Surgery Pharmacology

Isoflurane blood:gas partition coefficient

1.4; The alveoli need to be 100% full and the blood stream 40% more than that to meet MAC. Has a longer recovery time bc it is the only one where the alveoli must be full and on top of that have 40% more in the blood to reach MAC- therefore it relies solely on the drug being in the BLOOD.

Lidocaine (local anesthetic)

Works outside the cell; redistributes to tissues within minutes of being given IV and has a high affinity for fat cells/is bound to plasma proteins (caution: OD). Short acting. Lidocaine with epinephrine should never go IV (epinephrine acts as a vasoconstrictor/decreases bleeding/keeps lidocaine in the same vicinity. Makes it last longer)! Acidic- can be mixed with sodium bicarb to reduce pain (use caution-don't make too alkaline). Only used for ventricular tachycardias

Metronidazole

Abx used perioperatively; broad spectrum drug w good anaerobic action. Can treat giardia and act as anti-inflammatory. Used for diarrhea after FB sx. IV can be given q8-12hrs, but must be given over 15-20 mins or can cause toxicity (neuro signs). Dosage: 5-25 mg/lb

Clindimycin

Abx used perioperatively; lincosamide, very effective against anaerobes. Most common PO/IV med used in dentistry; IV diluted and used at time of sx, PO given for infected teeth. Side effect is C.Diff. Do NOT refrigerate after reconstituting. Dosage: 11-33 mg/kg

Sedatives

Alpha-2 adrenergic agonists are sedative analgesics, although poor analgesics. The analgesia will wear off before the sedation does. Due to this, a sedated patient is completely capable of responding violently to painful stimuli. These drugs better control visceral pain as in colic in horses, versus somatic pain. Produces CNS mediated skeletal muscle relaxation. Can still have effects on alpha 1 receptor (side effects). Many cause AV block- caution w heart disease

Guaifenesin

An expectorant/central acting muscle relaxant used primarily in horses for pain management of muscles and used in their induction anesthetic protocol. Very little to no respiratory depression. May increase heart rate. Short acting drug sometimes used for maintenance anesthesia as part of a CRI. Horse - 110 mg/kg IV Push the first ½ over 20-30 seconds until the horse falls and then give the remainder. Cattle - 55-110 mg/kg IV

Calcium Gluconate (for hyperkalemia)

Antagonizes the cardiac effects of hyperkalemia without altering the plasma concentration of potassium. Ca++ stretches the time between depolarization/repolarization of heart- can cause bradycardia. Should be given over 10-20mins at 50-100mg/kg while EKG is monitored.

Atropine (as an anesthetic adjunct)

Anticholinergic/Parasympatholytic; Competitively block acetylcholine at the muscarinic receptors. Commonly used to prevent and treat bradycardia and decrease salivary secretions. Derived from deadly nightshade; lasts 60-90mins. Can cross the blood brain barrier which can produce some sedative effect. Dosage as an adjunct 0.01 mg/kg IV,IM,SQ

Glycopyrrolate (as an anesthetic adjunct)

Anticholinergic/Parasympatholytic; Synthetic quaternary ammonium compound, lasts about 2-3 hours. Can not cross the blood brain barrier. Glycopyrrolate dosage as adjunct - 0.011 mg/kg IV,IM,SQ

Anesthetic Agent

Any drug used to induce a loss of sensation with or without unconsciousness.

Bupivacaine (local anesthetic)

Blocks the sodium channels intracellularly which is why it can be so toxic. Should NEVER be given IV-can cause cardiac arrest if done so. Longer acting than lidocaine, lasts 4-6 hours, but onset takes about 20 minutes. This is why they are commonly mixed together. Toxicity has the same signs as lidocaine, but at much lower doses. Do not exceed 2 mg/kg in dogs, 1 mg/kg in cats

What are the goals of preanesthetics?

Calm or Sedate (reduce anxiety= tranquilizers), minimize adverse side effects of other drugs administered, reduce the required dose of drug, produce a smoother anesthetic induction and recovery, decrease pain and discomfort before, during and after surgery, & finally produce muscle relaxation

Sedative

Calming or sleep inducing effect.

What can be used if local anesthetics are overdosed?

