Week 3 - ADR/SE/Types Flashcards
Types of Medication Effects
- Therapeutic Effect
- Secondary Effects
Therapeutic Effect
Effect wanted to be done - done by the main ingredient
Seconary Effects
Different terminology - may be beneficial - may not be beneficial or even unexpected
ex: Sedation/Drowsiness from Benadryl
ADR
Adverse drug effect
any unintended or undesirable consequence of drug therapy
What is the difference between side effect and ADR
SE tends to be used for expected non-emergency things, while ADR is for more emergency
However, in this class it is used interchangeable
Predictable Variables that influence drug action and also ADRs
Sex
Age
Body Mass
Environment
Genetics
Pathologic State
Psych Factors
Chronobiology
Pregnancy and Lactation
Drug Administration Factors
There are higher numbers of ADR in ___ and why?
females
This could be reported incidence, but also the hx of drug testing was always on men not women - so there was underrepresentation occurring
Why does age influence ADRs and drug action in Geriatrics
- Decreased GI Absorption as we age
- Blood flow increased to brain and heart; decreased to kidney (excretion) and liver (metabolism)
- Change in plasma proteins (less inactivated = more free drug); increased fat%; decreased metabolism
- Many diseases common to elderly are treated with drugs
Why does age influence ADRs and drug action in Children
Children have numerous peculiar ADRs as well as predicted ones
- Liver and kidney not yet mature
- Decreased protein stores in general
- Weight and fat distribution varies among children
Why is body mass more important than weight when it comes to drugs
because it tells compositions - obese, thin, muscular but weight does not tell fat and muscle distribution
In what ways is body mass influencing ADRs and drug action
- Nutritional state will affect drug action - proteins are important!!!
- Dosages get suggested based on an “average”
- Body surface area is important
What is the most accurate way to decide dosage in children
Body Surface Area - they have large skin SA to size
What sort of environmental factors influence drug action and ADRs
physical - altitude, light, temperature, stress
chemical - O2 tension, pollution, climate, diet
What sort of factors are impacted by environment predictable factors
blood flow
hepatic renal and gastric function
How does genetics impact drug action and ADRs
PROBABLE susceptibility to ADRs is partially geneticall induced
ex: penicillin allergies, anesthesia
partial influence on ADR
WHy can pathologic state influence ADR and drug action
disease states can alter pharmacokinetics and responses; liver working, kidney working, heart pumping? etc
How does psychological factors impact drug action
symbolic meaning is very powerful
ex: Placebo
Chronobiology
study of the rhythms in biologic phenomena
If we look at body rhythms and correlate with drug and kinetics the body may become more responsive to different drugs at different times of day (ex: steroids have natural increase during pre-dawn time due to stimulation by liver)
Basically some things work better at different times of day
How is drug action and ADRs influenced by pregnancy and lactation
physical changes will induce altered response to some drugs in pregnant women
Also, infants are exposed to a wide variet of food and medications - and breast milk can also hold these things - and dependency can start in the fetus
Immune system lowers during pregnancy
What sort of drug administration factors influence ADRs and drug action
Amount of Drug
Route
Bioavailability
Degree of Exposure
Mult. Drug Therapy
Drug Interactions
How is topical medication an example of how route can influence ADRs
topical drugs have high sensitization - can cause sensitivity where at first you do not see a problem but over time you become more sensitive and notice effects like a rash or redness when using
How is parenteral medication an example of how route can influence ADRs
Anything injected or IV
More severe reactions can be seen this way
Less than 30% of drugs have the first pass
Bioavailability
Drugs vary in ingredients and from process of drug manufacture - so secondary ingredient influences can influence drug action
Degree of Exposure
SE: more likely with higher dose and prolonged administration - so you want to start at hte lowest amount for the shortest amount of time and adjust from there
ex: Ibuprofen if taken once in a while is ok, but 4 times a day leads to increased risk for GI bleeding and ulceration
What sort of things can interact with drugs
lab tests
foods
diseases
other drugs
Rest and Digest system
PNS
Fight or Flight system
SNS
Summation Drug Interactions/Actions
(additive) 2 or more drugs added together - give double/added effect
