ANS Pharmacology CIS Lecture TEST 3 Flashcards
Parasympathetic vs Sympathetic
PARASYMPATHETIC:
A) Neurotransmitter: ACh
B) Receptors: nAChR and mAChR
SYMPATHETIC:
A) Neurotransmitter: NE> Epi (DA); ACh
B) Receptors: Alpha, Beta, (D), nAChR, mAChR
Rules of Thumb for Smooth Muscle and Autonomic Receptors
1) ALPHA 1 Receptors:
- Stimulate CONTRACTION of ALL SMOOTH MUSCLE
a) Vascular Smooth Muscle: VASOCONSTRICTION
b) Glandular Smooth Muscle: SECRETION
2) BETA 2 Receptors:
a) Relax Smooth Muscle: VASODILATION
3) MUSCARINIC RECEPTORS:
a) CONTRACTION SMOOTH MUSCLE (Different Intracellular Signal than Alpha Receptors)
b) ACH and MUSCARINIC AGONISTS given IV Cause VASODILATION due to release of NITRIC OXIDE (NO)!!!!!!!!!!!!
Parasympathetic vs Sympathetic Described
PARASYMPATHETIC:
- CHOLINERGIC
- Salivation, Lacrimation
- Pupil Constriction (MIOSIS)
- DECREASE in HR
- Urination, Defecation
- INCREASED Secretion and Motility
- *** REST and DIGEST!!!!!
- *** SMOOTH Muscle CONTRACTION!!!!
SYMPATHETIC:
- ADRENERGIC (Anticholinergic)***
- Cutaneous VASODILATION
- Pupil Dilation (Mydriasis)
- INCREASE in HR
- Reduction/ Elimination of the DESIRE to Urinate
- DECREASED Secretion and Motility
- *** FIGHT or FLIGHT!!!!!!!!
- *** Smooth MUSCLE CONTRACTION!!!!!!!!!
Parasympathetic Nervous System Clinical Aspect
- Urinary INCONTINENCE
- Adult Diapers and Bladder training
WHAT Drug Classes would help alleviate these Symptoms?
- MUSCARINIC AChR ANTAGONIST!!!!!!!!!!!!!!!!!!!
(INHIBIT Bladder Contraction)
What would be some ADVERSE Side Effects of being traded with Muscarinic AChR Antagonist?
- CONSTIPATION
- DRY MOUTH/ EYES
- DIZZINESS
- BLURRED VISION
Anticholinergic Agents for GENITOURINARY Disorders
- mAChR ANTAGONISTS can provide Symptomatic RELIEF in the treatment of Urinary Urgency caused by MINOR INFLAMMATORY BLADDER DISORDERS
- Agents with SELECTIVITY of M3 Subtype of mAChR are BENEFICIAL due to PRESENCE in BLADDER WALL and SPHINCTER SMOOTH MUSCLE!!!!!!!
- Oxybutynin is prototype SELECTIVE M3 ANTAGONIST but has Side Effects (Dry Mouth/ Eyes, Dizziness, Constipation, Blurred Vision)
- DARIFENACIN, SOLIFENACIN, and TOLTERODINE are selective for the M3 Subtype and are ADVANTAGEOUS because of their HALF-LIVES and REDUCED Incidence of XEROSTOMIA and CONSTIPATION!!!!!!!!!
How does activation of mAChRs cause TRIGONE and SPHINCTER Relaxation?
- Activation of mAChRs on Epithelial Cells causes PRODUCTION and RELEASE of ENDOTHELIUM-DERIVED RELAXING FACTOR (EDRF), also know as NITRIC OXIDE (NO)
- Stimulation of NO release can occur from ACh, VASOACTIVE PRODUCTS, and PHYSICAL STIMULI
A 52 y/o male smoker presents with daily cough and mild dyspnea on exertion with strenuous activity. He notes that walking up two flights of steps bothers him when previously it did not. He reports wheezing but no chest pain. His past medical history is unremarkable. Physical exam is unremarkable aside from mild wheezing. Spirometry testing confirms a diagnosis of chronic obstructive pulmonary disorder (COPD). Which agent is appropriate in this situation?
Answer:
*** mAChR ANTAGONIST!!!!!!!!!
Smoking cessation and inhaled tiotropium (mAChR antagonist) are prescribed. Which adverse effect is most likely?
ANSWER:
*****DECREASED MUCUS PRODUCTION, May lead to INFECTION!!!!!!!!!!!!!!!!!
Respiratory Disorders
A) Asthma and chronic obstructive pulmonary disease (COPD)
B) IPRATROPIUM and TIOTROPIUM
- INHALATION mAChR ANTAGONISTS!!!!!!!!!!!
- Tiotropium has a longer bronchodilator action than ipratropium and can be dosed once daily
C) mAChR Antagonists such as ATROPINE and SCOPOLAMINE were used in preoperative settings to LIMIT AIRWAY SECRETIONS that were Increased by irritant anesthetics (e.g., ether)
- Now replaced by Inhalational Anesthetics
A 32 y/o female presents with intermittent attacks of headache, perspiration, palpitations, and anxiety. During these attacks, she reports having feelings of impending doom and tremors. She notes that the attacks often occur after exercise or drinking coffee. Laboratory values are unremarkable. Current blood pressure is 165/98 mmHg. A plasma fractionated free metanephrine test is positive and a 24-hour urine specimen supports a diagnosis of:
Answer:
** PHEOCHROMOCYTOMA!!!!!!!!
Which of the following will most IMMEDIATELY reduce her BLOOD PRESSURE?
