Pharmacology Semester 2 > Anesthetics > Flashcards
Anesthetics Flashcards
Ester local anesthetics
cocaine, procaine, oxiprocaine, propoxicaine, chlorprocaine, benzocaine, tetracaine,piperocaine,butacaine,meprilcaine,izobucaine, monocaine
Amide local anesthetics
lidocaine, mepivacaine, bupivacaine, hostacaine, cincocaine, articaine, prilocaine, etidocaine, centabucaridine
Local anesthetics mechanism
drugs that produce a temporary loss of pain, local anesthetics block reversible CNS and PNS conduction in a circumscribed area of body; act locally after reach blood concentration @ admin site is decreased and psychodynamic effects also diminished, etc read.
Cocaine was the
first local anesthetic
Lidocaine
Lidocaine is the first amino amide-type local anesthetic and was first synthesized under the name Xylocaine, first marketed in 1948.
Procaine
ester of para-aminobenzoic acid (metabolized by plasma esterase’s); onset of 6-10 min, excreted in urine as unchanged 2%; CI in children under 7, shock, hypotension, hepatic/renal disorders; AE: low toxicity (2x less than lidocaine), high allergenic risk (needs to be tested on PT before use), potency low (4x less than lidocaine), anti arrhythmic, vasodilator (arteriolospasm), anti-aging and low anti spastic action
Mepivicaine
Mechanism of action
like Lidocaine amide, but without vasodilator properties.
Pharmacokinetics
somewhat longer (20%) duration of action than Lidocaine .
Contraindications
not used in obstetrics since “trapped” in neonatal circulation due to lower pH of neonatal blood and hence greater potential for toxicity.
Adverse effects
low toxicity;
low allergenic risk.
Bupivacaine
amide with 2x longer duration than Lidocaine, greater cardio toxicity than Lidocaine due to slow dissociation from cardiac sodium channels in diastole, high toxicity, produces large vasodilation (bleeding during surgery thar Epinephrine cannot solve).
Tetracaine
prolonged duration of action due to slow ester hydrolysis, CI not in peripheral nerve blocks due to prolonged duration of action and potential for toxicity, high toxicity, significantly more potent than procaine, spinal anesthesia 1%,2% Tetracaine sol.
Prilocaine
Biotransformed in liver, lungs, kidney to toluidine and capable of causing methemoglobinemia; CI:methemoglobinemia, anemia, pregnancy, AE: very low toxicity
Inhalation (gaseous) anesthetics
halothane, isoflurane, enflurane, sevoflurane, methoxiflurane, desflurane
Inhalational analgesic
nitrous oxide
IV agents - antianxiety - benzodiazepines
midazolam, diazepam
IV agents - sedative/hypnotics - barbiturates
sodium thiopental, thiamylal sodium
IV agents - anesthetic agents
propofol, etomidate
IV agents - neuroleptic agent
droperidol
IV agent - dissociative agent
ketamine
IV Agent. - narcotic analgesic
Fentanyl
Nitrous oxide
Nitrous oxide is a widely used inhalation anesthetic agent, a colourless, odourless and not inflammable gas
Pharmacokinetics
due to limited solubility in blood, nitrous oxide has rapid onset and offset of effects;
increased pressure in “closed” compartments:
Nitrous oxide diffuses over 30 times more rapidly than oxygen;
preferential transfer leads to increased volume or pressure in air-filled cavities (due to 2nd gas effect);
increases in volume of pneumothorax, tympanic membrane rupture and increased gastric volume/pressure have been reported.
Adverse effects
at doses used for sedation: relaxation, body warmth, auditory effects and euphoria;
at high doses: dysphoria, nausea and vomiting;
studies have demonstrated that women exposed chronically to high levels of nitrous oxide (due to lack of scavenging of expired gasses) have decreased fertility.
