Pharmacology MCQs - ANZCA Flashcards
GP01 [Mar96] A drug is given at a dose of 50 mg/kg to a 70 kg man. The plasma concentration after giving it is 10 mg/ml. The elimination half-life is 8 hours. Clearance would be: A. 1.3 l/h B. 3 l/hr C. 0.03 l/hr D. 125 l/hr
Vd = dose / concentraion = 3500 mg/10 mg/ml = 350 ml Clearance = 0.693 x Vd / t1/2 = 0.693 x 350 ml / 8 hrs = 30 ml / hr = 0.03 L / hr Therefore answer C is correct —Comment— OK, the maths is fine, but is it possible for a drug to have a VD of 350ml?? Is it possible for any drug to have a VD less than plasma volume?? Help please!
GP02 [Mar96] A drug is given orally and 95% absorbed. Only 25% reaches the general circulation due to hepatic first pass metabolism. If hepatic blood flow is 1500 mls/min, the hepatic clearance is: A. 400 mls/min B. ? C. 1100 mls/min D. ? E. 1425 mls/min
Hepatic clearance = HER x HBF = ( (0.95 – 0.25) / 0.95 ) x 1,500 ml / min = 1,105 mls/min Extraction ratio= conc of inflow-conc outflow/conc of inflow
GP03 [Jul97] Histamine release (no other details) GP03b [Feb12] Histamine when given IV causes: A. Bronchoconstriction B. ?
Bronchoconstriction through activation of H1 receptors - true. Histamine actives H1 receptors to constrict bronchial smooth muscles, whereas stimulation of H2 receptors relaxes bronchial smooth muscles. In normal patients the bronchoconstrictor action of histamine is negligible. Conversely, patients with obstructive lung disease, such as asthma or bronchitis, are more likely to develop increases in airway resistance in response to histamine. References Stoelting 4th ed p431.
GP04 [Jul97] Rectal administration of drugs: A. Gives predictable blood levels B. From lower 1/3rd avoids first pass & upper 2/3rds doesn’t C. None undergoes first pass metabolism D. All of it undergoes first pass metabolism E. ?
Jul97 version: Best answer is B A false - “unpredicatable responses… follow rectal administration of drugs” (Stoelting 3rd Ed. p.9) B best answer - “Drugs administered into the proximal rectum are … transported via the portal venous system to the liver (first pass hepatic effect)… drugs absorbed from a low rectal administration site reach the systemic circulation without first passing through the liver.” (Stoelting 3rd Ed. p.9) C false - beware absolutes like all or none D false - beware absolutes. Also regarding pulmonary first pass below: I’m pretty sure they’re talking about hepatic first pass metabolism and not looking for esoteria like that. This question is basically about effect of rectal administration on first pass metabolism.
GP04b Mar09 Rectal administration of drugs: A. Provides reliable absorption B. Administration in the lower third (below the dentate line) completely avoids hepatic first pass C. Is rapid due to the anastomoses between the superior and inferior haemorrhoid plexuses D. ? E. None of the above
his question is basically about effect of rectal administration on first pass metabolism. Katzung “Basic & Clinical Pharmacology” 7th ed (1998) on p42: The hepatic first-pass effect can be avoided to a great extent by use of sub-lingual tablets and transdermal preparations, and to a lesser extent by use of rectal suppositories. . Sub-lingual absorption provisdes direct access to systemic - not portal - veins. The trandermal route offers the same advantage. . Drugs absorbed from suppositories in the lower rectum enter vessels that drain into the inferior vena cava, thus bypassing the liver. . However, suppositories tend to move upwards in the rectum into a region where veins that lead to the liver, such as the superior hemorrhoidal vein, predominate. . In addition, there are extensive anastomoses between the superior and middle hemorrhoidal veins; thus, only about 50% of a rectal dose can be assumed to bypass the liver. Stoelting (2nd ed p7) also comments that a result of this unpredictable variability in percent of drug absorbed in the lower rectum versus the upper rectum that this explains “‘the unpredictable responses that follow rectal administration of drugs” Related Stuff The liver is NOT the the only organ invloved in a first pass effect. Drugs administered systemically have to pass through the lungs before reaching peripheral capillary beds, and the lung can take up (and even metabolise) some drugs. An example is fentanyl (& also pethidine) where the lungs act as a large inactive storage site. An estimated 75% of the initial fentanyl dose undergoes first-pass pulmonary uptake. Stoelting ( 2nd ed 1991 p85) references the following source: Roerig et al. First pass uptake of fentanyl, meperidine, and morphine in the human lung. Anesthesiology. 1987 Oct;67(4):466-72 . “ . . . . The total uptake (mean +/- SE) during the first pass through the human lung for fentanyl and meperidine was 75.2 +/- 3.2% and 64.7 +/- 7.8% of the injected dose, respectively. The pulmonary uptake of morphine was very small, with 96.5 +/- 7.1% of the injected dose recovered in arterial blood after the first pass through the lung. . . . “ [1] Aug 15- C
GP04c 15B Aug15 version with different options Regarding rectal administration of drugs A. Rectal indomethacin does not cause gastric symptoms B. Rectal administration is predictable and effective. C. Superior haemorrhoidal vein absorption results in hepatic first pass metabolism D. paracetamol cannot be given rectally
his question is basically about effect of rectal administration on first pass metabolism. Katzung “Basic & Clinical Pharmacology” 7th ed (1998) on p42: The hepatic first-pass effect can be avoided to a great extent by use of sub-lingual tablets and transdermal preparations, and to a lesser extent by use of rectal suppositories. . Sub-lingual absorption provisdes direct access to systemic - not portal - veins. The trandermal route offers the same advantage. . Drugs absorbed from suppositories in the lower rectum enter vessels that drain into the inferior vena cava, thus bypassing the liver. . However, suppositories tend to move upwards in the rectum into a region where veins that lead to the liver, such as the superior hemorrhoidal vein, predominate. . In addition, there are extensive anastomoses between the superior and middle hemorrhoidal veins; thus, only about 50% of a rectal dose can be assumed to bypass the liver. Stoelting (2nd ed p7) also comments that a result of this unpredictable variability in percent of drug absorbed in the lower rectum versus the upper rectum that this explains “‘the unpredictable responses that follow rectal administration of drugs” Related Stuff The liver is NOT the the only organ invloved in a first pass effect. Drugs administered systemically have to pass through the lungs before reaching peripheral capillary beds, and the lung can take up (and even metabolise) some drugs. An example is fentanyl (& also pethidine) where the lungs act as a large inactive storage site. An estimated 75% of the initial fentanyl dose undergoes first-pass pulmonary uptake. Stoelting ( 2nd ed 1991 p85) references the following source: Roerig et al. First pass uptake of fentanyl, meperidine, and morphine in the human lung. Anesthesiology. 1987 Oct;67(4):466-72 . “ . . . . The total uptake (mean +/- SE) during the first pass through the human lung for fentanyl and meperidine was 75.2 +/- 3.2% and 64.7 +/- 7.8% of the injected dose, respectively. The pulmonary uptake of morphine was very small, with 96.5 +/- 7.1% of the injected dose recovered in arterial blood after the first pass through the lung. . . . “ [1] Aug 15- C
GP05 [Mar99] [Jul00] [Apr01] [Jul04] [Feb07] LD50 is: A. Median lethal dose B. Determined in phase I clinical trial C. Determined from log-dose response curve D: Dose causing death in 50% of animals within ?1/?4 hours E. Half the mean lethal dose. F. Best expressed as ratio of lethal dose in 50% of animals to effective dose in 50%
Answer is A I agree A is most correct. But C appears to also be correct? Katzung (7th ed 1998 p29): “The quantal dose-effect curve is often characterised by stating the median effective dose (ED50), the dose at which 50% of individuals exhibit the specified quantal effect. (Note that the abbreviation ED50 has a different meaning in this context from its meaning in relation to graded dose-effect curves.) Similarly the dose required to produce a particular toxic effect in 50% of animals is called the median toxic dose (TD50). If the toxic effect is death of an animal, a median lethal dose (LD50) may be experimentally defined. “ Also: “Quantal dose-effect curves may also be used to generate information regarding the margin of safety to be expected from a particular drug used to produce a specified effect. One measure, which relates the dose of a drug required to produce a desired effect to that which produces an undesired effect, is the therapeutic index. In animal studies, the therapeutic index is usually defined as the ratio of the TD50 to the ED50 for some therapeutrically relevant effect” A few important points to bear in mind: Some candidates start talking about LD50 as though this was something that could be determined for humans! If you are asked what method you would use to determine the LD50 of a new drug in humans be very wary. You should always very quickly remark that such is NEVER done in humans for obvious ethical reasons. The therapeutic index can be not very useful in some cases, for example if there is significant overlap between the effective and toxic curves. OECD countries in 2000 agreed to minimise the use of LD50 testing to minimise the number of animals killed. (The examiners are unlikely to know this - useful info for a viva) As regards the phase 1 clinical trials option: “Phase 1 includes the initial introduction of an investigational new drug into humans. These studies are closely monitored and may be conducted in patients, but are usually conducted in healthy volunteer subjects. . These studies are designed to determine the metabolic and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness. During Phase 1, sufficient information about the drug’s pharmacokinetics and pharmacological effects should be obtained to permit the design of well-controlled, scientifically valid, Phase 2 studies. “ [1] SO: You NEVER determine a LD50 during phase 1 trials because these trials are done in HUMANS.
GP06 - [Mar99] [Feb00] [Jul02] [Mar03] -Aug15 Which ONE of the following crosses the blood-brain barrier? A. GABA B. Propranolol C. Suxamethonium D. Edrophonium E. Dopamine
Answer is B Propranolol: Yes. From Stoelting 2nd ed p306: “Beta-blockers may cross the blood-brain barrier to produce side effects. For example, fatigue and lethargy are commonly associated with chronic propranolol therapy.” Suxamethonium-No: is charged (and rapidly metabolised). Does not cross BBB but can have indirect effects on brain function (eg apnoea->cerebral hypoxia). Edrophonium-No: It is a quaternary amine so is charged and cannot cross the blood-brain barrier. (In contrast, physostigmine is a tertiary amine anticholinesterase which can cross the BBB). Dopamine-No: From [1]: “Of importance for PD, dopamine, a neurotransmitter that is depleted in PD, does not’ pass the BBB but L-dopa does. In the brain L-dopa is converted to dopamine. This is important for treatment of PD symptoms with levadopa alone or in combination with carbidopa.” Carbidopa is a dopa decarboxylase inhibitor which inhibits the peripheral conversion of L-Dopa to dopamine (but not centrally as it does not cross the BBB). GABA -No. It is a non-essential amino acid and as such can be synthesised in the brain. It has difficulty crossing the BBB. References Bioavailability of Drugs to Brain and Blood brain barrier
GP07 [Jul98] [Jul99] [Apr01] With regard to drug-receptor binding: A. A competitive antagonist has no intrinsic activity B. A partial agonist has less receptor affinity than a full agonist C. KD is maximal intrinsic efficacy
GP07 A - correct B - false C - false - “intrinsic affinity” is a confusing term for “efficacy”. KD relates to “affinity” / “potency” KD is the equilibrium dissociation constant, with units mmol/L. KA is the equilibrium affinity constant and is the reciprocal of KD, with units L/mmol. From Peck and Hill: The potency is determined by a drug’s KD; the lower the KD, the higher the potency. For many drugs, the ED50 (dose producing 50% of maximum response) corresponds to the KD. KD = [ligand] x [receptor] / [ligand-receptor complex] = k2/k1 = 1/KA Katzung 6e p16 says “…partial agonists competitively inhibit the responses produced by full agonists” - but doesn’t say “always” and I agree to be wary of questions with absolutes. A partial agonist at high concentrations may antagonise a full agonist, but at low concentrations they will exert an additive effect together.
GP07b [Feb00] [Feb04] [Jul04] A partial agonist: A. Always antagonises a full agonist B: Can never be used to antagonise a full agonist C: Has a dose response curve similar to that of a full agonist in the presence of a non-competitive antagonist. D. ?
GP07b A - false - beware always B - false - beware never C - correct KD is the equilibrium dissociation constant, with units mmol/L. KA is the equilibrium affinity constant and is the reciprocal of KD, with units L/mmol. From Peck and Hill: The potency is determined by a drug’s KD; the lower the KD, the higher the potency. For many drugs, the ED50 (dose producing 50% of maximum response) corresponds to the KD. KD = [ligand] x [receptor] / [ligand-receptor complex] = k2/k1 = 1/KA Katzung 6e p16 says “…partial agonists competitively inhibit the responses produced by full agonists” - but doesn’t say “always” and I agree to be wary of questions with absolutes. A partial agonist at high concentrations may antagonise a full agonist, but at low concentrations they will exert an additive effect together.
