Mod 1 Respiratory diseases + pharmacology Flashcards
What are 2 parasympathetic receptors
- Nicotinic receptors
- Muscarinic receptors
What is a significant trait of Ligand-gated ion channel?
Fast acting/stimulate quickly
Which parasympathetic receptor takes longer to take action/see change?
Muscarinic Receptors
-ases ending is usually associated with what?
Enzymes -> that breakdown certain things?
What role does Cholinestrate have in the body?
Breakdown enzymes, to be specific Acetylcholine
What are the terms used to describe nerve fibres that stimulate or inhibit the sympathetic nervous system?
- Sympathomimetic: Stimulate
- Sympatholytic: inhibit
What nerve fibres stimulate or inhibit the parasympathetic nervous system?
- Parasympathomimetic - Stimulate/mimic
- Parasympatholytic - inhibit/block
Which neurotransmitters/receptors stimulate or inhibit the sympathetic nervous system?
Recall: Adrenergic = anything associated with epinephrine and norepi
- Adrenergic - stimulate
- Antiadrenergic - inhibit
Which neurotransmitter/receptors stimulate or inhibit the parasympathetic nervous system?
- Cholinergic: stimulate
- Anticholinergic: inhibit
Afferent is a sensory nerve signal that carry’s signals…
From the periphery to the CNS
- (Toward the body)
Efferent motor signals carry signals to…
From the CNS site to action (away from the body)
- Efferent nerve fibers transmit commands from the CNS
What are the 2 exclusive neurotransmitters of the Peripheral Nervous System (PNS)
- Acetylcholine (ach)
- Norepinephrine
Acetylcholine (ach) is released by…
- Sympathetic and parasympathetic preganglionic neutrons
- Parasympathetic post ganglionic neutrons
- Somatic motor neutrons
- Sympathetic post ganglion if neurons that innervate sweat glands
Norepinephrine is released by…
All post ganglion neurons of the sympathetic nervous system except those innervating sweat glands
Neurophysiology of the PNS: Where does Acetylcholine stimulate nicotinic receptors?
On sympathetic and parasympathetic postganglionic neurons at the neuromuscular junction
Neurophysiology of the PNS: Where does Acetylcholine stimulate muscarinic receptors?
On sweat glands and on tissue innervated by parasympathetic postganglionic neutrons
Neurophysiology of the PNS: Where does Norepinephrine stimulate Alpha and Beta adrengeric receptors?
on tissues innervated by sympathetic postganglionic neutrons
Why do Muscarinic Receptors take longer to see changes?
G protein coupled receptors see larger change than ion channels
Which sites are affected/stimulated by Muscarinic receptors?
Parasympathetic terminal sites:
-Exocrine glands (i.e exocrine glands, salivary, bronchial mucus glands)
-cardiac muscle
-GI smooth muscle
Why is degradation of acetylcholine important?
Prevents unwanted activation of neighbouring neutrons or muscles
ensure proper timing of signalling at the postsynaptic cell.
What are Adrenergic receptors identified as?
Alpha and Beta Receptors sympathetic receptors; they’re G-coupled receptors
Where can Alpha 1 receptors be found?
Heart
+
Smooth muscles:
-Bronchial smooth muscle
-Vascular smooth muscle
-Intestinal smooth muscle
+
Liver
What are some of the functions of Alpha 1 receptors
Contraction of smooth muscle
- Increased inotrophy (contraction) and excitability of the heart without increasing hr
- Glycogenolysis and glucenogensis
What action does Alpha 2 receptors have?
Inhibitory
what are some common results of Alpha 2 activation?
Reduce insulin secretion
Decrease in norepinephrine release
Why do Alpha 2 receptors further inhibits norepinephrine release?
Alpha 2 receptors provide a negative feedback control mech
Where are beta 1 receptors located
Heart and kidneys
what response can you expect by the release of Beta 1 receptors?
Increased chronotropy and inotrophy
Increased AV node conduction velocity
Increased overall heart rate (SA node)
Increased Renin secretion via the kidneys
Where are Beta 2 receptors located?