Can use intralipids to help the drug come back to the circulatory system because it is seeking fat and then it binds to the fat emulsion. (bupivicaine and lidocaine are both highly lipophillic)

Ketamine

Dissociative Anesthetic (cyclohexamines); NMDA receptor antagonist (takes away the memory of pain/increases pain threshold). Used alone to immobilize a patient or in combination w opioids/ tranquilizers to induce and maintain anesthesia. Increases HR and BP. May cause apneustic breathing or respiratory depression. Can cause seizures/hypersalivation/holding eyes open in cats, and malignant hyperthermia in different species. Good for wind up pain. Metabolized by liver and excreted in urine

Tiletamine (Telazol)

Dissociative Anesthetic (cyclohexamines); Not a drug that is sold by itself; part of the drug called Telazol mixed with zolazepam which is a benzodiazepine tranquilizer. Used as a short-acting anesthetic in which only a moderate amount of analgesia is required due to the dissociative. Dosage - Dogs/Cats 3-10 mg/kg IM or SC, 2-5 mg/kg IV

Analgesic

Drug that relieves pain.

Preanesthetics

Drugs given before inducing general anesthesia.

Induction

Drugs used to induce general anesthesia.

Maintenance

Drugs used to maintain general anesthesia.

flumazenil (Romazicon)

Emergency sx drug; Benzodiazepine antagonist (reverses diazepam and midazolam). Half life is similar to naloxone, so it will need to be redosed. Dosage: 0.01 mg/kg IV

furosemide (Lasix)

Emergency sx drug; Loop diuretic works on the loop of henle by blocking the reabsorption of sodium and chloride. Water follows Na+ out of the nephron to the collection duct and out of the body. Used for patients who have side effects of CHF such as cardiogenic pulmonary edema, ascites or pleural effusion. CHF dose is 2-4 mg/kg q4h IV

naloxone (Narcan) as an emergency drug

Emergency sx drug; Opioid receptor antagonist with the highest affinity for the mu receptor. Used in patients who have had an overdose of an opioid or are having severe cardiac depression while on them. Dosage: 0.04mg/kg IV. Effects only last for 1-2 hours while effects of opioids can last longer- may need to repeat doses

Atropine (as an emergency drug)

Emergency sx drug; anticholinergic. Allows sympathetic NS to take over, blocking acetycholine release from the vagus nerve which in turn increases HR. Emergency dosage is 0.05 mg/kg IV, Bradycardic dose is 0.02 mg/kg IV, Premed dose is 0.01 mg/kg SQ. Concentration? (mg/ml) 1/120gr x 64.8mg/grain = 0.54mg/ml

lidocaine (as an emergency drug)

Emergency sx drug; class 1B sodium channel blocker. Blocks initial sodium influx needed for depolarization. Used for cardiac ventricular premature contractions, NOT supraventricular arrhythmias. Emergency Dose is 2-8mg/kg IV

epinephrine (adrenaline)

Emergency sx drug; sympathomimetic. Works to increase CO by binding to beta 1 receptors and increases peripheral vascular tone by binding to alpha 1 receptors. Emergency dose (low dose) is .01mg/kg IV.

activated Charcoal (Toxiban/UAA gel)

GI drug that should NOT be used perioperatively. It is an adsorbent to prevent absorption of the toxin into the body. Should never be administered into a body cavity (in the case of perforation/FB suspected)

pantoprazole (Protonix)

GI drugs; Proton Pump Inhibitor which has been shown to be more effective IV than famotidine (Pepcid)- histamine 2 blocker- in canines when treating Gastroesophageal Reflux Disease. Given IV 1mg/kg after FB sx SID

maropitant (Cerenia)

GI drugs; antiemetic. Works by inhibiting the neurotransmitter "Substance P" from triggering receptor NK1. Can cause retroperistalsis, contraindicated in FBO. used off-label as a preanesthetic that encourages animals to eat when recovering from anesthesia and provide some analgesia. Has also been found to decrease requirements of anesthetic gas in dogs/cats

ondansetron(Zofran)/dolasetron(Anzemet)

GI drugs; antiemetics classified as 5-HT3 antagonists. Block receptors peripherally (GIT) and centrally (CRTZ). Zofran cheaper/more readily available, both are 1mg/kg IV.

