ACEM Pharm part 1 - acem primary pharmacology Flashcards
What is potency?
How is it measured.
The amount of drug required to produce an effect of given intensity.
Potency is measured by the ed50 which is the amount (dose) of drug required to produce 50% of the drug’s maximal effect
What is efficacy?
measure of the maximum clinical respose to the drug regardless of dose
What is the ec50?
the dose at which 50% of people exhibit a quantified effect.
What is td 50?
The dose required to produce a toxic response in 50% of subjects (LD 50 has same definition but the toxic response is death)
What is the therapeutic index?
TD50/EC50 ratio Quantitatively, it is the ratio given by the lethal (animal studies) or toxic dose (human studies) of a drug for 50% of the population (LD50 or TD50) divided by the minimum effective dose for 50% of the population (ED50). Remifentanyl 33,000:1; tetrahydrocannabinol 1000:1, while diazepam 100:1 and morphine 70:1
Give examples of lipid soluble ligands that cross the membrane and act on intracellular receltors?
steroids such as corticosteriods, sex steroids and vitamin D These bind to the nucleus to stimulate transcription of genes and make new proteins- therefore the lag is 30 minutes to hours while the proteins are being made. They persist in their effect over days when the agonist concentration goes to zero due to slow turnover of most enzymes and proteins
Give examples of substances that trigger ligand gated ion channels? How does this work?
acetylcholine, gaba, excitatory amino acids Receptor alters transmembrane conductance of ions and thereby alters electrical potential across the memebrane
Describe the nicotinic acetylcholine receptor?
pentamer made up of 5 polypeptide units (2 alpha, 2 beta, 1 gamma) which each cross the lipid bilayer 4 times and form a cylindrical structure. Binding of ach causes structural change that opens sodium channel. Occurs in milliseconds.
Give examples of substances that bind to a transmembrane receptor that stimulates a tyrosine kinase.
Insulin, platelet derived growth factor (PDGF) & atrial natriuritic peptide (ANP)
How do tyrosine kinase receptors work in general?
Receptor polypeptide consists of a hormone binding domain (extracellular) and an enzyme domain (cytoplasmic) which are connected through the membrane. Hormone binds with extracellular receptor, resulting conformational change that brings together the protein tyrosine kinase domains that become enzymatically active.
What are the three mechanisms by which a drug/ligand binding to a transmembrane protein can cause change?
- The transmembrane receptor contains an ion channel which changes shape e.g. gaba, ACh
- The transmembrane receptor has a tyrosine kinase on the in side e.g. insulin, pdgf, anf
- Transmembrane receptor stimulates a g-protein- the activated g-protein changes the activity of a receptor element (usually an enzyme or an ion channel)
What is the advantage of signalling via g-proteins?
Signalling via G proteins allows effect to persist long after the extracellular receptor has dissociated from its agonist molecule
What do Gs G-proteins do?
increase adenylyl cyclase, causing increased cAMP
Give example of Gs G-proteins?
Beta adrenergic amines, glucagons, histamine, serotonin.
What do Gi G-proteins do? Give examples of these?
Decrease adenylyl cyclase, causing decreased cAMP
Alpha2 adrenergic amines, acetylcholine (muscarinic only), opioids, serotonin
The ACh M2 muscarinic receptors cause inhibition of voltage-gated Ca2+ channels, and increasing efflux of K+, in general, leading to inhibitory-type effects to decrease heart rate
What do Golf g-proteins do
Stimulate adenylyl cyclase causing increased cAMP. They are stimulated by odourants
What do Gq G-proteins do? Give examples of these?
Increase adenylyl cyclase causing increased cAMP Increase phopholipase C resulting in increased IP3, diacylglycerol and cytoplasmic calcium. Acetylcholine (muscarinic), serotonin or noradrenaline in alpha1 receptors within peripheral vasculature.
