Transcript general principals of ph... 967KB Jan 14 2015 08:21:46 AM

General
Pharmacology
Better living through
pharmacology, pharmokinetics,
and pharmodynamics,
P. Andrews
Case # 1
Case 1, cont.
Case 1, cont.
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CAREFUL AND JUDICIOUS USE OF
MEDICATIONS CAN TRULY MAKE A
DIFFERENCE
Things to know
about drugs
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Pharmokinetics
Pharmodynamics
Generic names
Trade names
Schedules of drugs
FDA approval
process
The Harrison Narcotic
act of 1914
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Enteral drug
administration
Parenteral drug
administration
Mechanism of action
Route of
administration
Pure food and drug
act of 1906
Things to
know, cont.
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The Federal Food,
Drug and Cosmetic
act of 1938
The DurhamHumphrey
Amendments to the
1938 Act
The Controlled
Substance Act of
1970
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OTC medications
Bioequivalence
Six rights of
medication
administration
Absorption
Bioavailability
Biotransformation
First-pass effect
More things to
know!
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Blood-brain barrier
Placental barrier
Oxidation
Hydrolysis
Elimination
Agonist
Antagonist
Agonist-antagonist
Extrapyramidal
symptoms
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Idiosyncratic response
Tolerence
Side effect
Cumulative effect
Synergism
Potentiation
Onset of action
Therapeutic index
Half-life
Minimum effective
concentration
Historical trends
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Ancient health care
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Herbs & minerals - 2,000 BC
Pharmacology by end of
Renaissance; separate from
medicine
Vaccinations 1796 (Smallpox)
Insulin, Penicillin early 20th century
Modern health care
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Human insulin
tPA
Pharmacology
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Chemical name
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Precise description chemical composition and
molecular structure
Vecuronium Bromide:

Chemical compound: piperidinum, 1-[(2, 3, 5,
16, 17)-3, 17-bis (acetyloxy)-2-(1piperidinyl)androstan-16yl]-1-methyl-, bromide.

Molecular structure C34H57BrN2O4
Generic name –
Non-proprietary name
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FDA approved
First manufacturer
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Trade (Proprietary) name
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Registered to a specific manufacturer
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vecuronium bromide
Marsam Pharmaceuticals, Inc.
Vecuronium
TM
Official name

Assigned by USP

Vecuronium Bromide USP
Drug Sources

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Plants
 Atropine – Deadly
nightshade plant
 Morphine –
Opium plant
 Digitalis –
Foxglove
Animals and
Humans
 Insulin
 Glucagon
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Minerals
 Calcium chloride
 Sodium
Bicarbonate
 Magnesium
Sulfate
Synthetics
 Bretylium tosylate
 Lidocaine
 Procainamide
Drug Profiles
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Names
Classification
Mechanism of Action
Indications
Pharmacokinetics
Side effects/ adverse reactions
Routes of administration
Contraindications
Dosage
How supplied
Special considerations
Legal stuff
- Federal
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Protect the public
Pure Food and Drug Act, 1906
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Harrison Narcotic Act, 1914
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Improve quality and labeling of drugs
Regulating importation, manufacture, sale, use of
opium, cocaine, derivatives
Federal Food, Drug, Cosmetic Act, 1938
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Empowers FDA to enforce, set premarket safety
standards
More Federal stuff
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Durham-Humphrey Amendments, 1951
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Prescription drug amendments, 1938 act;
requires written or verbal prescription
from physician to dispense some drugs
Created OTC category
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Comprehensive Drug Abuse
Prevention & Control Act, 1970
(Controlled substance act)
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Replaces Harrison Narcotic Act
Establishes 5 schedules of drugs
Prohibits refilling of Rx for Schedule II
drugs, & requires original Rx to be
filled within 72 hours
Other regulations
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Prescription drugs
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Designated sufficiently dangerous to require
supervision
OTC
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Available in small doses; present low risk
General issues

Drugs must be secured
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State laws vary; generally set scope of
practice for EMS
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Medical directors can delegate authority to
paramedics
Standards
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Assay
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Bioequivalence

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Determines amount & purity
Relative therapeutic effectiveness of
chemically equivalent drugs
Bioassay

Attempts to ascertain drugs availability in
biological model
New Drug Development
You Are Responsible!