GP08 [Jul98] [Jul01] [Mar02] Placental transfer of drugs: A. Increases in late pregnancy B. Increases late because of decreased albumin C. Do not cross if MW > 600 daltons D. Lipid soluble drugs diffuse through placenta depending on concentration gradient E. Increased diffusion if greater plasma protein binding in fetus
A - no idea B - no idea C - no idea but may not be true (think facilitated transport for larger proteins) D - correct: From first principles (Fick’s law of diffusion, net flux across a semi permeable membrane is proportional to “D”, the diffusion coefficient, the surface area and the concentration gradient; and inversely proportional to the thickness. “D” itself is proportional to the solubility of the substance to the membrane and inversely proportional to the square root of the molecular weight of the substance.) Also Peck, Hill and Williams state that being “phospholipid in nature, the placental membrane is more readily crossed by lipid-soluble than polar molecules” (p.19) E incorrect - “plasma protein binding influences the rate and degree of diffusion of LAs across the placenta. Bupivacaine, which is highly protein bound (approx 95%) has an umbilical vein-maternal arterial concentration ratio of about 0.32 compared with a ratio of 0.73 for lignocaine (approx 70% protein bound) and a ratio of 0.85 for prilocaine (approx 55% protein bound)” (Stoelting 3rd ed. p.163) Whilst I hate to disagree, Peck and Williams p19 states “high protein binding in the foetus increases drug transfer across the placenta since foetal free drug levels are low.” hence I would say E is correct. M2C: I agree E is correct. C is also correct - I think it is Stoelting who says anything greater than around 500da crosses less easily. Whilst the objections to D being correct and the support of E are noted, the numbers quoted in Stoelting would appear to support that E is incorrect. i.e. at least in the case of bupivicaine vs lignocaine, only around 30% is transferred compared with around 75% for lignocaine which has the lower protein binding. Everyone however is free to make their own decision and we won’t really know who is right and who is wrong come exam time. Only the examiners (or the computer marking it) will know. :-) I think the quote from stoelting regarding option E is referring to maternal protein binding, while the question is referring to fetal protein binding. I agree that high protein binding in the mother will decrease diffusion across the placenta, but for 2 drugs with identical maternal protein binding, the one with higher fetal protein binding will have greater placental transfer (assuming pKa, lipid solubility the same for each) I agree - also, just saw in UptoDate that if drugs are unionised/lipid-soluble, they freely cross the placenta if MW 1000 g/mol) do not cross the placental membrane[11]” D and E likely true (as per above)
GP09 [Jul98] [Jul99] Regarding pharmacokinetics: A. ? B. Half-life is inversely proportional to clearance C. ? D. Half-life is proportional to steady-state E. B & D
B definitely correct as clearance = 0.693 x Vd/ half life Discussion about D and E below just a thought, IR (infusion rate) = Cl * Css Cl = ke * Vd Ke = ln2 / T1/2 = 0.693 / T1/2 Hence, rearranging IR/Css = 0.693Vd / T1/2 Css = (IR * T1/2) / 0.693Vd so that steady state concentration is proportional to its half life at a given infusion rate. perhaps E ??? any thoughts?? D would be correct if the word “concentration” was put at the end of the option, to make it less ambiguous. In that case, E would be correct. I’m not entirely sure but i think the algebraic reasoning above may be incorrect…if you expand the terms IR & T1/2 out, everything cancels and you end up with Css=Css.
GP10 [Jul99] [Jul04] An ether bond: A. Formed from condensation of 2 alcohols B. Hydroxyl group on middle bond C. ?
A - maybe right. If you combine two hydroxyls to form an ether, then you produce water (see the Wiki entry below), but is it the same as condensation? B - definitely WRONG Ether - “Any of a class of organic compounds in which two hydrocarbon groups are linked by an oxygen atom.” (“ether.” The American Heritage® Dictionary of the English Language, Fourth Edition. Houghton Mifflin Company, 2004. Answers.com 17 Feb. 2007.) From Wikipedia Ethers can be prepared in the laboratory in several different ways. One of the 3 ways is Dehydration of alcohols: R-OH + R-OH → R-O-R + H2O Is this the same as condensation? Yes! Condensation reactions also include formation of ester bonds from an alcohol and acid, and also forming peptide bonds from two amino acids. I think dehydration is the specific subset of condensation when water is produced. There are other condensation reactions that result in other, non-water, small molecules being formed…can’t think of any examples at present
GP11 [Feb00] [Mar03] The NMDA receptor A. Ketamine is an agonist B. Requires glycine as a modulating protein to have its effect C. Mg+2 blocks the receptor D. Is not permeable to Calcium
C is the best answer Ketamine is an ANTAGONIST Glycine is an AMINO ACID (not a protein) - several persons submitting this question noted the “protein” wording) Mg+2 normally blocks the ion channel in the molecule When open, it is permeable to Na+, K+ and Ca+2 Regarding the NMDA Receptor: “The NMDA receptor gates a cation channel that is permeable to Na+, K+ and Ca+2 and is gated by Mg+2 in a voltage-dependent fashion. Agonists (glutamate, NMDA) and the coagonist glycine, required for full activation, bind to the extracellular domain” (from Hemmings & Hopkins “Foundations of Anesthesia” p250) Opening of the channel in the NMDA receptor requires ALL of the following: partial depolarisation of the cell membrane (to relieve the Mg+2 obstruction of the channel) binding of BOTH glutamate AND glycine (on extracellular side)
GP12 [Feb00] [Jul02] Activated charcoal: A. Should be given with sorbitol B. Is not effective against theophylline C. Should be given with ipecac D. Should be given in a drug:charcoal ratio of 1:10 E. ?
Answer is D What is Activated charcoal? Chemically it is just pure carbon, but the way it is produced gives it a HUGE surface area. A tennis court has a SA of about 260m2 so just one gram has an average of more than TWICE that. Ref [1]. “Activated charcoal is used in water filters, medicines that selectively remove toxins, and chemical purification processes. Activated charcoal is carbon that has been treated with oxygen. The treatment results in a highly porous charcoal. These tiny holes give the charcoal a surface area of 300-2,000 m2/g, allowing liquids or gases to pass through the charcoal and interact with the exposed carbon.” (from [2]) Activated charcoal is a fine, black, odorless, and tasteless powder. It is made from wood or other materials that have been exposed to very high temperatures in an airless environment. It is then treated, or activated, to increase its ability to adsorb by reheating with oxidizing gas or other chemicals to break it into a very fine powder. Activated charcoal is pure carbon specially processed to make it highly adsorbent of particles and gases in the body’s digestive system. . Activated charcoal has often been used since ancient times to cure a variety of ailments including poisoning. Its healing effects have been well documented since as early as 1550 B.C. by the Egyptians. However, charcoal was almost forgotten until 15 years ago when it was rediscovered as a wonderful oral agent to treat most overdoses and toxins. (from [3]) ??15 years The sorbitol option Some activated charcoal products contain sorbitol. Sorbitol is a sweetener. It also works as a laxative, for the elimination of the poison from the body. Products that contain sorbitol should be given only under the direct supervision of a doctor because severe diarrhea and vomiting may result. - from Medline plus Regarding Sorbitol, In AMH (July 2008) there are two types of Activated Charcoal mentioned that are thus Available in Australia: “oral liquid, 50 g, in 46% sucrose, 250 mL, Carbosorb X (PL) oral liquid, 50 g, in 40% sorbitol, 250 mL, Carbosorb XS (PL)” But in “practice points” it mentions: “Sorbitol provides no additional benefit to charcoal in most poisonings and may result in diarrhoea and volume depletion.” Regarding 1st dose: “1 g/kg to a maximum of 50–100 g for each dose of activated charcoal.” So you can use it with sorbitol, but it is just one option. The theophylline option Consider this abstract: Effect of the surface area of activated charcoal on theophylline clearance GD Park et al. Journal of Clinical Pharmacology, 1984; 24:289-292 . The effect of the surface area of activated charcoal on theophylline clearance was studied. Eight fasting, healthy men received intravenous infusions of either aminophylline (6 mg/kg, N = 3) or theophylline (5 mg/kg, N = 5) over 1 hour followed by either 5 Gm standard activated charcoal every 2 hours, 20 Gm every 2 hours, or 5 Gm PX-21 activated charcoal (with 3.6 times the surface area) every 2 hours. …..(some content deleted) … . We conclude that the clearance of theophylline is related to the surface area of activated charcoal administered and that PX-21 may be a more potent activated charcoal product for enhancing theophylline removal. and this from a page about treatment of theophylline overdose: Gastrointestinal decontamination . To block absorption, administer oral activated charcoal (1 mg/kg, not to exceed 20 g) every 2 hours until the serum theophylline level has fallen to less than 20-25 mcg/mL. . For vomiting, administer metoclopramide, droperidol, or ondansetron. Avoid ipecac because it does not reduce absorption. Avoid phenothiazine antiemetics (eg, prochlorperazine, perphenazine) because they lower the seizure threshold from [4]. The ipecac option What’s the sense of giving something (charcoal) only to give another drug (ipecac) to vomit it up? However, the two can be used together IF ipecac is given first, then activated charcoal after a period of time: Activated charcoal is available without prescription. However, in case of accidental poisoning or drug overdose an emergency poison control center, hospital emergency room, or doctor’s office should be called for advice. In case that both syrup of ipecac and charcoal are recommended for treatment of the poison, ipecac should be given first. Charcoal should not be given for at least 30 minutes after ipecac or until vomiting from ipecac stops. Activated charcoal is often mixed with a liquid before being swallowed or put into the tube leading to the stomach.” (from [5]. The drug:charcoal ratio option For those (?rare) occasions when the dose of ingested drug/toxin is known, there is a recommendation on a drug:charcoal ratio: Give 10 times as much charcoal BY WEIGHT as drug ingested. Initial dose, 1 g per kg of body weight or 25 to 100 g orally or via gastric tube (as a slurry in water) or if the quantity of toxin ingested is known, 10 times the amount of ingested toxin by weight is given. Repeat-dose, 0.25 to 0.5 g per kg of body weight (15 to 30 g) every 2 to 4 hours is given orally or by gastric tube. Following administration of activated charcoal, it is recommended that a cathartic be administered to enhance removal of the drug-charcoal complex since failure to excrete the drug-charcoal complex promptly may result in enhanced toxicity. When multiple doses of activated charcoal are required, administration of a small dose of cathartic with every second or third charcoal dose is recommended. Do not use cathartic with every activated charcoal dose. Warning 1. It should be used with caution in patients with absence of bowel sounds. 2. It may cause swelling of abdomen or pain and black stools. 3. The effectiveness of oral acetylcysteine and other oral medications may be decreased when used concurrently with activated charcoal. 4. Chocolate syrup or ice cream or sherbet should not be used as vehicles for the administration of activated charcoal since they will decrease the adsorptive capacity of the activated charcoal. from p29 [6] When NOT to use activated charcoal Just in case this is an option in future versions of this question. Activated charcoal is used in the emergency treatment of certain kinds of poisoning. It helps prevent the poison from being absorbed from the stomach into the body. Sometimes, several doses of activated charcoal are needed to treat severe poisoning. Ordinarily, this medicine is not effective and should NOT be used in poisoning if - Corrosive agents such as alkalis (lye) and strong acids, - Alcohols or - Miscellaneous: boric acid, iron, lithium, - Petroleum products (e.g., cleaning fluid, coal oil, fuel oil, gasoline, kerosene, paint thinner), have been swallowed, since it will not prevent these poisons from being absorbed into the body. from [7] Mnemonic: Avoid if CAMP BAIL - where the BAIL coverrs the miscellaneous ones My notes: a. Teik Ok ICU book p.948 says don’t give with sorbitol. Found an A&E book which stated there was no evidence that it does any good. b. G&G 11e p1748 says “serial doses enhance elimination of theophylline” and other sources list theophylline as one of the few intoxications where a.c. is definitely recommended. c. no advantage over charcoal alone and charcoal can adsorb the emetic agent and reduce it’s effect - think this was also from G&G d. this is definitely true as above G&G: 11e p.1748
GP13 [Apr01] [Jul04] Therapeutic index: A. Easy to determine in humans B. ? C. D. E. Derived from LD50/ED50
From Yentis: Therapeutic index is defined experimentally as the ratio of median lethal dose to median effective dose -therefore answer is E THERAPEUTIC INDEX “The ratio of the drug dose which produces an undesired effect to the dose which causes the desired effects is a therapeutic index and indicates the selectivity of the drug and consequently its usability. It should be noted that a single drug can have many therapeutic indices, one for each of its undesirable effects relative to a desired drug action, and one for each of its desired effects if the drug has more than one action. “ An alternative more general definition: “Therapeutic index can be evaluated as the relative position of the dose-efficacy and the dose-side effect curves.” The “position” of each curve is determined from its 50% response position, and the “relative” aspect is determined by taking the ratio of the 2 curve positions - with the undesired effect in the numerator and the desired effect in the denominator. The point of getting this ratio is that it provides some information about the “margin of safety” with use of the druug.
GP14 [Apr01] [Jul04] (A Basic drug with a pKa of 8.7) A. ? B. ? C. Will be predominantly ionised at plasma pH
A basic drug will be predominantly ionised at a pH below its pKa For a drug with a pKa of 8.7 undegoing the reaction: B + H+ BH+: At pH = pKa we can calculate the following: pH = pKa + log([B]/[BH+]) (Henderson-Hasselbalch equation) If pH = pKa then this simplifies to pKa = pKa + log([B]/[BH+]) log([B]/[BH+]) = 0 Thus, taking anti-logs (easy as log 1 = 0): ([B]/[BH+]) = 1 so [B] = [BH+] -> 50% ionised & 50% unionised By doing similar calculations using the Henderson-Hasselbalch equation, the ratio B/BH+ can be determined at any pH value. For example: For pH = pKa + 1 -> 10% ionised & 90% unionised (approx) For pH = pKa -> 50% ionised & 50% unionised For pH = pKa - 1 -> 90% ionised & 10% unionised For pH = pKa - 2 -> 99% ionised & 1% unionised “Bases ionised Below, Acids ionised Above”
GP15 [Apr01] [Jul02] [Mar03] Oxygen toxicity A. Causes convulsions at less than 100 kPa B. Causes lipid peroxidation at less than 100 kPa C. ? D. ? E. ?
