2)
•inc glucagon release (beta2 receptors in
alpha cells of pancreatic islets
•inhibited insulin secretion (alpha2, beta2)
-Lipolysis
•by activation of beta1 & 2 receptors in
adipose tissue = inc cAMP = activation of
hormone-sensitive lipase = TG hydrolysis
Metabolism:
-by MAO and COMT —> metanephrine and vanillyl-mandelic acid (VMA)
Uses:
- anaphylactic shock: trtmnt of Type I HS rxns
- asthmatic attacks
- cardiac arrest: to restore cardiac rhythm
- in local anesthetics: inc duration of local anesthetic by producing vasoconstriction @ injection site —> anesthetic can persist at site longer before being absorbed into circulation and become metabolized
PK:
- rapid onset; brief action
- in emergencies, given IV. Others: SC, by endotracheal tube, by inhalation or topically to eye. Oral admin = ineffective d/t inactivation by intestinal enzymes.
Adverse:
- enhanced CV effects in pts w/ HYPERTHYROIDISM or individuals taken COCAINE (blocks catecholamine re-uptake)
- w/ Beta-blockers = unopposed alpha receptor activation = inc PVR and BP
Norepinephrine
- direct acting adrenergic antagonist
- alpha adrenergic receptors MOST affected by NE; has relatively little effect on beta2 receptors
CV Effects:
- vasoconstriction (alpha1) Both systolic and diastolic pressures increase.
- baroreceptor reflex: inc cardiac contractility (beta1) = inc in BP, which stimulates baroreceptors and inc vagal activity = reflex bradycardia
- CO unchanged
Metabolic effects:
Similar to epinephrine (ie: hyperglycemia), but only seen @ high doses
Uses:
- BP control in acute hypotensive states
- Cardiogenic and septic shock
Dopamine
Direct- acting adrenergic agonist
CV Effects:
-@ low rates of infusion
•selectively activated D1 receptors, in renal and other vascular beds = vasodilation and inc in GFR, renal blood flow and sodium excretion
-@ intermediate rates of infusion
•activates beta1 receptors in the heart = inc cardiac contractility and CO
•inc systolic BP, diastolic BP unchanged significantly. MAP inc, PVR unchanged d/t vasodilatory effects.
Albuterol, terbutaline, pirbuterol
Inhaled short-acting beta2 selective agonists (SABA)
Used in the management of asthma
Bronchodilators
Salmeterol, Formoterol
Long-acting beta2 selective agonists
Used in the management of asthma
Bronchodilators
SAMAs
Short acting muscarinic antagonists
Used in asthma
Bronchodilators
Ipratropium
LAMAs
Long acting muscarinic antagonists
Used in asthma
Bronchodilators
Tiotropium
Methylxanthines
Bronchodilators used in asthma
Theophylline and aminophylline
MOA: inc cAMP & induce bronchodilation via inhibition of phosphodiesterase (PDE) enzyme
Adverse effects: narrow TI, many drug interactions,toxicity: GI, CV (tachyarrhythmias), CNS ( seizures) & metabolic (dec K+, inc glucose)