Therapeutic notes
weak anesthetic agent with a short induction and a duration of action for about 20–30 minutes;
analgesia occurs with inspired concentrations of 20% and is used clinically in concentrations up to 70%;
it is used most often in combination with either IV or inhalational anesthetic agents to reduce potential cardiovascular effect of anesthetic;
in high concentrations 80% or more produces anesthesia and severe hypoxia and its unsuitable for use as a sole anesthetic agent;
it is mixed with 20% oxygen (the mixture has little or no effect on the cardiovascular and respiratory system).
Nitrous oxide has no significant effects on the respiratory, hepatic, renal, autonomic nervous systems and does not usualy produce any clinically significant cardiovascular effects.
Halothane
Pharmacodynamic effects
cardiovascular effects of Halothane:
affects both, the heart and peripheral circulation in a concentration-dependent manner;
hypotension;
decreases contractility and cardiac output;
changes in cardiac rhythm and conduction can occur with administration of inhalational anesthetic agents;
depresses the pacemaker activity resulting in sinus bradycardia (increased vagal tone) and A-V nodal rhythm;
sensitizes the heart to catecholamines and can produce premature ventricular contractions;
respiratory effects of Halothane:
depressed respiration;
bronchodilatation;
CNS effects of Halothane:
vasodilation on central vessels with increased central blood flow and increased CSL pressure;
produce an irregularly descending depression of the central nervous system;
renal effects of Halothane:
decreased renal blood flow and decreased glomerular filtration;
hepatic effects of Halothane:
decreased liver function;
“Halothane hepatitis” appears in two to five days after administration; the patient becomes pyrexic and complains of nausea and vomiting; the incidence is 1 in 7000 patients; death occurs in half of these patients;
these effects don’t appear in children;
precautions should be used in patients with hepatic disease and those previously exposed to Halothane;
muscular effects of Halothane:
relaxation appears in children and the uterine muscles.
desflurane
DESFLURANE
Pharmacodynamic effects
cardiovascular effects of Desflurane:
rapid increases in anesthetic concentration produces apparent activation of the sympathetic nervous system resulting in increased heart rate and HBP and that limits some use of Desflurane;
respiratory effects of Desflurane:
increased incidence of airway irritation (laryngospasm, coughing etc.) when it is used as a single anesthetic agent, especially during induction;
recent studies have demonstrated that carbon monoxide forms from the reaction of Desflurane with the material which absorbs CO2 in the anesthetic circuit; the amount of carbon monoxide formed depends upon the temperature and moisture of the material; there have been reports of patients experiencing a significant increase in carboxyhemoglobin with Desflurane.
GI effects of Desflurane:
incidence of nausea and vomiting is quite variable from patient to patient, and depends to some extent on the length of anesthetic administration.
Therapeutic notes
it has low solubility in blood which results in rapid onset and recovery;
it is not indicated for the induction of anesthesia especially in pediatric patients and patients with heart dissease.
Enflurane
depressant effects on blood pressure and myocardial contractility, same effects as halftone on organ systems, most respiratory depressant at low anesthetic concentration, high clinical concentration with hypocapnia associated with development of grand Mal seizures in small percentage of patients, not used much anymore, less potent than halothane, maintenance of anesthesia in adult patients
Isoflurane
same effect as halothane on organ systems, less hepatotoxic than others, more potent than enflurane, rapid induction of anesthesia
Methoxiflurane
AE: hypotension, depressed cardiac function, hepatotoxicity, nephrotoxicity; long induction of anesthesia, analgesic effects a couple;e of hours, produces muscle relaxation (doesn’t affect uterus)
Midazolam, diazepam
IV agents, (Benzodiazepines) are most useful during diagnostic studies (endoscopy); Midazolam (water soluble) and diazepam are used to produce sedation; combination of these drugs and regional anesthesia, nitrous oxide, or potent narcotic can produce effective clinical anesthesia.
Sodium thiopental
AE: decreased blood pressure and increased HR, irritating to tissues; CI: used in head and neck surgery because of hyperreflexitivity of carotidian sinus
Propofol
Pharmacodynamic action
cardiovascular effects of Propofol:
hypotension, reduced systemic vascular resistance;
infusions of Propofol have produced a 15-30% reduction in various cardiac indices (cardiac output, stroke work, stroke index).
respiratory effects of Propofol:
dose-dependent depression of respiration with possible apnea.