Dilation of bronchial smooth muscle
What is an example of a Beta 2 receptor response?
Dilation of bronchial smooth muscle
Where are Beta 3 receptors located?
adipose tissue
what do Beta 3 receptors activate?
Lypolysis
Therapeutic effect
The intended effect of a drug
What does Efficacy reflect about drug use?
The ability of a drug to produce a desired effect
What does affinity reflect on about drug use?
The tendency of a drug to combine with a matching receptor
Acetylcholine is used primarily for which system?
The parasympathetic nervous system
(preganglionic)
Post ganglionic innervates which group?
Muscles or sweat glands associated with the sympathetic nervous system.
Usually to help regulate our body.
What does the therapeutic dose refer to?
The amount of agent that provides the desired clinical effect
What does bioavailability refer to?
The amount of agent that reaches systemic circulation to produce th effect required.
What factors affect bioavailability?
Absorption, route of admin, and metabolic
what is a loading dose?
an initial dose of agent that may be given at the beginning of a course of treatment
it is followed up by a maintaince dose.
Why do we admin ventolin for heart related issues?
It is primarily a Beta 2 agonist, but can still bind with Beta 1 sites at the heart.
Why are loading doses useful?
they’re useful for drugs that eliminate from the body slowly (long systematic half-life)
Maintaining dose
amount of agent required to keep a desired mean steady state concentration in the tissues
TLDR; Top up
What does half-life refer to?
Time necessary to reduce an initial dose by half
What factor effects half-life in relation to dosage?
Affected by plasma protein binding, metabolism, and elimination
Median lethal Dose (LD50)
does at which 50% of the test animals die
Median effective dose (ED50)
Dose at which 50% of the test animals show the desired effect
Therapeutic index (TI)
The ratio of (LD50)/(ED50) gives a relative as to the safety of the drug
How do you know how toxic a drug is with the TI ratio?
the greater the difference between ED50 and ED50 the safer the drug.
the close to TI is to 0 = more toxic
Agonist vs Antagonist response
Agonist: Excite
-full and partial agonists
Antagonist: inhibit or stop.
Define Synergism
Occurs when 2 drugs together produce an effect greater than the 2 drugs along could produce
Define potentate
1 drug has no affect but can increase the effect of the other drug.
What does tolerance infer about drug use?
Progressive decrease in effectiveness over time, requiring increase the drug amount to produce the same effect due to increased metabolism of the drug by the body
Tachyphylaxis
Repeated admin of the same dose of a drug results in reduced effect of drug over time
What does hypersensitivity mean in relation to drug use?
An allergic or immune-mediated reaction to a drug
What is a Teratogens effect?
Drugs that are known to cause birth defects
Carcinogens
drugs/substances that produce cancer (or increase) risk of developing cancer
Phases of drug action (slide 9) from “the nervous system”
Define pharmacokinetic action?
How drugs get to where it needs to be
- i.e absorption or metabolism
(the effect of drug on body)
What is pharmacodynamic action?
how a drug produces (or doesn’t) a effect.
What are 4 routes of drug admin?
Enteral (tablets, capsules, liquids)
Parenteral (injection)
Inhalation
Transdermal/topical (topical)
What is the purpose of lidocaine?
A topical sedative/anesthetic
Installation route: Lean or Navel?
Direct admin of an agent via the ETT to obtain a systemic/local effect.
Lean is used when IV/IO access is not an option.
-lidocaine, EPI, Atropine, Narcan
NAVEL: Narcan, atropine, ventolin, EPI, lidocaine.
What is IO access?
Typically drilling down to bone when a line can’t be inserted
What are 2 ways neurotransmitters can effect agents?
Edit
direct acting: binds directly to a neurotransmitter to produce a excitatory/inhibit response
indirect acting: does not interact with a receptor but with the neurotransmitter instead
Agonist vs Antagonist
Agonist: produce a excitatory response (via binding) to a a full or partial effect
Antagonist: inhibit the ability of their targets to be activated (or inactivated)
What does Cholinergic pharmacology reflect about the properties of acetylcholine?
