Lecture 3 Flashcards
pharmacology includes ___ and ___
pharmacokinetics (body on the drug) and pharmacodynamics (drug on the body)
___ is the study of the uptake, distribution, metabolism, and excretion of drugs in the human body
pharmacokinetics
includes uptake, distribution, metabolism/biotransformation, and elimination
what is uptake, and what are the different types?
- represents a drug’s entry into the body
- enteral - GI (pills, capsules, tablets) and PO (nitroglycerin and oragel)
- parenteral - IM, IV, subcutaneous (insulin and morphine)
- topical - topical lidocaine, nicotine patches
how do LAs affect the vasoactivity on local vasculature?
- most LAs are vasodilators
- amides produce relative vasodilation
- esters produce potent vasodilation
which local anesthetic is the most potent vasodilator and what is it used for?
procaine is used to reverse the effects of hypoxia and necrosis; it reverses the affects of intra-arterial injections
what are some things that intra-arterial injections can cause?
might have slurred speech, muscle twitching, increase in pulse and BP, CNS depression, headache, dizziness, blurred vision, ringing ears, drowsiness, numb feeling, and the patient may possibly go unconscious
which nerve block is most likely to be accidentally given intra-arterially?
IA
what vasoactivity affect does cocaine have on local vasculature?
initially causes vasodilation, then intense and prolonged vasoconstriction
can cause nasal septum perforation due to hypoxia and tissue necrosis
describe the rate of absorption of LAs in the blood stream
- dependent on the route of administration
- oral route is poorly absorbed - goes into GI tract
- topical route varies in rate of absorption - dependent on type of tissue
what is first pass metabolism?
drug passes through the liver
why is it that the area in the bloodstream where the injection was placed will not be numb?
because the anesthetics will be traveling away from this site
once absorbed, the drug is distributed through the body to all tissues. what are the highly perfused tissues (aka higher initial levels)?
brain, kidneys, liver, lungs, spleen, skeletal muscle
___ is the largest tissue type that has the highest percent (highest potential for being overdosed)
skeletal muscle
blood levels depend on what 3 things?
- rate of cardiovascular absorption
- rate of distribution into tissues - can affect the toxicity of the drug; occurs faster in healthy patients as opposed to those who are medically compromised
- elimination - half life = time necessary for 50% reduction in blood level
what is a half life, and how do you calculate it?
- time necessary for 50% reduction in blood levels
- 1 half life = 50%
- 2 half lives = 75%
- 3 half lives = 87.5%
- 4 half lives = 94%
- 5 half lives = 97%
- 6 half lives = 98.5%
how is the blood brain barrier affected by LAs?
- all LAs cross it readily
- important in the process of CNS effects of systemic toxicity
how is fetal/placental blood barrier affected by LAs?
- all LAs readily cross it
- once crossed, local anesthetics enter fetal circulatory system
- presumably distributed to fetal tissues
- systemic toxicity
how do esters affect biotransformation/metabolism?
- hydrolized in plasma by pseudocholinesterase (hydrolized to PABA)
- rate of hydrolysis impacts systemic toxicity
- faster hydrolysis = less toxic
- slower hydrolysis = more toxic
- longer it takes for a drug to be excreted = greater chance of toxicity
how do amides affect biotransformation/metabolism (complex hepatic process)?
- complex hepatic process (liver metabolism)
- lidocaine, mepivocaine, bupivocaine, and etidocaine = liver only
- prilocaine = primary metabolism in the liver with additional metabolism in the lungs
- articaine = contains an ester and an amide, so metabolizes in plasma and liver
how do amides affect biotransformation/metabolism (compromised liver function)?
- compromised hepatic function leads to problems metabolizing LAs
- normal liver function - 70% undergoes hepatic metabolism
- compromised liver function - less than 70% undergoes hepatic metabolism
- increased risk of systemic toxicity and complications
what is the toxic metabolite that prilocaine produces, and what can is cause?
produces orthotoludene, which induces the production of methemoglobin, which causes methemoglobinemia
what are the implications if a person has compromised kidney function (renal dysfunction)?
- kidneys are responsible for excretion and elimination, so a person with compromised kidney function cannot eliminate the drug
- causes elevated blood levels and an increased potential for toxicity
- these patients are usually an ASA 4 or 5
- this is worse than compromised liver function
T or F:
some LAs are excreted and eliminated completely unchanged
true
the percent varies by drug
describe the systemic actions of local anesthetics
- reversibly blocks action potentials
- concentrates in highly perfused organs
- CNS effects
- cardiovascular effects
what are the systemic actions of LAs on the CNS?
- convulsions - higher LA doses that can cause toxicity can also cause tonic klonic convulsions (aka seizures)
- anticonvulsions
- analgesia
- euphoria
- lower blood levels, non-toxic therapeutic doses do not cause these effects
what are the systemic actions of LAs on the cardiovascular system?
- decreased electrical excitability of myocardium
- decreased conduction rate
- decreased force of contraction - helps treat dysrhythmias
___ is the only LA that consistently produces vasoconstriction; all the others are vasodilators
cocaine
vasodilation leads to increased ___
dispersion - away from the site of injection
what is the implication of a patient with malignant hyperthermia being given an LA?
- malignant hyperthermia is a genetic disorder in which the patient response to certain drugs is altered
- when given LAs, the malignant hyperthermia patients cardiovascular system will basically collapse
___ are drugs that constrict blood vessels
vasoconstrictors
what are the benefits of vasoconstrictors?