Therapeutic notes
induction of anesthesia is rapid and comparable to Thiopental;
maintenance of anesthesia can be achieved with either continuous IV infusion or intermittent bolus injections;
regional anesthesia, Nitrous oxide or potent narcotics are required to provide analgesia;
induction and recovery is rapid with less “hang over” compared to Thiopental.
Etomidate
involuntary muscle movement and tremors, dose dependent respiratory depression can occur and cause apnea, after continuous infusion can cause marked adencortical suppression for as long as 4 days after discontinuation, postoperative nausea and vomiting, least effects on CV system, rapid onset of sleep lasting 7-14 minutes, lacks analgesic properties
Droperidol
can cause cataleptic immobility, patient appears to be in a tranquil, trance like state free from pain and dissociated from surroundings, droperidol is not an analgesic alone, alpha adrenergic blockade can reduce PVR and produce hypotension at higher dosages
Ketamine
produces cataleptic trance-like state, patient may be awake with eyes open and profound analgesia, increased BP, increased HR, increased CBF and intracranial pressure, little respiratory depresseion and pharyngeal and laryngeal reflexes maintained, muscle tone frequently increased. I” any settings where painful procedures performed (burn); AE: adults may experience disagreeable dreams and hallucinations days or weeks after administration (controlled with adm of diazepam), relatively rapid acting with return of consciousness in 15 min, complete recovery can be slow.
Anesthetics mechanism of action
they are drugs which produce a temporary loss of pain; the local anesthetic agents block reversible, both central and peripheral nerve conduction, in a circumscribed area of the body; Cocaine was the first local anesthetic identified;
they act locally (after they reach the blood, the concentration at the administration site is decreased and the pharmacodynamic effects are diminished, too): by stimulating large fibre nerve activity, thus blocking the perception of smaller diameter (pain) fibre transmission, by blocking transmission at sensory nerve endings or along nerve fibres and by releasing of pain;
Lidocaine has ventricular antiarrythmic action because it blocks the miocardial sodium channels.
Anesthetics pharmacokinetics
Absorption and distribution is reflected in:
efficacy of local anesthesia as measured by onset, potency (affected mainly by lipid solubility) and duration of anesthesia;
entry and distribution of agent in the systemic circulation to produce toxic effects.
The absorbtion topical local anesthetics depends on the mucosa:
oral mucosa – rapid and short action;
traheal mucosa – rapid absorbtion;
pharyngeal mucosa – low absorbtion;
esophageal mucosa- very low absorbtion;
skin – no absorbtion;
skin with lesions-absorbtion.
A number of factors influence the absorption and distribution of local anesthetic agents:
dosage and volume of injectate;
site of injection;
local blood flow; highly perfused organs such as the brain, liver, kidneys are capable of receving high levels of local anesthetics; they will cross both the BBB and the placenta;
local anesthetic formulation;
physicochemical and pharmacologic properties of the agent;
protein binding;
Biotransformation:
the ester compounds are esters of para-amino benzoic acid or benzoic acid, by virtue of this structure they are hydrolyzed by plasma cholinesterase (pseudocholinesterase) to water-soluble metabolites that are eliminated by the kidney;
amides are metabolized largely by the liver to water-soluble metabolites which are excreted in the urine; liver disease can significantly reduce the metabolism of amide local anesthetics resulting in a 2-3 fold increase in plasma t1/2;
excretion occurs via the kidney, normally less than 3% of an administered dose of the commonly used dental local anesthetic agents is excreted unchanged in urine; local anesthesia is contraindicated at patients with severe renal problems.
Anesthetic indications
infiltration and nerve block anesthesia, typically used in dental operative setting; surface (topical) anesthesia, used by dentists to pre-numb point of injection; spinal anesthesia, a denser block (blocks all transmission from below) than epidural (inject into subarachnoid space); epidural and caudal anesthesia, blocks the nerve root (injected into epidural space); IV anesthesia (“Bier block”).