A is incorrect. CNS toxicity occurs at > 200 kPa B. correct In general, “hazards” associated with oxygen use include hypoventilation, i.e. in pts with CPOD who are chronic CO2 retainers Absorption Atelectasis ( alveolar collapse)- high oxygen concentrations can cause atelectasis in areas of low ventilation relative to perfusion. VC can be decreased by 500-800ml as a consequence Retinopathy of prematurity ( previously called retrolental fibroplasia) - FIO2 > 0.50 to neonates can encourage “disorganized vascular proliferation and fibrosis”.. which can make the retina opaque, .” as well as retinal detachment” Bronchopulmonary dypasia - in neonates Fire hazard Pulmonary toxicity In the acute situation, use of 100% O2 ( PaO2 > 600mm Hg,) is not associated with toxicity. Dose time toxicity curves state that 100% O2 administered longer than 12 hours are associated with toxic effects, namely tracheobroncial irritation ( manifested as coughing, retrosternal burning, chest tightness, “substernal distress”). The pathophysiology of oxygen toxicity may arise from several mechanisms, such as: inactivation of enzymes, release of inflammatory mediators, action of dioxygen moecule as a free radical, formation of a superoxide free radicals, formation of hydrogen peroxide. Ultimately oxygen derived free radicals act on DNA, lipids ( disrupts alveolar capillary membrane), and sulphydryl contatining proteins. With regards to hyperbaric O2 therapy, the degree of toxicity is related to the pressures used as well as duration of usage. At > 2 atmospheres ( > 200 KPA) the risk of CNS toxicity emerges, i.e. convulsions, muscular twitches, behavior changes. From my reading, B appears to be true, assuming they are referring to “100 kPa” as alveolar PO2. “ Chronic O2 administration of 100% O2 at 1atm results in PO2 of 713 mm Hg/ 95 kPa, which can lead to lipid peroxidation”. References Faunce - ANZ Intensive care & Primary exam, 9th ed. p 60, Lange- Clinical Anaesthesiology 4th ed p. 1028-9
GP16 [Jul01] With regard to log/dose response curves: A. The response is fairly linear over the 20-80% range. B. The Dose is fairly linear over the 20-80% range C. The ED50 and slope are characteristic for each drug D. ? E. ?
Best answer is probably A From Aitkenhead 4th p. 21: “Conventionally, log-dose is plotted against effect, resulting in a sigmoid curve which is approximately linear between 20 and 80% of maximum effect” Could they all be right? C sounds right, as does B (although this does not mention response) or is it not B because it is not really linear if you have to use a logarithmic scale to get that shape graph? I think A is most correct. B seems incorrect - the dose is not linear on a logarithmic scale C could be true also Stoelting page 17 4th Ed cover it faily well with regard to C and seems to indicate this is correct. Slope influenced by number of receptors drug must ocupy to have effect, and ED50 measure of potency which shouldn’t change for each drug. I haven’t found anything regarding the 20-80% thing though
GP18 [Jul01] With regards to diffusion through a membrane: A. Directly proportional to thickness B. Inversely proportional to thickness C. Inversely proportional to Surface area D. Inversely proportional to concentration difference E. ?
Fick’s Law of Diffusion: A - False B - True C - False D - False Law is: . v_gas ~ A.D.(p1-p2) / T where D ~ solubility / sqrt (MW) See: West, p.26
GP19 [Mar02] [Mar03] [Mar08] Which of the following has it’s action related to a ligand gated ion channel? A. Metoclopramide B. Phenylephrine C. Morphine D. Vecuronium E. Salbutamol
Answer D. Vecuronium Lengthy notes Sorry about my lengthy notes here (mainly to convince myself I know it, but also, this is core stuff that didn’t leap out when I first read about these drugs). First part is unreferenced and my interpretation of the action of drugs at the Nicotinc Ach receptor. The second part on opioids is a cut and past from wiki on opioid receptors. Good luck. NMJ nACh Receptor The Nicotinic Ach receptor is a ligand gated ion channel (2 alphas beta gamma and delta or epsilon). To activate the channel two Acetylcholine molecules bind to each of the alpha subunits and open the channel, then dissociate and are quickly metabolised by acetylcholinestarase in the NMJ. Because the enzyme is in the NMJ there is a gradient rapidly for Ach to dissociate from the receptor back into the NMJ. Suxamethonium binds both alphas and activates the channel –> action potential spread –> fasciculation. Sux is not metabolised in the NMJ as the Plasmacholinesterase is in the – yep you guessed – plasma. So there is no rapid gradient to dissociate from the receptor until some sux begins to diffuse out of the NMJ into the plasma then the bound sux can dissociate. So receptors are held open for much longer by sux than Ach. Non-depolarizers all have a molecular structure which includes an-Ach like portion. This binds to a single alpha subunit and the bulky molecule blocks the receptor. As it only binds a single alpha subunit the channel is not opened and no depolarisation occurs. Opioid receptors Opioid receptors: G protein linked with opioids as ligands (but no channel). The endogenous opioids are dynorphins, enkephalins and endorphins. The opioid receptors are ~40% identical to somatostatin receptors (SSTRs). There are three major subtypes of opioid receptors: [1] delta opioid receptor (δ) OP1 δ1, δ2 kappa opioid receptor (κ) OP2 κ1, κ2, κ3 mu opioid receptor (μ) OP3 μ1, μ2 (Sigma receptors (σ) were once considered to be opioid receptors, but are not usually currently classified as such.) The receptors were named using the first letter of the first ligand that was found to bind to them. Morphine was the first chemical shown to bind to mu receptors. The first letter of the drug morphine is `m’. But in biochemistry there is a tendency to use Greek letters so they converted the ‘m’ to μ. Similarly a drug known as ketocyclazocine was first shown to attach itself to kappa receptors.[2] The opioid receptor types are ~70% identical with differences located at N and C termini. The μ receptor (the μ represents morphine) is perhaps the most important. It is thought that the G protein binds to the third intracellular loop of the opioid receptors. Both in mice and humans the genes for the various receptor subtypes are located on different chromosomes. Separate subtypes have been identified in human tissue. Research has so far failed to identify the genetic evidence of the subtypes, and it is thought that they arise from post-translational modification of cloned receptor types.[3] An additional opioid receptor has been identified and cloned based on homology with the cDNA. This receptor is known as the nociceptin receptor or ORL 1 receptor. From Stoelting 4th Ed: pg 89. “All 3 receptor classes couple to G proteins and subsequently inhibit adenylyl cyclase, decrease the conductance at voltage gated calcium channels, or open inward flowing potassium channels.” Suggests that opioid act via ligand gated ion channel and hence C correct. I think you have looked into it a bit too deeply. potassium channels are most likely activated in a similar way to those related to M2 muscarinic receptors in the AV node. ie Beta and delta (rather than usual Alpha subunit) of G protein activated ion channel (ie Still ligand activating G protein which THEN activates ion channel). Prob the same for Calcium channel but not sure. Would have to go for D Vec is a competitive antagonist for ligand gated ion channel. ::Agreed. A G-protein-coupled-receptor is a metabotropic receptor and IS NOT an ionotropic receptor (ligand-gated ion channel). References 1. Corbett AD, Henderson G, McKnight AT, Paterson SJ (2006).75 years of opioid research: the exciting but vain quest for the Holy Grail. Brit. J. Pharmacol.147, S153–S162 2. [1] 3. Fries, DS (2002). Opioid Analgesics. In Williams DA, Lemke TL. Foye’s Principles of Medicinal Chemistry (5 ed.). Philadelphia: Lippincott Williams & Wilkins. ISBN 0-683-30737-1.
GP20 [Jul02] Zero order kinetics means: A. ? B. ? C. Drug is eliminated at a constant rate regardless of dose. D. Elimination half time will vary according to dose. E. ?
Most correct answer is C, but would be better if worded “drug is eliminated at a constant rate regardless of plasma concentration” Zero-order kinetics (also referred to as saturation kinetics): the rate of elimination of a drug from the plasma is constant irrespective of the plasma concentration this differs from the exponential patterns of elimination seen in first-order kinetics A good example of this is ethanol, which is cleared from plasma at approx 4mmol/L/hour regardless of plasma concentration. The underlying reason for this constant rate of elimination is that the rate of oxidation by the enzyme alcohol dehydrogenase reaches a maximum at low ethanol concentrations (due to limited cofactor availability). Consequences of zero-order kinetics: duration of action is strongly dependent on drug dose the relationship between steady-state plasma concentration and dose is unpredictable D is also correct I think; elimination half-life is constant for first order processes, but varies with dose (and is thus a half-time) for zero order processes. in relation to D it is explained n wikipedia [1] t1/2 = initial conc/(2k) where k = r which is the constant rate of elimination. So increasing the dose or initial concentration will proprtionally increase the T1/2. D also seems correct.
GP21 [Feb04] All exist as racemic mixtures except: A. Thiopentone B. Lignocaine C. Bupivacaine D. Isoflurane E. Enflurane
Answer is B. Lignocaine is achiral and therefore does not have enantiomeric forms. A racemic mixture contains equal amounts of two enantiomers (non-superimposable mirror image molecules) of a chiral molecule; polarized light can be pass through a solution of these without being rotated. (Things get more complicated when the molecule has more than one chiral centre.) NB I think sodium thiopentone exists as a mixture of tautomers, which by definition have different connections between the same atoms, and therefore can’t be enantiomers and can’t give rise to a racemic mixture. (Stoelting p.127 implies, and Hemmings/Hopkins p.299 clearly states that thiopental is a racemic mixture - given both are texts I’d be happy to accept that thiopental is a racemic mixture and the answer is “B”). Furthermore, the tautomerism confers asymmetry to the barbituric ring thus making the C2 carbon chiral. NO - the C2 carbon has a double bond in the enol AND keto form. No carbon with a double bond can be chiral (ever, anywhere). If you meant the C5 carbon, it is not chiral either. Why? Because keto-enol (or in the case of thiopentone, thial-thioketone) tautomerism is a rapidly reversible process, in the supposedly asymetric form (thial) the double bond can point toward C4 or C6, those electrons are delocalised between C4 and C6 thus removing any asymmetry. The C5 carbon is never chiral in thiopentone. It only has 1 chiral centre which is the carbon attached to C5 in the longer of the 2 chains on C5. PS I’d disagree with that definition of a racemic mixture being only composed of enantiomers. Mivacurium is a unequal racemic mixture of diastereoisomers (geometric).
GP22 [Feb04] Clearance of a drug with a high hepatic extraction will be: A. Decreased in shock ??? B. Increased in high output states ??? C. ? D. ? E. ?
The clearance of drugs with a high hepatic extraction ratio are highly dependent on the flow through the liver. For example, a drug with a hepatic extraction ratio of 1.0 will have twice the clearance when the hepatic blood flow is doubled. Conversely a drug with a low hepatic extraction ratio will have its clearance minimally affected by doubling the hepatic blood flow. Therefore: A - correct as shock will decrease hepatic blood flow and hence clearance B - correct as increased cardiac output will increase hepatic blood flow and hence clearance Both are true I think. The clearance of drugs with a low extraction ratio (ER) is minimally affected in absolute terms by changes in blood flow (a 50 % increase or decrease of very little is still very little), whereas it will have a much larger (in absolute terms) impact for drugs with a high ER. Clearance = ER x blood flow. I think A is more correct because high output does not always correlate to higher hepatic blood flow whereas in shock, hepatic blood flow will definitely decrease.
GP23 [Feb04] The chemoreceptor trigger zone: A. Contains 5HT3 and D2 receptors B. Not involved in inner ear mediated nausea C. ? D. ? E. ?
Both A and ?B are correct. From Ganong (21st ed) p235-236: The Vomiting Centre exists in the reticular formation in the medulla. Afferents to this include: Viceral afferent pathways from the Upper GI Mucosa relayed via Sympathetic and Vagal Nerves Vestibular Nuclei afferents located in the inner ear that respond to motion, causing motion sickness Other afferents from the diencephalon and limbic systems - the response to nauseating smells and sickening sights The Chemoreceptor Trigger Zone (CTZ) whose cells are located in the area postrema (on the lateral wall of the 4th ventricle). This area is known as one of the circumventricular organs and is outside the Blood Brain Barrier. Lesions of the CTZ do not abolish the response to GI irritation or the motion sickness response. The Area Postrema has 5-HT3 and D2 receptors. This is why 5-HT3 antagonists and D2 antagonists are effective anti-emetics. Regarding part B - Kam p174 states that “impulses arising from endolymph movements in the utricle and saccule of the vestibular apparatus are relayed via the vestibular nucleus and VIIIth nerve to the CTZ”. KB’s books also states “The pathway is partly via the CTZ and partly directed to the vomiting centre. Drugs which block the CTZ do not completely prevent or treat motion sickness. Anticholinergic drugs such as hyoscine are more effective.” Therefore B is probably wrong. A : true B : false CTZ has all the receptors for 5-HT3, muscarinic, histamine-1, dopamine-2 and opioid receptors; it also receives input from vestibular labyrinth
GP24 [Feb04] [Jul04] Glutamate A. Dissociates slowly from the NMDA receptor B. Does not act at AMPA and kainate receptors C. Inhibitory neurotransmitter in CNS D. ?
A - correct (see below) B - incorrect (has actions at NMDA, kainate and AMPA receptors according to Ganong Ed.22 2005 Table 4-2) C - incorrect; glutamate is an excitatory neurotransmitter Ref: Glutamate unbinding reveals new insights into NMDA receptor activation Alasdair J. Gibb The Journal of Physiology Volume 574 Issue 2 Page 329 - July 2006 doi:10.1113/jphysiol.2006.114017 Volume 574 Issue 2
GP25 [Feb04] Regarding pharmacokinetics in pregnancy: A. Paracetamol uptake increased B. Increased sensitivity and faster onset with thiopentone C. Hepatic clearance decreased by decreased protein binding D. ? E. ?