mirtazapine

GI drugs; appetite stimulant in felines (more alpha 2 receptors). Noradrenergic and specific serotonin antidepressant (NaSSA); acts by antagonizing alpha 2 receptors as well as by blocking 5-HT3 (serotonin) receptors. 3.75mg every 3 days

metoclopramide (Reglan)

GI drugs; will help to prevent nausea, vomiting and reflux after surgery. Light sensitive, commonly used as a CRI (2-3mg/kg/day). Antagonist to the D2 dopamine receptors & at higher doses the serotonin receptors in the CRTZ (works better in dogs). Prokinetic activity increases upper GI motility and relaxes pyloric outflow; thus preventing gastric stasis and therefore vomiting

Why is hyperkalemia such an issue with an anesthetic patient?

High levels of potassium cause abnormal heart and skeletal muscle function by lowering cell-resting action potential and preventing repolarization, leading to muscle paralysis.

Factors that increase MAC

Hyperthermia, hyperthyroidism, and use of CNS stimulant

Factors that reduce MAC

Hypotension, hypothermia, pre medications, pregnancy, disease, analgesics, and hypothyroidism.

highly volatile

If something is "Highly Volatile" it is said to have a high vapor pressure.

Isoflurane

Inhalent anesthetic (halogen); Vapor Pressure: 238 mmHg Blood:gas coefficient: 1.4 MAC: 1.3% (canine/equine) 1.6% (feline) Poor analgesic with moderate muscle relaxation. Dose dependent respiratory (equine) and cardiovascular depression. Liver metabolism is very low. Fairly safe for cardiovascular compromised patients.

Propofol

Injectable anesthetic; hypnotic agent. Works directly on GABAA receptor to decrease action potential of the neuronal cell and inhibits NMDA receptor producing an anesthetic effect. Usually given prior to intubation, can be used to stop seizures (but may cause them in sensitive patients). Apnea is common. Irritating to the tissues (must be given IV). Lipophillic; rapidly distributes to tissues and is very short acting. Safe for renal/hepatic patients

alfaxalone (Alfaxan)

Injectable anesthetic; neurosteroid given prior to intubation. Works by binding with the GABAA receptor and allows the chloride channels to open in turn decreasing the action potential of the neuronal cell. Apnea expected. Metabolized by the liver eliminated by both the kidneys and liver, but safe for liver patients. Can be used to stop seizures, wide therapeutic window. SAFE FOR PREGNANT ANIMALS!

Humulin

Insulin (other drugs used perioperatively). Synthesized w a strain of E coli bacteria, which has been genetically altered w recombinant DNA to produce biosynthetic human insulin. Short/intermediate acting. IM: 4-6hrs SQ: 6-9hrs U-100 syringe = 100 U/ml

Insulin (for hyperkalemia)

Insulin uptakes free roaming potassium/glucose in the tissues/blood into the cell. If K+ is not reuptaken by the insulin, it creates elyte imbalances and issues with Na:K pumps. It effects repolarization at the T wave; electrical potential unable to fully reset due to high potassium in the system (taller T wave= more severe). To correct the hyperkalemia, insulin + dextrose can be given together to allow for the translocation of potassium into the cell (given w dextrose so as to prevent hypoglycemia).

Reversal Agents

Lessen or abolish the effects of other anesthetic agents.

Yunnan Baiyao

Nutraceutical; Aids with hemostasis within the body and externally. >2000 mg is an OD and poison control should be called. Said to have liver side effects if overused. Recc'd 100mg/kg every other day or 5 days on 2 days off. Unknown what is in it, kept a secret by Chinese

Silybin A+B

Nutraceutical; a naturally occurring liver protectant found in sunflower seeds. Produced and consumed mainly by liver, it is the bioactive form of methionine (important for biosynthesis of proteins). Found in Denamarin along with SAMe.