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Know precautions and
contraindications
Practice proper
technique
Know how to observe
and document effects
Establish and maintain
professional
relationships with other
health care providers
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Understand pharmacokinetics,
pharmacodynamics
Have current references
available
Take careful drug histories
Evaluate compliance, dosage,
adverse reactions
Consult with medical direction
when appropriate
SIX RIGHTS OF MEDICATION
ADMINISTRATION
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Right medication
Right dose
Right time
Right route
Right patient
Right documentation
AND SEVEN – Right to refuse
Cells talk to each other

Three distinct languages

Nervous system
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Endocrine system
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neurotransmitters
hormones
Immune system

cytokines
In disease, all systems are
affected

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The three systems can’t exist without each
other
The actions of one impact the actions of
the others

I.e., stress (nervous system) disrupts
endocrine system which may respond with
glucocorticoid production = suppressed
immune response
Drug Class Examples

Nitroglycerin
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Indications for nitroglycerin
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Body system: “Cardiac drug”
Action of the agent: “Anti-anginal”
Mechanism of action: “Vasodilator”
Cardiac chest pain
Pulmonary edema
Hypertensive crisis
Which drug class best describes this
drug?
Another way to classify drugs

Mechanism of Action

Drugs in each category work on similar sites in the
body and will have similar specific effects/side
effects
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Beta blockers: metoprolol
ACE inhibitors: lisinopril
Alpha blockers: prazosin
Calcium-channel blockers: verapamil
Example: beta blocker actions and impacts
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Suppress the actions of the sympathetic nervous
system
Prehospital administration of epinephrine may not
produce as dramatic effects with a patient taking a
drug in this class
Prehospital example:
Hyperglycemics
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Dextrose 50% and glucagon
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Mechanism of action
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Both will raise blood glucose
Glucagon: hormone that works in the liver to
convert stored chains of carbohydrate to glucose
Dextrose 50%: ready-made simple sugar that is
ready to enter into the cell
Which drug is considered first-line for
hypoglycemia? Why?
What are some limitations for glucagon in the
presence of severe hypoglycemia?
Sources of drug information
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AMA Drug Evaluation
Physician’s Desk Reference (PDR)
Hospital Formulary
Drug Inserts
Other sources
Controlled
substances
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Schedule I. High potential for abuse; no
accepted medical indications
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Heroin, LSD, Crack, Marijuana
Schedule II. High potential for abuse, but
have accepted medical indications

Morphine, Meperidine, Dilaudid, Oxycodone,
Cocaine, Codeine, Opium, Methadone

Schedule III. Less potential for abuse,
and accepted medical indications
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Tylenol #3, Vicodin
Schedule IV. Low potential for abuse,
but may cause physical or psychological
dependence.
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Diazepam, lorazepam, Phenobarbital
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Schedule V. Low potential for abuse, but
have small quantities of narcotics
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Cough medicine (Vicks 44)
Standardization of Drugs
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A necessity
Techniques for measuring a drug’s
strength and purity
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Assay
Bioassay
The United States Pharmacopeia
(USP)
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Official volumes of drug standards
Medical Control
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Medication administration is ALS skill
Medical Director
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Actively involved in and ultimately responsible
for all clinical and patient care.
We are extension of physician’s license
Special ConsiderationsPregnant patients
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Evaluate benefit vs. risk to fetus
FDA has a scale (A,B,C,D,X) to
indicate drugs that may have
documented problems
Many drugs are unknown to
cause problems
Drugs may cross placental
barrier or through lactation
FDA Pregnancy Categories
A
B
Adequate studies have not
demonstrated a risk to the fetus
Animal studies have not demonstrated a
risk to the fetus; no adequate studies in
humans OR
Adequate studies in pregnant women
have not demonstrated a risk to fetus in
first and last trimester BUT animal
studies show adverse effects
FDA Pregnancy Categories, cont.
C
D
X
Animal studies have demonstrated
adverse effects, but there are no
adequate studies in pregnant woman
Fetal risk has been demonstrated; in
certain circumstances, benefits could
outweigh risks
Fetal risk has been demonstrated. This
risk outweighs any possible benefit to
mother. Avoid using in pregnant
patients.
Special Considerations –
Pediatric patients
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Based on weight or BSA
Length-based resuscitation tape
(Broslow’s)
Absorption of oral meds less due to
differences in gastric pH, emptying
time, low enzyme levels
Pediatrics, cont.
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Unexpected toxicity common in topically applied
meds
Drugs that bind to protein have higher availability
Neonates have much higher % of extracellular
fluid – may require higher doses
Lower metabolic rate & hepatic system ; higher
risk for toxicity
Special Considerations - Geriatric
patients
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MULTIPLE MEDS A
PROBLEM
Physiological effects of
aging can lead to altered
pharmacodynamics and
pharmacokinetics.
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Absorb oral meds slower
Distribution altered
Lipid soluble drugs have
greater deposition
Drug action delayed or
prolonged
Pharmacology
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The study of drugs and their interactions
with the body
Drugs do not confer any new properties on
cells or tissues – only modify or exploit
existing functions
Given for local or systemic action
Pharmacokinetics