What is the structure of g-protein coupled receptors?
serpentine receptors- polypetide chains which cross the membrane 7 times.
How does cAMP work?
G protein stimulates membrane adenylyl cyclase that converts ATP to cAMP. cAMP exerts most effects by stimulating cAMP dependent protein kinases.
How does calcium and phospholipase second messaging work?
G protein stimulates membrane enzyme phospholipase that hydrolyses PIP2 to DAG and IP3. DAG is confined to the membrane and activates protein kinase C. IP3 diffuses through the cytoplasm to trigger release of calcium from internal stores. Calcium binds to calmodulin, which regulates calcium dependent protein kinases.
How are DAG and IP3 inactivated?
DAG inactivated by phosphorylation back to phospholipid. IP3 rapidly inactivated by dephophorylation.
How does cGMP work?
small role -mainly intestinal mucosa and vascular smooth muscle. G protein stimulates membrane guanylyl cyclase which converts GTP to cGMP. cGMP exerts most effects by stimulating cAMP dependent protein kinases.
What is the volume of distribution? What are the units?
- It is a theoretical value used clinically when trying to determine the loading dose necessary for a desired blood concentration of a drug or for estimating a blood concentration in the treatment of overdose. - Vd is the volume of plasma that would be necessary to account for the total amount of drug in the patient’s body, if that drug were present throughout the body at the same concentration as found in the plasma. - This value is usually further divided by the patient’s body weight, and the result expressed in terms of litres per kilogram - Vd=Amount of drug in body /concentration.
Give an example of a drug that is distributed in the total body water? What is the volume of distribution?
ethanol and other small water soluble molecules 0.61L/kg (42L)
Give an example of a drug that is distributed in the extracellular water? What is the volume of distribution?
Mannitol, gentamycin larger water soluble molecules 0.2l/kg 14 L
What is the volume of distribution of blood?
0.08l/kg= 5.6L
Give an example of a drug that is distributed in plasma? (and explain why it is largely confined to plasma) What is the volume of distribution?
Heparin 0.04l/kg Bound to a plasma protein
Give an example if a drug that is distributed in fat? What is the volume of distribution?
DDT (insecticide) 0.2-.35l/kg (14-24l)
Give an example if a drug that is distributed in bone? What is the volume of distribution?
0.07l/kg (4.9L) lead and flouride
What drugs cannot be removed by dialysis?
drugs with large volumes of distribution
Give examples of drugs with large volumes of distribution? (5-10L/kg)
Antidepressants Phenothiazines Propanolol Verapamil
Give examples of drugs with small volumes of distribution? (<1l/kg)
Theophylline Salicylate Phenobarbitone Lithium Phenytoin Heparin Warfarin
What is the half life of a drug?
Time required to change the amount of drug in the body by 1/2 during elimination or during a constant infusion T1/2=0.7xVd / CL Half life can refer to the drug itself or the active metabolites of the drug
What is allosteric action?
drugs that bind to the same receptor but do not prevent binding of the receptor molecule, may enhance or inhibit action
How is the action of transmembrane receptors terminated?
ligand binding often causes acellerated endoscytosis of reception followed by the degradation of the receptors and their bound ligands
Why are volumes of distribution greater than actual volumes found in the human body?
because it is the volume apparently necessary to contain the concentration found in blood, plasma or water Drugs with very high volumes of distribution have much higher concentrations in the extravascular compartment then in the vascular compartment- i.e. not homogenously distributed. Drugs that are completely retained within the vascular compartment have a minimum volume of distrubution
What is drug clearance?
Rate of elimination/concentration, this is additive when more than one organ clears it i.e. CL(liver)= rate of elimination by liver/C kidney generally excretes unchanged drug while liver metabolises
What is the rate of elimination?
CLx C when clearance is first order calculated using the area under the time concentration curve (dose/AUC)
When is rate of elimination not first order?