Answer:
**** ALPHA 1 ANTAGONIST!!!!!!!!!!
An antagonist of which receptor will most likely reduce her HEART RATE?
Answer:
*** BETA 1 ANTAGONIST!!!!!!!
If a Beta-Receptor selective ANTAGONIST (Propranolol) is administered, which of the following is most expected?
Answer:
** WORSENING OF HYPERTENSION (Possible Death)!!!!!!!!!!!!!!!!!!
Effects of Beta- Blockers on the Heart and Blood Vessels
- The use of a selective beta-blocker in a patient with a pheochromocytoma will result in symptoms of ‘unopposed alpha’ stimulation (i.e., vasoconstriction)
- Although Nonselective Beta-BLOCKERS (e.g., LABETALOL) can be used to BLOCK BOTH Alpha- and Beta-receptors, use as the INITIAL Antihypertensive agent may cause Paradoxical Hypertension (labetalol 3:1 β:a)!!!!!!!!!!!!!
Imaging shows a large, right-sided inhomogeneous adrenal mass (white arrows) with a central area of low attenuation that represents hemorrhage or necrosis. If a CENTRALLY-ACTING Alpha-2 receptor agonist (clonidine) is administered to this patient, which is the most likely result.
Answer:
*****NO CHANGE IN SYMPTOMS!!!!!!!!!!!!
CLONIDINE SUPPRESSION TEST:
- Clonidine activates CENTRAL Pre-Synaptic ALPHA-2 Receptors and SUPPRESSES the release of Catecholamines from Neurons
- Clonidine has NO EFFECT on CATECHOLAMINE SECRETION from a PHEOCHROMOCYTOMA!!!!!!!!!!!!!!!
A 2 y/o female presents to the ED after an accidental overdose of antihistamines. Her temperature is 102.5° F and pupils are fixed and dilated. Heart rate is 160 bpm (normal 120 bpm). She shows signs of delirium and is noted to have marked cutaneous vasodilation upon physical exam. She is exhibiting symptoms of over- activity of which division of the nervous system?
ANSWER:
***** SYMPATHETIC NERVOUS SYSTEM!!!!!!!!!
The presenting symptoms (see below) are most likely due to which of the following? • Temperature - 102.5° F • Pupils are Fixed and Dilated • Heart rate - 160 bpm (normal 120 bpm) • Delirium • Marked cutaneous vasodilation
ANSWER:
** INHIBITION of MUSCARINIC ACETYLCHOLINE RECEPTORS!!!!!!!!!!!!!
Stimulation of which receptor will most likely correct her symptoms?
Answer:
*****MUSCARINIC ACETYLCHOLINE RECEPTOR (mAChR)!!!!!!!!!!!!!!
She shows signs of Delirium and Agitation. Marked cutaneous VASODILATION is noted upon physical exam. Which of the following agents is most appropriate?
Answer:
** ACETYLCHOLINESTERASE INHIBITOR (INDIRECT ACTING AGONIST)!!!!!!!!!!!
A 46 y/o female presents complaining of dry eyes and a dry mouth. Her symptoms have been present for the past 6 months and have progressively worsened. She saw an ophthalmologist 3 months ago and has been using artificial tears with little relief. She often has to wake up in the night to drink water and frequently has to drink to help swallow her food. She experiences the feeling of grit or sand in her eyes on a daily basis.
Which agent is most appropriate in this situation?
Answer:
***** mAChR AGONIST!!!!!!!!!!!!
Cevimeline (mAChR agonist) is prescribed. Which adverse effect is most likely?
Answer:
**DIAPHORESIS!!!!!!!
Which concomitant condition would most likely be EXACERBATED by Cevimeline if prescribed?
Answer:
***ASTHMA!!!!!!!!!
A 29 y/o male presents to the emergency department unconscious with
nonreactive, pinpoint-sized pupils, massive oral foaming, and muscle fasciculations. His pants are wet with urine and feces. Information provided by his wife reveals that he has a history of depression and attempted suicide 3 years ago. He is not taking any current medications.
What Receptor Family is most likely involved in his presenting symptoms?
Answer:
** CHOLINERGIC!!!!!!!
An agent from which drug class was most likely ingested?
Answer:
*** AChE INHIBITOR!!!!!!!!!
AChE (Organophosphate) Inhibitor Toxicity
SLUDGE– Salivation, Lacrimation, Urination, Defecation, Gastrointestinal pain & gas, Emesis
DUMBELS – Defecation, Urination, Miosis, Bronchorrhea/Bronchospasm/Bradycardia, Emesis, Lacrimation, Salivation
INGESTION: GI symptoms occur first
PERCUTANEOUS ABSORPTION: localized sweating and muscle fasciculations
LIPID-SOLUBLE AGENTS: CNS involvement follows rapidly
