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Cell-to-cell communication occurs via what compounds?
Name 3 examples of Kinins (vasodilator).
- 1. Bradykinins
- 2. Natriuretic peptides
- 3. Vasoactive
Name 4 examples of Intestinal Peptides (Vasodilators).
- 1. Substance P
- 2. Neurotensin
- 3. Calcitonin gene related peptide
- 4. Adrenomedullin
Name 5 vasoconstricting peptides.
- 1. Angio II
- 2. Vasopressin
- 3. Endothelins
- 4. Neuropeptides Y
- 5. Urotensin
T or F. The activation of renin is usually caused by vasoconstriction of the blood vessels.
FALSE (renin is stimulated by vasodilation and then causes vasoconstriction)
What is an example of renin release inhibitor?
Angio II (negative feedback cycle)
What are 4 stimulators of renin?
- 1. Decrease Na+ delivery
- 2. Decrease renal arteriole pressure
- 3. Sympathetic Nerve stimulation (B1)
- 4. cAMP
Where is vasopressin produced?
Vasopressin--> produced in hypothalamus & supraoptic nucleus
What stimulates vasopressin production?
Reductions in plasma volume
What is the main result of vasopressin simulation?
-Increase WATER reabsorption
T or F. Vasopressin is an arterial vasoconstrictor in times of physiologic stress, like shock.
True (improves BP)
What are the 3 types of functions of vasopressin?
- 1. V1a--> mediates vasoconstriction
- 2. V1b--> potentiates release of adrenocorticotropic hormones
- 3. V2 --> mediate ADH hormones
Vasopressin is a V1 & V2 agonist or antagonist?
Vasopressin is a V1/V2 agonist
What are 3 examples of synthetic vasopressin and the name of a brand drug?
- -Terlipressin, relcovaptan, Conivaptan
- -BRAND- Pitressin
What are 2 adverse effects of vasopressin?
- 1. Severe vasoconstriction
- 2. Water intoxication
What are the 3 forms of endothelin and where do they come from?
- ET-1--> MAIN ONE, vascular endothelium
- ET-2--> kidneys & intestine
- ET-3--> brain, GI, kidneys
Are ET-1 dose-dependent or time-dependent?
ET-1--> dose dependent
What are some physiologic action T-1? (5)
- 1. rapid ⇓ in BP (nitric oxide) followed by prolonged ⇑
- 2. ⇑ BP as result of vascular smooth muscle contraction
- 3. Positive inotropic/chronotropic actions on the heart
- 4. Renal vasoconstriction (⇓ GFR,⇓ excretion)
- 5. Proliferation of vasc. smooth m, cardiac cells, glomerular cells
Where are ETa receptors located?
smooth muscle cells (affinity for ET1&3)
Where is ETb receptors located?
Vascular endothelial cells (affinity for ET1&3)
What is an example of a nonselective endothelin receptor blocker and what is it's physiological result?
Bosentan--> causes vasodilation & decrease arterial pressure
Kinins are a vasoconstrictor or vasodilator?
What are 2 significant roles of kinins?
In inflammation & pain
What is the MOA of kinins?
-Vasodilation of vasculature in heart, skeletal muscle, & liver
What is the respiratory effect of kinins?
Bronchoconstriction--> contraction of smooth muscles
What is bradykinin found in the body?
Describe the 2 active roles of bradykinin?
- -Symptoms of inflammation
- - Eliciting pain in nociceptive afferents of skin & viscera
What HTN medication can also stop circulation of bradykinin?
What does natriuretic mean?
Excretion of sodium into the urine
What stimulates ANP production?
- Stretch of the aorta
- --> like in CHF, renal failure, SIADH
What is the major effect of ANP?
Vasodilation and decrease arterial blood flow
Where are BNP mainly synthesized?
HEART (released in response to atrial blood volumes)
What is an adverse effect of BNP?
fatal renal failure (avoid BNP synthetics in patients with comorbidities_
Where are C-type peptides mainly located?
Which of the natriuretic peptides is a potent vasodilator?
