Lecture II-IV Flashcards
Alpha 1
Tissue:
- Vascular Smooth Muscle
- Pupillary dilator muscle
- Pilomotor smooth muscle
Actions: Contracts causing
- Increased Vascular resistance
- Mydriasis (Dilation)
- Erects hair
Alpha 2
Tissue:
- Adrenergic and Cholinergic Nerve terminals
- Platelets
- Some vascular smooth muscle
Actions:
- Inhibits NT release
- Stimulates Platelet Aggregation
- Contracts some vascular smooth muscle
Beta 1
Tissue:
- Heart
- Juxtaglomerular Cells
Actions:
- Stimulates HR and Increases Contractility
- Stimulates Renin release (renin increases BP)
Beta 2
Tissue:
- Respiratory, uterine, and vascular smooth muscle
- Liver
- Pancreatic B Cells
- Voluntary muscle
Actions:
- Relaxes
- Increases glycogenolysis
- Stimulates insulin release
- Causes tremor
Beta 3
Tissue:
*Fat Cells
Actions
*Stimulates Lipolysis
Alpha 1 Receptor Signaling
Coupled to Phospholipase C via G-alpha-q protein to increase IP3/DAG. IP3 receptor activated by IP3 and that causes release of stored calclium, increasing the cytoplasmic calcium.
Alpha 2 Receptor Signaling
Negatively coupled to Adenylyl Cyclase via G-alpha-i subunit that inhibits the formation of cAMP, reducing activation of PKA. This causes a decrease in NT release due to decreased calcium influx which is needed for the vesicles to dock via SNAREs.
Beta 1 Receptor Signaling
Coupled to G-alpha-s causing an increase in cAMP. cAMP activates PKA and phosphorylates Calcium channels, increasing calcium in the cell causing faster depolarization and increased contraction by increasing calcium storage.
Beta 2 Receptor Signaling
Coupled to adenylyl cyclase via G-alpha-s protein, increasing cAMP. cAMP activates PKA that phosphorylates and inactivates myosin light chain kinase (MLCK- normally this light chain kinase phosphorylates the myosin light chain causing an increase in actin and myosin cross bridge formation causing contraction). Phosphorylation of MLCK by PKA reduces the affinity of MLCK for Ca-calmodulin that results in the reduced activity of the enzyme so can’t phosphorylate myosin light chain.
In Beta 2- PKA Inactivates MLCK causing muscle relaxation. In Alpha 2 receptors- PKA is inhibited so it can activate MLCK causing muscle contraction.
Epinephrine
alpha 1, alpha 2, beta 1, beta 2 agonist
Effects:
- CV: B2 decreases diastolic BP, B1 increases HR and CO, A1 increases vasoconstriction
- Bronchiole Effect: B2- bronchodilation, A1- decreases bronchiole secretions
Toxicity: Arrhythmias
Therapeutic Uses: Anaphylaxix, Cardiac Arrest, Bronchospasms
Norepinephrine
alpha 1, alpha 2, beta 1
Effects:
*CV: A1 increases vasoconstriction (increase in TPR and diastolic BP), B1 increases HR and CO- ALL OF THIS CAUSES A BAROREFLEX THAT DECREASES THE HR.