Edit
Generally involve the neuromuscular junction (interface between nervous system muscular system), the autonomic nervous system, particularly the parasympathetic system, and the CNS.
Parasympathomimetics are affected by what?
Cholinergic agonist or Cholinergic
why is Methacholine is used during pulmonary function tests?
reflects bronchoconstriction in the lungs to measure the response by irritation response.
TLDR; a diagnostic tool
Nicotinic agonist vs Nicotinic antagonist?
paralytic response
(insert more later)
Parasympatholyics are referred to as?
cholinergic antogists = anticholinergic
Andrenrgic pharmacology modulate which functions?
vital functions, rate and force of contraction, resistance of blood vessels, and release of insulin and the breakdown of fat (sympathetic response)
Adregergic pharmacology act on which pathways?
mediated by endogenous catecholamines norepinephrine, epinephrine, and dopamine
In the ICU, what is the primary PHARMACOLOGICAL way to affect blood pressure?
Admin of norepinephrine (bc it is a A1 and A2 agonist)
Effect of Adrengeric agents?
Act on pathways mediated by endogenous catecholamine: norepinephrine, epinephrine, and dopamine.
They modulate vital functions such as:
-heart contraction (rate and force)
-resistance of blood vessels (and bronchioles)
-release of insulin
-breakdown of fat (sympathetic response)
what are Sympathomimetics?
Adrenergic agonists:
- Norepinephrine (a1 & b1) agonist
- Epinephrine ( (both a1 + a2 and b1 + b2 agonist)
- phenylephrine (a1 agonist)
- Dobutamine (b1 agonist)
- salbutamol (b2 agonist)
What are sympatholytics?
Adrenergic antagonists
-Doxazosin (a1 antagonist)
- metoprolol (b1 antagonist)
What is a function of Alpha 2 receptors ?
needs an edit
Alpha 2 acts a negative feedback loop
- stop the release of norepinephrine
- activation decreases in BP
Define Obstructive Lung Pathology
Diseases that reduce a patients ability to exhale fully
- Characterized by increased airway resistance as a major contributing factor
Define Restrictive lung pathology
Characterized by a loss of lung volume
Major contributing factor is a decrease in pulmonary compliance
What are examples of obstructive lung pathology or factors obstructive process?
Excess mucous
Air trapping (dynamic compression)
Tumour
Swelling (such as edema)
3 types of obstruction
insert image from slide 6
Intraluminal
Extramural
Intramural
Intraluminal obstruction
Something inside the airway lumen blocking/narrowing airway
i.e foreign bodies or secretions
Extramural obstruction
external pressures causes airway narrowing
i.e enlarged lump nodes, carcinoma, lymphoma
Intramural obstruction
Lesions inside the bronchial wall, swelling.
Neoplasm
Examples of restrictive pathology or causing factors?
Pulmonary fibrosis
pulmonary edema (create fluid or consolidation)
pneumonia
Is the compliance and elastance relation inverse or direct?
As one increases, the other decreases
Can diseases be both obstructive and restrictive characteristics?
Yes, think about edemas or swelling.
Which of the 3 airway obstruction estiologies cause upper airway obstruction or lower airway obstructions?