Synergism Drug Interactions/Actions
two drugs, but causes a GREATER EFFECT THAN EXPECTED from the 2 drugs
Potentiative Drug Interactions/Actions
intensify effects og drug (positive or negative) - used interchangeably with synergism
But it can be used for positive OR negative effects not just positive
Antagonism Drug INnteractions/Actions
effect is decreased or blocked when two drugs are given - one blocks effect
Cumulation Drug Interactions/Actions
body cannot metabolize one dose of a drug before another dose is administered
drugs are excreted slower than absorbed - so they accumulate over time
Tolerance
Decreased physical response to repeated adminsitration of a drug
You respond less to medication doses than you used to (ex: opioid for pain relief needs more for the same response)
Dependence
Reliance on drugs to maintain state of well being
WHO recommends this term rather than using addiction and habituation
Involves mental and emotional factors on top of physical - which is different than tolerance which is just physical ones
No drug is totally safe …
and absolutely free of toxic effects
Side effects are often ___
predictable
Black Box Warnings
strongest safety warning a drug can carry - has to do with FDA labelling requirements, and they are significant and people should be aware of them before taking a drug
OTCs can even have this - serious and common enough ADRs would occur that the public needs to know
Adverse Drug Reactions
one way to characterize drug responses that have NOT been optimally, clearly, or distinctly defined
__-__% of ADRs are predictable and __-__% are not predictable (suprising and unknown); allergy and idiosyncrasy
70-80% predictable; 20-30% non-predictable
Predictable Drug Reactions
Often an extension of the action of a drug
documented in testing of the drug
Iatrogenic Disease
Iatro = Physician’ Genic = Produce
It is a disease occurring as a result of care, treatment, or medication result - will look like a real condition but is due to a medication (or other treatment)
a specific predicatable reaction to medicaiton oftentimes
What are some of the adverse effects caused unintentionally/iatrogenically that we will need to treat despite predicting them due to medications
Blood Dycrasias (Agranulocytosi, thrombocytopenia)
Hepatic Toxicity (hepatisi - inflamed liver)
Renal Damage (glomerular)
Teratogenic Effects (malformation in fetus)
Dermatologic Effects
Ocular Effects
Sexual Dysfunction
What sort of iatrogenic conditions can ASA and steroids cause
gastric and blood ulcers
ASA
aspirin
What sort of iatrogenic conditions can oral contraceptives cause
thrombi/emboli (blood clots)
Carcinogenic Effects
cancer causing effects
chemo meds can even cause this
What are 2 types of non predictable suprising responses to medication
- Drug allergy (could be allergic to one person but not another)
- Idiosyncracy
Idiosyncracy Effect
any abnormal or peculiar response to a drug
generally thought to result from genetic enzymatic deficiencies that lead to abnormal mechanisms of metabolized drugs
What sort of things does ANS control
heart
secretory glands
saliva
sweat
gastric and bronchial
smooth muscle like blood vessels, bronchi, GI, GU
Principal Functions of PNS
slow heart rate
increased gastric secretion
emptying bladder
emptying bowels (Cleaning out the system)
focus eye for near vision
constriction of pupil
contract bronchial smooth muscle (narrower airways)
rest and digest
Principal Functions of SNS
regulate CV system (increase HR and BP)
dilate bronchi
dilate pupils
mobilize stored energy
shunt blood to skeletal muscles
regulate body temperature
fight or flight
What is not a part of ANS
skeletal muscles
75% of PNS fibers leave the CNS via the ___ cranial nerve (___)
10th - Vagus
Vasovagal response drops things
Major NTs
Acetylcholine (ACh)
EP
NEP
Dopamine
How do skeletal muscle innervation differ from PNS and SNS innervation
they do secrete NTs, but the synapse axons directly with skeletal muscle neuromuscular junction - and have no ganglion (so its just one neuron)
NT types (Major 4 in ANS)
Adrenergic (NEP/EP)
Cholinergic (ACh)
Nicotinic
Muscarinic
NTs in the ANS do what 4 things
synthesized
stored
released
inactivated
Why is information on Dopamine not clear regarding the ANS
it may have a modulating role at ganglion
it is a precursor for NEP
its prominent in the CNS
also has renal, mesentary, and heart effects
Cholinergic NT
Acetycholine - PNS System
Adrenergic NT
“Catecholamines”
NEP/EP - SNS
Where is ACh found
skeletal - neuromuscular junction
ANS: Preganglionic fibers of BOTH PNS and SNS; Postganglionic fibers of SNS; a FEW postganglionic fibers of SNS (Sweat glands, pilomotor)
ACh is inactivated by ?