B is correct (See Gin et al in ref section) Some notes unreferenced as they are from memory only: A. False - Delayed gastric emptying = delayed absorption B. True - Increased cardiac output increases speed of onset C. False - Decreased PPB = Increased free drug available for hepatic extraction B is correct, but I don’t think it is due to the increased cardiac output. The increased cardiac output will result in a lower thiopentone concentration in blood leaving the heart (essentially indicator dilution), and as cerebral blood flow remains constant, an increased CO will result in the same flow to the brain, but this flow will be a smaller percentage of total cardiac output. Therefore, the pregnant brain will receive the same volume per unit time of blood but with a lower thiopentone concentration which would normally causes an apparent resistance to a stated dose, so other factors must cause the observed response of increased sensitivity (eg decreased PPB or the effects of progesterone) “The dose of thiopentonal needed to produce anaesthesia in early pregnancy (7-13weeks gestation) is decreased about 18% compared with that for nonpregnant females.” Stoelting. 4th ed. p132. “The half-emptying time and the final gastric emptying time did not differ in the first and third trimesters and postpartum, but gastrointestinal transit time was significantly longer in the third trimester of pregnancy than postpartum” - Journal of Gastroenterology August 2001 http://www.ncbi.nlm.nih.gov/pubmed/11519832 B true : My reason would be that during pregnancy there is a reduction in plasma albumin and hence, unbound STP is more readily available for its effect site. I too feel an increase in cardiac output will cause a delay in speed of onset of the drug. For example, a patient with low cardiac output state require lower dose during induction
GP26 [Jul04] Which is an antagonist at the NMDA receptor? A. Dexamethasone B. Dextropropoxyphene C. Dexmedetomidine D. Dextromethorphan E. Dexmethamphetamine
Answer is D - “Although dextromethorphan is known to function as an NMDA-receptor antagonist, the dextromethorphan-binding sites are not limited to the known distribution of NMDA receptors (Elliott et al., 1994).” from Goodman and Gilman Dextromethorphan, marketed primarily as an antitussive, is an antagonist of the glutamatergic NMDA receptor (Ref:Wikipedia ) A - synthetic glucocorticold steriod B - Dextropropoxyphene napsylate is a centrally acting, synthetic opioid analgesic structurally related to methadone (MIMS) C - full alpha 2 agonist E - Sympathomimetic
GP27 [Jul04] Comparing dexamethasone and hydrocortisone: A. Both are endogenous hormones B. Dexamethasone has 8x potency of hydrocortisone C. Both have mineralocorticoid activity D. Dexamethasone is the only water-soluble compound
From Peck, Hill and Williams: A - Incorrect as dexamethasone is synthetic B - incorrect as dexamethasone has 25 times the potency (use 4mg qid vs 100mg qid) C - ?incorrect as ?dexamethosone has very little if no mineralocorticoid activity D - ? correct - beware absolutes (dex is the ONLY…) but below seems convincing. Glucocorticoids are steroid hormones and thus will be naturally less water soluble and more lipophilic hydrocortisone (ie cortisol) is the main endogenous glucocorticoid in humans, dexamethasone is synthetic dexaethasone has 25 times the anti-inflammatory potency of hydrocortisone glucocorticoids have weak mineralcorticoid activity hydrocortisone is made up in water for injection Therefore, it would seem that C is the correct answer From MIMS: Dexamethasone is synthetic, hydrocortisone is endogenous Dexamethasone is 25x as potent as hydrocortisone. Dexamethasone and betamethasone have almost no mineralocorticoid activity Dexamethasone is water soluble (about 3000 x as H2O soluble as hydrocortisone, which is listed as practically insoluble in H2O [1]). ‘Solu-Cortef’ is the sodium succinate ester, which adds to its water solubility, and explains why it appears to be H2O soluble in a clinical setting. Hydrocortisone can’t be that water soluble - there’s a preparation available with cyclodextrins Comparison of potency Glucocorticoid activity Mineraldocorticoid activity Dose Equivalent Hydrocortisone 1 1 100mg Prednisolone 4 0.8 25mg Methyl Pred 5 0.5 20mg Dex 25 0 4mg Fludrocortisone 10 125 N/A Just so happens the usual doses make sense!
GP28 A drug has hepatic extraction ratio of 0.7 and is 30% abosorbed, what is the bioavailability A. 0.3 B. 0.7 C. 0.21 D. 0.09 E. 0.03
0.3 x (1- 0.7) = 0.09
GP29 Which of the following drugs cannot cross the BBB? A. Ondansetron B. Scopolamine C. Metoclopramide D. Droperidol E. Domperidone
E
GP30 Mar09 [Mar10] With regard to LD50: A. Is the mean lethal dose in animals B. Something about probit’s relation to standard deviation C. Animals are given increasing doses of a drug until they die D. ? E. Something about log concentration being plotted against something using probits to linearize the data for humans
NOTE: Similar MCQs: GP05 LD50: GP13 Therapeutic index: Comments GP 30 ( mar 09) very difficult question we know A wrong C sounds tempting. B, D ,E god knows. quick google search in wikipedia about dose response relationship brought out the following Statistical analysis of dose-response curves may be performed by regression methods such as the probit model or logit model, or other methods such as the Spearman-Karber method. Empirical models based on nonlinear regression are usually preferred over the use of some transformation of the data that linearizes the dose-response relationship. Dose-response curves can be fit to the Hill equation (biochemistry) to determine cooperativity. Problems exist regarding non-linear relationships between dose and response, thresholds reached and ‘all-or-nothing’ responses. These inconsistencies can challenge the validity of judging causality solely by the strength or presence of a dose-response relationship. A threshold model or linear no-threshold model may be more appropriate, depending on the circumstances. Endocrine disruptors have also been cited with producing one effect at high dose and a different effect at low doses.’ follow up on the matter proved too time consuming and confusing so just gave up! March10 D quantal dose response curve sound right as we re looking at population % effect to drug (ED50or LD50 in this case) as opposed to graded dose response curves which look at an individual response eg muscle relaxants and 95% reduction in twitch height (EC50). [goodman] D is correct - Quantal dose-response curves Wrong answers: A - ??What?? Wrong by exclusion! B - is the ‘median’ lethal dose! C - no, quantal E - no, you group the animals and give each group a fixed dose. JB2012 Re probit crap: “Method A: Using your hand drawn graph, either created by eye or by calculating the regression by hand, find the probit of 5 in the y-axis, then move down to the x-axis and find the log of the concentration associated with it. Then take the inverse of the log and voila! You have the LC50.” [http://userwww.sfsu.edu/efc/classes/biol710/probit/ProbitAnalysis.pdf] So A is wrong as Probit = 5 is the LC50 (?or LD50) TW
GP30 (Mar10 version) Which is true for LD50? A. a probit score of 5 means it is 5 SD away from the median B. mean lethal dose C. calculated from graded dose-response curves D. calculated from quantal dose-response curves E. you keep giving a bunch of animals a drug until the animals die
NOTE: Similar MCQs: GP05 LD50: GP13 Therapeutic index: Comments GP 30 ( mar 09) very difficult question we know A wrong C sounds tempting. B, D ,E god knows. quick google search in wikipedia about dose response relationship brought out the following Statistical analysis of dose-response curves may be performed by regression methods such as the probit model or logit model, or other methods such as the Spearman-Karber method. Empirical models based on nonlinear regression are usually preferred over the use of some transformation of the data that linearizes the dose-response relationship. Dose-response curves can be fit to the Hill equation (biochemistry) to determine cooperativity. Problems exist regarding non-linear relationships between dose and response, thresholds reached and ‘all-or-nothing’ responses. These inconsistencies can challenge the validity of judging causality solely by the strength or presence of a dose-response relationship. A threshold model or linear no-threshold model may be more appropriate, depending on the circumstances. Endocrine disruptors have also been cited with producing one effect at high dose and a different effect at low doses.’ follow up on the matter proved too time consuming and confusing so just gave up! March10 D quantal dose response curve sound right as we re looking at population % effect to drug (ED50or LD50 in this case) as opposed to graded dose response curves which look at an individual response eg muscle relaxants and 95% reduction in twitch height (EC50). [goodman] D is correct - Quantal dose-response curves Wrong answers: A - ??What?? Wrong by exclusion! B - is the ‘median’ lethal dose! C - no, quantal E - no, you group the animals and give each group a fixed dose. JB2012 Re probit crap: “Method A: Using your hand drawn graph, either created by eye or by calculating the regression by hand, find the probit of 5 in the y-axis, then move down to the x-axis and find the log of the concentration associated with it. Then take the inverse of the log and voila! You have the LC50.” [http://userwww.sfsu.edu/efc/classes/biol710/probit/ProbitAnalysis.pdf] So A is wrong as Probit = 5 is the LC50 (?or LD50) TW
GP31 [Mar10] Which is not a ligand gated channel?. A. Alpha-2 Receptor B. 5HT3 Receptor C. Nicotinic cholinergic receptor D. GABA receptor E. NMDA receptor
A. Alpha-2 Receptor - receptors linked to G protiens A is correct B. 5HT3 Receptor - is ligand gated C. Nicotinic cholinergic receptor - is ligand gated D. GABA receptor - ligand gated E. NMDA receptor - is ligand gated Comment: odd question “Which is not a ligand gated channel?” - then lists a bunch of receptors Aren’t all receptors ligand gated ? - given that is the definition of a receptor ? wording remembered incorrectly ? possibly which of the following receptors is directly linked to a ion channel (ie ionotropic) which would make A correct (still) bah Ion channels: gated / ungated Gated: ligand / voltage / 2nd messenger / mechano Receptors: ionotropic, metabotropic, nuclear Ionotropic receptors are directly linked to ion channels Metabotropic receptors act via second messengers G-proteins (assoc with GPCR) mainly affect second messangers (metabotropic) but can also directly affect ion channels eg Kir (ionotropic) Adrenoreceptors are metabotropic 5-HT3 receptors are ionotropic (all the others are metabotropic) Nicotinic receptors are ionotropic (unlike muscarinic which are metabotropic) GABAa receptor is ionotropic (but GABAb is metabotropic) NMDA receptor is ionotropic (but also voltage sensitive)
GP32 G proteins: A. Always have 3 subunits B. Alpha subunit has intrinsic GTPase activity C. One G protein only attached to one G protein coupled receptor D. Spans membrane 7 times
A Always and Never! B Sounds about right to me (Yentis) C only! Who knows. D Its Gprotein coupled receptor does. A - Not true, there are large and small G proteins (see below) B - True; it’s intrinsic but allosterically activated (see below) C - True, although this is inferred from GPCR diagrams (see below) D - The G protein receptor does, not the G protein itself From Wikipedia (http://en.wikipedia.org/wiki/G_protein) “G protein can refer to two distinct families of proteins. Heterotrimeric G proteins, sometimes referred to as the “large” G proteins that are activated by G protein-coupled receptors and made up of alpha (α), beta (β), and gamma (γ) subunits. There are also “small” G proteins (20-25kDa) that belong to the Ras superfamily of small GTPases. These proteins are homologous to the alpha (α) subunit found in heterotrimers, and are in fact monomeric.” “The Gα subunit will eventually hydrolyze the attached GTP to GDP by its inherent enzymatic activity” Also from Wikipedia (http://en.wikipedia.org/wiki/G_protein-coupled_receptor) “Upon receptor activation, the GEF domain, in turn, allosterically activates the G-protein by facilitating the exchange of a molecule of GDP for GTP at the G-protein’s α-subunit.” “GPCRs are integral membrane proteins that possess seven membrane-spanning domains” “When the receptor is inactive, the GEF domain may be bound to an also inactive α-subunit of a heterotrimeric G-protein.” This wording and all diagrams on the page suggest one G-protein beinds to each GPCR. - Comment: Peck and Hill, p27: “The G-protein system produces signal amplification… A single activated GCPR can stimulate multiple G-proteins and each G-protein can activate several intermediate messengers.” As a result I would answer B.
GP33 [Aug11] When is the safest time to give a drug to a lactating mother? A. 3 - 4 hours before breastfeeding B. Immediately before breastfeeding C. Immediately after breastfeeding D. 30 - 60 minutes after breastfeeding E. Either A or D
Answer E - lifted straight from the book: “If the nursing mother must take medications and the drug is a relatively safe one, she should optimally take it 30-60 minutes after nursing and 3-4 hours before the next feeding.” -from Katzung 11th ed, Ch59 Why do you have to take it 30-60 minutes after nursing? If the purpose is to minimize the concentration of the drug in breast milk, the only thing that matters is the duration elapsed prior to the next feeding. The 30-60 minutes bit doesn’t make much sense. –Yy 19:10, 10 May 2014 (CDT)
GP34 [Aug11] Which of the following drugs has low first pass metabolism A. Lignocaine B. Morphine C. Metoclopramide D. Midazolam E. Aspirin
A. Lignocaine: has high lung uptake, but is this truly “first pass metabolism” (as the lung is more like storage, less actual metabolism). However, if given orally it would probably have a high hepatic first pass metabolism. B-E: Bioavailability values of the others (from Smith, “Drug in Anaesthesia and Intensive Care” 4Ed) Morphine: 44% Metoclopramide: 32-95% Midazolam: 44% Aspirin: 70% No good answer, but aspirin seems best. Thoughts anyone? JB2012 From Wikipedia (http://en.wikipedia.org/wiki/First_pass_effect) Notable drugs that experience a significant first-pass effect are imipramine, morphine, propranolol, buprenorphine, diazepam, midazolam, demerol, cimetidine, and lidocaine (lignocaine). Lignocaine, morphine and midazolam are all mentioned there. Metoclopramide bioavailability varies from 30-100% (Bateman, 1983, Clinical pharmacokinetics of metoclopramide). Aspirin bioavailability 80-100% according to reference.medscape.com. Thus I’d say the answer is A. Aspirin. Comment: Stoelting 4E p282 states aspirin is rapidly hydrolysed in the liver - but it doesn’t give a bioavailability figure. The same text also states that metoclopramide undergoes “extensive” first pass metabolism. Combined with the Wiki reference above, I’d probably agree that aspirin is the best answer to a bad question.
GP35 [Aug11] All are secreted by the proximal tubule in the kidney except: A. Diazepam B. Morphine C. Probenicid D. Penicillin E. Frusemide
A - Diazepam is not. B - Morphine is C - Probenicid is D - Penicillin - main mechanism of clearance E - Frusemide - is part of it’s mechanism of action Useful table at [1]] http://en.wikipedia.org/wiki/Table_of_medication_secernated_in_kidney I don’t know about others, but I had a hard time finding the specific site of excretion in the recommended texts!
