PHAR 736 Exam 1 Flashcards
a1 tissue locations and corresponding effects
Major blood vessels and vasculature in dermal, GI, renal, bladder and nasal membranes (constriction, increase peripheral resistance, increase diastolic BP)
Eye (contraction of radial muscles –> mydriasis)
Bladder and GI sphincters (constrict sphincters, decrease outflow)
a2 tissue locations and corresponding effects
Eye (decrease aqueous humor production)
Pancreatic islets (decrease insulin release, increase blood glucose)
Presynaptic nerve terminals (decrease NT release, e.g. NE)
CNS/brainstem (decrease blood pressure/inhibit baroreflex)
Spinal cord (inhibit pain transmission)
Nasal vasculature (constriction)
B1 tissue locations and corresponding effects
Heart (increase HR, increase contractility, increase force –> increase CO)
Kidney (increase renin secretion –> vasoconstriction)
Eye (increase production of aqueous humor)
B2 tissue locations and corresponding effects
Hepatic and skeletal muscle - vascular smooth muscle (relaxation, increased blood flow to liver and skeletal muscle)
Pulmonary smooth muscle (relaxation –> increased airflow)
GI long smooth muscle (relaxation, decreased motility)
Bladder detrusor muscle (relaxation, decreased outflow)
Pregnant uterus (relaxation)
Skeletal muscles (increased glycogenolysis, increased K+ intake)
Mast cells (decreased degranulation)
Pancreas (increased glucagon secretion)
Liver (glycogenolysis –> increase in blood glucose)
Eye (increase production of aqueous humor)
Somatic Nervous System
Innervation of striated (skeletal) muscle
Control of voluntary movement
No ganglia between spinal cord and target
Autonomic Nervous System
Innervation of smooth muscle, glands, organs, blood vessels, fat and skin
Involuntary bodily functions (respiration, BP, secretions, body temp, digestion, heart rate)
Sympathetic division (SNS) produces fight or flight response | adrenal medulla functions like sympathetic ganglion but releases epinephrine into bloodstream
Parasympathetic (PNS) produces rest and digest state | target organs are activated as needed
Describe parasympathetic innervation/cell bodies
Long pre-ganglionic neuron
ACh released at ganglion and at target organ | Neuronal nicotinic receptor on post-ganglionic neuron | Muscarinic receptor at target organ
Describe Sympathetic Innervation/cell bodies
ACh released at ganglion | NE released onto alpha and beta receptors OR EPI released by adrenal medualla into blood | short pre-ganglionic neurons
Neuronal nicotinic receptors on ganglia and adrenal medualla
Describe somatic innervation/cell bodies
1 long neurone | releases ACh onto muscular nicotinic receptor located on striated muscle
ACh is used by all neurons that originate in the ______________
Spinal cord
Ganglia in the PNS
Ganglia are close to target organs due to long pre-ganglionic neurons, therefore, target organs are discretely activated
Define ganglia
Collections of synapses protected by a barrier
Basal tone at rest of most organs is __________________
parasympathetic
In GI and bladder sphincters, the _____ indirectly controls the _____
PNS
SNS
The SNS __________ insulin and _________ glucagon
inhibits; stimulates
Decrease in secretions of eye is SNS or PNS?
SNS
Decreased secretions = better visual acuity
PNS and SNS cooperation
Sweat: generalized skin hydration by PNS, localized sympathetic cholinergic sweating in palms and underarms
Pulmonary secretion: PNS control mucus secretions in lungs, SNS controls watery secretions
Male Sex Response: Point and Shoot
Pregnany uterine myometrium inhibited with ____ stimulation
SNS
Exclusive __________ control of major blood vessels
sympathetic; they provide basal tone
Sympathetic innervation of skeletal muscle and liver is _____________
vasodilating
Skeletal muscle metabolism controlled by _________________ nervous system
sympathetic
Partial agonists tend to cause very little receptor
Desentiziation
Supersensitization occurs with ___________
antagonists
beta-blockers are most relevant (increases likelihood of MI for 2 weeks following)
Agonists tend to cause _______________
desensitization
How does the body prepare for blood loss? (which adrenergic receptors)
a2 mediated potentiation of platelet aggregation
b1 mediated increases in renin secretion leading to vasoconstriction
Norepinephrine
a1 a2 and b1 activity
Useful in hypotensive crisis, as seen in SNS degenerative disease
Only vasoconstrictive effects
Epinephrine
Activity at all adrenergics
First-line in anaphylactic shock and acute cardiac arrest
Supports BP and maintains cardiac perfusion
Droxidopa
Approved for neurogenic orthostatic hypotension, including autonomic degeneration
Converted to NE and EPI in CNS and PNS
Only proven useful for 2 weeks
Isoproteronol
Beta selectivity
Useful in severe bradycardia, especially heart block, to raise HR and CO
