Wakade - Adrenergic Pharmacology IV Flashcards
Antiasthmatic Agents:
EPI, ISO, Ephedrine
EPI:
Effects:
Used for:
EPI: potent beta2 agonist used for severe cases of asthma (status asthmaticus)
ISO:
Effects
Why is it no longer used?
ISO: potent beta2 agonist that is no longer used (risk of cardiac stimulation because of beta1 R)
Ephedrine:
May also be used prophylactically to:
Nose and eyes:
Ephedrine: used to treat asthma and chronic bronchitis
May also be used prophylactically to prevent asthma attacks
Nasal decongestant and pupil dilator
More Selective Beta2 Agonist: although not 100% selective (4)
Orciprenaline
Salbutamol
Terbutalin
Salmeterol (TOSS)
Anaphylactic Shock:
Treat
Anaphylactic Shock: parenteral EPI, NE or phenylephrine
Circulatory Shock:
Treat
Circulatory Shock: IV NE, metaraminol (may not be useful and may even worsen condition)
Use with local ansthetics:
EPI/PE (phenylephrine)
EPI/PE: employed with local anesthetics to cause vascoconstriction and to keep drug at injection site longer
Use with local ansthetics:
EPI/PE/Methoxamine/NE
Employed to maintain BP during spinal anesthesia
Urticaria (Hives)
Nasal decongestant:
Mydriatic agent:
CNS stimulant:
Urticaria: EPI
Nasal Decongestant: Phenylephrine (PE), naphazoline
Mydriatic Agent: PE, ephedrine (topical to the eyes)
CNS Stimulant: amphetamine, methamphetamine
Dobutamine (Unique Adrenergic Agonist):
L Isomer:
D Isomer:
Use:
Racemic Mix:
L Isomer: acts on both types of receptors
Alpha agonist
Weak beta1 agonist
D Isomer:
Alpha1 antagonist
Potent beta1 agonist
- Overall Result: selective beta1 agonist
Acute management of heart failure (improve cardiac output)
o Stimulate heart for stress test
ADRENERGIC RECEPTOR BLOCKING AGENTS:
• General:
Inhibit Agonist Actions: NE, EPI and others at the level of the RECEPTOR (inhibit effector organ responses)
Alpha Adrenergic Antagonists
2 major classes
Alpha 1——–postsynaptic- smooth muscles of blood vessels, secretory glands, GI muscle,
etc,
Alpha 2 ——-presynaptic- sympathetic neurons, CNS, blood platelets, Beta cells of
pancreas, etc.
Selectivity:
Alpha1| Prazosin > Phenoxybenzamine > Phentolamine > Yohimbine |Alpha2
Result of Alpha Adrenergic Blockade:
Both Alpha 1 and 2
Just alpha 2
Both Alpha1 and 2 (General):
- Decrease in BP due to decrease in vascular resistance
- Decreased blood pressure causes reflex tachycardia and increased CO
Alpha2 Antagonists:
- Exaggerate these reflexive effects because of enhanced release of NE that acts on beta1 receptors of the heart
- Blockade in the CNS (pontomedullary region) can “disinhibit” SS drive to the periphery, resulting in increase SS outflow and NE release in heart and blood vessels
Alpha Adrenergic Antagonists Drugs Divided into 3 Chemical Groups:
- Haloalkylamines: phenoxybenzamine
- Imidazolins: phentolamine
- Qunazolins: prazosin (gaining popularity)
Haloalkylamines (Phenyoxybenzamine):
Mechanism
Mechanism: non-competitive reversible inhibitor of alphaR
- Forms a covalent bond with alphaR (occupies for 12-24 hours)
Other Actions:
- Blocks neuronal/extraneuronal uptake of NE
- Blocks 5-T, ACh and histamine receptors as well
Use:
- Management of pheochromocytoma and severe HTN
- Treatment of peripheral vascular disease (Raynaud’s Syndrome)
Imidazolins (Phentolamine):
Mechanism:
Use:
Imidazolins (Phentolamine):
Mechanism: competitive reversible antagonist of alphaR
Use:
- Control HTN in patients with pheochromocytoma
- Treatment of hypertensive crisis following abrupt withdrawal of clonidine or the ingestion of tyramine when using MAOIs
Quanazolins (Prazosin):
Mechanism:
Use:
Duration:
What is Doxazosin?
Mechanism: selective alpha1 antagonist (1000 times greater affinity for alpha1 than alpha2)
Use: favored over previous two
- Primary HTN (decreases BP)
- Congestive cardiac failure (reduces preload and afterload)
Short duration of action: 6 hours (downfall)
Doxazosin: newer alpha1 blocker with longer duration of action (20 hours)
Tamulosin
Mechanism:
Use:
(Flomax):
Mechanism: targets specifically alpha1A receptors that are abundant in the smooth muscle of the human prostate gland
Use: treatment of patients with urinary issues due to BPH
Beta Adrenergic Antagonists:
Basics:
Most important agents from clinical standpoint
Conditions Treated with Beta Blockers: many, including the following
o High blood pressure o Angina o Irregular heart rhythms o Prevention of a second heart attack o MI o Migraines o Tremors o Alcohol withdrawal o Anxiety (PTSD) o Glaucoma
Propanolol:
Mechanism:
Partial agonist activity?
Effects: Alone? What activates it? What results in decreased HR and CO? Blockage of exercise/stress induced effects result in: How is peripheral resistance affected? Renin:
Protypic classic beta blocker
Mechanism: selective competitive beta-receptor antagonist
No partial agonist activity
Membrane stabilization activity (local anesthetic-like activity)
Effects: has very little effect of its own on the heart or CV system; however, exerts profound effects when SS control is elevated (ie. exercise or stress)
- Blockage of B1 receptors of heart results in decreased HR and CO
- Also reduces sinus rate and slows conduction
- Blockage of exercise/stress induced effects result in decreased O2 demands (use in angina and coronary artery disease)
- Peripheral resistance increased (beta2 block) –> possible increase in BP initially
- This could produce compensatory decrease in SS discharge to the heart
- Blocks release of renin from juxtaglomerular apparatus (beta1 block)
- Anti-HTN effect
Other general beta blocker effects:
Hyperthyroidism
Glaucoma/Occular HTN
Anxiety
migraine
Hyperthyroidism: reduce peripheral manifestations(increased HR/CO, tremors)
Glaucoma/Occular HTN: reduce intraocular pressure (reduction in aqueous humor)
- Timolol Issue: also non-specific (blocks beta1 and beta2), and some entered system complicating asthma (block beta2 receptors leading to ↓ bronchodilation)
Anxiety: normally due to increased activity of SNS
Prophylaxis of migraine headaches: blockage of CNS beta receptors, reducing vasodilation