C-type natriuretic peptide
T or F. Histatmines are inflammation modulators
True (stored as basophils/mast cells)
Quick review of the immunologic release.
- -IgE binds w/ mast cell on membrane
- -Cell degranulates--> release histamines
- -Cause immediate Type I rxn
- -Negative feedback loop mediated by H2 receptor
What are 5 effects of H1 stimulation?
- 1. Increased venular permeability
- 2. Increased bronchial/intestinal smooth m contraction
- 3. Increase nasal mucous production
- 4. Widened pulse pressure
- 5. Increased HR/CO
What are 3 responses to H2 stimulation? (GI)
- 1. Increased venular permeability
- 2. Increased gastric acid secretion & airway mucous
- 3. Inhibition of neutrophil/eosinophil influx
What are the 2 effects of histamine of the nervous system (H1 receptor)
What are the 4 effects of histamine of the Cardio system
- 1. Decreased BP (vasodilation of arterioles
- 2. Reflex tachy
- 3. Flushing, H/A (vasodilation)
- 4. Edema--> leading to urticaria
What is the bronchial smooth muscle effect of histamine?
What is the GI effect of histamine?
contraction of intestinal smooth muscle
Which H receptor plays the major role in stimulating gastric acid secretion?
What is the "triple response" of histamines?
- 1. erythema at site
- 2. Edema
- 3. Pruritis
- (4. flare)
- ***Primarily H2 effects
Which anti-histamine generation has anti-cholinergic side effects?
First generation (very sedating too)
Which histamine generation is used most for allergic rhinitis?
Which Anti-histamine generation are mostly metabolized by CYP3A4 therefore having more drug interactions?
T or F. 2nd generation have little or no sedation effects
Which anti-H1 generation is useful in preventing nausea, motion sickness.
What are 6 pharmacodynamics of anti-histamines (mostly 1st).
- 1. Sedation
- 2. Anti-nausea/anti-emetic
- 3. Anti-parkinson effects (treat dystonia)
- 4. anticholinergic actions (dry secretions, blurred vision, constipation)
- 5. alpha blocking actions (orthostatic hypotension)
- 6. Local anesthesia
What are 3 side effects of Anti-H 1st generation.
- 1. CNS depression
- 2. Urinary retention
- 3. Difficulty urinating
What body functions does serotonin have an impact (4)?
- 1. mood
- 2. sleep
- 3. appetite
- 4. temperature regulation
T or F. The effects of serotonin are similar to Histamines.
True (stimulant of pain/itch & role in symptoms from insect/plant stings)
T or F. Serotonin can can tachycardia and hypertension.
True (activates chemoreceptor reflex)
What the effects of serotonin on the respiratory system?
- -Bronchoconstriction (with cancer patients)
- -Hyperventilation during chemoreceptor reflex
What are some effects of serotonin on the cardio system?
- -Contraction of vascular smooth m
- -Constricts veins
- -causes platelet aggregation
What are the effects of serotonin on the GI tract?
- -promotes peristalsis
- -Cisapride--> enhances motility at 5-HT4 receptors
What are the 2 serotonin receptors in the brain that are responsible for migraines?
**activation causes vasoconstriction and pain diminishes
Which drugs are 5HT1D/1B agonists?
What is the peak concentration time and half life of Triptans?
peak in 15min, half-life 2-4hrs
What are some adverse effects of Triptans (4)?
- 1. altered sensation (warm/tingly)
- 2. muscle weakness
- 3. dizziness,
- 4. coronary vasospasm
What patients should NOT receive Imitrex (triptan)?
-Patients w/ known CAD, uncontrolled HTN, or PVD because can cause coronary vasospasm
What are 3 adverse reactions of Sumatriptan (imitrex)?
- 1. Dizziness/hot sensation
- 2. burning, heaviness, flushing
- 3. N/V
What type of meds should not be taken concurrently with a sumatriptan?
SSRIs--> can cause serotonin syndrome
What are common symptoms associated with asthma?
- History--> wheezing (esp at night), chest tightness, difficulty breathing
- **symptoms at night are key
When mast cells degranulate, what mediators are released?
