Cardiovascular I Flashcards
CNS Neurotransmitters
Epi, NE, dopa, serotonin, GABA, ACh
Agonists
Natural Catecholamines
Epi, NE, dopa
Agonists
Synthetic Catecholamines
Isoproterenol & dobutamine
α
Receptor Potency
NE > epi > Isoproterenol
β
Receptor Potency
Isoproterenol > epi > NE
α1 Receptors Location
Post-synaptic
Locations: CV (heart), vasculature, glands, & gut
α1 Receptors MOA
Activation causes vasoconstriction & GI tract relaxation
Eye - iris (radial muscle) contraction → pupil dilation (mydriasis)
α2 Receptors Location
Pre-synaptic AND post-synaptic
α2 Pre-Synaptic
1° location pre-synaptic
Location: CV (coronaries), peripheral vascular smooth muscle, & brain
Activation causes NE release inhibition & inhibits sympathetic outflow → vasodilation
↓BP ↓HR → inhibit CNS activity
α2 Post-Synaptic
Location: CNS & coronaries
Activation causes constriction, sedation, & analgesia
β1 Location
ONE HEART
Cardiac muscle (myocardium), SA node, ventricular conduction system, coronaries, & kidney
β1 MOA
Activation causes ↑inotropy, chronotropy, myocardial conduction velocity, coronary relaxation, & renin release
β2 Location
TWO LUNGS
Vascular, bronchial & uterine smooth muscle, skin smooth muscle, myocardium, coronaries, kidneys, & GI tract
β2 MOA
Vasodilation, bronchodilation, uterine relaxation, gluconeogenesis (↑glucose), glycogenolysis (breaks down glycogen → glucose), insulin release, K+ uptake (cellular)
Ephedrine MOA
Direct & indirect (NT release) α/β
→ vasoconstriction ↑HR ↑inotropy
Phenylephrine (Neo-synephrine) MOA
Direct α vasoconstriction → reflex bradycardia
What determines blood pressure?
BP = CO x SVR CO = (HR x SV)
What factors influence SV?
Contractility
Preload - venous tone & intravascular volume
How do β blockers & Ca2+ channel blockers ↓BP?
↓HR & contractility
BP = HR x SV x SVR
What drugs impact venous tone & therefore preload?
α1 agonists
α blockers
Angiotensin converting enzyme inhibitors ACEi -pril
Angiotensin II receptor blockers ARBs -sartan
Direct vasodilator - Nitroprusside
How do diuretics, ACEi, & ARBs influence BP?
Renin-angiotensin-aldosterone
Na+ & H2O retention/excretion → PRELOAD
What drugs directly innervate SVR?
α1 antagonists
α2 agonists
What drugs influence circulating regulators that determine SVR?
α1 antagonists
α1 agonists
ACEi & ARBs
What drugs influence local SVR regulators? How?
- Endothelin antagonists
- Nitroprusside
- ACEi
- ARBs
α Adrenergic Receptors
GPCR
Ligands - NE, epi, dopa (↑doses)
α1 → excitatory ↑Ca2+ → smooth muscle contraction
α2 → inhibitory ↓CAMP ↓NE release
β Adrenergic Receptors
β1, β2, β3
GPCRs
1st line HTN treatment
Thiazide diuretic
UNLESS diabetes or CKD
α Antagonists
Non-selective
- Phentolamine
- Phenoxybenzamine
α1 selective ↓SVR/BP → postural HoTN common SE
- Prazosin
α2 selective ↑NE release → tachycardia d/t cardiac β stimulation
- Yohimbine
Phentolamine
Non-selective α antagonist
↓SVR → vasodilation ↓BP
Reflex mediated ↑HR/CO
Intraop HTN emergency
- Pheo manipulation
- Autonomic hyperreflexia (spinal cord injury)
SQ to prevent tissue necrosis associated with sympathomimetic agents extravasation
Phentolamine Dose
HTN emergency 30-70 mcg/kg
SQ extravasation 2.5-5 mg
Phenoxybenzamine
Non-selective α antagonist Binds covalently α1 > α2 ↓SVR → vasodilation Pro-drug Onset 1 hours Elim 1/2 time 24 hours
PO preop BP control in pheochromocytoma patients 0.5-1 mg/kg
Start 1-2 weeks prior to OR
Prazosin
Selective α1 antagonist
Tachycardia less common
Dilates arterioles & and veins
Prazosin Uses
PO preop BP control in pheochromocytoma patients
Essential HTN combined w/ thiazides
↓afterload in heart failure
Raynaud phenomenon - vasodilation ↑peripheral blood flow
Yohimbine
Selective α2 antagonist
Less common
↑NE release from the post-synaptic neuron
Used to treat orthostatic HoTN & impotence
Selective α1a Antagonists
Terazosin & Tamsulosin
Long-acting
Effective prostate smooth muscle relaxation to ease micturition
Most common SE → orthostatic HoTN
β Blocker Effects
CV - bradycardia, ↓contractility/conduction velocity, & improve MVO2 supply/demand balance
Blood vessels - skeletal muscle vasoconstriction ↑peripheral vascular disease
Airway - bronchoconstriction & bronchospasm (asthma & COPD patients)
JG cells - ↓renin release ↓volume → indirect ↓BP
Pancreas - ↓insulin release at β2 & mask β1 hypoglycemia S/S
What is chronic β blocker use associated with?