- Capacity limited elimination e.g. phenytoin and ethanol, aspirin - Also known as dose/concentration and saturatable elimination - cannot use AUC to measure rate of elimination 2. Rate of elimination = vmax x c/ km x c
What is flow-dependent elimination?
Relevant for drugs that are cleared mainly on the first pass and therefore elimination depends on blood flow to the organ
What is bioavailability?
The fraction of the drug reaching the systemic circulation following administration by any route- IV has greatest bioavailability because it avoids first pass metabolism, extent of absorption (liphophilicity, reverse transporter associated with p glycoprotein)
How do your calculate the dosing rate for a drug?
CL x target concentration (TC)
How do you calculate the maintenance dose?
Drugs are usually administered in order to achieve a steady state where dosing equals elimination. Dosing rate=CL X target concentration (TC) Maintenance dose=dosing rate x dosing interval
When is a loading dose needed? How does one calculate the loading dose?
Loading doses are required if the half-life of a drug is prolonged and the time taken to reach steady state would otherwise be prolonged If the target concentration is known the clearance will determine the dosing rate Loading dose=Vd X TC(target concentration)
Give a formula for systemic clearance of a drug?
Clearance can pertain to each organ and is additive in effect CLrenal+CLliver+CLother=CLsystemic.
What is another word for capacity limited clearance?
zero order kinetics
Describe how zero order kinetics works?
Drug elimination pathway becomes saturated at high concentration of drug. Elimination is proportional to concentration of the drug at low concentrations but at high concentrations elimination is constant. e.g. Aspirin, Phenytoin, Ethanol
What is first order clearance?
First order clearance = clearance proportional to concentration
What is flow dependent elimination? Give 3 examples of drugs efected by this principle?
- Extraction is chiefly dependent on blood flow through the organ and the drug is almost completely extracted by the liver on first pass
- Morphine Lignocaine Propanolol
What are some limitations to drug absorption in the gut?
Lipophilic (acyclovir) versus hydrophilic (atenolol) drugs Bacterial metabolism within the gut (digoxin) Absorption abnormalities in small bowel.
What is the extraction ratio?
Extraction ratio defines the degree of first pass metabolism. ER=CL liver /Q (Q is hepatic blood flow = 90l/h)
Where does first pass elimination occur?
Can occur in gut wall, portal blood, or by excretion in bile. Most important is metabolism by liver.
What is the formula for systemic bioavailability?
Systemic bioavailability (F) =extent of absorption (f) X (1-ER) [extraction ratio]
How do you avoid hepatic first pass metabolism?
Hepatic first pass metabolism can be avoided by sublingual, transdermal and to a lesser extent, rectal administration
What is biotransformation?
- Biotransformation is the metabolism of drugs that allows for the renal excretion of lipophilic, un-ionised or partially ionised drugs that would otherwise fail to be effectively excreted and have a prolonged duration of action.
- Biotransformation transforms a lipophilic molecule into a more polar and therefore more readily excretable product.
Where does biotranformation occur?
Biotransformation can occur in GIT (eg clonazepam, penicillin), lungs, skin, kidneys, but most important site is liver.
What are the two phases of biotransformation reactions?
Phase 1 reactions
- Convert the parent drug to a more polar metabolite by introducing or unmasking a functional group such as OH, NH2, SH.
Phase 2 reactions
- The introduced functional group combines with an endogenous substrate to form a highly polar conjugate.
- Enzymes for phase 2 reactions may be located in microsomes or in the cytosol.
- Phase 2 reactions can sometimes precede phase 1 reactions.
What are four (4) key features of phase 1 biotransformation reactions?
- Includes oxidative, reductive, and hydrolytic reactions.
- In these type of reactions, a polar group is either introduced or unmasked, so the drug molecule becomes more water-soluble and can be excreted.
- Reactions are non-synthetic in nature and in general produce a more water-soluble and less active metabolites.
- The majority of metabolites are generated by a common hydroxylating enzyme system known as Cytochrome P450.