The study of the basic processes that
determine duration and intensity of a
drug’s effect
Transport

Active transport
 Requires energy to move a substance
 ATP  ADP
 Sodium – potassium pump
 Facilitated diffusion
Binds with carrier protein, configuration of cell
membrane changes, allows large molecule to
enter body
 I.e., Insulin increases glucose transport from
10-20 fold

Transport, cont
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Passive transport
movement of substance without energy
Diffusion
 Movement of solute in solvent
Osmosis
 Movement of solvent
Filtration
 Molecules move across membrane
down pressure gradient
Absorption
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IM faster than SC
Enteral administration; must survive digestive
process
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Enteric coating; dissolve in duodenum
Many drugs ionize
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Ionized drugs don’t absorb across cell membranes
Most drugs reach equilibrium
pH affects ionization
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Concentration affects absorption
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Loading dose – maintenance dose
Bioavailability
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Amount of drug still active after reaching
target tissue
Distribution
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Some drugs bind to proteins in blood and
remain for prolonged period
Therapeutic effects due to unbound
portion of drug in blood
Drug bound to plasma proteins can’t cross
membranes
Changing blood pH can affect proteinbinding action of drug.
TCA’s are strongly bound to plasma
proteins.
Case #2
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
You are dispatched to a report of a
possible suicide attempt. You arrive to find
a 50 year old woman CAO PPTE. She is
crying, and says that she wants to die.
She admits to taking pills about ½ hour
pta. PMH: Vascular H/A.
Her B/P is 140/90, P 100, RR 28, Skin
PWD, PERL. BBS =, clear. Wt. ~ 60 kg.
Case # 2, cont.
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
You continue assessing her while your
partner goes to check the trash containers
in the house. He returns with an empty
bottle of desipramine. The label shows
that the Rx was filled yesterday, and there
were 50 tablets of 100 mg ea.
What is the total dose she probably
ingested?
Case # 2, cont.

You put her on the ecg monitor, and note
that her QRS is widening. Her heart rate is
now 110, her B/P is 110/64, RR 28, and
she is c/o dry mouth and blurred vision.

What medication will you give her?
Case # 2, cont.
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Tx:
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Oxygen
Ecg
IV
Sodium Bicarbonate 1 mEq/kg
Rapid transport
Case #2, cont.
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What does Sodium Bicarbonate do for this
patient?
What is her prognosis?
Drugs bind to proteins
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Albumen is one of the chief proteins in the
blood available for binding with drugs.
When a pt. Is malnourished, albumen is
low.
What significance does this have re; drug
therapy?
The blood – brain barrier
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Tight junctions of capillary
endothelieal cells in CNS form a
barrier
Only non-protein-bound, highly
lipid-soluble drugs can enter CNS
Placental barrier similar
Other deposits
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Fatty tissue serves as drug reservoir
Bones and teeth can accumulate drugs
that bind to calcium
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Ie., tetracycline
Biotransformation
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Drugs are metabolized – broken
down into metabolites
Transforms drug into more or less
active metabolite
Make drug more water soluble to
facilitate elimination
Protein-bound drugs are not
available for biotransformation
Biotransformation, cont.
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Occurs in liver primarily
Also occurs in kidney, lung, GI
tract
First-pass effect
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Some drugs can’t be given orally
Elimination
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Most drugs excreted in urine
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Glomerular filtration
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Some in feces or air
A function of glomerular filtration pressure (BP
and kidney blood flow)
Active transport system; requires ATP
Tubular secretion
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Urine pH affects reabsorption in renal tubules
Elimination, cont.