Acetylcholinesterase/Cholinesterase
How is NEP inactivated
- 50-80% reuptake by the neuron to be reused or broken down (by MAO)
- Diffusion to surrounding body fluids and destroyed by enzymes (COMT outside neuron or in distance in liver/GI tract)
Types of Cholinergic Receptors
Nicotinic
Muscarinic
Nicotinic Receptor 1 (n)
ACh receptor that stimulates effects on ganglia, adrenal medulla
Nicotinic Receptor 2 (m)
ACh receptor stimulating effects of skeletal muscle
Usually when discussing cholinergic receptors it is in reference to ___ receptors
muscarinic
Muscarinic Receptors
ACh receptors
named after the effect of some mushrooms
affect receptorsat effectors in post ganglionic areas (especially cardiac muscle, smooth muscle, and glands)
2 Types of Adrenergic Receptors
Alpha
Beta
Alpha 1 Adrenergic Receptors
VASOCONSTRICTOR
generally - contract and mediates vasoconstrictor effects with NEP
Also impacts sex organs and the eye
Alpah 2 Adrenergic Receptors
Controls amount of NEP released
Dose not have much effect on pharmacology in ANS - therefore not many meds are this kind (some are)
Beta Adrenergic Receptors are huge for what areas
Respiratory and Cardiac
Beta 1 Adrenergic Receptors
Cardiac Control (increases atrial firing and contraction from SA node)
Beta 2 Adrenergic Receptors
Controls smooth muscles of bronchioles, arterioles and other viscera
Dilates bronchi, relaxes uterus, dilates vessels in the heart, lung, and muscles
Promotes Glycogenolysis (breakdown of glycogen to glucose)
What is Dominant Organ Control (Basal Control) regarding PNS/SNS
Most organs are dominantely controlled by one or the other of PNS and SNS yet are innervated by both
So, usually in the same organ they will produce opposite and mutually antagonistic effects
ex: HEART SNS - increased heart rate (SA node); PNS decreased heart rate (vagus)
ex: Somtimes they do complementary effects though like PNS-erection and SNS-ejaculation
Discrete Discharge is
PNS
Mass Discharge is
SNS
Tone of the PNS/SNS
not everything is all or nothing all of the time - in general airways and blood vessels are in the middle in order to go down or up when needed
So, there is a balance like with SNS - vasoconstriction but there is a middle ground where vessels are kept at 1/2 blood vessel maximum diameter - so it can constrict or relax
What is the general pathway of the PNS/Cholinergic System
Spinal Cord –> Pre Ganglionic and Post Ganglionic (2 Fibers) w/ ACh –> Organ
Only 1 NT: ACETYLCHOLINE
What is the general pathway of the SNS/Adrengeric System
3 Paths:
- Pre-ganglia releases ACh –> NEP released at various organs
- Pre Ganglia releases ACh –> sweat glands use ACh (exception for ACh)
- Pre ganglia –> EP at the adrenal gland
____ is always the pre ganglia synaptic NT
acetylcholine
What is the general pathway of the Somatic Motor (Skeletal Muscle) pathway
ACh is used in one long neuron (no ganglion) working on skeletal muscle
Usually ACh works in the PNS on organs, what are the exceptions where it works for SNS effect
1 Sweat Glands - It is used in the SNS system to cause sweating
- Pilomotor - goosebumps and body hair rising
What are the NT and Receptors available pre-ganglia in the SNS and PNS
Acetylcholine - NT
Cholinergic - nicotinic - Receptor
(Both systems are the same pre ganglia)
What are the NT and Receptors post ganglia in the PNS
Cholinergic
ACh (All ACh in PNS)
Cholinergic – Muscarinic Receptors
What are the NTs and Receptors post ganglia in the SNS
- Adrenergic Receptors with NT Catecholamines like NEP, EP, and Dopamine
- ACh (exceptions): Cholinergic-Sympathetic on Pilomotor and Sweating
Receptors: Adrenergic Alpha 1 and 2, Beta 1 and 2
4 Groups of Autonomic Drugs that mimic (imitate) or block (inhibit) SNS or PNS
- Cholinergic
- Cholinergic Blocking
- Adrenergic
- Adrenergic Blocking
Cholinergic Drugs
act like mediators of the PNS (mimic PNS - slow things) (Parasympathomimetic)
generally PNS with the normal exceptions
Cholinergic Blocking Drugs
block PNS (parasympatholytic)
Adrenergic Drugs
Act like SNS (Sympathomimetic - mimic SNS)
Adrenergic Blocking Drugs
Blocks SNS (Sympatholytic - lytic means break up or disrupt)
What are Cholinergic Drugs used to do
lower intraocular pressure of glaucoma (decrease muscle contraction and eye secretions)
Terminate curarization (paralysis; adjunct to anesthesia; Curare causes paralysis) so this stops paralysis
Treats myasthenia gravis (muscle weakness disorder destroying ACh receptors in muscles so weak by end of day) but stimulates muscles with ACh
Promote salivation and sweating (exception to ACh)
Dilate peripheral blood vessels in conditions of vasospasm, stimulate intestines and bladder postoperatively
Cholinergic fibers are ___ and stimulate what
widespread; stimulate motor and secretory action
Side Effects of Cholinergic Drugs
Bradycardia
Decreased BP
Salivation
Vomiting
Diarrhea
Cramps
Heartburn
Bronchoconstriction
tearing (Eye)
Visual disturbances
(The results of the PNS or too much ACh - extreme rest and digest)
2 Types of how Cholinergic Stimulating Medications work
- Med is like ACh and works and acts like it - DIRECT ACTING
- Does not go right to receptor, rather inhibits ACh breakdown - INDIRECT ACTING
Cholinergic Meds mostly do what?