Toxicity: Ischemia
Therapeutic Uses: Vasodilatory shock
Contraindications: Pre-existing excessive vasoconstriction and ischemia
Dopamine
D1 receptors at low affinities, B1 and alpha receptors
Effects:
*CV: D1 decreases TPR, B1 increases HR and CO increases systolic BP, Alpha receptors lead to increased BP and TPR
Toxicity: Hypotension in low doses, ischemia in high doses
Therapeutic uses: Hypotension due to low C.O. during cardiogenic shock
Contraindications: Uncorrected Arrhythmias
Dobutamine
B1 selective agonist
Effects:
*CV: Increases HR and CO
Toxicity: Hypotension due to B2, Arrhythmia due to B1
Therapeutic Uses: Short-term for CHF or cardiogenic shock
Isoproterenol
B1, B2
Effects:
*CV: Decreases TPR (B2), Increases CO (B1), Small decrease in MAP (B2), Bronchodilation (B2)
Toxicity: Tachyarrhythmias
Indications: Bradycardia
Contraindications: Angina w/arrhythmias
Terbutaline & Albuterol
B2
Effects:
- Bonchodilation
- Uterine Relaxation
Toxicity: Tachycardia (B1), Muscle Tremor (B2), Tolerance (B2)
Therapeutic Use: Bronchospasm or chronic obstruction of airways
Phenylephrine
A1
Effects:
- Increases TRP and MAP
- Decrease HR (Baroreflex)
- Pupillary dilation
- Decrease secretions
Toxicity: Hypertension
Therapeutic Use: Hypotension during anesthesia SV tachycardia
Clonidine
A2
Effects:
*Increase in BP (Peripheral effect)
*Reduced BP (central effect) because crosses the BBB and there it reduces Vasoconstriction
MAINLY DECREASES BP
Toxicity:
Dry mouth, Hypertensive crisis (After acute withdrawl when the receptors become hypersensitive)
Therapeutic Uses: Hypertension due to sympathetic activation
Amphetamine, Methamphetamine, Methylphenidate, Ephedrine, Pseudoephedrine, Tyramine
Effects:
- Increase TPR and BP (A1+A2)
- Increase HR & CO, increasing systolic BP (B1)
- CNS Stimulant (increased NE)
- Anorexia (increased DA)
Toxicity: Tachycardia (B1)
Therapeutic Uses: ADD, Narcolepsi, Nasal congestion
Contraindications: Rx w/MAO inhibitors within 2 weeks.
Propranolol, Nadolol, Timolol
Non-selective Beta Blockers (Potentially harmful to patients with respiratory disease)
Effects:
- Reduced Heart rate, contractility, renin release, vasoconstriction
- Bronchoconstriction
Therapeutic Use:
- Hypertension
- Angina
- Glaucoma (aqueous humor produced by B1)
- Heart failure
- Arrhythmia
Toxicity:
- Bronchospasm
- Hypoglycemia (Decrease in response to epi)
- Bradycardia
Atenalol, Metroprolol
Cardioselective Beta Blockers
Effects:
- Reduced Heart rate, contractility, renin release, vasoconstriction
- Bronchoconstriction
Therapeutic use:
- Hypertension
- Angina
- Arrhythmia
Toxicity:
*depression, insomnia, hypotension, bradycardia
Contraindications:
- Cardiogenic shock
- Heart block
Pindolol
Partial Agonists (Good for when hypertension is due to high sympathetic output)
Effects:
- Reduced Heart rate, contractility, renin release, vasoconstriction
- Bronchoconstriction
Therapeutic Use:
*Hypertension in those who are less tolerant of bradycardia
Toxicity:
*Bronchospasms, hypoglycemia, bradycardia
Contraindications:
- Asthma
- heart blocks
Phentolamine
Non-selective alpha receptor antagonist (Reversible)
Effects: Inhibits vasoconstriction, increased inotropy and chronotropy due to blockade of pre-synaptic alpha-2 receptor (increase release of NE), Vasodilatory effect of EPI
Therapeutic uses: dermal necrosis
Toxicity:
Prolonged hypotension, reflex tachycardia, nasal congestions
Phenoxybenzamine
Non-selective alpha receptor antagonist (irreversible)
Effects: Inhibits vasoconstriction, increased inotropy and chronotropy due to blockade of pre-synaptic alpha-2 receptor (increase release of NE), Vasodilatory effect of EPI
Therapeutic uses: dermal necrosis
Toxicity:
Prolonged hypotension, reflex tachycardia, nasal congestions
Prazosin, doxazosin, terazosin
Selective A1 receptor blockers
Effects:
- Inhibit vasoconstriction
- Less cardiac stimulation than non-selective since A2 receptors are preserved
Therapeutic uses: Hypertension, benign prostatic hyperplasia