GP36 [Aug11] Elimination coefficient Units (Repeat) A. ? B. mcg/ml C. mg/ml D. ? E. ?
Presumably these questions specified whether the drug in question underwent First or Zero Order kinetics assuming that it was for First Order Kinetics, the answer will always be time-1
GP36b [Feb12] [Jul12] The units of rate constant k are? A. mg/min B. mcg/kg/min C. min D. min-1 ( true - see below) E. ml-1
Presumably these questions specified whether the drug in question underwent First or Zero Order kinetics assuming that it was for First Order Kinetics, the answer will always be time-1
GP37 [Aug11] Which drug reversibly inhibits platelet aggregation?* Repeat* A. clopidogrel B. warfarin C. [[heparin] D. diclofenac E. aspirin
Answer: diclofenac Aspirin covalently, ie. irreversibly binds to cox-1 Diclofenac reversibly binds to cox-1 clopidogrel binds irreversibly to platelet ADP receptors, thus inhibiting ADP activation of the GPIIb/IIIa complex Heparin does not affect platelet function- is involved in clotting cascade Warfarin does not affect platelet function - is involved in clotting cascade
Which of the following causes reversible inhibition of platelet function? A. aspirin B. heparin C. warfarin D. diclofenac E. clopidogrel
Answer: diclofenac Aspirin covalently, ie. irreversibly binds to cox-1 Diclofenac reversibly binds to cox-1 clopidogrel binds irreversibly to platelet ADP receptors, thus inhibiting ADP activation of the GPIIb/IIIa complex Heparin does not affect platelet function- is involved in clotting cascade Warfarin does not affect platelet function - is involved in clotting cascade
Which one causes reversible impairment of platelet function? A. Aspirin B. diclofenac C. clopidogrel D. heparin E. warfarin
Answer: diclofenac Aspirin covalently, ie. irreversibly binds to cox-1 Diclofenac reversibly binds to cox-1 clopidogrel binds irreversibly to platelet ADP receptors, thus inhibiting ADP activation of the GPIIb/IIIa complex Heparin does not affect platelet function- is involved in clotting cascade Warfarin does not affect platelet function - is involved in clotting cascade
Which one is not a second messenger? A. c-AMP B. c-GMP C. Ca2+ D. G Proteins E. Nitric oxide
A - True B - True C - True D - True - G-Proteins are coupled to receptors and they activate second messengers E - True
Feb 2012 options: A. c-AMP B. c-GMP C. Guanine cyclase D. G Proteins E. Nitric oxide (Edit: I thought option C may have been Ca++, not guanine cyclase)
A - True B - True C - True D - True - G-Proteins are coupled to receptors and they activate second messengers E - True
G proteins A. binds 4 sites B. has 2 alpha subunits C. D. E.
A - not sure B - False - heteroTRImeric - 3 different subunits - alpha, beta and gamma
If a drug has a Vd of 0.6L/kg, it is reasonable to assume: A. It distributes throughout TBW, and is not lipid soluble. B. Something about Vd equals body water volume …
A - false - seems counterintuitive to be able to distribute throughout TBW whilst being lipid insoluble. PH&W divides VD into 3 groups: drugs that are confined to the plasma - highly protein bound or too large to cross the vascular endothelium; those with limited distribution e.g. NDMRs which are polar, poorly lipid soluble and bulky, hence limited to tissues with fenestrated capillaries (i.e. muscle) - they cannot cross cell membranes and work extracellularly those with extensive distribution - highly lipid soluble, small MW and weak plasma protein binding, and others which are sequestered by tissues B - true total body water for a 70kg man is 42litres or 42/70 = 0.6L/kg Brandis p1: “What is the total body water in an adult male?” - “42 litres in the 70 kg man. This is 60% of total body weight (le 600 mls H2O/kg body wt.) “
[[GP41] Feb11 Which drug is optimally given as a racemic mixture? A. morphine B. bupivacaine C. noradrenaline D. methadone E. dexmedetomidine
Comments re the Feb11 version: Dexmedetomidine is not racemic. Methadone is and there is some vague google discussion about an enantiomer being better than the other. What does optimally mean because bupivacaine (racemic) is more potent but more toxic. Evers and Maze make no discussion on the chirality fo norepinephrine (they also have an entry for noradrenaline in the index!). At a guess, the only answer where racemic applies with a real discussion would therefore be B. If only they had put tramadol there. Comment - answer D - methadone L isomer is an opioid receptor agonist, d isomer blocks the NMDA receptor, therefore optimal effect from methadone is the racemic mixture The question should read “Which drug is most effective given as a racemic mixture”. It is asking which racemic mixture is most effective, not if its better than an enantiomer. Racemic morphine, noradrenaline, and methadone are not as efficacious as their active enantiomer (the “inactive” enantiomer has weaker actions). Dexmetetomidine is not racemic. Therefore, this leaves bupivacaine. Racemic bupivacaine is equally as efficacious as levobupivacaine but racemic bupivacaine has more toxicity. Answer is B. Re the [Aug11] version: A. Noradrenaline ->false - d-norad (and d-adren) are half as active as the levo forms (levo isoprenaline is 1000x more active than dextro (Stoelting 4th ed page 294) B. Morphine -> False morphine has 5 chiral centres and only one stereoisomer has significant activity. C. Methadone -> TRUE - d isomer of methadone has N-methyl-D-aspartate (NMDA) receptor antagonist activity, L- isomer has mu agonist activity D. Bupivacaine -> false levobupivacaine has a similar potency and efficacy to bupivacaine, but with a better CVS toxicity profile E. Dexmedetomidine -> false DEXmedetomidine - it could hardly be dextrorotatory in a racemic mixture.
GP41 [Aug11] Drug given optimally as racemic mixture: A. Noradrenaline B. Morphine C. Methadone D. Bupivacaine E. Dexmedetomidine
Comments re the Feb11 version: Dexmedetomidine is not racemic. Methadone is and there is some vague google discussion about an enantiomer being better than the other. What does optimally mean because bupivacaine (racemic) is more potent but more toxic. Evers and Maze make no discussion on the chirality fo norepinephrine (they also have an entry for noradrenaline in the index!). At a guess, the only answer where racemic applies with a real discussion would therefore be B. If only they had put tramadol there. Comment - answer D - methadone L isomer is an opioid receptor agonist, d isomer blocks the NMDA receptor, therefore optimal effect from methadone is the racemic mixture The question should read “Which drug is most effective given as a racemic mixture”. It is asking which racemic mixture is most effective, not if its better than an enantiomer. Racemic morphine, noradrenaline, and methadone are not as efficacious as their active enantiomer (the “inactive” enantiomer has weaker actions). Dexmetetomidine is not racemic. Therefore, this leaves bupivacaine. Racemic bupivacaine is equally as efficacious as levobupivacaine but racemic bupivacaine has more toxicity. Answer is B. Re the [Aug11] version: A. Noradrenaline ->false - d-norad (and d-adren) are half as active as the levo forms (levo isoprenaline is 1000x more active than dextro (Stoelting 4th ed page 294) B. Morphine -> False morphine has 5 chiral centres and only one stereoisomer has significant activity. C. Methadone -> TRUE - d isomer of methadone has N-methyl-D-aspartate (NMDA) receptor antagonist activity, L- isomer has mu agonist activity D. Bupivacaine -> false levobupivacaine has a similar potency and efficacy to bupivacaine, but with a better CVS toxicity profile E. Dexmedetomidine -> false DEXmedetomidine - it could hardly be dextrorotatory in a racemic mixture.
GP42 [Feb12] When calculating loading dose which of the following factors is not taken in to account? A. T1/2 Keo B. Vd C. Target concentration D. ?? Maybe previous doses given? E. ? maybe clearance
Re Feb12 version: A. T1/2 Keo -> TRUE - is the effect site equilibration time, and does not affect the required plasma concentration to be acheived B. Vd -> false - this is definitely needed C. Target concentration -> false - this is definitely needed D. ?? Maybe previous doses given? -> not sure E. ? maybe clearance ? -> don’t think so Bioavailability is relevant for oral administration ?15A version also present on 14B paper? For 14B/15A version, context sensitive half life (option E) likely is the best answer. I have no idea what Leo is.
15A version When calculating a loading dose prior to infusion of a drug, what factors are NOT considered: A. Vd B. Leo C. Toxicity and side effects D. Plasma concentration E. Context sensitive half time
Re Feb12 version: A. T1/2 Keo -> TRUE - is the effect site equilibration time, and does not affect the required plasma concentration to be acheived B. Vd -> false - this is definitely needed C. Target concentration -> false - this is definitely needed D. ?? Maybe previous doses given? -> not sure E. ? maybe clearance ? -> don’t think so Bioavailability is relevant for oral administration ?15A version also present on 14B paper? For 14B/15A version, context sensitive half life (option E) likely is the best answer. I have no idea what Leo is.
GP43 [Feb12] The liver oxidation reactions generally: A. Increase hydophobicity B. Decrease lipophylicity C. Decrease polarity D. Make more water-soluble
A. Increase hydophobicity -> false B. Decrease lipophylicity -> TRUE, as a consequence of increasing polarity and water solubility C. Decrease polarity -> false D. Make more water-soluble -> true
GP44 [Feb12] Drugs cause Hypersensitivity reaction: A. Type 1 hypersensitivity is IgG mediated B. Type 3 - something about happen…eh? C. T cell involved in all types of hypersensitivity D. ? E. ?
A False -> IgE B ? C - False -> in type IV only Hypersensitivity Type I -> Immediate hypersensitivity - IgE Mediated - occurs within minutes of exposure to an antigen - cross linking of membrane bound IgE on blood basophils or mast cells causes degranulation - release of histamine, leukotrienes, and eosinophil chemotactic factor, inducing anaphylaxis, asthma, hay fever or urticaria in affected individuals. Type II -> Cytotoxic hypersensitivity -aka: Antibody-mediated hypersensitivity - IgG or IgM + antigen -> complex -Transfusion reactions - if not matched preformed Ab in recipient serum bind to donor RBC cell membrane antigens -> activate complement cascade -> Membrane Attack Complex -> cell lysis. -Mechanism of ABO and Rhesus incompatibility. Rhesus disease preventable by admininstration of anti D Ab to Rh D-ve mother 24-48hours post partum with a Rh D+ve baby. Type III -> Immune complex hypersensitivity - due to presence of elevated levels of antigen-antibody complexes that deposit on basement membranse of tissues and vessels. -> complement activation -> chemotaxis and anaphylatoxic - >increased vascular permeability and neutrophil recruitment. -> skin rashes, glomerulonephritis and arthritis. - 3-4 days post exposure to antigen Type IV -> Cell-mediated (or delayed) hypersensitivity - AKA: T cell mediated hypersensitivity - 2-3 days post exposure - T helper1 cells -> local inflammation recruited under influence of
GP45 [Feb12] Dopamine receptors: A. 3 subtypes (receptors, not antagonists) B. GPCRs C. effect on cAMP or something (yeah, or some intracellular second messenger) D. something about D2 receptors
A - false - 5 types B - True - all are GPCR (some Gs(D1 and D5) and some Gi (D2, D3, D4) C - True - they either Stimulate (Gs) or Inhibit (Gi) cAMP D - Dopamine Receptors 5 types D1 like receptor family - Gs protein ↑cAMP – D1, D5 D2 like receptor family - Gi protein ↓cAMP – D2, D3, D4 CNS: There are 3 main dopaminergic pathways containing D1-5 Nigrostriatal – motor control. Mesolimbic/mesocortical – behavioural effects Tuberohypophyseal – endocrine control (prolactin) The medulla contains D2 at the chemoreceptor trigger receptor zone – causes nausea & vomiting Action Agent Selectivity Usage Agonist Bromocriptine Carbergoline Non selective D2 Selective Rx of Parkinson’s & prolactinomas. Antagonist Prochlorperazine Droperidol Metoclopramide All D2 selective Antiemetics Periphery: D1 receptors are postsynaptic on renal, mesenteric, splenic & coronary vascular smooth muscle causing vasodilation. Renal effects are strongest ↑blood flow. Also located in the proximal tubule → natriuresis through inhibition of Na+/K+ATPase pump. D2 receptors are presynaptic and inhibit noradrenaline and perhaps acetylcholine release. Action Agent Selectivity Usage Agonist Dopamine Fenoldopam Non selective D1 Selective Inotrope Antihyopertensive Antagonist Domperidone D1 selective (prokinetic effects may be due to ↑ Acetylcholine in the gut.) Antiemetic
GP46 [Feb12] Bromocriptine? A. Is a dopamine agonist B. …?COMT C. ?
Bromocriptine? A. Is a dopamine agonist -> TRUE B. …?COMT -> not a COMT inhibitor Agonist at dopamine receptors: http://www.kerrybrandis.com/wiki/mcqwiki/index.php?title=GP46
GP47 [Aug11] [Feb12] (NB: This Q also recorded as FE08) Hartmanns solution: A. calcium 2mmol/l B. lactate 5mmol/l C. isotonic with plasma D.
A - true B - False - 29mmol/litre C - False - very slightly hypotonic Plasma tonicity is 290mOsmol/litre (clearly a simplistic answer with no account for haematocrit etc.)* hartmanns contains 278mmol/litre According to wikipedia Hartmann’s contains: 131 mEq of sodium ion = 131 mmol/L 111 mEq of chloride ion = 111 mmol/L 29 mEq of lactate = 29 mmol/L 5 mEq of potassium ion = 5 mmol/L 4 mEq of calcium ion = 2 mmol/L 131+111+29+5+2= 278mmol/litre
GP43 Aug15 All of the below act via increasing cAMP except A. Digoxin B. Glucagon C. Adrenaline D. ? E. ?
?