Milk thistle

Nutraceutical; contains silymarin and silybin, antioxidants that are known to help protect the liver from toxins, including the effects of alcohol. Also known to have antiinflammatory effects. Given to dogs suspected of having hepatitis due to a toxicity (drugs or otherwise)

S-adenosylmethionine (SAMe)

Nutraceutical; in Denosyl. Increases levels of major antioxidant glutathione (formed from metabolization of SAMe) in the liver, which reduces damage to the liver caused by free radicals and is important to overall liver health. Can also protect liver cells and may help repair/regenerate

Hydromorphone

Opiod; strong agonist. 5x the potency of morphine, works at the mu receptor +/- delta receptors. Many of the side effects as morphine, but less likely to have vomiting. IV injection may cause dogs to defecate. Cats can become hyperthermic after receiving hydro. Dogs - 0.1 - 0.2 mg/kg IV,IM,SQ q2-4h Cats - 0.05 - 0.1 mg/kg IM,IV, SQ q2-4h

Fentanyl Patches

Opiod; strong agonist. Great post op pain management, take 12hrs to begin working and can be left on for 3-5days

Fentanyl

Opiod; strong agonist. Greater potency than morphine (100x), but very short duration or action. Must be delivered as a CRI or patch. Acts on the mu receptors, but not kappa.

Methadone

Opiod; strong agonist. Mu agonist least likely to produce vomiting, but also blocks the NMDA receptor (memory) which depresses activity of parts of the brain reducing stimulation. Psychological pain. Only 3-4x more potent than morphine. Dogs- 0.5 - 1 mg/kg IV,IM,SQ q6h Cats- 0.1- 0.2 mg/kg IV,IM,SQ q6h

Morphine

Opiod; strong agonist. Prototypical drug against whose potency all other opioids are measured. Increased potency means that it takes a lesser dose of drug A to reach the same effect of morphine. Does not have a high efficacy for surgical pain when used alone. IM/SQ admin causes vomiting due to stimulation of dopamine receptors in the CRTZ, which respond more to low doses (v less likely with IV bc levels are made immedietly higher and the CRTZ cannot react d/t being depressed). Strong affinity for the mu receptors and at higher doses can have some activity on the kappa receptors. Dysphoria in cats/horses common

buprenorphine (Buprenex)

Opiods; Partial Agonists (Agonist/Antagonist). Partial mu agonist with moderately strong analgesic properties. It is also a kappa antagonist. Degree of analgesia limited bc of ceiling effect. Less efficacy than morphine but is 30x more potent. Absorbs well sublingually and across mucous membranes. Can come as a 0.3 mg/ml or 0.5 mg/ml concentration. Dosage: Dogs/Cats 0.01-0.02 mg/kg IM/IV/Buccal/SL/SQ q8-12h

butorphanol (Torbutrol/Torbugesic)

Opioids; Partial Agonists (Agonist/Antagonist). Mixed agonist/antagonist w weak partial mu receptor affinity to mu antagonist activity, but has a strong kappa agonist effect. Also has a ceiling effect, but 4-7 times more potent than morphine. Very short duration of analgesia. Used commonly for patients who have CHF or respiratory issues. Can be used with stronger opioids such as morphine to counteract respiratory depression. Good analgesic for horses, esp colic pain

buprenorphine (Simbadol)

Opioids; Partial Agonists (Agonist/Antagonist). SQ injection labeled for use in cats and good for up to 24hrs of pain relief. Can be given for 3-5d. Dosing slightly different than generic buprenorphine d/t formulation. 1.8mg/ml Cats - 0.24mg/kg q24h SQ

Tranquilizer

Reduces tension or anxiety.

Barium

Should NEVER be given on an animal that MAY need sx. Insoluble; cannot be absorbed/excreted by the body if outside the GIT. Can cause granulomatous peritonitis when exposed to the abdominal cavity. May cause aspiration if given prior to sx.

