Pharm Quiz #8 Flashcards
List naturally occurring catecholamines
Epinephrine
Norephinephrine
Dopamine
List synthetic catecholamines
Isoproterenol
Dobutamine
List synthetic non-catecholamines
Ephedrine Amphetamines Phenylepherine Methoxamine Mephentermine
List pharmacologic effects of adrenergic agonists
Vasoconstriction (arterioles, capacitance vessels) Vasodilation (skeletal muscle) Bronchodilation Cardiac stimulation Lipolysis, glycogenolysis CNS stimulation Modulation of insulin
What is the structure of adrenergic drugs?
Adrenergic agonists derived from beta-phenyl-ethylamine
Hydroxyl groups on the 3 and 4 carbon positions of the benzene ring designate catechol status
Non-catecholamines are deficient at the 3 and 4 carbon substitution
List the six steps of adrenergic transmission
Synthesis Storage Release via Ca++ mediated exocytosis Binding Degradation Recycling
Epi and NE binding to receptors alter the ___ conformation - three dimensional shape of the receptor
chemical
A1 couples to Gq which results in increased intracellular ___
Calcium
A2 couples to Gi causing a decrease of ___ activity
cAMP
B receptors couple to Gs and increase intracellular ___ activity
cAMP
Sympathomimetic drugs have their effect on adrenergic receptors located in the ___ and ___
CNS and ANS
In the adrenergic system (SNS), what is the post-gangionic neurotransmitter? Pre-ganglionic?
Post - Epi or NE
Pre - Ach
In the PNS, what is the post-ganglionic neurotransmitter? Pre-ganglionic?
Ach for both
Where are A1 receptors found and what do they do?
Post synaptic sites
Vasoconstriction, mydriasis, relaxation of GI, contraction of GI sphincters, contraction of bladder sphincters
Where are A2 receptors found and what do they do?
Pre-synaptic sites
Inhibition of NE (post-synaptic), platelet aggregation, hyperpolarization of cells in the CNS, sedation
What happens when adrenergic receptors are activated?
Heart rate increases, pupils dilate, energy is mobilized, and blood flow diverted from non-essential organs to skeletal muscle
What are the subtypes of beta receptors?
B1, B2, and B3
Phenylephrine is an agonist of what receptors?
alpha only
All adrenergic receptors are linked to Gs proteins, which are linked to ___. Agonist binding causes a rise in the second messenger ___.
Adenylate cyclase
cAMP
Downstream effectors of cAMP include ___ which mediates intracellular events following homrone binding.
protein kinase (PKA)
What are the mechanism, agonist, and antagonist of alpha 1 receptors?
Selected agonist actions: smooth muscle contraction
Mechanism: Gq
Agonist: NE, phenylephrine, methoxamine
Antagonists: phenoxybenzamine,, phentolamine
What are the characteristics of alpha 2 receptors?
Agonist potency: NE > epinephrine > isoproterenol
Selected agonist actions: smooth muscle contraction, neurotransmitter inhibition
Mechanism: Gi
Agonists: dexamedetomidine, clonidine
Antagonists: yohimbine
Where are alpha 2 receptors found?
In the peripheral and central nervous systems, platelets, and a variety of organs, including the liver, pancreas, kidney, and eye
Alpha 2 G proteins - modulate cellular activity by… what?
Activated G proteins modulate cellular activity by signaling a second messenger system or by modulating ion channel activity
What characteristics to Beta 1 receptors?
Selected agonist actions: increased myocardial contractility
Mechanism: Gs, increased cAMP
Agonists: isoproterenol, dobutamine, epi, NE
Antagonists: Metoprolol, atenolol
What are characteristics to Beta 2 receptors?
Selected agonist actions: smooth muscle relaxation
Mechanism: Gs, cAMP increased
Agonists: Albuterol, terbutaline, isoproterenol
Antagonists: Propranolol
What are characteristics to Beta 3 receptors?