IN01 [Mar96] Which compound(s) is/are broken down in soda-lime? A. Nitrous oxide B. Halothane C. Sevoflurane D. Desflurane E. All of the above
Comments A - False B - True C - True D - False E - False The above answers were obtained from Table 2-1 p.37 of Stoelting 3rd Ed. Of the six gases listed (N2O, halothane, enflurane, isoflurane, desflurane, sevoflurane), only halothane and sevoflurane were NOT stable in soda lime at 40 degrees. See Stoelting: Carbon monoxide results from the degradation of CF2 containing moieties of volatiles (Des> En> Iso)… Sodalime (and baralyme) degrades all halogenated anaesthetics (due to the interaction of the anaesthetic with the small amounts of NaOH or KOH in the absorbant), although desflurane appears to be more stable at below 80 degrees celcius than the others. Sevoflurane degrades the most. Increased temperatures lead to greater degradation, whilst increased water concentration in the absorbent decreases degradation. The temperature in the absorbant with low flow closed circuit anaesthesia is about 40-60 degrees. The main consequences of degradation are: loss of anaesthetic agent (clinically not significant if the absorbent is kept moist), and toxicity. exploding sodalime canisters (if it gets hot enough!) Toxicity from the production of compound A from Sevoflurane, and from the degradation product of halothane as well. Compound A has been shown to cause proteinuria and enzymuria in humans (dose-related exposure) but has only been shown to be nephrotoxic in rats. Dry absorbants can degrade desflurane, isoflurane and enflurane producing carbon monoxide, although rarely in clinically significant amounts. Doesn’t Des/En/Isoflurane react with CO2 absorbent producing carbon monoxide? Or is this not considered as a “breakdown” process? References & related material ‘The Pharmacology of Inhaled Anaesthetics’, Eger et al.
IN02 [Mar96] Regarding nitrous oxide at 70%: A. Synthetised from ? & N2 at 273C B. Decreases muscle blood flow by 30% C. Decreases cerebral autoregulation 24% D. ?
INO2 A - incorrect. “Manufactured by heating ammonium nitrate to 240 degrees celsius and removing impurities… by passage through scrubbers and waters” (Yentis et. al., Anaesthesia and Intensive Care A-Z, 2004, p.371) B - probably incorrect - “Nitrous oxide does not change SVR” (Stoelting 3rd ed p46) C - ?correct. “increases cerebral blood flow and ICP slightly” (Yentis 2004, p.371, and Stoelting), which indicates a decrease in autoregulation, but is it by 24%?! Correction: Nitrous oxide does NOT relax skeletal muscles (page 72 Stoelting)
IN02b [Jul97] Nitrous oxide (N2O): A. ?Increases/decreases CBF B. Is an effective oxidant C. Is made by heating nitrogen and oxygen in an iron retort D. Decreases pulmonary artery pressure in neonates
IN02b A - correct if says INCREASES CBF, see answer for C IN02 B - Note the yellow warning sticker on the cylinder [1] C - Incorrect, see answer A for IN02 D - Incorrect. NITRIC oxide is used to treat pulmonary hypertension, not nitrous oxide
IN02c [Feb08] Nitrous oxide at 70% A. 99% equilibration at 3 minutes B. About 10L uptake within first 3 minutes C. Reduces muscle blood flow by 30% D. Decreases cerebral autoregulation by 70% E. ?
IN02c Nitrous oxide at 70% A. 99% equilibration at 3 minutes - incorrect; takes longer than this - Stoelting p27 ‘ Inhalation of a constant PI of nitrous oxide… for 10 minutes results in a PA that is >80% of the PI).’ Figure 1.18 indicates around 90% equilibtration at 3 mintues, 98% at 10 minutes. B. About 10L uptake within first 3 minutes - Incorrect Stoelting p27 ‘up to 10 liters during the first 10 to 15 minutes’. C. Reduces muscle blood flow by 30%. - I think this is the only likely answer. Recall that it has a muscle relaxant effect, reducing metabolic requirements thus vasoconstricting via metabolic autoregulation. D. Decreases cerebral autoregulation by 70% - Incorrect. Recall that this is 0.69 MAC - CBF will be minimally altered.
IN03 [Mar96] [Jul96] [Jul97] [Jul98] [Jul99] The following drugs are (potent) triggers for malignant hyperthermia EXCEPT: A. Decamethonium B. Suxamethonium C. Isoflurane D. Halothane E. Calcium F. Sevoflurane G. Tubocurarine H. Nitrous oxide (Different options on different papers)
The drugs which are triggers for MH are: All potent inhalational agents All depolarizing muscle relaxants (ie succinylcholine, decamethonium) Safe Drugs: All other anesthetic drugs including N2O, thiopentone, benzodiazepines, droperidol, ketamine, etomidate, propofol, narcotics, non-depolarizing muscle relaxants, anticholinergics, anticholinesterases, local anesthetics Avoid verapamil, diltiazem potential hyperkalemia if Dantrolene given (Ref: UCLA MH site From the MHAUS site: Use local or regional anesthesia but general anesthesia with non-triggering agents is acceptable. Safe drugs include: barbiturates, benzodiazepines, opioids, nondepolarizing neuromuscular blockers and their reversal drugs, and nitrous oxide. For this MCQ,the options which are NOT triggers are: Calcium Tubocurarine Nitrous oxide - considered safe but a weak trigger, increased risk 1.3 times (Stoelting 3rd ed p65) The depolarisers are the most potent triggers, increasing the risk of triggering an episode by a factor of about four (from 1/250,000 adult anaesthetics, to 1/60,000). References Oh’s Intensive Care Manual, 5th, ISBN:0750651849, p768 UCLA Malignant hyperthermia The ABCs of MH (at MHAUS)
IN04 [Mar96] [Mar03] IPPV with Isoflurane at 1 MAC results in: A. Depresses cardiovascular reflexes more than halothane B. Causes decreased conduction velocity C. Maintains cerebral autoregulation D. Equal respiratory depression to enflurane E. Reduction in cardiac output by 25% F. Increased vasodilatation
A - False - Isoflurane reduces SVR with a baroceptor mediated increase in heart rate. Halothane reduces contractility as well as abolishing baroceptor mediated tachycardia. Decreased cardiac conductivity with halothane causes bradycardia and catecholamine sensitivity. (Peck 2nd ed 110-119) B - False - No effect on conduction at 1 MAC, however may decrease at >1.5MAC (see reference below) C - True: “autoregulation of CBF in response to changes in systemic blood pressure is retained during administration of 1 MAC isoflurane but not halothane”; Fig 2-7 (Stoelting 3rd ed, p.41) D - False - Enflurane is the worst regards respiratory profile. Most reduced tidal volume and highest pCO2. E - False: “Halothane, but not isoflurane… produce dose dependent decreases in cardiac output when administered to healthy human volunteers” (Stoelting 3rd ed, p.45) F - True: “Isoflurane… decrease(s) systemic vascular resistance… reflect(ing) substantial (up to fourfold) increases in skeletal muscle flow”; Fig 2-15 (Stoelting 3rd ed, p. 46) Volatiles I have loved: Halothane: Worst on heart contractility, heart rate low and catecholamine sensitising and incr. CBF. Preserves SVR and resp. Hepatitis (two forms) Isoflurane: Remember coronary steal, cardiac pre-conditioning (ATP dependant K channels), no change CBF up to 1 MAC. Pungent. Enflurane: Worst respiratory depression, epileptiform EEG. Sevo: Only memorable stuff is physical…largest MW, BP, lowest SVP. remember Cpd A. Des: Pungent - breath hold and secretions, sympathetic stim if rapid increase in Fi. High MAC. Lowest B:G coeffic. Carbomonoxide poisoning (also iso and enfl). All this from Peck Hill and Williams 2nd 110-119. Ozaki S, Nakaya H, Gotoh Y, Azuma M, Kemmotsu O, Kanno M. Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan. This study was undertaken to determine whether isoflurane, a volatile anesthetic that is reported to possess a wide margin of cardiovascular safety, exerts electrophysiological effects on cardiac tissue. By use of standard microelectrode techniques, effects of isoflurane on the maximum rate of rise of action potential upstroke (Vmax) and conduction velocity were examined in guinea pig papillary muscles. Isoflurane decreased action potential amplitude and action potential duration in a concentration-dependent fashion. Isoflurane at 1.5 and 2.0 MAC decreased conduction velocity with as little influence on the maximum rate of rise of action potential upstroke as that exerted by halothane and enflurane. However, the effect of isoflurane in slowing intraventricular conduction was less than that of halothane and enflurane when compared at equi-MAC concentrations. Thus, isoflurane may be a safer anesthetic for the patients with intraventricular conduction abnormalities.
IN05 [Mar96] [Mar98] The effect of increased cardiac output on Pa versus time for volatile agents is: A. No effect B. Decrease slope C. Decrease then increase slope D. Increase then decrease slope
B- decreases slope, as Pa equilibrates with PA. PA will be reduced (Decreased FA/FI curve) due to transport away from lungs by increased C.O.
IN06 [Mar96] [Jul97] [Apr01] Nitrous oxide: A. Supports combustion B. Is flammable C. Causes muscle rigidity D. In tissues is slower to reabsorb than oxygen E. Has a partition coefficient of 0.76 F. All of the above G. Is formed by heating oxygen & nitrogen H. Induces methionine synthetase I. Oxidises the cobalt in vitamin B12
06 A true - “Although… nonflammable, it will support combustion” (Stoelting 3rd ed. p.37) B false - see above C uncertain - “it causes minimal skeletal muscle relaxation” (Stoelting 3rd ed. p.37) D uncertain E false - partition co-efficient 0.46: Table 2-1 (Stoelting 3rd ed. p.37) F false G false - “The gas is prepared commercially by the thermal decomposition of ammonium nitrate” (“nitrous oxide.” The Columbia Electronic Encyclopedia, Sixth Edition. Columbia University Press., 2003. Answers.com 16 Feb. 2007. http://www.answers.com/topic/nitrous-oxide) H false - see below I true - see below For option (C) - True: “N2O does not relax skeletal muscles, and in doses >1 MAC (hyperbaric)it may produce skeletal muscle rigidity” - p65 Stoelting for D - would it not be reabosrbed from tissues quicker due to being not very soluble in tissues? Therefore having a higher partial pressure in the tissues, and therefore maintaining a higher partial pressure gradient for reabsorption… (Have a look at Resorption of a Pneumothorax in Brandis for the principles I was thinking about)
IN06b [Mar98] [Jul98] Nitrous oxide: A. Has MW of 42 B. Critical temperature 32 C C. Formed by using iron as a catalyst D. Does not support combustion E. ?? has saturated vapour pressure of 24]] kPa F. Produced using ammonium sulphate in an iron retort G. Boiling point 32C H. ??. . . ammonium nitrate . . . copper vessel ?? (Multiple options as this represents 2 separate N2O questions on Mar98 paper)
06B A false - MW 44 B false - see below C uncertain D false - see above E false - it is a gas at 20 degrees, therefore no SVP F False - formed from ammonium NITRATE not sulphate G False - see below H uncertain E - In Peck, Hill, Williams it states the SVP as 5200kPa (p.111), so, wrong anyway, but it is listed as a SVP E -> it is a vapour until the critical temperature is exceeded, then it becomes a gas. Vapour can be compressed into liquid whereas a gas cannot. The critical temperature of nitrous is 36.4 degrees celcius. The vapour pressure is the pressure seen in the nitrous cylinders in theatre and is usually ‘fixed’ at 5200kPa until the tank is near empty (ie. when there is no liquid nitrous left inside, then it begins to drop linearly until the tank is empty). [lewildbeast] Regarding vitamin B12 & N2O: The cobalt ion on B12 is oxidised by nitrous oxide so that it cannot act as the cofactor for methionine synthase. This reduces the synthesis of methionine, thymidine, THF, and DNA. N2O is also thought to directly inhibit Methionine synthetase which catalyses the synthesis of tetrahydrofolate, a substrate for thymidine in DNA synthesis. The MW of N2O is 44, and its critical temperature is 36.5. Its boiling point is -88 degrees. It does support combustion but is not flammable. (Peck and Williams, “Pharm for Anaesthesia and Intensive Care”) There is a good article called “The risks and benefits of nitrous oxide” referring to this in Anaesthesia and Intensive Care by Paul Myles et al, in 2004. Flammable is a substance which under normal conditions has the ability to catch fire with a minimal ignition source (such as a spark). An example of this might be a substance such as propane. - Combustible materials would be any material that will burn. In this category we could also place propane and the like but it would also include materials that need more vigorous conditions to burn and are not likely to catch fire with a simple spark. An example of a combustible material of this sort would be wood or paper. In my opinion therefore, all flammable materials are combustible, but all combustible materials are not necessarily flammable.
IN07 [Mar97] [Mar03] Desflurane: A. Takes 5 minutes to reach equilibrium B. Is fastest to approach equilibrium of any inhaled anaesthetic agent C. Is a fluorinated diethyl ether D. ?