Some drugs and metabolites are
eliminated in expired air
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Breathalyzer
Feces, sweat, saliva, breast milk
Autonomic Nervous
System
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Responsible for control of involuntary actions.
Exit the central nervous system and enter
structures called the autonomic ganglia
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nerve fibers from CNS interact with nerve fibers from
the ganglia to target organs
Pre-ganglionic nerves - exit CNS and terminate in
autonomic ganglia
Post-ganglionic nerves - exit ganglia and teminate in
target tissues
No actual connection between nerve cells - a
synapse
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The space between nerve cell and target
organ is a neuroeffector junction.
Neurotransmitters - specialized chemicals to
conduct impulse
Neurotransmitters released from pre-synaptic
neurons and act on post-synaptic neurons or
target organ.
Two functional divisions of
autonomic nervous system
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Parasympathetic - Vegetative functions feed or breed
Sympathetic - Fight or Flight
the two neurotransmitters of the
autonomic nervous system

Acetylcholine -used in pre-ganglionic
nerves of the sympathetic system and in
pre and post-ganglionic nerves of the
parasympathetic system

Norepinephrine - the post-ganglionic
neurotransmitter of the sympathetic
nervous system.
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Cholinergic synapses - use acetylcholine
as neurotransmitter
Adrenergic synapses - use norepinephrine
as neurotransmitter
Sympathetic nervous system
stimulation
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Sweating
Peripheral vasoconstriction
Increased blood flow to skeletal muscle
Increased HR and cardiac contractility
Bronchodilation
Energy
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Reduced blood flow to abdominal
organs
Decreased digestion
Relaxation of bladder smooth muscle
Release of glucose stores
Also stimulation of the adrenal
medulla - release of hormones
norepinephrine and epinephrine
Adrenergic receptors
norepinephrine crosses synaptic cleft and
interacts
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alpha 1-peripheral vasoconstriction, mild
bronchoconstriction, stimulation of
metabolism
alpha 2-inhibitory - prevent overrelease of
norepinephrine in synapse
beta 1 - increased heart rate, cardiac
contractility, automaticity, conduction
beta 2 - vasodilation, bronchodilation

Dopaminergic receptors
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Sympathomimetics 
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not fully understood - believe to cause
dilation of renal, coronary, cerebral arteries
meds that stimulate the sympathetic nervous
system
Sympatholytics

inhibit the sympathetic nervous system
Nervous System
Central Nervous System
Peripheral Nervous System
Somatic Nervous System
Voluntary control
Autonomic Nervous System
Sympathetic
"Fight or Flight"
Neurotransmitters:
Norepinephrine
Epinephrine
Receptors:
Alpha 1 and 2
Beta 1 and 2
Parasympathetic
"Feed and Breed"
Neurotransmitter:
Acetylcholine
Parasympathetic nervous system
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Acetylcholine release - very short-lived deactivated by chemical acetylcholinesterase
Parasympathetic actions
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Pupils constrict
Secretions by digestive glands
Increased smooth muscle activity along digestive
tract
Bronchoconstriction
Reduced heart rate and contractility

Parasympatholytics
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Anticholinergics
block the actions of the parasympathetic
nervous system
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Atropine
Parasympathomimetics
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Cholinergics
Stimulate the parasympathetic nervous
system
Nervous System
Central Nervous System
Peripheral Nervous System
Somatic Nervous System
Voluntary control
Autonomic Nervous System
Sympathetic
"Fight or Flight"
Neurotransmitters:
Norepinephrine
Epinephrine
Receptors:
Alpha 1 and 2
Beta 1 and 2
Parasympathetic
"Feed and Breed"
Neurotransmitter:
Acetylcholine
The Parasympathetic NS

What organs will help out
the typical couch potato?
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Digestion
Slow heart rate
Smaller bronchioles
Pupil size

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Normal or constricted
This system works best at
rest
Couch Potato
Over-stimulation of the
Parasympathetic NS

A little is a good thing, but too much
stimulation of this system leads to trouble

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
Very slow heart rates
Bronchoconstriction
Major gastrointestional actions
Vomiting
 Diarrhea