Selected agonist actions: lipolysis
Mechanism: Gs, cAMP increased
Agonists: None in current use
Antagonists: double cheeseburgers
How are catecholamines metabolized?
By monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT)
What are metabolites to catecholamines?
Pharmacologically inactive and include 3-methoxy-4-hydroxymandelic acid, metanephrine, and nor-metanephrine
Inhibition of reuptake produces greater ___ that inhibition of enzymes.
potentiation
Synthetic non-catecolamines not affected by COMT and thus depend on ___
MAO
Inhibition of catecholamine uptake by drugs such as ___ and ___ produce sympathomimetic effects
cocaine
tricyclic antidepressants
Synthetic non-catecholamines activate adrenergic receptors by evoking release of ___ from post ganglionic sympathetic nerve endings
NE
Indirect acting drugs
Mephentermine
Metaraminol
Ephedrine
Cocaine -blocks the re-uptake of monoamines
Amphetamine - promotes NE release from nerve endings and blocks NE re-uptake
Methylphenidate
Indirect acting sympathomimetics require endogenous catecholamines to produce effects, little activity if catecholamines are ___
depleted
What are uses of indirect acting adrenergics?
Cocaine is used as a local anesthetic with vasoconstriction
Appetite suppression
ADD, ADHD, narcolepsy
Abuse
Direct acting adrenergics do not require endogenous catecholamines to produce effects - active even if catecholamines are ___
depleted
Two structural classes of alpha 1 agonists
phenethylamines - related in structure to epi
imidazolines - related in structure to Afrin
List uses for alpha 1 agonists
Hypotension
Ophthalmic preparations to induce mydrasis
Cough and cold preparations - induces constriction of nasal mucosa, decreases resistance to air flow
Alpha 2 agonists, name one
Dexmedetomidine
Effects:
sedation, analgesia, sympatholysis, anxiolysis
What is the infusion rate of dexmedetomidine?
1 mic/kg loading dose, administered over 10 min, followed by maintenance infusion of 0.2-1 mic/kg/hour
Beta 1 adrenergic agonists, list direct acting agonists
Dopamine
Dobutamine
Epinephrine
Isoproterenol
What are beta 1 agonists used for?
CHF
Cardiogenic shock
Increase myocardial contractility and CO
Stimulation of beta 1 receptors induces positive ___, ___, and ___ effects
Chronotropic
Dromotropic
Inotropic
Stimulation of renal beta 1 receptors causes ___ release, mediating extracellular volume and regulating mean arterial pressure
renin
Stimulation of beta 2 receptors induces smooth muscle ___, induces tremor in skeletal muscle, and ___ glycogenolysis in the liver and skeletal muscle
relaxation
increases
Stimulation of beta 3 receptors induces ___
lipolysis
Describe where the three types of beta receptors work?
B1 - heart and kidney
B2 - lungs, GI tract, liver, uterus, vascular smooth muscle, skeletal muscle
B3 - fat cells
List the effects of epinephrine
Increases HR and SV
Dilates the pupils
constricts arterioles in the skin and GI tract
Dilates arterioles in skeletal muscles
Elevates blood sugar by catabolism of glycogen to glucose in the liver
Begins the breakdown of lipids in fat cells
Suppresses the immune system
Epinephrine is a ___ agonist of adrenergic receptors
Non-selective
What amino acids make epinephrine?
Phenylalanine and tyrosine
List the steps for the production of Epi in the body
Tyrosine - DOPA - dopamine - NE - epinephrine
What nerve from the SNS stimulates the release of epinephrine?
Splanchnic nerves to the adrenal medulla
___ triggers exocytosis of chromaffin granules and release of epinephrine and NE into the bloodstream
Calcium
Explain the varying doses in epinephrine
Doses of 1-2 mcg/min stimulate beta 2 in peripheral vasculature
Doses of 4 mcg/min stimulate beta 1 in heart
Doses of 10-20 mcg/min stimulate both beta1 and beta2 with alpha predominating in vascular beds
What routes can epi be given?
IV, SQ, ETT, aerosol, topical