- decreased tissue perfusion
- decreased cardiovascular absorption
- decreased potential for toxicity (due to lower blood levels)
- increased duration of action (because LA stays where it is)
- increased hemostasis
why are vasoconstrictors compounded with LAs?
to keep the LA where you inject it (as opposed to it traveling throughout the bloodstream)
describe the structure of vasoconstrictors
- sympathomimetic - chemical structure closely resembles sympathetic nervous system mediators like epinephrine and norepinephrine
- catechols - benzene with two hydroxyls (no amine group)
- catecholamines - attached to aliphatic side chain (has amine group)
what is the mode of action of vasoconstrictors?
- direct acting (exerts action directly on adrenergic receptors) - epinephrine, norepinephrine, levonordefrin
- indirect acting (releases NE which binds to receptors) - tyramine, amphetamine, methamphetamine
- mixed - ephedrine
adrenergic receptors are found in most tissues. what are the two types?
- alpha - contraction of smooth muscle and blood vessels
- alpha 1 - excitatory post synaptic receptors
- alpha 2 - inhibitory post synaptic receptors
- beta - relaxation of smooth muscles (vasodilation and bronchodilation) and cardiac stimulation (increased HR and strength of contraction)
- beta 1 - found in heart and small intestines
- beta 2 - found in bronchi, vascular beds, and uterus; produces bronchodilation and vasodilation
dilution of vasoconstrictors is referred to as a ___
ratio (1:1000)
1:1000 = 1 gram (1000mg) of drug (solute) in 1000ml of solution
same as 1000mg in 1000ml or 1.0mg/ml
in dentistry, more diluted forms are needed
what is the concentration of epinephrine (emergency medicine - IM/SC anaphylaxis)?
1:1000
what is the concentration of phenylephrine?
1:2500
what is the concentration of epinephrine (emergency medicine - IV/ET cardiac arrest)?
1:10,000
what is the concentration of levonordefrin - local anesthetic?
1:20,000
90micrograms per cartridge (1.8ml)
what is the concentration of norepinephrine - local anesthetic?
1:30,000
75micrograms per 2.2ml cartridge
what is the concentration of epinephrine - local anesthetic?
1:50,000; 36micrograms per 1.8ml cartridge
or
1:100,000; 18micrograms per 1.8ml cartridge
or
1:200,000; 9micrograms per 1.8ml cartridge
or
1:400,000; 4.5micrograms per 1.8ml cartridge
patients with heart issues and thyroid issues should not be given which anesthetic?
epinephrine causes intense vasoconstriction - increase in blood pressure
what are safety concerns of vasoconstrictors?
cardiac output, stroke volume, blood pressure, heart rate
is epinephrine water soluble?
yes
what is added to epinephrine to increase the stability?
sodium metabisulfite (acidifies solution - process of acidification)
what is the shelf life of epinephrine?
18 months for epinephrine and epinephrine-containing drugs
what is the source of epinephrine?
- natural - harvested from adrenal medulla of animals (80% of medullary secretions are epinephrine)
- synthetic - can be created in a laboratory
what is the mode of action of epinephrine?
acts directly on alpha and beta receptors - the beta effects are more prominent
what are the systemic actions of epinephrine?
- myocardium - beta 1 receptors
- pacemaker cells - beta 1 receptors
- coronary arteries - produces dilation
- blood pressure - beta 2 sensitivity
epinephrine increase what 6 cardiovascular functions, and what is the cumulative effect?
- systolic and diastolic, cardiac output, stroke volume, heart rate, strength of contraction, myocardial oxygen consumption
- cumulative effect is a decrease in cardiovascular efficiency
the effects of epinephrine on the cardiovascular system can be see with as little as ___ carpules of local anesthetic
2
each 1.8ml carpule is 18mcg of vasoconstrictor, so in two carpules, there will be 36mcg of vasoconstrictor
what are the hemostatic effects of epinephrine?
- vasoconstrictive action can provide secondary hemostasis
- not permanent; vasculature returns to normal as epinephrine levels decrease
what are the effects of epinephrine on the respiratory system, CNS, and metabolism?
- respiratory - B2 (bronchodilation)
- CNS - effects can occur at excessive doses
- metabolism - glycogenolysis
describe the termination of action and elimination of epinephrine
- reuptake
- catechol-O-methyltransferase and hepatic MAO inactivate what is not taken up
- urinary excretion
what are the side effects of epinephrine?
CNS stimulation, restlessness, throbbing headache, tremor, weakness, dizziness, pallor, respiratory difficulty, palpitation, cardiac symptoms
what are the clinical uses in medicine of epinephrine?
anaphylactic shock, status asthmaticus, cardiac arrest, hemostasis, decreased absorption of LA in cardiovascular system, increase depth and duration of anesthesia, pupillary dilation
what is the dosage and max dose of epinephrine?
- dosage - 18ug/cartridge (1:100,000)
- max dose
- healthy = 0.2mg or 200ug/appt
- compromised = 0.04mg or 40ug/appt
when considering giving your patient epinephrine, what things do you want to look for in the patient assessment?
- risk to all - significant for ASA 3, 4
- cardiovascular disease, MAOI, TCAs, thyroid problems, diabetes, sensitivity to sulfites (not same as sulfa allergies), patients with resting BP of 200/115
in assessing whether or not to use epinephrine on your patient, what is the risk assessment for the following conditions:
acute MI/damage, angina at rest, dysrhythmias with refraction, hyperthyroid, MAOI, TCA
- acute MI/damage, angina at rest, dysrhythmias w/refraction, and hyperthyroid = high risk
- MAOI and TCA = moderate risk
what are the overall benefits of using epinephrine?
- slower rate of systemic absorption
- lower systemic blood levels
- prolonged duration of anesthesia
- more profound anesthesia
- lower risk of systemic toxicity