IN07 [c] Desflurane A. False - equilibrium approx >20-30 minutes (??source) B. Perhaps true - “Solubility characteristics and potency permit rapid achievement of an alveolar partial pressure necessary of anaesthesia” (Stoelting 3rd Ed. p. 38) Also note that blood:gas coefficient is 0.42 (the lowest ratio in table 2-1 c.f. nitrous oxide 0.46) and therefore is should theoretically have fastest equilibrium. C. False - desflurane is a fluorinated methyl ethyl ether, not a diethyl ether (Stoelting 3rd ed. p.38) D. ? Nitrous is faster to achieve equilibrium than Des because the oil:gas partition coefficient of N2O is so much lower (1.4) cf Des (18.7) Nitrous however is not really considered a volatile anaesthetic (just as you wouldn’t consider Xenon a volalite anaesthetic) so b is still correct. I disagree that B is correct: the question refers to inhaled anaesthetic, which N2O indisputably is… Note regards option B: Nitrous has a few features that allow more rapid equilibrium. PA = Pa = PB at equilibrium. Factors helping keep PA high are needed therefore. Yes the lower oil:gas partition is important in preventing the fat stores soaking up the N2O. Remember also that N2O has the unique feature of concentrating effect whereby large amounts of nitrous diffuse from alveoli into blood, thus concentrating the remaining gases in the lung. This also creates a gradient of pressure for more nitrous to move into the lung. These two factors allow nitrous to have the fastest onset to equilibrium despite not having the lowest blood:gas coefficient. Now if the question says volatiles forget xenon and N2O, but if it says agent/inhaled anaesthetic etc then include them for sure. –> agree time vs FA/FI graph peck and hill page 116 - N2O is at the top for a reason: very low solubility / blood:gas PC (0.46) and concentration effect - yes des has a slightly lower solubility / blood:gas PC (0.42) but lacks the concentration effect
IN08 [Mar97] [Jul97] Regarding sevoflurane: A. The vapour pressure is less than enflurane B. The vapour pressure is greater than isoflurane C. Cardiovascular side effects are similar to isoflurane D. Molecular weight less then isoflurane E. Boiling point greater than enflurane
Tip (this is easier than memorising the table below): Sevo has the HIGHEST MW and BP; It has the LOWEST SVP; It has a relatively high MAC (only DES and N2O are greater); It has a relatively low blood:gas coefficient (only DES and N2O are lower IN08 A true B false C unsure - has effects similar to isoflurane AND halothane D false E true Note: Option C is false - Isoflurane has the potential for coronary steal and halothane is the most potent for both conduction disturbances and reduced contractility. Halothane leaves the SVR alone compared with other volatiles….it’s effects are on the heart. http://www.kerrybrandis.com/wiki/mcqwiki/index.php?title=IN08
IN08b [Jul97] [Feb00] Sevoflurane: A. Is a methylethyl ether B. Is odourless C. Is stable in soda lime at 37 degrees D. Has a boiling point higher than enflurane E. Has a molecular weight lower than desflurane
Tip (this is easier than memorising the table below): Sevo has the HIGHEST MW and BP; It has the LOWEST SVP; It has a relatively high MAC (only DES and N2O are greater); It has a relatively low blood:gas coefficient (only DES and N2O are lower) IN08b A false - it’s a fluorinated methyl isopropyl ether B uncertain C false - produces compound A D true E false B- uncertain?? Are you kidding..have a sniff next time. It’s described as sweet smelling to hint to us we can use it for gas induction. Reply: it is so NOT sweet, I don’t like the smell, neither do most of the kiddies that got gassed, even with the strawberry mask guys, it has a smell. And you are not supposed to like it much. http://www.kerrybrandis.com/wiki/mcqwiki/index.php?title=IN08
IN08c [Jul98] [Jul99] Sevoflurane: A. Molecular weight greater then enflurane B. MAC less than enflurane C. Contains Cl & F D. SVP sevo > enflurane
Tip (this is easier than memorising the table below): Sevo has the HIGHEST MW and BP; It has the LOWEST SVP; It has a relatively high MAC (only DES and N2O are greater); It has a relatively low blood:gas coefficient (only DES and N2O are lower) IN08c A true B false C false D false See table http://www.kerrybrandis.com/wiki/mcqwiki/index.php?title=IN08
IN09 [Mar97] [Jul98] [Jul00] Uptake of N2O when breathing 70%: A. More than one litre absorbed in the first minute B. Equilibrium (?90%) is achieved in 3mins C. Absorb 10 litres ?at time of ?90% equilibration / ?in first 3 mins D. At steady state, uptake is 200mls/min E. Produces surgical anaesthesia
The Severinghaus formula for N2O uptake is VN2O=1000.t-0.5 Where VN2O is ml/min at time t (in minutes) A) Uptake is 1L in the first minute. B) Equilibrium (90%) is achieved at 3 minutes (see graph in Stoelting) C) Do the maths (okay, I’ve done it) uptake in first three mins is 2285ml. D) In the 90th minute, 105ml is taken up. I guess steady state is after this??? E) MAC of N2O is 104-106% not 70% “Due to its relative insolubility, the alveolar concentration of N2O approaches the inspired concentration fairly rapidly; 90% equilibration occurring within 15 minutes and 100% equilibration within 5 hours.” - Sasada & Smith I agree that the graph(s) in Stoelting suggest that FA/FI approaches 0.9 within 3 mins, however, combining 2 sources may mean that C is the correct answer as stated above, Sasada says that 90% equilibration is achieved within 15 mins Stoelting (p.27, 4th ed) says that at inhaled concentration of 60-70%, about 10L of nitrous is taken up within the first 10-15 mins Therefore, C could be correct combining these 2 sources Stupid question: at steady state, isn’t net uptake of N2O zero? It’s not metabolised, therefore when PI=PA there will be no uptake or excretion. Therefore D is wrong.
IN10 [Mar97] [Jul98] [Mar99] [Jul01] [Jul04] N2O causes the second gas effect because: A. It is relatively insoluble B. Reaches equilibrium faster than the more soluble second gas C. Larger volume D. Its high concentration
Most correct answer D (or C could be argued to be true… see below). The second gas effect refers to the situation where volatile agents used alongside N2O achieve an accelerated rise in alveolar partial pressure (and hence reduced induction time) compared to what they would achieve if used as a single agent. A. N2O is relatively insoluble when compared with other potent inhaled anaesthetics with a blood:gas partition coefficient of 0.47. It should be noted however that desflurane has an even lower blood:gas coefficient of 0.42 and hence is more insoluble. Desflurane does not cause the second gas effect and so it is not the low solubility that is responsible for the second gas effect. A low blood gas coefficient is important solely in determining a rapid achievement of an alveolar and brain partial pressure of the drug. B. The lower the blood:gas partition coefficient then the faster a gas will reach equilibrium as already stated in (A) above. This does not contribute to the second gas effect. C. The large volume uptake of N2O is an important contributing factor in creation of the 2nd gas effect (see (D) below). The reason that large volumes of N2O are absorbed from the alveoli is due to the high concentration of nitrous oxide that is inspired and the initial steep concentration gradient that is generated, during or soon after induction. Due to this sequence of events, option D appears to be technically “more correct” as the high inhaled concentration precedes the uptake of large volumes of N2O from the alveoli. D. The relatively low potency of N2O ensures that effective administration requires concentrations of 40-70%. The high concentrations that are administered result in the uptake of a large volume of gas (in the initial phases). This initial large uptake (as much as 1-2L/min) has 2 effects: The gases remaining in the alveoli are concentrated (including the remaining N2O) Negative pressure is created which draws bronchial and tracheal gas into the alveolar space to replace it. It is these 2 effects which together accelerate the rate of rise in alveolar partial pressure of the 2nd gas. Nitrous oxide is distinguished by the fact that it is the only inhaled anaesthetic to be administered in such high concentrations hence D appears to be the correct answer. - I also read that it is due to the fact that nitrous is 20 x more soluble than nitrogen and oxygen, so the rapid/large uptake of N2O (into the pulmonary capillaries) is far greater than the nitrogen diffusing out of the pulmonary capillaries into the alveoli (thereby decreasing the volume of the alveoli and concentrating other gases that are still present) - Comment: Stoelting (p. 25): “The second gas effect reflects the ability of high-volume uptake of one gas (first gas) to accelerate the rate of increase of the PA of a concurrently administered ‘companion’ gas (second gas). For example, the inital high-volume uptake of nitrous oxide accelerates the uptake of companion (second) gases such as oxygen and volatile anaesthetics. This increased uptake of the second gas reflects increased tracheal inflow of all the inhaled gases… due to the high-volume uptake of the first gas.” This would suggest C to be the correct answer but I’d be keen to hear other people’s opinions.
IN11 [Jul97] Desflurane: A. Is non-irritant to the airways B. Is more/less potent than sevoflurane C. Has a higher molecular weight than ?isoflurane/?enflurane D. Is a chlorinated methyl ethyl ether
Des is quite irritant to airways. Des is less potent (MAC 6.35, range 5.75-10.65%) than sevoflurane (MAC 2.0, range 1.71-2.05%). Des has a lower molecular weight (168) than any other volatile used in anaesthetics (though the ambos use methoxyflurane MW 164). Des is a FLUORINATED methyl ethyl ether.
IN12 [Jul97] [Apr01] Effects of volatile agents include: A. Halothane increases hepatic artery and portal blood flow B. Isoflurane causes hypotension by reducing cardiac output C. ? D. ?
Halothane acts as a vasoconstrictor on hepatic circulation. Decrease in MAP due to isoflurane results from a decrease in systemic vascular resistance * so A and B are both false References Stoelting & Hillier 4th ed page 51 & 65
IN12b [Feb04] Volatiles A. Halothane causes less cerebral vasodilation than enflurane B. Isoflurance causes less cerebral vasodilation than halothane
The vasodilating effect of halothane is greater than isoflurane, sevoflurane or desflurane. Additional info: Sevoflurane has dose-dependant cerebral vasodilatory effect but is less than that of iso and desflurane. Isoflurane is best at maintaining CBF relative to cerebral metabolic oxygen requirements. Autoregulation of CBF is maintained in response to changes in MAP during the use of 1MAC Isoflurane but not in the case of halothane,hence greater brain swelling seen in animals anaesthetised with this drug. “Halothane increases CBF more than any other volatile agent” - Peck + Williams 2nd Ed p111 * so A is false, B is true References Miller 6th ed page 829 Stoelting 4th ed page 49
IN13 [Jul97] [Jul98] [Jul99] [Apr01] Problems with MAC: A. Large interspecies variability B. Affected by temperature and other factors C. Affected by obesity D. ?
?
IN13b [Mar96] [Jul98] [Feb00] [Jul01] MAC: A. Is decreased in the elderly B. Is unchanged throughout pregnancy C. Increases in hypothermia D. ?Decreased/?increased with hyper/hypo-kalaemia E. ? Alt version (Jul 01) All the factors decrease MAC except: A. Pregnancy B. Hyperthermia C. Hypothermia D. Hypoxia E. ?
MAC is affected by temperature (decreased by hypothermia (4-5% for each degree C), increased by hyperthermia, is decreased in the elderly by about 6-7% per decade over 40, and is decreased by acidosis and hypoxia. Therefore: 13 B is correct. 13b, A is correct. Alt version B is correct. 13c: MAC-Bar is the minimum alveolar concentration of volatile at one atmosphere that ablates the sympathetic (adrenergic) response to a standardised noxious stimulus (skin incision). Whilst there is considerable variability between agents for MAC-BAR, it is universally reduced by opioids. A (13c) - MAC is 0.29 in 70% N2O (Sasada & Smith) 13c A) False - from birth, MAC increases to a peak at the age of 6 months, then declines gradually until the adult value is reached (Aitkenhead + Smith) B) False - pregnancy decreases MAC (Peck + Williams) C) False - see above D) False - MAC of halothane in 70%N2O is 0.29% July 01 Version: A) True B) False - 50% of patients C) ????? - see above for definition D) False - increased CO2 causes sympathetic stimulation -> increases MAC (Aitkenhead + Smith 5th ed p14) According to Stoelting (4th Ed, p.34), hypoxia only affects MAC when paO2 95mmhg) References Eger et al. “Age, minimum alverolar anaesthetic concentration and minimum alverolar anaesthetic concentration-awake”. Anesthesia and Analgesia2001;93:947-53 MAC article in BJA In relation to age q13c A Miller 6th Edn writes…. In humans, MACs of volatile agents are maximal in infants at approximately 6 months of age. MAC values gradually decrease with increasing age, and the MAC in the octogenarian is approximately one half that in the infant. The increase in potency (i.e., decrease in MAC) with increasing age is seen for all inhaled anesthetics, and the change averages approximately 6% per decade of age.[15] on “The Worldwide Anaesthetist” website, it says that hypercarbia does lower the MAC - anyone else got a reference for this? (for the last question)
IN13c [Mar99] [Apr01] [Jul01] MAC: A. Highest between ages 2 to 5 yrs B. Increases with pregnancy C. MAC BAR is concentration at which 95% do not move D. Is 0.2% halothane in 70% N2O E. ?
MAC is affected by temperature (decreased by hypothermia (4-5% for each degree C), increased by hyperthermia, is decreased in the elderly by about 6-7% per decade over 40, and is decreased by acidosis and hypoxia. Therefore: 13 B is correct. 13b, A is correct. Alt version B is correct. 13c: MAC-Bar is the minimum alveolar concentration of volatile at one atmosphere that ablates the sympathetic (adrenergic) response to a standardised noxious stimulus (skin incision). Whilst there is considerable variability between agents for MAC-BAR, it is universally reduced by opioids. A (13c) - MAC is 0.29 in 70% N2O (Sasada & Smith) 13c A) False - from birth, MAC increases to a peak at the age of 6 months, then declines gradually until the adult value is reached (Aitkenhead + Smith) B) False - pregnancy decreases MAC (Peck + Williams) C) False - see above D) False - MAC of halothane in 70%N2O is 0.29% July 01 Version: A) True B) False - 50% of patients C) ????? - see above for definition D) False - increased CO2 causes sympathetic stimulation -> increases MAC (Aitkenhead + Smith 5th ed p14) According to Stoelting (4th Ed, p.34), hypoxia only affects MAC when paO2 95mmhg) References Eger et al. “Age, minimum alverolar anaesthetic concentration and minimum alverolar anaesthetic concentration-awake”. Anesthesia and Analgesia2001;93:947-53 MAC article in BJA In relation to age q13c A Miller 6th Edn writes…. In humans, MACs of volatile agents are maximal in infants at approximately 6 months of age. MAC values gradually decrease with increasing age, and the MAC in the octogenarian is approximately one half that in the infant. The increase in potency (i.e., decrease in MAC) with increasing age is seen for all inhaled anesthetics, and the change averages approximately 6% per decade of age.[15] on “The Worldwide Anaesthetist” website, it says that hypercarbia does lower the MAC - anyone else got a reference for this? (for the last question)
Jul 01 version: With regards to MAC: A. The MAC of Halothane with 70%N2O is 0.29 B. Concentration at which 95% of patients don’t move after a surgical stimulus C. MAC-BAR ?? D. Decreased by increased CO2 E. ?