Ceiling Effect

The dose beyond which there is no additional effect of the drug. Higher doses do not provide any additional benefits but may increase the likelihood of side effects and prolong half lives. (mostly when you are speaking of opioids)

zolazepam (Telazol)

benzodiazepines - tranquilizer; Not a drug sold by itself; part of the drug Telazol mixed with tiletamine (a dissociative like ketamine). Metabolized in the liver and excreted by the kidneys. Used as a short-acting anesthetic in which only a moderate amount of analgesia is required due to the dissociative. Dosage - Dogs/Cats 3-10 mg/kg IM or SC, 2-5 mg/kg IV

diazepam (Valium)

benzodiazepines -tranquilizer; Enhances the activity of the GABAA receptor that is located on an excitatory neuron and causes the GABA inhibitory transmitter to bind more tightly which opens the chloride channels and decreases the action potential of the cell. Does not allow for excitatory stimulation of neurons; produces CNS mediated skeletal muscle relaxation. Poorly water soluble, should only be mixed w ketamine to avoid precipitation. Light sensitive, reacts with plastic. Risk for liver damage in cats

midazolam (Versed)

benzodiazepines- tranquilizer; Greater affinity for the GABAA receptor and a higher potency (more effect for less dose) than diazepam. Better compatibility with water based drugs than diazepam. May stimulate cats to eat, not as much risk of liver damage as with diazepam. IV/IM

Acepromazine

phenothiazine tranquilizer; Work by blocking dopamine receptors while also blocking alpha-1, muscarinic cholinergic, and histamine (H1) receptors in the brain (prevents vasocontriction, relaxes smooth muscle). Also crosses into the CRTZ and emetic center. May cause idiosyncratic reaction in cats (aggression). Metabolized by liver, "hub of ace"= 0.03ml. Paraphimosis in stallions is side effect

Neuromuscular Blockers

relax or paralyze skeletal muscles during ophthalmic, orthopedic or other surgeries.

MAC - (minimum alveolar concentration)

the percent concentration of an agent required to prevent a response to surgical stimulation in 50% of patients. Needed to achieve a safe level of anesthesia. Essentially measures the potency of a drug. *Cats tend to be higher as they are naturally stressed so it takes more

Clavamox

Abx used perioperatively; Amoxicillin/Clavulanic acid. Light and moisture sensitive. Given PO after sx for 7-10d. Drops must be refrigerated after reconstituting. Dosage: 6.25mg/lb q12h

Local anesthetics

induce a loss of sensation in a localized area of the body.

Sevoflurane

inhaled anesthetic (halogen); Vapor Pressure: 157 mmHg Blood:gas coefficient: 0.6 MAC: 2.36% (canine/equine) 2.58% (feline) Induction and recovery is very quick because of the low blood:gas coefficient. In equine can cause emergence excitement. Higher liver metabolism than isoflurane. Safer in cardiovascular and respiratory compromised patients because of faster recovery times.

Desflurane

inhaled anesthetic (halogen); Vapor Pressure: 669 mmHg Blood:gas coefficient: 0.42 MAC: 7.2% (canine) 7.6% (equine) 9.8% (feline) Very fast induction and recovery periods. Specialized vaporizer has to be used because of it's extremely high vapor pressure. Most cardiovascular signs (depression) are similar to other halogens, however, it can cause tachycardia. Very expensive so not widely used in the veterinary field.

Etomidate

injectable anesthetic; exact mechanism of action is not known, but seems to work similarly to benzodiazepines as to its inhibitory action on the GABAA receptor. Minimal cardiac effects from this drug (wonderful for high risk surgical patients or trauma patients). Does not increase intracranial pressure. No analgesic properties and can cause pain on injection. Expensive drug Dosage - Dogs/Cats 1 - 2 mg/kg IV

General anesthesia

loss of sensation over the entire body, accompanied by unconsciousness.

Efficacy

maximum effect of a drug

Neuroleptanalgesics

opioid drugs combined with a tranquilizer (aka neuroleptics)

Properties of inhalents

-Vapor Pressure -Blood:gas partition coefficient -Minimum alveolar concentration

Desflurane blood:gas partition coefficient

0.42; There does not need to be a volume built up in the alveoli to meet MAC

Sevoflurane blood:gas partition coefficient

0.6; There does not need to be a large volume built up in the alveoli to meet MAC

Vapor pressure of sevoflurane

157 mmHg

Unasyn

Abx used perioperatively; ampicillin sulbactam - penicillin antibiotic potentiated with sulbactam. Used after clean contaminated surgeries, easy to transition from this to Clavamox. Refrigerate after reconstituting. Dosage: 30-40 mg/kg IV q8h

Vapor pressure of isoflurane

238 mmHg

Cefazolin

Abx used perioperatively; 1st gen cephalosporin. Most common IV ab given during sx, usually given at time of induction. Must be refrigerated after reconstituting. Dosage: 22mg/kg IV

Convenia

Abx used perioperatively; 3rd generation cephalosporin. Used after sx upon recovery SQ once, lasts 14days. Dosage: 8mg/kg

Vapor pressure of desflurane

669 mmHg

Anesthetic Adjunct

A drug used during anesthesia to produce other desired effects such as sedation, muscle relaxation, analgesia, reversal, neuromuscular blockade or parasympathetic blockade.