non-cartilougs airway = lower
cartilaginous airway = upper
Lower airway obstruction causes
distal airway and also lay weakening (emphysema)
Excessive bronchial secretions (consolidation)
Bronchospasm
all end with a potential airway collapse or potential hypoxemia from blockage
4 cardinal signs of upper airway obstruction
hot potato voice (muffled)
difficulty in swallowing secretions
dyspnea
strider
strider is the only that may result in immediate obstruction
inhalation sound or exhalation that refer to obstruction (lack of air exchange)
exhalation = wheezes
inspiration = strider
Intrapulmonary conditions leading to decreased compliance (7)
- Lung compression
- Atelectasis
- consolidation
- calcification (tuberculosis, asbestosis)
- Fibrosis (pneumoconiosis, chronic interstitial lung disease i.e sarcoidosis)
- Bronchogenic tumor (squamous cell carcinoma)
- Cavitation (tuberculosis or lung abscess)
Extrapulmonary conditions leading to decreased lung compliance
pleural disorders; restriction of lung expansion by something occupying the pleural space
TLDR;something that’s gonna compress the lungs
- chest compression
- obesity
- deformities of spine
- deformities of the chest cage
Extrapulmonary conditions of nerves that decrease compliance
interference of nerve transmission (or decreased resp. muscle function)
-aka issues with the diaphragm
inability of generate normal resp. pressures
-decreased TLC, increased RV, normal FRC
normal lung/ chest wall compliance
-if you don’t inhale, you can’t exhale it
What does Intrapulmonary refer to w/restrictive lung pathology
Interstitial disorders (issues w/lung tissue itself)
-results in decrease in compliance of lung tissue
i.e surfactant dysfunction
What does extrapulmonary refer to w/restrictive lung pathology
Pleural, neuromuscular, or skeletal/thoracic issues
Clinical manifestations of obstructive disease
-Dyspnea on exertion
-productive cough
-hyper-resonant percussion notes
-wheezing
-Diminished breath + heart sounds
-prolonged expiration
Clinical manifestations of restrictive lung disease
-Dyspnea on exertion
-non-productive cough
-hypo-resonant or normal percussion notes
-fine bilateral inspiratory crackles
-rapid shallow breathing
What does Idiopathic pulmonary fibrosis?
sound like if you rub your hair beside your ear or velcro separation
Andrenergic agonists vs antagonists effects?
What is Obstructive lung pathology characterized by?
Decreased ability to exhale fully
- Increased airway resistance is the major contributing factor for obstructive diseases
What is restrictive lung pathologies characterized by?
loss of lung volume
- Decreased pulmonary compliance is one major contributing factor in restrictive process
Traits of Type 1 respiratory failure?
Hypoxemic failure (not enough O2 in blood)
- PaO2 (arterial) less than 60mmHg @ room air
- most common cause is V/Q mismatch
Traits of Type 2 respiratory failure?
Hypercapnic failure or ventilatory failure (too much CO2)
- PaCO2 greater than or equal to 50mmHg
Primary causes of hypoxemia
-Diffusion defect
-hypoventilation
-hypoxic environment
-anemia
-CO poisoning
-hemoglobin dysfunction
Signs for impending respiratory failure type II?
-Demand for CO2 elimination is beginning to reach capacity
-Tachypnea with normal PaCO2 and normal pH
Chronic respiratory failure type I
progressive lung pathologies that damage the AC interface.
Patients have > 60mmHg @ room air at all times.
Describe the complications of Chronic respiratory failure type II
Progressive lung pathologies continue to reduce efficient ventilation.
when COPD is involved (or obesity-hypoventilation syndrome) it can prompt a renal response.
-Kidneys retain HCO3 to elevate low blood pH
-renal system takes over when it isn’t efficient, it compensates.
Acute on chronic respiratory failure
An acute respiratory failure type II superimposed on chronic respiratory failure type II
Patients with chronic hypercapnic respiratory failure are at a significant risk of this condition
Late vs early inspiratory crackles?
excessive secretions vs atelectasis
Idiopathic pulmonary fibrosis (IPF)
Why can pneumothorax cause cardiac arrest?
extra pressure pushing on one side can affect if the heart contracts or not. Blood cannot be pumped properly/effectively
fine bilateral inspiratory crackles is indicative of what?
atelectasis
FEV of a normal person is typically what percentage in comparison to someone with COPD?
80% in a healthy person, 30% for someone with COPD
Primary causes of hypoxemia
(Perfusion w/no ventilation) pulmonary shunt:
ARDS, pneumonia, atelectasis, pulmonary edema
-can cause refractory hypoxemia: when SpO2 is not affected w/oxygen therapy because of shunt. no gas is transferring
Hypoventilation: OD, sedation, PNS conditions (guillain-barre)
V/Q mismatch (unequal distribution of ventilation and perfusion) : COPD, PE,
Decreased inspired O2: high altitude low O2 content, enclosed breathing spaces
How do you know that a person is expierecing a chronic . failure rather than a partial compensation from an ABG?
larger or lower than normal BE usually indicates that a ABG is chronic rather than acute/partial response
what could a Acidosis or alkalosis tell us about a persons breathing?