How do phase 1 reactions work?
Phase 1 reactions utilise mixed function oxidases located on the ER of liver cells and other tissues. Require oxygen and NADPH to function. Mixed function oxidases include NADPH-cytochrome P450 reductase and cytochrome P450.
What are the three (3) key features of phase 2 biotransformation reactions?
- These reactions involve covalent attachment of small polar endogenous molecule such as glucuronic acid, sulfate, or glycine to form water-soluble compounds.
- This is also known as a conjugation reaction.
- The final compounds have a larger molecular weight.
How many major CYP450 isoforms are there? What is the most important one?
Different P450 isoforms are responsible for metabolism of different drugs. 7 main isoforms account for most metabolism. CYP3A4 is the largest component, responsible for 60% of clinically prescribed drugs metabolised by the liver.
Where do phase 1 and 2 reactions occur?
Whase 1 occur on the ER, Phase 2 occur in microsomes and the cytosol
List some examples of genetic factors that affect biotransformation?
- Suxamethonium - genetic defect in pseudocholinesterase causes suxamethonium to remain active for prolonged periods.
- The “asian gene” where there is increased effectiveness of alcohol oxidase that metabolises ethanol (reducing the “buzz”) but a reduced capacity of acetaldehyde dehydrogenase to metabolise the toxic acetaldehyde that produces the the “asian flush” and other associated symptoms
- N-acetyltransferase a phase-II conjugating liver enzyme. The slow acetylator phenotype often experiences toxicity from drugs such as isoniazid, sulfonamides, procainamide, and hydralazine, whereas the fast acetylator phenotype may not respond to isoniazid and hydralazine in the management of tuberculosis and hypertension, respectively.
What are some environmental factors that affect biotransformation?
Enzymes may be induced or inhibited by environmental factors. Charcoal - induction grapefruit juice -inhibition of CYP3A4 (responsible for 60% of drug metabolism)
What does phenytoin do to digoxin metabolism?
Phenytoin enhances digoxin metabolism
What cytochrome metabolises warfarin and list examples of drugs that inhibit or enhance this CyP.
Warfarin is a racemic mixture of S and R isomers. The S isomer is five times more potent than the R isomer.
The S isomer is metabolised CyP 2C9 enzyme whereas the R isomer is metabolised via CyP 3A4
- Inhibitors of CYP2C9 (eg. metronidazole,
trimethoprim/sulfamethoxazole (bactrim) may result in significant rise in the INR
- Dilitiazem and ciprofloxacin inhibits the metabolism of the R isomer and only has a modest effect
- Amiodarone can have a profounde increase because it interes with the clearance of both isomers
Enhance metabolism
- Barbiturates (i.e. phenobarbitol) enhance warfarin metabolism by inducing CyP3A4
Cimetidine (histamine H2 antagonist) effects the metabolism of what drugs?
Cimetidine inhibits warfarin and diazepam metabolism
The metabolism of what drugs is affected by cardiac disease?
Cardiac disease can affect drugs that are flow-limited e.g. Morphine, Verapamil
What are the four (4) physical barriers to drug distribution?
- Aqueous diffusion - generally determined by fixed law though if a drug is charged its flux will be influenced by electrical fields.
- Lipid diffusion - most important limiting factor for drug permeation. Lipid:aqueous partition coefficient determines how readily the molecule moves between acid aqueous and lipid media. The abililty of weak acids and bases to move between aqueous and lipid mediums depends on pH.
- Special carriers (active transport/facilitated diffusion) - for molecules that are too large or too insoluble - eg peptides, amino acids, glucose
- Endocytosis and exocytosis for very large molecules -eg vit B12, iron
What is fick’s law of diffusion
FICK’S LAW OF DIFFUSION STATES: “The rate of transfer of a gas through a sheet of tissue is proportional to the tissue area and the difference in gas partial pressure between the 2 sides and inversely proportional to the tissue thickness.”