PNS effects AND stimulate sweat glands
Cholinergic Blocking Agents
“Parasympatholytic” / “Anticholinergics” / Antimuscarinics (opposite of SNS)
What is the action of cholinergic blocking agents
they do NOT stop ACh release; they just take the spot on the receptor and ACh cannot connect and stimualte action that way
Uses for Cholinergic Blocking Meds
Relax Smooth muscles - especially bronchioles
Inhibit secretion of duct glands (including sweat and salivary)
Pre-op use for decreasing secretions
Dilate pupils (local action) for diagnostic purposes
GI - decrease motility and secretion (maybe slow down loose stools)
GU - relax motility and secretion but constrict bladder sphincter (allows filling and encourage urinary retention)
Treat Enuresis
Cardiac - stop or prevent bradycardia if due to vagus/vasovagal nerve/response (large doses) - Like with anesthesia
Dilates airways since PNS will constrict
Dries up pre op secretions to prevent aspiration and aspiration pneumonia
Why would we give an anticholinergic (like Atropin) pre-op/intra-op
lots of anesthesia will slow heart rate too much, so Atropin will stop or prevent bradycardia so the heart does not go too slow
ADRs of Anticholinergics
Wide margin of safety
However, toxic effect could be paralysis
Large doses can cause CNS excitement - main use is due to peripheral action
Adrenergic Medication
Sympathomimetic drug
Mimics SNS
Affects alpha and beta - used for respiratory and cardiac conditions
In general, Alpha Adrenergic Drugs produce what kinds of effects
Excitatory Effects - EXCEPT GI and Eye
In general, Beta Adrenergic Drugs produce what kinds of effects
Inhibitory Effects - EXCEPT Heart (Beta will be excitatory on heart, alpha not much effect)
The Inhibitory Effects (Exceptions to the Normal Excitatory Effe ts) of Alpha I Adrenergic Drugs
- Vasoconstriction! of arterioles of skin and splanchnic area
- Pupil dilation
- Relaxation of GI
Examples of Exictatory Actions of Adrenergic Alpha I Drugs
Contract pylorus
Constrict bladder trigone and sphincter
Contract uterus
Blocks insulin release
Stimulates Ejaculation
Alpha 2 Drugs/Receptors are…
not used much at this time for therapeutics
4 Receptors used with Adrenergic Drugs
Alpha 1 and 2
Beta 1 and 2
Beta 1 Drug effects on the heart
Cardiac Acceleration and Increased Contractility
Chronotropic, Dromotropic, Inotropic
Chronotropic
Cardiac Rate
Beta 1 Drugs will increase pulse rate
Dromotropic
Cardiac Condutction
Beta 1 Drugs will increase conduction
Inotropic
Cardiac Contractility
Beta 1 Drugs will increase contraction (force of contraction)
Beta 1 Drugs stimulate cardiac receptors but…
you will increase cardiac need for O2 consumption so you may eventually diminish heart efficiency
Beta 2 Drug Effects
- Bronchial Relaxation (increases breathing capacity)
- Vasodilation of arterioles supplying skeletal muscle for fight or flight
- Uterine Relaxation
- Metabolism - Glycogenolysis (increase Glc levels)
- Decrease Stomach Motility and Tone
- Relax Bladder Detrusor (increase peeing)
- Increase free fatty acid release
Adrenalin
EP - comes from adrenal medulla
used in emergencies
NEP
highest proportion NT in the body
Important transmitter of nerve impulses
EP stimulates Alpha (1), and Beta 1 and 2 Receptors - so what does it due in emergency conditions or Fight or Flight
B1 - Stimulates heart, increases rate force and conduction - makes heart more responsive to defibrillation in cardiac arrest
B2 - dilate bronchi (increase tidal volume and vital capacity) - dilates arterioles to vital organs and muscles
Alpha - Constricts arterioles of bronchioles and inhibits histamine release - prevents edema and congestion; decreases nasal congestions
What is EPs overall effect on the CNS
it stimulates - yet we do not know how since it doesnt cross the blood brian barrier directly
ADR of EP
CNS - nervousness, dizziness, restlessness, HA
CV - palpitation, tachycardia, angina, increased BP, arrhythmia
Skin - pallor (blood vessels constricted and shift blood to vital organs when stressed)