Acidosis = hypoventilation (breathing too slowly)
Alkalosis = hyperventilation (breathing too fast)
Acute resp. failure type II vs. Chronic resp. failure type II
Acute:
pH decreases by 0.08 for every 10mmHg increase in PaCo2
Chronic:
pH decreases 0.03 for every 10mmHg increase in PaCO2
Acute on chronic falls between those values.
For chronic patients with a abnormal ABG (but normal for them), what value do you pay to attention to for change?
pH
What does the acronym LEAN represent?
Drug admin when IV/IO access is not a option for the following drugs:
-Lidocaine
-Epi
-Atropine
-Narcan
emergency drugs to “lean” on
Which meds can be administered via endotracheal tube
LEAN
What action does Lidocaine have?
What is its main use?
Action: Suppresses automaticity of ventricular cells, decreasing diastolic depolarization and increasing ventricular fibrillation threshold.
USES: Ventricular arrhythmias, topical/local anesthetic
Extra: Bonus: Produces local anesthesia by reducing sodium permeability of sensory nerves, which blocks impulse generation and conduction.
Epinephrine action and use?
ACTION: Stimulates alpha- and beta-adrenergic receptors, causing relaxation of cardiac and bronchial smooth muscle and dilation of skeletal muscles.
USE: bronchodilation; anaphylaxis; hypersensitivity reaction; Acute asthma attack; Chronic simple glaucoma
Atropine sulfate action and use?
ACTION: Inhibits acetylcholine at parasympathetic neuroeffector junction of smooth muscle and cardiac muscle
-blocking sinoatrial (SA) and atrioventricular (AV) nodes to increase impulse conduction and raise heart rate.
USE: Decreases respiratory secretions, treats sinus bradycardia, reverses effects of anticholinesterase medication
Naloxone (Narcan) action and use?
ACTION: used to treat opioid emergency (overdose)
USE: Opioid induced toxicity; opioid-induced respiratory depression; used in neonates to counteract or treat effects from narcotics given to mother during labor
What does the Pharmacology pneumonic “NAVEL” represent?
NARCAN, ATROPINE, VENTOLIN, EPI, LIDOCAINE
What do receptors at skeletal neuromuscular junctions and what kind of receptors are they?
Muscle activation.
cholinergic receptors
What do cholinergic receptors in the CNS (brain) do?
leads to excitation
How many Muscarinic receptors are there?
5, m1-m5
Where are M2 receptors found?
The heart, activation causes bradycardia
Where are M3 receptors found?
Smooth muscles:
-bronchial and vascular smooth muscle
-mucous glands
-mast cells
What do muscarinic 3 (m3) receptors do?
-Bronchoconstriction
-increased mucus production
-mast cell degranulation
Alpha (⍺) 1 function and location
Vasoconstriction.
found in peripheral vascular smooth muscle
Alpha (⍺) 2 function and location
Vasodilation; activation causes less norepinephrine.
centrally located
Beta (𝛃) 1 function and location
Increases heart rate and contractility.
found on the heart.
Beta (𝛃) function and location
Bronchodilation and vasodilation
found on bronchial and vascular smooth muscles
Dopaminergic function and location
Multiple functions: vasoconstriction, increased HR, CNS excitement
chemically similar to norepi and can activate alpha and beta receptors.
found throughout the body.
What are non-depolarizing neuromuscular blockers commonly used as?
Muscle relaxants
Where are nicotinic receptors found?
autonomic ganglia, neuromuscular junctions , and CNS
What are cholinergic receptors?
Nicotinic
Muscarinic
Receptors for the parasympathetic nervous system?
Muscarinic and nicotinic
Receptors for the sympathetic nervous system?
Alpha, beta, and dopaminergic
What are neurotransmitters for the parasympathetic nervous system?
Acetylcholine at all sites
What are neurotransmitters for the sympathetic nervous system?