Autonomic Nervous System
Sympathetic Receptor Site
Action
1)
2)
3)
Brain sends out the response via nerve paths
Nerve moves the response: depolarization
Depolarization stimulates norepinephrine sacks
•
Sacks move to the end of the nerve and
dump out their contents
2
3
4)
5)
Norepinephrine travels across the synapse
•
Attaches to a receptor on the organ, organ
responds to the signal
Norepineprhine detaches and is deactivated
•
2 options: destroy it or move it back into its sack
5
2
3
4
Drug Routes

Enteral
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
Oral (PO)
Orogastric/Nasogastric
(OG/NG)
Sublingual (SL)
Buccal
Rectal (PR)
Drug routes, cont.
Parenteral





Intravenous
(IV)
Endotracheal
(ET)
Intraosseous
(IO)
Umbilical
Intramuscular
(IM)
Subcutaneous
(SC, SQ,
SubQ)
 Inhalation/
Nebulized
 Topical
 Transdermal
 Nasal
 Instillation
 Intradermal

Drug forms





Liquid: (solute - solvent) Solution
Tinctures: drug extracted
chemically with alcohol.
Suspensions - liquid
preparations don’t remain mixed
Spirits: Volatile chemicals
dissolved in alcohol
Gaseous – Oxygen, Nitrous
Oxide





Emulsions: oily substance mixed with a
solvent that won’t dissolve it. (oil and
vinegar).
Elixirs: Drug in an alcohol solvent.
(Nyquil)
Syrups: Drug dissolved in sugar and
water (cough syrup).
Solids: capsule, tablet, lozenge, powder
Topical use: ointment, paste, cream,
aerosol
Drug storage

Properties may be altered by environment.




Temperature
Light
Moisture
Shelf-life
Pharmacodynamics

Most drugs bind to a receptor




Protein molecules
Can be stimulated/inhibited by chemicals
Each receptor’s name generally corresponds
to the drug that stimulates it
Affinity


Force of attraction between a drug and a
receptor
Different drugs may bond to same receptor
site, but strength of bond may vary – binding
site’s shape determines receptivity to
chemicals



Drug’s pharmacodynamics involves its
efficacy
Generally, drugs either stimulate or inhibit
the cell’s normal actions.
Efficacy and affinity not directly related


Drug A causes a stronger response than drug
B
Drug B binds to the receptor site more
strongly than drug A

When drug binds to receptor,
chemical change occurs

Drugs
Interact with receptor and
result in desired effect
 Interact with receptor and
cause release/production of a
second compound

Second messenger

Calcium or cyclic adenosine
monophosphate (cAMP)



Number of receptor sites on target cell
constantly changes



Most common second messenger
Activates other enzymes; cascading
Receptor proteins destroyed during function
Reactivated or remanufactured
Down regulation

Binding of a drug or hormone that causes number of
receptors to decrease
Agonists and Antagonists

Agonist


Antagonist


bind to receptor and cause a response
Binds to receptor but does not cause it to
initiate the expected response
Agonist-Antagonist


Do both
Nubain; stimulates opioid agonist analgesic
properties but partially blocks respiratory depression
Antagonists


Lock and key – key fits but won’t open the lock
Competitive antagonist


Drug binds and causes the expected effect and also
blocks another drug
Noncompetitive antagonist


Drug binds and causes a deformity of binding site that
prevents an agonist from fitting and binding
Naloxone

Drugs that change physical properties


Drugs that chemically bind with other
substances


Osmotrol
Isopropyl alcohol – denatures proteins on
surface of bacterial cells
Drugs alter a normal metabolic pathway

Anticancer, antiviral drugs
Response to drug
administration


We must carefully weight risk vs benefit!
Allergic reaction


Idiosyncrasy


Hypersensitivity
Effect unique to person; not expected
Tolerence

Decreased response to drug after repeated
administration

Cross tolerence


Tolerence for a drug that develops after
administration of a different drug
Tachyphylaxis

Rapidly occuring tolerance to a drug


Decongestants, bronchodilators
Cumulative effect

Increased effectiveness when a drug is given in
several doses

Drug dependence


Drug interaction


Effects of one drug alters response to another drug
Drug antagonism


Pt becomes accustomed to drug; will suffer
withdrawal symptoms
Effects of one drug blocks response to another drug
Summation

