Sympathomimetics Flashcards
What are catecholamines?
Sympathomimetic amines that contain the 3,4-dihydrobenzene group
List the catecholamines
Epinephrine
Norepinephrine
Isoproterenol
Dopamine
Describe some of the properties of the catecholamines
High Potency
= they are the strongest sympathomimetics.
Rapid Inactivation
= metabolised by COMT postsynaptically and MAO intraneuronally.
COMT is in the gut wall.
MAO is in the liver and gut.
Poor penetration into the CNS
= they are polar
Describe Epinephrine synthesis, action and side effects.
Synthesised in the Adrenal Medulla
Tyrosine __ Tyrosine Hydroxylase __ DOPA
DOPA __ DOPA deCarboxylase __ Dopamine
Dopamine __ ß-Hydroxylase __ Norepinephrine
NE __ methyl transferase __ Epinephrine.
Interacts with both alpha and Beta receptors
Low doses = ß effects = Vasodilation
High doses = a effects = Vasoconstriction
**** Actions ******
Heart = increase heart rate & contractility
Kidney = increase renin = increase BP
Constriction of arterioles - skin, viscera, etc
Dilation of vessels going to liver and skeletal.m
= Increased systolic BP + decreased Diastolic BP
Respiratory = Bronchodilation
Liver = increased gluconeogenesis
Pancreas = increase glucagon release
= Hyperglycemia
Adipose tissue = Lipolysis!!
Metabolised by;
COMT
( catechol - O - methyltransferase )
MAO
( Monoamine Oxidase )
Final metabolites;
= METANEPHRINE & VANILLYLMANDELIC ACID
Indications;
- Bronschospams
- Anaphylactic shock (0.3 - 0.5 mg sc.)
- Cardiac Arrest / complete heart block
- given together with Local anesthetic
Pharmacokinetics;
- Rapid onset and brief duration
- given Intramuscular or in emergency I.V
Adverse Effects;
- CNS disturbances e.g anxiety, headache, tremor
- Hemorrhage (due to BP)
- Cardiac arrhythmia
- Pulmonary edema
Interactions;
- Hyperthyroidism = increase cardiovascular effect
- Cocaine = exaggerated effect ( inhibits reuptake )
- Diabetes = need more insulin
- ß-blockers = increased BP ( alpha unopposed )
Describe Norepinephrine synthesis, actions, side effects etc
Levarterenol (other name )
Synthesised in Nerve Terminal
Tyrosine __ Tyrosine Hydroxylase __ DOPA
DOPA __ DOPA deCarboxylase __ Dopamine
Dopamine __ ß-Hydroxylase __ Norepinephrine
NE __ methyl transferase __ Epinephrine.
Therapeutic doses = alpha receptors are most affected
**Small effect on ß2 receptors!*
****ACTIONS*****
Vasoconstriction
= both Systolic and Diastolic BP increased
Baroreceptor reflex
= reflex bradycardia due to increased BP
****indications****
- Treat early stages of shock
- can be used to locally reduce blood flow
- causes extravasation along injection site **
Pharmacokinetics;
- given I.V
- duration = 1-2 mins following end of infusion
Metabolism - same as Epinephrine
Adverse Effects - same as Epinephrine
Describe Isoproterenol
Potent
Selective for ß receptors (both ß1 & ß2 )
action on alpha receptors is insignificant
rarely used therapeutically
****Actions*******
- Heart = increased heart rate & contractility = ^CO
= moderate increase in systolic pressure - Vessels in skeletal.m = VASODILATION
= significant decrease in peripheral resistance.
= decreased Diastolic pressure - BRONCHODILATION
- Hyperglycemia
- increased lipolysis
**Therapeutic use *******
- used to stimulate heart in emergency
- treat AV block or Cardiac Arrest
Adverse effects ; similar to Epinephrine
- stable to MAO and marginal substrate for COMT *
Describe Dopamine
Occurs naturally in the CNS & adrenal medulla
Tyrosine __ Tyrosine Hydroxylase __ DOPA
DOPA __ DOPA deCarboxylase __ Dopamine
Can activate;
■ alpha & ßeta receptors
■ D1 and D2 receptors (in mesenteric & renal vessels) = Vasodilation
D2 receptors in presynaptic neurone = interfere with NE release
Low doses = D1 receptors = Vasodilation
** Increase renal blood flow **
Medium doses = ß1 receptors = ^ HR & contractility
High doses= acts as Epinephrine (loses selectivity)
****Actions*********
- Heart = ^ HR & contractility - high dose-vasoconstr
- Renal & Splanchnic arterioles = Vasodilation
= increase blood flow
** useful in treatment of shock where significant increase in SYMP may compromise kidney **
**Therapeutic use ******
- Drug of choice for Cardiogenic & Septic Shock
= raises BP (ß1 receptor)
= increases TPR (a1 receptor)
= perfusion to kidney & splanchnic (D1 receptor) - used to treat Hypotension & severe CHF
Adverse effects;
- Tachycardia
- overdose = Sympathetic stimulation
List and describe selective alpha 1 agonists
**** Phenylephrine ****
- Not a catechol derivative
= prolonged duration of action.
________Therapeutic use__________
= Mydriasis
= Nasal decongestant
= raise BP
Side effects;
- Rebound hyperemia
- ischemic changes of mucous membrane
- swallowing gives systemic changes
**** Midodrine *****
A prodrug
Hydrolyzed to == Desglymidodrine
_________ primary indication __________
- treatment of Orthostatic Hypotension
(due to impaired ANS function)
Adverse effects;
- Supine Hypertention
**** Methoxamine ****
Acts like Phenylephrine
Available for parenteral use
Adverse effects;
- prolonged increase in BP due to Vasoconstriction
- Reflex Bradycardia
List and describe ß1 receptor agonists
Prenalterol
Ibopamine - derivative of methyldopamine
( broken down in blood to methyldopamine)
Dopamime - medium doses
- ** indications ***
- Cardiogenic Shock
- Chronic heart failure
Adverse effects
- Tachycardia
**** Dobutamine ****
( Causes less Tachycardia than dopamine )
- consists of 2 stereoisomers (racemic mixture)
+R = potent ß1 agonists (also activates ß2)
-S = activates alpha 1 receptors
Actions_____
- increased Heart rate and CO with few vascular effects
- *** indications ****
- Cardiogenic Shock
- Acute Congestive Heart Failure ( increases CO and does not elevate oxygen demand of heart )
Adverse effects;
- increases AV conduction (*atrial fibrillation)
- Tolerance may develop
List and describe selective ß2 agonist
**Main actions and indications*****
= Bronchodilation
= Relaxation of the pregnant uterus (Tocolytics)
Anti-asthmatic therapy
- Metaproterenol
- Salbutamol
- Terbutaline
- Fenoterol
- Pirbuterol
Longer acting anti-athmastics
- Salmeterol
- Formoterol
Tocolytics
- Ritodrine
- Terbutaline