Resp - bronchial irritation, pulmonary edema, rebound bronchospasm - too much stimulation
Metabolic - increased blood glc
Adrenergic Blockers (Antagonist) Drugs
Stop SNS Activity - these would act a lot like cholinergic stimulating drugs and have some similarities
Some of these drugs are used in HTN and other cardiac conditions (ex: Beta blockers)
Alpha Adrenergic Blocking Agents (Drugs) can be used for what
- HTN - postural hypotension is a problem but you can get other SE as well
- BPH - improve flow to prostate
ADRs of Alpha Adrenergic Blocking Agents
- CV - distinct fall in BP, especially postural hypotension (IMPORTANT)
- GI - increased motility (can lead to diarrhea)
- GU - impotence
- CNS - most have few CNS; can have sedation and depression though
Beta Adrenergic Blocking Agents (Drugs)
more useful overall than alpha blockers (as they do a lot more) can affect B1 and B2 if non-selective Beta, or just B1 or B2 if selective
Action of Beta Adrenergic Blocking Agents
Beta blockers antagonize all throughout the body
Potentiates effects of epinephrine on alpha receptors by blocking its beta receptor effects
Uses for Beta Adrenergic Blocking Agents
Cardiac Arrhytmias (BB1 will slow down)
Angina (slow down heart and need less O2 and then chest pain can go away)
HTN
Digoxin Toxicity
ADRs of Beta Adrenergic Blocking Agents
- Serious, due to heart action, low BP and HR
- CNS - insomnia, dizziness, and depression - blockage of SNS caused
- Suppress normal SNS reflex to hypoglycemia (dont have hypoglycemic symptoms though from SNS such as sweating, increased pulse and anxiety) - adrenergic usually give hypoglycemic symptoms but if on a beta blocker you may not have the normal symptoms and may miss that you are hypoglycemic
- N/V, diarrhea, visual issues, skin reactions
Why should beta blockers not be discontinued abruptly
Wean them off - HR can fly back up and put them into angina
never want them running out of beta blockers
Ganglionic Agents
Works on the ganglion and blocks something there which stops info transfer early on - so this blocks entire organ action not just specific things
only used in specific situations
Always acts on ACh since thats what is there
Ganglionic agents have widespread action effects on the body, why?
Because they act on the NS at the ganglion much earlier than the others
The NT at all ANS ganglia is ___
ACh - nicotinic 1 receptor
WHy are ganglionic agents rarely used
widespread effects - both planned and adverse
2 Types fo Ganglionic Agents
- Ganglionic Stimulator
- Ganglionic Blocking
Ganglionic Stimulator
Mimics ACh
Only therapeutic use is nicotine gum or patches to help stop smoking
Ganglionic Blocker
interrup entire ANS - but overall effect given for is decreased SNS tone, especially Cardiovascular
Sometimes helpful with HTN (sever and malignant) but is not the first choice drug
May use with autonomic dysreflexia which occurs in spinal cord injury (drop in BP and restore fxn in autonomic dysreflexia)
Your pt. has chronic renal failure. He is receiving a medication that is excreted via the kidneys. You would expect to use:
A - A larger dose than normal
B - A smaller dose than normal
C - more frequent dosing
B - A smaller dose than normal
This is because if the kidneys do not work well we need to give a lower dose since they are not excreting the old drugs
If a drug is nephrotoxic, what would you monitor:
A - ALT and AST levels
B - Cognitive Fxn
C - I&O’s
D - Balance and Strength
C -I&O’s
Nephro = Nephron = Kidney; With the kidneys we worry about excretion (I&O)
Which timing is more likely to lead to teratogenic effects of drug therapy?
A - First Trimester
B- Second Trimester
C - Third Trimester
D -All 3 have equal risk
A -First Trimester
In the elderly pt., fat soluble drugs may need to be ___ to avoid toxicity.
A - Increased
B - Decreased
C - Neither of the Above
A - Decreased
As people age they have a higher fat % to lean muscle so they hold onto drugs more if it is fat soluble