Additive effect; two drugs that both have same effect
are given together

Synergism


Potentiation


Two drugs that have the same effect are given
together and produce a response greater than the
sum of their individual responses
One drug enhances the effect of another
Interference

One drug affects the pharmacology of another drug
Drug response
relationship

Plasma level profiles


Onset of action


Length of onset, duration, termination of action,
minimum effective concentration and toxic levels
A medication reaches it’s minimum effective
concentration
Minimum effective concentration

Level of drug needed to cause a given effect

Duration of action


Termination of action


Time from when a drug drops below minimum
effective concentration until it’s eliminated
Therapeutic index


How long the drug remains above it’s minimum
effective concentration
Ratio of a drug’s lethal dose for 50% of population to
its effective dose for 50% of population
Half-life

Time the body takes to clear one half of the drug
What alters drug response?








Age
Body mass
Sex
Environmental
Time of administration
Pathologic state
Genetic factors
Psychological factors
Case # 3

You are dispatched to a report of a 30 y/o
male not breathing. You arrive on scene to
find a male, wt ~ 150 lb, supine on the
sidewalk outside REI. Bystanders tell you
he just sat down, and then slumped over
about 2 minutes pta. He is unresponsive,
apneic, and has a carotid pulse. His pupils
are pinpoint, and his skin is warm, pale,
cyanotic at lips and nailbeds.



What is your DDX?
As you continue your assessment,
you notice fresh needle tracks on
his arms.
What is happening?

Your treatment of choice includes:








Oxygen via BVM
ecg
Naloxone, IV or IM
ET if no response
Restrain and transport
CBG enroute
Repeat Naloxone
Thiamine if available



What do you think his
prognosis is?
What does Naloxone do?
What is it’s half-life?


Why is this important?
Why do you want to assess
his CBG?
Be cautious – know when to be
aggressive!

Once you’ve
given a drug,
you can’t take
it back – make
sure you’re
right!

Using your field-guide, Drug book, and a
PDR for information –
GROUP EXERCISE!
The nervous system master
system


Makes thought and movement possible
Axons and dendrites are the wiring – neurons
send and receive messages




Axons carry messages from neurons
Dendrites receive messages
Neurons produce chemical messenger
molecules and secrete them into the synapse
Neurotransmitters lock onto receptors on
dendrites of neurons upstream or downstream
The nervous system master
system, cont.

Neuronal communication is based on the
shape of neurotransmitters and receptors


Key & lock – must fit receptor sites
Insertion of neurotransmitter sets off a chain
reaction;



Sodium and chloride outside the membrane enters
the cell through channels
Potassium exits the cell through its channel
= wave of energy; at the end of the energy sweep,
calcium enters axon and pushes neurotransmitters
out of their storages into other synapse
Spinal cord

Most primitive structure of nervous system



Carries messages back and forth
Also contains reflex arcs – pain response
Under control of brain stem, cerebellum,
basal ganglia, & cerebral cortex.
The brain stem


Tops off spinal cord and sends messages to
provide most basic functions; breathing,
vasoconstriction, cardiac action
Reticular activating system rises up from brain
stem


Rouses us into consciousness
Limbic system

Acts as gatekeeper of memory

Food, sex, fight & flight
The brain stem, cont.



Twin hippocampal structures are
responsible for encoding new memory
Amygdalae – on each side of the limbic
system; react to threatening stimuli with
fear
The thalamus – in the center of the limbic
system; aids in memory – stores memory
for ~ 3 yrs, then other structures take over
The brain stem, cont.

Hypothalamas – monitors and controls
hormonal activities




Maternal bonding, etc
Oversees endocrine functions
Serves as connection between mind and
body
Cortex – wraps around limbic structures


Rises up from thalamus & is folded &
wrinkled
Conscious control over movement, sensory
interpretation, speech, cognitive function


Prefrontal lobes – anticipate the future, make
plans, realize our mortality
The cerebellum


Under cortex
Source of athletic grace
The sensory (peripheral) system

Sends constant information back to brain

I.e., pressure, position, temperature
The motor system

Somatic system



Long single axons to specific skeletal muscles
Can override the autonomic system
Autonomic system




Controls vegetative function
Divides into sympathetic & parasympathetic systems
Uses two neurons – preganglionic neurons &
postgangleonic neurons
Sympathetic & parasympathetic systems are a TEAM