Does NOT support blood pressure; reduces BP
Dopamine
Drug of choice for hemodynamic shock and useful for septic shock
Administer with plenty of fluid
Low dose = D1 agonist (increase renal blood flow and perfusion, increase coronary blood flow)
High dose = b1 agonist
Highest dose = a1 agonist (increase vasoconstriction to support BP, may have detrimental effects on renal perfusion)
Dobutamine
Used for systolic dysfunction in those with late-stage CHF (for patients who cannot tolerate an increase in heart rate; has similar b1 agonism effect to NE)
Only use for 4 days
S (-) isomer = B1/B2/a1 agonism
R(+) isomer = B1/B2 agonism; a1 antagonism
R = 10x more potent than S
b2 Sympathomimetics contraindications
Coronary artery disease (some b1 activation will occur)
Patients currently on b-blocker, MAO inhibitor, or tricyclic antidepressant
Hyperthyrdoisim
Diabetes (b2 will increase blood sugar through increased glucagon secretion)
Glaucoma (b2 will increase aqueous humor production)
b2 sympathomimetic side effects
CNS stimulation (includes headache)
Tachycardia and arrhythmias
Electrolyte imbalances (hypokalemia)
Nervous muscle twitches due to hypermatbolic state of skeletal muscles
Decreased bronchoplasticity from chronic use may exacerbate symptoms in long run
Terbutaline
Tocolytic agent; b2 agonist
Used off label to prevent labor for up to 48 hours
No use beyond 48 hours due to receptor desensitization
Also used in status asthmaticus (patient is unable to move air and may be unconscious)
SABAs
Desensitization if used to often, may lead to non-compliant airways
Albuterol, Ventolin and Metoproterenol
Inhalers
Terbutaline also used if patient can’t move air (subcu or IV)
LABAs
Good for night time therapy
Longer time of onset
Formoterol, Formoterol + Budenoside steroid
Receptor desensitization controlled by concurrent administration of steroids
Salmeterol is partial agonist with little desensitization; slower onset (20 minutes) compared with formoterol (6-7 minutes)
Ultra long acting b2 agonists for COPD
Indacaterol, VIlanterol (partial agonists with little receptor desensitization)
Once daily dosing
Faster onset of activity similar to formoterol (~6-7 minutes)
No true ____ selective agonists with therapeutic utility
B1
B2 selective sympathomimetic indications
Asthma and COPD
Acute respiratory distress
Allergic reactiosn
Uterine hyperactivity in premature labor
a1-selective sympathomimetic indications
Nasal congestion
Hypotension
Tachycardic arrhythmias, specifically PAT (increased BP = reflex bradycardia)
Adjuvants with topical anesthetics (vasoconstriction maintains local concentration of topical anesthetics)
Mydriatic for eye exams
a-1 selective sympathomimetic contraindications
Hypertension
a1-selective sympathomimetic side effects
Appetite suppression (reduced GI bloodflow)
Urinary retention (constriction of bladder sphincter)
Bradycardia and arrhythmias
Photophobia (from mydriasis)
CNS effects (nervousness, tremors, irritability, sweating)
Rebound congestion after discontinuation
Midodrine
Approved for orthostatic hypotension
Phenylephrine
Cyclomydril when used for eye exams
Direct a1 agonist nasal and ocular decongestant
Poor oral bioavailability
Tetrahydrazoline, Oxymetazoline
Ocular decongestants
Nasal decongestants (a1 and a2 activity)
Rebound congestion may be problem; possible tissue necrosis with chronic use
Loss of smell reported in some cases
a2-selective agents (general)
Considered sympatholytic agents
Lower BP by inhibiting NE release through a2 autoreceptors; block baroreflex so little effect on HR; CNS effects lead to lower BP; CNS effects calming, sedating and reduce anxiety; spinal cord effects decrease muscle spasms and reduce hyperalgesia
a2-selective agonist indications
Hypertension (CNS and autoreceptor effects) –>even more effective under stress by decreasing NE release onto heart
Glaucoma
Drug and alcohol withdrawal (reduce anxiety, hyperalgesia, and tachycardia)
ADHD (patients may benefit from calming)
Anti-spastic agents (decrease hyperalgesia associated with muscle spasm)
Dermal flushing (useful in perimenopausal women)
a2-selective agonist contraindications
Diabetes (decrease insulin release from pancreas)
a2-selective agonist side effects
Postural hypotension and suppressed heart rate (blocks bodies ability to compensate for gravitational effects from sitting or standing; huge problem in elderly with stiff arteries and compromised baroreflex)
Rebound hypertension
Sedation (sympatholytic CNS effects)
Contributors to long duration of LABAs (b2 agonists)
1) No COMT
2) No MAO
3) High lipophilicity from extended substituent on nitrogen = prolonged and selective binding to second non-polar domain on b2 receptor
4) Greater bronchiol tissue penetration leading to decreased clearance from lungs