Acetylcholine at ganglionic
Norepinephrine at receptor
3 common Neuromuscular blocking agents (NMB) agents?
needs a edit but not wrong
NMB = Neuromuscular blocking agents aka muscle relaxants = paralyzing agents
-Cisatracurium (nimbex)
-rocuronium (Zemuron)
-Succinycholine (Anectine) - not a non actually.
What are 3 adrenergic receptors?
Alpha
Beta
Dopaminergic
Adrenergic vs cholinergic receptors?
accuracy needs check
Adrenergic = sympathetic
- Responds to epi/norepi
Cholinergic = parasympathetic
- Responds to acetylcholine
What is used to reverse opioid overdose
Naloxone (Narcan)
-opioid antagonist
-has a high affinity to opioid receptors preventing their activation
Descending order for the pharynx?
nasopharynx
oropharynx
hypopharynx
What 2 neurotransmitters does the PNS use?
Acetylcholine
Norepinephrine
What releases norepinephrine?
All POSTganglionic neurons of the sympathetic nervous system except those innervating sweat glands
Acetylcholine is released by?
sympathetic and parasympathetic PREganglionic neurons
-parasympathetic postganglionic neurons
-somatic motor neurons
-sympathetic postganglionic neurons that innervate sweat glands
which of the following represent obstructive vs. restrictive disease?
A: obstructive
B: restrictive
What obstruction is this?
Intraluminal obstruction
something inside airway blocking/narrowing it.
(foreign body or excretion)
What obstruction is this?
Extramural obstruction
External pressure causing narrowing
(enlarged lymph nodes, carcinoma, tumor)
What is a neoplasm?
basically a tumor like clot or blocking agent
What obstruction is this?
Intramural obstruction.
Lesions inside bronchial wall
(swelling -> neoplasm)
Parasympathetic postganglionic neurons release what neurotransmitters?
Acetylcholine
sympathetic postganglionic neurons innervate sweat glands that release what neurotransmitter?
Acetylcholine
Sympathetic and parasympathetic preganglionic neurons release what NT?
Acetylcholine
All post ganglionic neurons of the sympathetic nervous system release what neurotransmitter?
Norepinephrine
(except those that stim sweat glands)
Norepinephrine stimulates which adrenergic receptors @ the tissues, and which neurons are innervated?
Alpha and Beta
Sympathetic postganglionic neurons are innervated
Difference between Nicotinic and muscarinic receptors?
Nicotinic has ion channels and is faster
Muscarinic takes longer to see changes
(G protein-coupled receptors)
which enzyme breaks down acetylcholine?
Cholinesterase
Why is the breakdown of acetylcholine important?
Prevents unwanted activation of neurons or muscle cells.
AND
Ensures proper timing of signals to postsynpatic cells
What are 3 main phases of drug action other than administration?
- Pharmacokinetic phase: How drugs are absorbed, distributed, metabolized, and excreted by the body. It involves the processes by which drugs are transported throughout the body, how they are metabolized and eliminated, and how long they remain in the body.
- Pharmacodynamic phase: How drugs interact with specific receptors and produce their effects. It involves the relationship between drug concentration and response, the onset and duration of drug action, and the mechanism of action of drugs.
- Pharmacogenetic phase: How genetic variations influence drug response. It involves the study of genetic polymorphisms that affect drug metabolism and drug-target interactions, which can lead to differences in drug response between individuals.
What is drug potentiation
Drug potentiation is the increased effect of a drug caused by another drug or substance that does not have an effect on its own.
What is drug desensitization
Drug desensitization is the process by which a drug loses its effectiveness over time. This can be due to repeated use of the drug, leading to a reduction in the number or sensitivity of the receptors that the drug targets.
What is Drug inactivation
Drug inactivation is the process by which a drug is rendered inactive or ineffective. This can occur through various mechanisms such as metabolism, excretion, or chemical reactions with other substances.
What is Down-regulation
Down-regulation is the process by which the number of receptors for a particular drug or substance is reduced. This can occur as a result of prolonged exposure to the drug or substance, leading to a decreased response to the drug.