Anesthetic adverse effects
although local anesthetics exert their effects largely on a limited anatomical area and are relatively safe (one death per 45 million administrations), absorption into the systemic circulation can occur; toxicity is directly related to blood levels of the local anesthetic; toxic effects due to ability to bind to sodium channels (same characteristic that provides desired effects); the general signs are: CNS stimulation: apprehension, salivation, tremor, convulsions with increasing blood concentrations, HBP and tachycardia followed by hypotension and cardiovascular collapse; treatment for toxicity is symptomatic (restore normal ventilation and circulation) and administration of benzodiazepines (midazolam, diazepam) used to treat the CNS effects; neurotoxicity occurs with placement of the local anesthetic in the epidural or subarachnoid space; transient numbness, radicular irritation of the lumbosacral nerves or myotomal weakness have been reported; permanent neurologic injury after regional anesthesia is more rare;
allergic reactions after ester type (e.g. Procaine) local anesthetics; bronchospasm and anaphylaxis have been reported.
Therapeutic notes
anesthetics are not adm. inhalationally, orally, or IM. the intensity of the anesthetic action depends directly on the concentration of the anesthetic sol.; for an anesthesia of a small territory, a small concentration is sufficient; for an anesthesia of a big territory, a higher concentration is necessary;
the duration of action of local anesthetics depends on: the bounding to plasma proteins, the dose and the vascularity of the tissues. A vasoconstrictor drug is added to prolong the action of the local anesthetic with 30 – 40%: Epinephrine 1/200.000; 1/20.000, Fenilephrine, Naphazoline;
an ideal local anesthetic should:
have a rapid induction;
have a suitable duration of action;
be efficient;
be chemically stable and sterilizable;
have a specific and reversible action;
produce no permanent damage;
produce muscle relaxation;
be able to be administered with other agents (vasoconstrictors) without loss of properties;
have no systemic toxicity;
be non-irritant;
have a high therapeutic ratio;
be active topically and by injection;
be non-allergenic;
be non-addictive.
advantages of local anesthesia:
easy to be administered;
the duration of action of local anesthetics can be prolonged by repeteaning the administration;
less bleeding (if the local anesthetic is associated with a vasoconstrictor);
less contraindications;
maintenance of the cooperation with the patient.
cardiovascular disease may lower the threshold for cardiac toxicity of local anesthetics;
concomitant therapy with drugs that inhibit myocardial impulse propagation (β-blockers, digitalis, calcium channel blockers) may also lower the threshold for cardiac toxicity.
Lidocaine pharmacokinetics
it is highly lipophilic and is rapidly absorbed; the absorbtion depends on the vascularity of the tissues;
it is metabolized in liver (70%); hepatic disease or decreased hepatic blood flow decreases metabolism; onset of action is about 0.8 – 2 min;
negligible amounts of unchanged drug (10%) are excreted in the urine; the excretion is done rapidly in the first hours after administration.
Lidocaine indications
local anesthesia;
pain: small doses (~ 3 mcg/ml) in central pain and medium doses (more than 3 mcg/ml) in peripheric pain;
to prevent bronchoconstriction (IV and inhalatory administration);
ventricular arrhythmia;
convulsions (at small doses).
Lidocaine contraindications
severe hepato-renal disorders; epilepsia (convulsive states;) bradycardia; A-V block; HBP; fever. contraindications of the association Lidocaine plus Epinephrine: arrhythmia, malign HBP, uncontrolled diabetes mellitus and glaucoma.
Lidocaine adverse effects
the toxicity is big (two times higher than Procaine’s);
the allergic risk is low.