Volume of gas (per unit time)=Area/Thickness x Diffusion constant x (Partial Pressure 1 - Partial Pressure 2)
dV/dt = A/T * D * (P1 - P2)
Define weak acid?
a neutral molecule that can readily dissociate into an anion and a proton
Define weak base?
A neutral molecule that can combine with a proton and form a cation
What is the pKa?
pKa is the logarithmic constant where pKa is equal to −log10 Ka of the acid dissociation constant (Ka).
The larger the value of pKa, the smaller the extent of dissociation at any given pH —that is, the weaker the acid. pKa =the pH at which the concentrations of ionized and and inionized forms are equal
When are weak acids and bases more likely to be in a lipid soluble form?
More of a weak acid will be in a lipid soluble from at an acid pH. More of a weak base will be in a lipid soluble form at an alkaline pH This is important for excretion of drugs by the kidney.
What is the henderson hasselbach equation?
pH = pKa + log [base]/[acid]
What is the general structure of local anaesthetics?
Consist of a lipophilic group, ester or amide chain and ionisable group (usually a tertiary amine)
What are the two types of local anaesthetics?
- Esters: Cocaine, procaine & benzocaine
- Amides: Lignocaine, bupivicaine & prilocaine (etidocaine)
What are the three (3) key the clinical differences between and ester and an amide local anasesthetic?
- The ester linkage is more easily broken than the amide bond so the ester drugs are less stable in solution and cannot be stored for as long as amides.
- Amide anaesthetics are also heat-stable and can therefore be autoclaved; esters cannot.
- The metabolism of most esters results in the production of para-aminobenzoate (PABA) which is associated with allergic reaction. Amides, in contrast, very rarely cause allergic phenomena.
For these reasons amides are now more commonly used than esters.
Define local anaesthetics?
Agents which reversibly block impulse conduction along nerve axons, thereby reducing pain sensation- usually do this by blocking voltage gated sodium channels
Where do local anaesthetics act on the sodium channel?
Blockade occurs at the intracellular end of the sodium channel
What are the pharmacodynamics of local anaesthetics?
- Activated channels have higher affinity for the drug, therefore drug effect is more marked in rapidly firing fibres.
- The progressive increase in drug concentration causes increased threshold, reduced action potential amplitude, then failure to produce an action potential.
What ion concentration changes increase and decrease the effects of local anaesthetics?
Local anaesthetic effect is increased by hyperkalaemia and decreased by hypercalcaemia
How does fibre type (size and myelination) affect how local anaesthetics work on the nerves?
- Large diameter fibres are less sensitive than small diameter fibres because three successive nodes required for blockade and nodes are further apart in large fibres.
- Myelinated fibres of the same diameter as unmyelinated fibres tend to become blocked first.
Why are sensory nerves more sensitive to local anaesthetics?
Sensory fibres tend to have a fast firing rate and long action potential therefore are more sensitive to blockade.
How does the position of a nerve in the bundle affect how sensitive it is to local anaesthetics?
Peripheral nerves exposed first -motor nerves tend to be peripheral in large trunks.
What are the safe doses for lignocaine with/without adrenaline?
2mg/kg IV, 3mg/kg SC, 5mg/kg with adrenaline.
What is 1% solution of drug?
10mg/ml
What is the safe dose of bipivicaine and prilocaine?
Bupivacaine 2mg/kg SC Prilocaine 3-5mg/kg IVRA
What are the relative potencies of the local anaesthetics, say lignocaine = 4
(if procaine = 1) Cocaine =2 Lignocaine =4 Bupivacaine = 16 Prilocaine = 3
What is the CNS toxicity of local anaesthetics?
Drowsiness, visual and auditory disturbance, restlessness, nystagmus, shivering, convulsions, CNS depression.
How do you manage convulsions caused by local anaesthetics?