MAC is affected by temperature (decreased by hypothermia (4-5% for each degree C), increased by hyperthermia, is decreased in the elderly by about 6-7% per decade over 40, and is decreased by acidosis and hypoxia. Therefore: 13 B is correct. 13b, A is correct. Alt version B is correct. 13c: MAC-Bar is the minimum alveolar concentration of volatile at one atmosphere that ablates the sympathetic (adrenergic) response to a standardised noxious stimulus (skin incision). Whilst there is considerable variability between agents for MAC-BAR, it is universally reduced by opioids. A (13c) - MAC is 0.29 in 70% N2O (Sasada & Smith) 13c A) False - from birth, MAC increases to a peak at the age of 6 months, then declines gradually until the adult value is reached (Aitkenhead + Smith) B) False - pregnancy decreases MAC (Peck + Williams) C) False - see above D) False - MAC of halothane in 70%N2O is 0.29% July 01 Version: A) True B) False - 50% of patients C) ????? - see above for definition D) False - increased CO2 causes sympathetic stimulation -> increases MAC (Aitkenhead + Smith 5th ed p14) According to Stoelting (4th Ed, p.34), hypoxia only affects MAC when paO2 95mmhg) References Eger et al. “Age, minimum alverolar anaesthetic concentration and minimum alverolar anaesthetic concentration-awake”. Anesthesia and Analgesia2001;93:947-53 MAC article in BJA In relation to age q13c A Miller 6th Edn writes…. In humans, MACs of volatile agents are maximal in infants at approximately 6 months of age. MAC values gradually decrease with increasing age, and the MAC in the octogenarian is approximately one half that in the infant. The increase in potency (i.e., decrease in MAC) with increasing age is seen for all inhaled anesthetics, and the change averages approximately 6% per decade of age.[15] on “The Worldwide Anaesthetist” website, it says that hypercarbia does lower the MAC - anyone else got a reference for this? (for the last question)
IN14 [Mar98] [Mar99] Systemic vascular resistance is LEAST changed with: A. Isoflurane B. Sevoflurane C. Desflurane D. Enflurane E. Halothane
Halothane minimally changes SVR but decreases MAP by decreasing contractility and cardiac output. References Stoelting & Hillier 4th ed page 53 Comments Halothane decreases SVR by 15-18% leading to a decrease in systolic and diastolic blood pressure. It has little effect on coronary vascular resistance.
IN15 [Mar98] [Jul98] [Mar99] MAC awake during emergence when patient will respond to command: A. 0.1 B. 0.2 C. 0.3 D. 0.5 E. ?0.7 ?0.8
MAC awake is typically one third of MAC. For halothane it is more than 50% and for nitrous oxide is more than 60% Some MAC awake concentrations Halothane 0.4% Iso 0.5% Sevo 0.6% Des 2.5% N2O 68% – Ref: Eger et al. 0.3 is the quoted value. But when did you last see a patient wake up from Sevo with 0.3 MAC onboard? Let alone following command? When have you ever used a purely sevoflurane anaesthetic? Try withholding your other drugs, and see when they respond to commands… References Eger, et al, The Pharmacology of Inhaled Anesthetics, 3rd ed, page 27
IN16 [Jul98] [Jul99] Isoflurane & enflurane are: A. Structural isomers B. Enantiomers C. Diastereomers D. Optical isomers E. Configurational isomers
A is correct A configurational stereoisomer is a stereoisomer of a reference molecule that has the opposite configuration at a stereocenter (e.g., R- vs S- or E- vs Z-). This means that configurational isomers can be interconverted only by breaking covalent bonds to the stereocenter, for example, by inverting the configurations of some or all of the stereocenters in a compound.
IN17 [Mar96] [Jul96] Sevoflurane: A. Is broken down in the body to Compound A which has been shown to be toxic to rats B. Has a blood:gas partition coefficient of 2.3 C. Is a irritant causing coughing on induction D. Has a boiling point of 24]] degrees centigrade E. Has Cl & F atoms in its structure F. None of the above (Note: Compound A is a breakdown product produced in the CO2 absorber; it is not produced by biotransformation)
Broken down to compound A in CO2 absorber Blood:gas partition coefficient 0.65 Produces bronchodilation and causes the least amount of airway irritation Boiling point is 58.5 Contains 7 F and no Cl atoms (anaesthesiauk.com)[1] Note that Stoelting is incorrect in its diagram of sevoflurane; Desflurane has 6 “F” by the way. References Stoelting & Hillier 4th ed pages 43 & 45
IN18 [Mar99] [Feb00] With isoflurane anaesthesia, MAC awake is: A. 0.1% vol B. 0.3% vol C. 0.5% vol D. 0.5% vol E. 1% vol
“Mean MAC-awake obtained with slow alveolar washout was similar for isoflurane (0.25 (SD 0.03) MAC), and enflurane (0.27 (0.04) MAC) and significantly greater than values obtained by fast alveolar washout (isoflurane: 0.19 (0.03) MAC; enflurane: 0.20 (0.03) MAC). The MAC-awake of isoflurane and enflurane was significantly less than that of halothane, which was 0.59 (0.10) MAC as evaluated by the slow and 0.50 (0.05) MAC as evaluated by the fast alveolar washout method.” Gaumann, Mustaki, Tassonyi, MAC-awake of isoflurane, enflurane and halothane evaluated by slow and fast alveolar washout in Br J Anaesth. 1992 Jan;68(1):81-4 Answer C is correct - 0.25x1.15%~=0.3% (Note: not sure if this is a good study or not, but it seems to give some concrete numbers) MAC awake of isoflurane is 0.49% therefore C and D are closest to right Perhaps one of the options were remembered wrong - or are the examiners really trying to make life difficult? Hmm..MAC awake of isoflurane is 0.38 of MAC. 0.38*1.15 is close to 0.4%(0.437%) perhaps that was what option C was. How did u derive 0.49%? Stoelting 4e says 0.4 Faunce says 0.4 Eger says 0.49 one third MAC would be 0.33x1.15=0.379 Maybe option c or d was actually 0.4?? Otherwise I’d probably go for 0.5 (err on the side of keeping the pt asleep :) ) Note: From a practical stance, MAC awake is the point where we can predict the patient can maintain their own airway at the end of an operation…so aim for the lower number. We don’t watch the number at the start and go….0.1…0.2…0.3…0.49..he’s MAC asleep now, lets start the case!! Obviously with a hat full of morphine this becomes an academic number rather than a practical one. Nitrous has the best MAC awake..0.6-0.7 MAC, so if you use nitrous you can turn the volatile off as they stitch and then at the last moment turn off the nitrous and they are often responsive when the ET nitrous is still quite high. !!MAC awake is the point when the patient responds to verbal command!! References Eger page 27
IN19 [Mar99] [Jul04] Isoflurane: A. Is a halogenated methyl ethyl ether B. Higher boiling point than sevoflurane C. No odour D. Enantiomer of enflurane
Halogenated methyl ethyl ether - True Boiling point is 48.5, Sevoflurane boiling point is 58.5 Pungent, ethereal odour Structural isomer of enflurane, not an enantiomer only halothane requires thymol as a preservative References Stoelting & Hillier 4th ed page 43-44
[IN19]b [Aug 11] Isoflurane: A. is a halogenated methyl ethyl ether B. an enantiomer of enflurane C. has a boiling point higher than sevoflurane D. requires thymol as a preservative E. ?
Halogenated methyl ethyl ether - True Boiling point is 48.5, Sevoflurane boiling point is 58.5 Pungent, ethereal odour Structural isomer of enflurane, not an enantiomer only halothane requires thymol as a preservative References Stoelting & Hillier 4th ed page 43-44
IN20 [Mar99] MAC of halothane with 70% N2O is: A. 0.25% B. 0.5% C. 0.75% D. 1.0%
Sasada and Smith says 0.29% Oxford handbook says 0.27% I think you can derive it: (1-70/104)*0.75=0.24 In other words MAC is additive, and with the MAC of nitrous being 105 (or 104, the 70% being roughly 2/3), the MAC of halothane is 0.75% and thus 1/3 of this is 0.25
IN21 [Mar99] All reduce MAC except: A. Aminopyridine B. hypothermia C. pregnancy D. hypoxia
MAC is decreased by hypothermia, pregnancy, hypoxia A is correct. Aminopyridines are presumably excitatory as can evoke glutamate and GABA release in presence of calcium. Aminopyridine is a voltage-gated, fast potassium channel blocker capable of improving axonal conduction by facilitating the propagation of action potentials in demyelinated nerve fibers. See: http://jpet.aspetjournals.org/cgi/content/full/316/1/216?ck=nck
IN22 [Jul98] Nitrous oxide is NOT relatively contra-indicated with: A. Pneumothorax B. Ear surgery C. Postoperative nausea & vomiting D. Renal failure
N2O has low blood solubility (0.46) so it tends to fill up body cavities. Pleural space, middle ear and bowel will be expanded by N2O. Therefore it should be avoided in patients with pneumothorax, middle ear or bowel surgery. N2O has side effect of post-operative nausea and vomiting. N2O is not metabolized by our body and is eliminated through exhalation. So it be can administered to patients with renal failure.
IN23 [Jul99] [Jul02] [Mar03] [Jul04] Which of the following does NOT affect the speed of induction with a volatile agent? A. FRC B. Obesity C. pCO2 D. Cardiac output E. Body mass F. MAC
A incorrect. FRC affects the rate of induction, e.g. in adults is 1.5:1; in neonates is 5:1 & onset is more rapid B is correct. (Although obesity can decrease FRC) C incorrect. PCO2 will affect ventilation (i.e. high PCO2 increases respiratory rate, increasing uptake & vice versa) D incorrect. Cardiac output will affect the speed of induction, especially of a highly fat soluble agent E basically same as B. F is incorrect. MAC is potency of inhaled anaesthetic, so much like other drugs (ie, muscle relaxants), the lower the potency, the higher the inspired concentration required (and faster the uptake), and therefore the higher the concentration gradient. This is really only clinically significant for Nitrous oxide (causing the “concentration effect”).
IN23 alt Regarding the time constant for volatile anaesthetic uptake in the lungs A. Affected by agent concentration B. Affected by obesity C. Not affected by FRC D. Affected by restrictive lung disease
Alternate version Time constant isn’t affected by agent concentration, is affected by FRC, and therefore is affected by obesity, and I’m not sure about restrictive lung disease. Any thoughts? For the first question if it is a choice for one correct answer, E (body mass) should be correct as body mass per se does not affect uptake. Option E is not the same as B as a high body mass does not entail obesity. Obesity will decrease FRC and is therefore an indirect contributor to speed of induction. However, since the previous versions of the question seem to not include body mass as an option, B, obesity probably is the best out of this lot. pCO2 may not increase respiratory rate depending on the status of respiratory reflexes in various pathological conditions, and in very high pCO2 may decrease respiratory rate. Further, it may increase cardiac output which has a different effect on speed of induction. However, which ever way it goes, it will always have some sort of effect on the speed of induction, albeit of variable significance.
IN24 [Feb00] 22g of Nitrous oxide at STP occupies a volume of: A. 3.6 litres B. 11.2 litres C. 22 litres (? or 22.4 litres) D. 44.1 litres
MW of N2O = 44 Daltons so one mole of N2O weighs 44g (and 22 g = 1/2 mol). 1 mol of gas at STP occupies 22.4 litres So, 0.5 mole (22g) of N2O at STP occupies 11.2 litres. Q: Is the MW of N2O 44 Daltons A: Yes, MW of N2O = 14+14+16 = 44 Da. The Dalton is an alternative name of the atomic mass unit (or molecular weight).(See ref below)
IN25 [Jul00] [Mar03] [Jul04] Wash in (? washout) of volatile anaesthetics is reduced in neonates because: A. Reduced FRC B. Increased cardiac index C. Decreased plasma protein levels? D. (Something about blood:gas partition coefficients being different in neonate)
Wash in (? washout) of volatile anaesthetics is reduced in neonates because: A. Reduced FRC B. Increased cardiac index - ?true - I presume neonates have a very high CI due to their high metabolism and relatively hyperdynamic state; this would reduce the time to equilibrium (in the wash in phase) C. Decreased plasma protein levels? - no idea D. (Something about blood:gas partition coefficients being different in neonate) - no idea The washout of inhalational anaesthetics A. Increases with elimination by the liver - true, drugs eliminated by the liver will be eliminated faster B. Related considerably with the duration of anaesthesia - don’t think so C. Increases in the neonates compared to an adult - no idea D. ? This question is probably poorly remembered. I couldn’t make sense of the comments below
The washout of inhalational anaesthetics A. Increases with elimination by the liver B. Related considerably with the duration of anaesthesia C. Increases in the neonates compared to an adult D. ?
Wash in (? washout) of volatile anaesthetics is reduced in neonates because: A. Reduced FRC B. Increased cardiac index - ?true - I presume neonates have a very high CI due to their high metabolism and relatively hyperdynamic state; this would reduce the time to equilibrium (in the wash in phase) C. Decreased plasma protein levels? - no idea D. (Something about blood:gas partition coefficients being different in neonate) - no idea The washout of inhalational anaesthetics A. Increases with elimination by the liver - true, drugs eliminated by the liver will be eliminated faster B. Related considerably with the duration of anaesthesia - don’t think so C. Increases in the neonates compared to an adult - no idea D. ? This question is probably poorly remembered. I couldn’t make sense of the comments below
Mechanism of IMOBILITY with volatiles / ? specific volatile?: A Stimulation of GABAa receptors - False B C E Stimulation of Glycine receptors - True
read stoelting 4th ed page 35-36