- 1. Histamine
- 2. Tryptase
- 3. Leukotrienes
What PFT level is usually diagnostic for asthma?
FEV1 <80% based on age/height
What are the 5 pathways that drugs work on to treat asthma?
- 1. Reduce amt of IgE bound to mast cells
- 2. Prevent mast cell degranulation
- 3. block actions of mediators (histamine/leukotrienes)
- 4. Inhibit effects of Ach
- 5. Directly relax smooth muscle
What 2 drugs are acute relief meds for asthmas?
- 1. short acting beta agonists
- 2. short acting corticosteriods (usually PO)
What 3 drugs help "control" asthma?
- 1. Long acting corticosteroids (ICS)
- 2. Long acting beta agonist (LABA)
- 3. Leukotriene pathway inhibitors
Where are alpha 1 receptors primarily found?
- Smooth muscles of arterioles, eye, gut, skin, veins
- **so stim usually cause contraction of smooth muscle cells
What are 3 effects of stimulation of Beta2?
- 1. Decrease GI motility
- 2. Bronchodilation
- 3. Vasodilation in skeletal/cardiac muscles
Sympathomimetics delivered by inhalation have a direct effect on:
Pulmonary smooth muscle
T or F. Epi stimulates which receptors?
alpha 1 & beta 1
Name 4 drugs that are B2 selective drugs, short acting.
- 1. albuterol
- 2. terbutaline
- 3. metaproterenol
- 4. pibuterol
Which B2 selective drugs can be given PO?
- 1. Albuterol
- 2. terbutaline
What 2 drugs are Long-acting beta agonists?
1. Salmeterol & formoterol
Why are LABAs not used as monotherapy?
-Have no anti-inflammatory effects and can make it worse by itself because it opens airways but has no effects on increase mucous
T or F. LABAs should NOT be initiated in patients with significantly worsening/acutely deteriorating asthma
When would Theophylline (a methylxanthine) be used for treatment?
Resistant COPD (a phosphodiesterase inhibitor--> ⇑cAMP--> smooth muscle relax, decreaes inflammation, stimulate cardio fxn)
What are 4 side effects of methylxanthines?
- 1. Nervousness, insominia
- 2. tachy (increased CO)
- 3. Stimulates gastric acid and digestive enzymes
- 4. weak diuretic
What is the therapeutic level of methylxanthines? What level does cardiac arrythmias occur?
- Therapeutic--> 5-20
- Arrhythmias--> >40
What are the effects of Anti-muscarinic agents and when are the normally used in respiratory cases?
- 1. Inhibit Ach--> blocks contraction of airway smooth muscle and increases the secretion of mucous (not good?)
- 2. Frequently used for COPD, occassionally for acute asthma
T or F. Anti-muscarinic agents may be used in combo with albuterol for enhancement effects.
What 5 things are Inhaled corticosteriods shown to improve?
- 1. severity of symptoms
- 2. Airway size
- 3. Airway reactivity
- 4. frequency of exacerbations
- 5. Quality of life
What asthma med is the "cornerstone" of long term asthma therapy?
What are 4 side effects of ICS with long-term use?
- 1. cataracts
- 2. osteoporosis
- 3. thrush
- 4. reduction in bone marrow density (flovent)
What hygiene teaching should be given to patients taking ICS?
Rinse mouth out after use--> can cause thrush
T or F. ICS can take weeks to achieve maximal effect.
After how many days of use should oral corticosteroids be tapered off of?
if used > 5days to avoid adrenal insufficiency
What are the effects of Leukotrienes in the airway?
- 1. Bronchoconstriction
- 2. increases reactivity
- 3. mucosal edema
- 4. mucus hypersecretion
- 5. hypersensitivity to histamine
Which leukotriene inhibitor prevents SYNTHESIS of leukotrienes?
Which leukotriene inhibitors prevent leukotriene BINDING to cell receptors?
- 1. Zafirlukast (Accolate)
- 2. Montelukast (SIngulair)
What are the effects of Leukotriene Pathway Inhibitors (3)?
- 1. Increase airway size
- 2. Decrease airway reactivity
- 3. Decrease airway inflammation