Nutraceuticals

A product derived from food which has natural health benefits.

Ceftiofur

Abx used perioperatively- Large Animal; 3rd generation cephalosporin used for surgical procedures in the field. Painful injection

Gentamicin

Abx used perioperatively- Large Animal; Aminoglycoside. Ototoxic and nephrotoxic, can cross placental barrier. Dosage 6.6 mg/kg (IV or IM) q24h

Excede

Abx used perioperatively- Large Animal; Ceftiofur crystalline free acid. Labeled for use in cattle, can be used off label in equine.

Excenel

Abx used perioperatively- Large Animal; Ceftiofur hydrochloride. Labeled for use in cattle. Dosage: 1.1- 2.2 mg/kg IM or SC daily for 3-5 days

Ceftiofur (as a crystalline free acid)

Abx used perioperatively- Large Animal; Labeled to treat various species. Dosage depends on the type of species but on average, its 2.2mg/kg SID for 3 days

Potassium Penicillin G

Abx used perioperatively- Large Animal; used for equine sx pre/post op and commonly used w gentamicin. IV/IM dosage: 22,000-44,000 IU/kg

Procaine Penicillin G (PPG)

Abx used perioperatively- Large Animal; used in equine/cattle. Painful injection (drug is acidic- can add bicarb) that causes vasoconstriction (stretching time you need before redosing), and can cause abscess. Dosage: 25,000 IU/kg IM ONLY!

Vapor pressure

The measurement of the tendency of a liquid to evaporate. Agents with high vapor pressure evaporate readily and need a precision vaporizer. These pressures are typically established at room temperature (20ºC) and at sea level. Drugs that have a high vapor pressure need to have the amount of molecules that are released controlled (otherwise pressure builds and the molecules will just eject quickly and go everywhere).

Blood:gas partition coefficient

The ratio of gas in the blood to gas in the alveoli, at 37 degrees Celsius (98.6 degrees farenheight), needed to meet effective concentration of the drug. Associated with speed of induction, recovery and change in anesthetic depth. Gas in blood: gas in alveoli ... _._

Flourine

Used as a carrying agent for inhalant anesthetics

Intravenous Lipid Emulsion (ILE)

Used to treat toxicities of medications which are lipophilic. The toxins binds to the ILE which are metabolized by the liver and eliminated via GI tract. Made up of 20% soybean oil, 1.2% egg yolk phospholipids, 2.25% glycerin and water for injection. Carrier solution for propofol. **Should never be disconnected/opened once hooked up to discourage bacterial growth

dexmedetomidine - DexDomitor

alpha 2 agonist/sedative; Most common sedative used in small animal medicine. Goes through biotransformation in the liver and is excreted primarily by the kidney. Used for short procedures such as laceration repairs or cat neuters along with other analgesics. "DKT aka Kitty Magic"

detomidine (Dormosedan)

alpha 2 agonist/sedative; Used primarily in equine medicine although it can be used off label for cattle and other ruminants. Oral formulation for readily absorbed through mucous membranes. Same side effects as dexmedetomidine has in small animal. Dosage 20-40 mcg/kg

xylazine (Rompun/Anased)

alpha 2 agonist/sedative; first alpha 2 agonist used in veterinary medicine. Used primarily in large animals. Used to be the drug of choice to induce vomiting in cats. Commonly used with a "triple drip" in large animal medicine along with guaifenesin, and ketamine for surgical anesthesia CRI's. Horse dosage - 1.1 mg/kg IV 2.2 mg/kg IM Cattle dosage - 0.05 mg/kg IV 0.1 mg/kg IM **not in dairy**