Receptor UPregulation
Sudden d/c → exaggerated SNS response
Non-Selective β Blockers
Propranolol
Nadalol
Timolol
Pindolol
Cardioselective β1 Blockers
Metoprolol Atenolol Acebutolol Betaxolol Esmolol
β Blocker SE
↓HR/contractility/BP PVD exacerbation d/t β2 vasodilation blocked Airway resistance → bronchospasm Altered carbohydrate & fat metabolism → masks hypoglycemia ↑HR Inhibit K+ uptake into skeletal muscles Fatigue & lethargy N/V/D ↓IOP d/t ↓aqueous humor production ↓HDLs ↑CAD risk (mechanism unknown)
What is the β blocker prototype?
Propranolol
Non-selective β antagonist
Metoprolol (Lopressor)
β1 selective antagonist PO 50-400mg IV 1-15mg Hepatic metabolism Elim 1/2 time 3-4 hours
What is the most selective β1 antagonist?
Atenolol
- Least CNS effects
Atenolol
Selective β1 antagonist
No hepatic metabolism
Renal excretion (increased elim 1/2 time in patients w/ renal disease)
PO only
Esmolol (Breviblock)
Selective β1 antagonist ONLY IV Onset 60 seconds Elim 1/2 time 9 minutes Rapid plasma esterase hydrolysis Poor lipid solubility (does not cross blood-brain barrier or placenta)
Labetalol
Combined non-selective α AND β antagonist
β»_space;> α
↓BP & attenuates reflex tachycardia (β2 blockade) CO unaffected
Onset (max effect) 5-10 minutes after IV admin
Dose 0.1-0.5 mg/kg (2.5-5 mg)
Glucuronic acid conjugation & renal excretion unchanged
Elim 1/2 time 5-8 hours prolonged w/ hepatic disease
α2 Agonists
Clonidine & Precedex
MOA: ↓sympathetic outflow from vasomotor centers in the brainstem
Used to treat HTN, induce sedation, ↓anesthetic requirements, improve periop hemodynamics, & analgesia
PO, transdermal patch, or IV
50/50 hepatic metabolism & renal excretion
Considerations with Clonidine administration
↓HR & peripheral vascular resistance →
↓CO & BP
*Wean off to prevent rebound HTN w/ abrupt cessation
Withdrawal syndrome occurs w/ doses > 1.2 mg/day
Occurs 18 hours after acute dc
Lasts 48-72 hours
Treatment - rectal or transdermal Clonidine
α2 Agonist SE
Bradycardia Sedation Xerostomia (dry mouth) Impaired concentration Nightmares Depression Vertigo Extrapyramidal symptoms Male lactation
Vasopressin
Antidiuretic hormone (ADH)
Vasopressin
Production & Storage
Produced in the hypothalamus
Stored in the posterior pituitary
Vasopressin MOA
Potent vasoconstrictor
Dilates renal afferent, pulmonary, and cerebral arterioles
Vasopressin Receptors
V1 - vasoconstriction
V2 - H2O reabsorption in the renal collecting ducts
V3 - located in the CNS & modulate corticotrophin secretion
Vasopressin Uses
Post cardiopulmonary bypass shock Refractory HoTN Reduce bleeding in von Willebrand DI antidiuresis Treat enuresis (involuntary urination or wetting the bed)
Vasopressin Dose
Bolus
1-2 units
Dilute 20 units in 20mL
Vasopressin Dose
Infusion
0.03-0.04 units/min
Max dose 0.1 unit/min
Vasopressin Onset
1-5 minutes
Vasopressin Peak
5 minutes
Vasopressin DOA
10-30 minutes
Vasopressin Complications
> 0.04 units/min
GI ischemia d/t potent vasoconstriction at the mesenteric artery
↓CO
Skin or digital necrosis
