2.06 Adrenergic Drugs Flashcards
Enumerate the four catecholamines
Norepinephrine
Epinephrine
Dopamine
Isoproterenol
Used for narcolepsy treatment
Modafinil
Mechanism of action of cocaine and TCA in increasing NE activity
Cocaine and TCAs inhibit uptake 1 or neuronal uptake
MOA of pargyline in increasing NE activity
MAO inhibitor
Epinephrine receptor selectivity
a1, a2, B1, B2, B3
Core drug for anaphylactic shock
Epinephrine
Primary neurotransmitter released in nerve endings
Norepinephrine
Norepinephrine receptor selectivity
a1, a2, B1, B3
Isoproterenol receptor selectivity
a1, a2, B1, B3
Selective a1 receptor agonists
Phenylephrine
Methoxamine
Midodrinel
Imidazole derivatives
Midodrine
Prodrug used for treatment of patients with autonomic insufficiency and postural hypotension
Selective a2 receptor agonists: properties, MOA
Sympathomimetic agonist, but the effect is sympathetic depression
Selective a2 receptor agonists
Clinidine Methyldopa Guanfacine Guanabenz Tizanidine Apraclonidine, Brimonidine
Tizanidine
Muscle relaxant in the treatment of muscle spasticity
Apraclonidine, Brimonidine
Used for the treatment of wide-angle glaucoma
Selective B1 receptor agonists
Dobutamine
Prenalterol
Selective B2 receptor agonists
Terbutaline Salbutamol Fenotero Bililetro Clenbuterol Prcatero Salmeterol Formoterol
Short active selective b2 receptor agonists that is short acting medication for acute asthma attach
Terbutaline
Salbutamol
Long acting B2 selective receptor agonists for asthma
Indicaterol
Salmeterol
Formoterol
Ritodrine
Tocolytic; uterine smooth muscle relaxant, prevents premature labor
Isoxuprine
Also a tocolytic agent
Used in treatment of peripheral vasospastic disease
Catecholamines are inactivated by
COMT
MAO
Norepinephrine is primarily eliminated by
Uptake 1
Epinephrine is primarily eliminated by
Uptake 2
Isoproterenol is primarily eliminated by
Uptake 2
Monoamine oxidase is present in ___
surface membrane of mitochondria in liver and intestinal epithelium
COMT is present in
Adrenal medulla, and other tissues, but not in nerve endings
a1 sympathomimetic effect on smooth muscles
a1 receptors:
vasoconstriction–> pallor
contraction of radial smooth muscles of the iris–> mydriasis
pilomotor contraction–> goosebumps
B2 sympathomimetic effect on smooth muscles
relaxation of walls of urinary bladder, contracted sphincter–> urinary retention
Relaxation of walls of GIT–> consitpation
Relaxation of bronchial smooth muscles
Relaxation of uterus
Receptor involved and sympathomimetic effect on the Heart
B1 receptor agonist
(+) chronotropy
(+) inotropy
(+) dromotropy
Receptor involved and sympathomimetic effect on metabolism
Glycogenolysis in liver and muscle
Hyperglycemia, hyperlipidemia, hyperlactacidemia
Receptor involved and sympathomimetic effect on pancreatic islets
B receptors: increased glucagon from a cells, increased insulin from beta cells
Catecholamine most potent on beta receptors
Isoproterenol
Epinephrine
Catecholamine most potent on alpha receptors
Norepinephrine
Considered asthe parent compound form which sympathomimetic drugs are derived
Phenyethylamine
Phenylethylamine consists of
a benzene ring
ethylamine side chain
Structure of dopamine as compared to phenyethylamine
OH group at c3 and c4
Structure of NOREPINEPHRINEas compared to phenyethylamine
OH group at c3 and c4
OH group at B carbon
Structure of EPINEPHRINE as compared to phenyethylamine
OH group at c3 and c4
OH group at B carbon
Methyl group at amino terminal–> increased B activity (with B2)
Structure of ISOPROTERENOL as compared to phenyethylamine
OH group at c3 and c4
OH group at B carbon
Bigger alkyl substitution–> activity on B1, B2, B3 but not on alpha receptors
Effect of increasing size of alkyl substituents
Increases B receptor activity and lowers alpha receptor activity
Example: Epinephrine - methyl substitution of NE
Isoproterenol - isopropyl substitution at amino group of E
Effect of substitution on alpha carbon
Blocks oxidation by MAO–> prolonged duration of action
Epinephrine: Give polarity, CNS penetration, metabolization, receptor selectivity