If convulsion occurs, the patient should be hyperventilated to induce respiratory alkalosis as this lowers extracellular potassium and favours rested, low affinity sodium channels
Which local anaesthetics cause the most CNS and CVS toxicity?
Bupivacaine>lignocaine> prilocaine Bipivicaine is most cardiotoxic -Although all local anesthetics potentially shorten the myocardial refractory period, bupivacaine avidly blocks the cardiac sodium channels, thereby making it most likely to precipitate malignant arrhythmias.
What are the cardiovascular effects of local anaesthetics?
- Depression of cardiac pacemaker activity, excitability and conduction.
- Negative inotropic effect and decreased peripheral resistance.
How is cocaine different from other local anaesthetics in its cardiovascular effect?
Whilst it is a Na channel blocker like other local anasthetics it also blocks reuptake of catecholamines in the presynaptic neurons in the central and peripheral nervous system, resulting in increased sympathetic output and increased catecholamines.
- Acute doses of cocaine suppress myocardial contractility, reduce coronary caliber and coronary blood flow, induce electrical abnormalities in the heart, and in conscious preparations increase heart rate and blood pressure.
- These effects will decrease myocardial oxygen supply and may increase demand (if heart rate and blood pressure rise). Thus, myocardial ischemia and/or infarction may occur.
What haemotological toxicity do local anaesthetics have?
Prilocaine in high doses can cause methaemoglobinaemia which can result in an increased O2 binding, reduced ability of RBC to release oxygen to tissues, a leftward shift of the dissociation curve and subsequent tissue hypoxia.
What drugs interract with local anaesthetics?
- Fentanyl and midazolam utilise same microsomal enzymes in liver
- Halothane, cimetidine and beta blockers decrease hepatic blood flow and therefore reduce metabolism
- Enzyme inducers such as phenytoin may increase metabolism
Are local anaesthetics acid or base?
most are weak bases, potency depends on how liphophilic it is and therefore depends on the pH of the tissue
What is the active form of local anaesthetics? Is this the form that gets into the tissues?
Most are in a charged, cationic form and this is the active form at the receptor site, but the uncharged form is required for penetration - hence poor penetration in acidic (infected) tissue
How protein bound are local anaesthetics?
bupivicaine 95%, prilocaine 50%
What affects systemic absorption of local anaesthetics? What does local effect depend on?
dose, vascularity of site of injection, drug-tissue binding, presence of vasoconstrictors (more effective for short acting highly lipid soluble drugs), chemical properties of the drug. Local effect is proportional to the amount of drug that penetrates the nerve fibre
What is the comparative duration of action of the common local anaesthetics?
Cocaine -medium Lignocaine -medium Bupivacaine - long (up to 12 hours for peripheral nerve blocks) Prilocaine - medium.
Why do ester local anaesthetics have a very short plasma half life?
Rapidly metabolised by pseudo- cholinesterase therefore half life less than 1 minute.
How are amide local anaesthetics metabolised?
Slowly hydrolysed by liver enzymes and excreted by kidney: Dosage reduction required in liver disease and reduced hepatic blood flow Prilocaine metabolised most rapidly, lignocaine intermediate, bupivacaine slowest: Prilocaine metabolism produces O- toluidine
What are guedel’s stages of anaesthesia?
Stage of analgesia Stage of excitement Stage of surgical anaesthesia Stage of medullary depression
What are the 5 factors that affect the brain uptake of an inhaled anaesthetic?
- Partial pressure of inspired anaesthetic agent 2. Solubility (blood:gas partition coefficient) The more soluble an agent the longer it takes for its partial pressure in blood to rise therefore the slower the onset of anaesthesia. 2. Pulmonary ventilation Increases the rate of induction of anaesthesia for drugs with high solubility - little effect on drugs with low solubility 3. Pulmonary blood flow Increased flow decreases the rate of induction with soluble agents, little effect with poorly soluble agents. 4. Arteriovenous concentration gradient (tissue:blood solubility coefficient) Gradient between arterial and mixed venous blood determined by uptake of agent by highly perfused organs such as brain, heart, liver, kidneys and gut. Drugs with high tissue:blood solubility coefficient take longer to reach equilibrium.