Lidocaine therapeutic notes and preparation
the potency is high (four times higher than Procaine’s);
efficient in parenteral administration (less efficient after topical administration);
effective topically and also parenteral as an antiarrhythmic agent;
intrinsic vasodilator properties;
preparations: Lignocaine, Xilocaine, Xiline, Xylestezin, Astrocaine, Octacaine, Novocol, Nuracaine, Xylonor
gel 2%, 5%
sol. 4%; 5% for topical use
aerosol 10%
Lidocaine 0,5%, 1% vials 2 ml, 10 ml for: infiltration anesthesia, plexal anesthesia, regional block anesthesia, ventricular arrythmia: IV 1,5 mg/kg body weight (150 mg) or drip 2 – 4 mg/min and prophylaxis of intracranian hypertension IV 1,5 mg/kg body weight;
Lidocaine 2% vials 2 ml plain sol. or sol. 2% with 1:100.000, 1:50.000 epinephrine for: infiltration, introserrous, intraligamentary and regional block anesthesia, local anesthesia in dentistry, spinal anesthesia and anesthesia in oftalmology;
Lidocaine 4% vials 2 ml, 20 ml for: topical anesthesia, epidural block;
Lidocaine 5% with 1:80.000 Epinephrine.
General anesthetics mechanism and pharmacodynamic action
they produce a fully reversible block of the CNS function at therapeutical doses;
the effects are amnesia (loss of memory), sedation/loss of consciousness, analgesia (loss of pain), hyporeflexia (sensory and autonomic) and muscle relaxation.
Gen anesthetics pharmacokinetics
kinetics of onset and offset of anesthesia depends upon the rate of change of concentration of inhalational agent in each of the various compartments: inspired concentration, alveolar concentration (minimal alveolar concentration = MAC), blood concentration and tissue (brain) concentration; the rate of onset of (and recovery from) anesthesia depends upon the speed with which equilibration occurs in each of the compartments; for each agent, the depth of anesthesia depends upon the concentration of anesthetic agent in the brain;
hepatic metabolism varies with agent:
minimal biotransformation occurs with Isoflurane, Desflurane and Nitrous oxide;
approximately 2-5% of administered Sevoflurane is metabolized and 20% of Halothane.
Consequences of metabolism:
Halothane is metabolized to intermediates that react with hepatic cellular proteins;
Enflurane (a previously used agent) and Sevoflurane metabolism results in the release of fluoride and increases serum fluoride levels;
Methoxyflurane is no longer used because of extensive hepatic and renal biotransformation (up to 70%) with the release of fluoride which produces nephrotoxicity.
Elimination:
most agents eliminated quantitatively in expired gasses;
metabolites and organic/inorganic fluoride eliminated by kidney.
gen anesthetics therapeutic notes
characteristics of an ideal anesthetic agent:
to provide a smooth and rapid induction;
to produce a state of unconsciousness or unresponsiveness;
to produce a state of amnezia;
to block a number of reflexes that might lead to bronchospasm, salivation, arrhythmias;
to produce muscle relaxation (not of the respiratory muscles);
to block the conscious perception of sensory stimuli;
to provide a smooth, rapid recovery with no long – lasting adverse effects.
premedication agents are defined as the administration of drugs before an anesthetic with a view to faciliting the operation and anesthesia; they diminish the anxiety, provide analgesia, some degree of postoperative amnesia and they reduce the adverse effects of the anesthetic agents and their doses (hypersalivation, arrhythmya):
barbiturics: Secobarbital, Pentobarbital;
opioids: Morphine, Phentanyl, Alphentanyl;
phenothiazines: Promethasine;
benzodiazepines: Diazepam;
anticholinergic drugs: Atropine, Scopolamine.
Sodium thiopental therapeutic notes
it is the most used barbituric agent for general anesthesia for short operative procedures;
it has rapid induction, of about twenty seconds and the anesthesia lasts for twenty minutes;
because of the incomplete muscle relaxation, it has to be administered togheter with a nondepolarizing muscle relaxant;
because of the weak analgesic effect, it needs to be associated with an analgesic agent;
it is an induction agent but it may also be used for maintenance in relatively short procedure or to treat seizure or elevated intracranial pressure.