Polar drug Poorly penetrates the CNS No oral preparation Rapidly metabolized in the intestinal mucosa and liver Activates all adrenoceptors
Location of a1 receptors
Vascular smooth muscles
Location of a2 receptors
Presynaptic adrenergic nerve terminals: decreased sympathetic outflow Platelets Lipocytes GI smooth muscles JG cells
Location of B1 receptors
HEART
lipocytes
brain
JG cells
Location of B2 receptors
Bronchial smooth muscles
Blood vessels
Heart muscle
Uterus
Location of B3 receptors
Lipocytes
In small doses, epinephrine will first affect __ with regards to effect on BP
B2 receptors–> decreased TPR
In large doses, epinephrine will affect __ with regards to effect on BP
ALL receptors will be activated
a1 and B2–> biphasic response
B1–> increased contraction
Epinephrine effect on metabolism
B2: enhanced glycogenolysis in the liver-> increased glucose and lactic acid release
a2: inhibition of pancreatic B cells–> decreased insulin
B2: stimulation of pancreatic a cells–> increased glucagon
B3 on adipocytes–> increased FFA
What is tachyphylaxis
Rapid increase in responsiveness of drugs given in successive intervals in small doses
Relative receptor affinities: Phenyephrine, methoxamine
a1>a2»»»>B
Relative receptor affinities: Clonidine, methylnorepinephrine
a2>a1»»»>B
Relative receptor affinities: Norepinephrine
a1=a2; B1>B3»»»>B2
Relative receptor affinities: Epinephrine
a1=a2; B1=B2
Relative receptor affinities: Dobutamine
B1>B2»»»a
Relative receptor affinities: Isoproterenol
B1=B2»»»a
Relative receptor affinities: Albuterol, Terbutaline, Metaproterenol, Ritodrine
B2>B1»»»a
Relative receptor affinities: Dopamine
D1=D2»B»a
Relative receptor affinities: Fenoldopam
D1»D2
Cardiovascular effect of Norepinephrine
B1: increased CO, SV
a1: vasoconstriction–> increased DP
Greater increase in BP that epinephrine
Adrenergic effect of dopamine in the CVS
Low dose: D1 receptor–> vasodilation, tissue perfusion, decreased peripheral resistance
Higher dose: B1 receptor–> (+) inotropic effect, tachycardia, release of NE from nerve terminals
Higher dose: A1 receptor–> vasoconstriction
Adrenergic effect of dopamine in the kidney
Low dose: D1 receptor: increased renal blood flow, increased GFR–> natriuresis and diuresis
Fenoldpeam
D1 receptor agonist
Moderate affinity to a2 adrenoceptors: decrease release of transmitter substance
Severe hypertension
Isoproterenol: affinity, inactivation
activates all b1, b2, b3 receptors
relatively poor substrate for MAO
potent bronchodilator
Used in Reynaud’s phenomenon, and Buerger’s disease
Isoproterenol
Dobutamine: affinity
B1>B2»»a
Therapeutic use for dobutamine
Shot term treatment of cardiac decompensation post cardiac surgery; CHF; AMI
General therapeutic use of B2 selective adrenoreceptor agonists
Treatment of asthma and COPD as bronchodilator
Most common ADR of long term use of B2 selective adrenoreceptor agonists
Physiological skeletal muscle tremor
Severe pulmonary edema
worsened hyperglycemia in diabetic patients
Terbutaline therapeutic use
Treatment of asthma, COPD, bronchitis
Management of premature labor
Agent of choice together with formoterol for nocturnal asthma
Salmeterol
Salmeterol
partial agonist
prolonged action
highly selective for B2 receptors
Formoterol
Full agonist
Long acting, lipophillic, high affinity for B2 receptors
Therapeutic use of ritodrine
Uterine relaxant to arrest premature labor and prolong pregnancy
Indicaterol
Ultra long acting, selective B2 agonist
Treatment ONLY FOR COPD
General actions of alpha 1 selective adrenoceptor agonists
Vasoconstriction reflex bradycardia Pupillary dilation Goosebumps Contraction of prostate Inotropy
Phenylephrine
Selective a1 agonists
activates b1 only at HIGHER CONCENTRATIONS
Midodrine
Selective a1 receptor agonist
ORTHOSTATIC HYPERTENSION
First orally active sympathomimetic drug
Ephedrine
Ephedrine
All adrenergic receptors, but less efficacious than epinephrine
Used to treat cardiogenic shock
Dobutamine
Dopamine
Selective a1 agonist which causes reflex bradycardia
Phenylephrine