Define the MAC (minimal alveolar concentration). Give an example of a drug with a high MAC? What are the limits to using MAC?
The partial pressure (% concentration) of an agent which results in immobility of 50% of patients undergoing a surgical incision. For nitrous oxide, MAC>100% means that even if the partial pressure of nitrous oxide is 760mmHg, incomplete anaesthesia is achieved. There may be vast individual differences and the MAC gives no indication where the other 50% lie on the curve.
Why is steady state alveolar concentration a useful measure of potency?
When steady state is achieved, the partial pressure of an inhaled anaesthetic in the brain equals that in the lung, therefore measurement of steady state alveolar concentration gives a measure of potency
How do inhaled general anaesthetic agents work?
Increase in cellular threshold to firing with subsequent decreased spontaneous and evoked neuronal activity. Ionic basis of effect includes activation of potassium currents to cause hyperpolarisation and opening of cation channels to decrease synaptic transmission. Research suggests that agents interact with lipid membranes to cause distortion of ion channels.
What are the cardiovascular effects of general anaesthetic agents?
Dose related variable reduction in mean arterial pressure and myocardial oxygen demand. Effects may be masked by nitrous oxide which causes sympathetic stimulation Nitrous oxide causes minimal depressant effects Halothane sensitises the myocardium to catecholamines and is arrhythmogenic.
What are the respiratory effects of general anaesthetics? List 5
- Respiratory depression due to reduced TV and inadequate increased rate. (except nitrous oxide) 2. Increase apneic threshold to pCO2. 3. Decrease ventilatory response to hypoxia. 4. Decrease mucociliary function leading to atelectasis. 5. Most have bronchodilator action.
What are the CNS effects of general anaesthetics?
Increase metabolic rate and blood flow to brain due to reduced cerebrovascular resistance. Hyperventilation reduces this effect.
What are the GI and GU effects of general anaesthetics?
GUS Reduced renal blood flow and GFR. Uterine relaxation (minimal with nitrous oxide) GIT Reduced hepatic blood flow.
Describe the acute and chronic toxicity of general anaesthetic agents?
Halothane -1 in 35000 cases of fatal hepatic necrosis. Methoxyflurane -fluoride related nephrotoxicity. Malignant hyperthermia -tachycardia, hypertension, acidosis, hyperkalaemia, muscle rigidity, hyperthermia ,more common if suxamethonium also used -treated with dantrolene. Chronic exposure to Nitrous oxide is associated with megaloblastic anaemia
What is the MAC of the common anaesthetic agents?
Nitrous oxide >100 Isoflurane - 1.4 Halothane - 0.75 Methoxyfluorane - 0.16
What are the solubilities and the brain:blood partition coefficients of the common anaesthetic agents?
Solubility (blood:gas partition coefficient) : Nitrous oxide - 0.47 Isoflurane -1.4 Halothane - 2.3 Methoxyfluorane - 12 Brain:blood partition coefficient Nitrous oxide ␣ 1.1 Isoflurane - 2.6 Halothane - 2.9 Methoxyfluorane - 2.0
Give some examples of IV general anaesthetics?
Barbiturates Benzodiazepines Opioids Propofol Ketamine
Give examples of barbituate general anaesthetics?
Phenobarbitone Thiopentone -ultra short acting barbiturate intravenous anaesthetic
How do barbituates work? (3 mechanisms)
- Barbiturates bind to components of the GABA receptor and facilitate its action by increasing the duration of chloride channel opening. 2. At high concentrations GABA may directly stimulate the receptor. 3. Also depress actions of other excitatory neurotransmitters and have non-synaptic membrane effects.
