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
Important Considerations Before Recommending Beta Blockers
Should not be given to patients with diabetes (mask signs of hypoglycemia)
Should not be given to asthmatic patients
Can worsen congestive heart failure, Raynaud’s syndrome and diabetes
Should not use concomitantly with Ca++ channel blockers (AV block)
Should be withdrawn gradually after prolonged use (avoid withdrawal, which can precipitate MI)
Other Non-Selective Beta Blockers (block both beta1 and beta2): (6)
o Carteolol (slight partial agonist activity) o Levobunolol o Nadolol (long half life compared to others) o Pindolol (partial agonist activity + slightly membrane stabilizing) o Timolol (slight partial agonist activity) o Penbutolol (slight partial agonist activity)
Selective Beta Blockers:
Examples of Beta1 Selective Blockers: heart specific (5)
Important Note: the higher the concentration of these drugs, the less selective they become
Acebutolol (some partial agonist activity)
Atenolol
Betaxolol (slight membrane stabilizing activity)
Esmolol (very short half life compared to others)
Metoprolol (slight membrane stabilizing activity)
Bystolic:
Effects:
Recently approved: more specific for beta-1 blocker
Effects:
Reduces cardiac force of contraction
Reduces HR
Causes vasodilation and reduction in TPR
Alpha and Beta Receptor Blocking Agents:
General:
Block both alpha and beta adrenergic receptors (relatively new)
Labetelol (Normodyne, Trandate):
Mechanism:
- Ratio of activity:
- Membrane stabilizing?
- Action on presynaptic alpha2R
- NET
Effects:
Effect on HR/CO:
Use:
Mechanism: nonselective competitive blocker (alpha and beta)
Ratio of beta:alpha activity is ~3:1 (orally) or ~7:1 (IV)
- Also has some intrinsic activity (partial agonist)
- Also has good membrane stabilizing action (less excitable membrane; local anesthetic-like action)
- Very little action on presynaptic alpha2 receptors
Can block NET
Effects:
Most prominent effect in humans is lowering peripheral vascular resistance WITHOUT a major change in HR or CO
Use:
- Primary hyptertension
- Hypertension with angina
- Preoperative management of patients with phechromocytoma
Alpha-methyl tyrosine
Site of Action:
For use in:
Alpha-methyl tyrosine
blockade of tyrosine hydroxylase
rarely used
Reserpine
Site of Action:
For use in:
Reserpine
inhibition of storage of NE
hypertension
Guanethidine
Site of Action:
For use in:
Guanethidine
inhibition of release & storage of NE
hypertension
Clonidine
Site of Action:
For use in:
Clonidine
inhibition of release of NE (alpha2)
hypertension Diarrhea In diabetic neropathy Narcotic, alcohol withdrawal Quit smoking Reduce menopausal hot flashes
Apraclonidine
Site of Action:
For use in:
Apraclonidine
inhibition of NE release (alpha2)
Decrease in intraoccular pressur
glaucoma
Brimonidine
Site of Action:
For use in:
Brimonidine
inhibition of NE release (alpha2)
glaucoma
Alpha-methyl –DOPA
Site of Action:
For use in:
Alpha-methyl –DOPA
inhition of release of NE (alpha2)
hypertension
Imipramine, desipramine
Site of Action:
For use in:
Imipramine, desipramine
inhibition of NE transporter
depression
Cocaine
Site of Action:
For use in:
Cocaine
inhibition of NE transport
no use, abused for CNS stimulation
Amphetamines
Site of Action:
For use in:
Amphetamines
inhibition of NE transport
narcolepsy, weight loss (?)
Epinephrine
Site of Action:
For use in:
Epinephrine
bronchodilation ( beta2 receptors): bronchospasm
Vasoconstriction (alpha1 receptors): anaphylactic shock, Urtcaria local & spinal anestesia
Isoproterenol
Site of Action:
For use in:
Isoproterenol
bronchodilation ( beta2 receptors)
bronchospasm
Orciprenaline
Site of Action:
For use in:
Orciprenaline
bronchodilation ( beta2 receptors)
bronchospasm
Salbutamol
Site of Action:
For use in:
Salbutamol
bronchodilation ( beta2 receptors)
bronchospasm
Terbutalin
Site of Action:
For use in:
Terbutalin
bronchodilation ( beta2 receptors) bronchospasm
relaxation of pregnant uterus (beta 2) delay premature labor
Ritodrine
Site of Action:
For use in:
Ritodrine
relaxation of pregnant uterus (beta 2)
delay premature labor
Ephedrine
Site of Action:
For use in:
Ephedrine
bronchodilation (beta2 receptors) bronchospasm
Release of NE ( alpha1 receptors) eye examination (mydriatic)
Phenylephrine
Site of Action:
For use in:
Phenylephrine
vasoconstriction (alpha1 receptors) local & spinal anesthesia
Constriction of mucous membranes (alpha) nasal decongestion
Methoxamine
Site of Action:
For use in:
Methoxamine
vasoconstriction (alpha1 receptors)
local & spinal anesthesia
Metaraminol
Site of Action:
For use in:
Metaraminol
vasoconstriction (alpha1 receptors)
local & spinal anesthesia
Dopamine
Site of Action:
For use in:
Dopamine
increase heart rate, contraction & cardiac output
( release of NE, beta1 receptors of the heart,
dilation of renal blood vessels, D1 receptor )
cardiogenic shock
Dobutamine
Site of Action:
For use in:
Dobutamine
direct activation of beta1 receptors,
dilation of renal blood vessels (D1)
cardiogenic shock
