Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Pharmacology Jeopardy Block 2 Part II Peter O. Beaumont, M.Sc. (Pharm) St. Vinnie’s Fall 2000 Local and General Anaesthesia The Five Goals of General Anaesthesia What are… Analgesia, amnesia, muscle relaxation, LOC and Loss of somatic & visceral reflexes – The first three are universal, the last two are somewhat secondary The Surgical Stage of Anaesthesia,and the easiest test to determine it What are… Stage III, and the eyelash reflex test The greatest medical concern in Guedel’s stage II of anaesthesia What is… Aspiration of vomit – During this stage, delirium and excitement are often accompanied by retching,vomiting and incontinence. – Intubation must unfortunately wait until the patient loses gag reflexes The earliest feature of Guedel’s stage I What is… analgesia – this is soon accompanied by amnesia, but consciousness is not lost. – Remember, not all anaesthetics show all stages, and further, not all agents are good analgesics e.g. halothane The only true anaesthetic ‘gas’ What is… Nitrous Oxide – The others are all volatile liquids The rate of onset of an excellently soluble anaesthetic What is… Very slowly – The sooner the point of saturation is reached, the sooner the blood is willing to give up the agent to the brain tissues The rate of onset of anaesthesia in a patient with heart failure What is… Faster than normal – This is is a tough concept – slowly flowing blood will reach its saturation sooner than fast flowing blood – A greater fraction of the CO goes to the brain in failure Once you stop the flow of Nitrous and oxygen, this may happen to the patient post-op What is… Diffusion Hypoxia – A high partial pressure of gas coming out of solution dilutes oxygen in the lungs in the post-op patient – Only happens with nitrous oxide, others are used a too low partial pressure When 1/2 your patients do not jump off the table following induction, this point is reached What is… MAC – By definition… when 50% of patients do not respond to a painful stimulus – highly dependent on degree of stimulation – Elderly and children have lower MAC This prototypic GA has good effect, but high metabolism makes it undesirable these days What is… Halothane – Release of halogens can cause hepatotoxicity (methoxyflurane does this as well, so it is rarely used) If you use halothane for a D&C, you must also use these two adjuncts What are… Opiods and oxytocin – Halothane has virtually no analgesic effect – oxytocin causes uterine contraction to counteract the relaxant effect of halothane Were it not for concurrent muscle paralysis, patients induced with this agent might hurt themselves What is… Enflurane – Seizure complexes on EEG – EEG goes with Enflurane This GA is great for maintenance, but rarely used for induction What is… Desflurane – Extreme sympathetic stimulation during induction. Also has a sharp irritating odour – Rapid post-op recovery Some consider this GA to be the ‘Cadillac’ inhalation agent for short procedures What is… Sevoflurane – rapid onset and recovery – little airway irritation – 2-5% hepatic metabolism makes it less desirable for long procedures – Sevo is the “Seville” Were it not for a high MAC, this agent would be a nearly ideal GA What is… Nitrous Oxide – No CV depression, excellent analgesia – Must be used with a second GA and paralytic agent This class of IV GA’s are the prototypical induction agents What are… Barbiturates – Thiopental was the first - Still used widely today – Onset in 1 minute While inhalation agents terminate their effect by exhalation, this is the mechanism for barbiturates What is… Redistribution – Also known as gamma phase redistribution – 99% hepatic metabolism to inactive compound AFTER termination of sedation effect Incapable or reaching stage III themselves, these agents provide sedation and amnesia What are… benzodiazepines – Diazepam, lorazepam and midazolam are short acting agents – Slower onset than barbiturates – used as part of “balanced anaesthesia” Occasionally used alone in Cardiac Sx, these agents typically support GA agents with analgesia What is… Opiods – patient may be ‘aware’ of or recall the Sx – Chest tightness impairing ventilation may occur Opiod + neuroleptic + Nitrous Oxide = What is… Neuroleptanesthesia – Important for painful, invasive procedures requiring patient cooperation Dr’s and patients agree, this drug is the ‘real Pro’ of the induction agents What is… Propafol – Similar induction to barbiturates, but faster recovery – Patients feel much better post-op – May even have anti-emetic properties – much much more expensive than thiopental Catatonia, amnesia and analgesia without LOC What is… dissociative anesthesia – Produced by ketamine alone – Similar to PCP – only CVS stimulant – good for Sx on patients in shock This untoward effect of ketamine is obviated by premedication with diazepam or fentanyl What is… Emergence Phenomenon – hallucinations and perceptual illusions This iv induction agents shares one shortcoming with halothane and one with nitrous oxide What is… Etomidate – No analgesia (halothane), no muscle relaxant effect (nitrous) This effect makes Etomidate unsuitable for long Sx and ICU sedation What is… inhibition of adrenal steroid synthesis – produces hypotension, electrolyte imbalance and oliguria The two chemical groups required for effect as a local anaesthetic What is… lipophilic group and ionizable group – Must be able to readily pass through lipid bilayer, yet interact with ion channel Relative effectiveness of locals on infected tissue What is… Decreased – lower pH of tissue causes more ionized agent, which is unable to enter the cell Major benefit of cocaine as a Local anaesthetic What is… vasoconstriction – All other agents are vasodilators – functions through blocked NE reuptake – prolongs anaesthetic effect – used in URT and ear Cocaine Tetracaine Benzocaine What are… The ‘ester’ locals – Typically shorter T1/2 due to hydrolysis by plasma cholinesterase Mechanism of action of the local anaesthetics What is… blockade of voltagedependent Na channels – Use-dependent – blocks from inside Characteristics of the earliest blocked nerve fibres What are… small, myelinated, rapidly firing, peripherally located on the bundle – why myelinated first - I don’t know! – Use-dependent means rapidly firing sensory fibres blocked before motor fibres CNS sedation, restlessness, nystagmus, seizures What is… Toxic effects of local anaesthetics – Premedication with benzos, and hyperoxemia are prophylactic for these symptoms Local that does not permeate the skin when applied topically What is… benzocaine Three LA agents that cross mucous membranes in therapeutic amounts What is… tetracaine, lidocaine and cocaine – tetracaine suitable for ophthalmic use - no irritation (cocaine too?) – epinephrine cannot be used in topical preps. Rationale for use of nerve blocks What is… Covers larger area, with smaller amount of drug – prevents systemic toxicity – (also, prevents distortion of wound when suturing!) Three techniques to prevent cephalad diffusion of spinal anaesthesia What are… Tilt the patients, use small amount, use ‘heavy’ diluent – Specific gravity determines whether agent will rise, sink or remain static Small muscles, trunk muscles, diaphragm What is… Order of effect of NMJ blockers Effect of presynaptic NMJ blockade of nicotinic receptors What is… ‘Fade’ – These receptors normally cause increased release of ACh required to maintain repetitive firing AChE inhibitors have this effect on non-depolarising NMJ blockers What is… antagonism – non-depol agents are essentially pharmacological antagonists. AChE inhibitors increase the amount of ACh – On the other hand, they would enhance depolarising blockade Primary use of depolarising NMJ blockers What is… temporary paralysis to allow intubation – Succinylcholine is the only agent in use – onset < 1 min, duration 5-10 min rapid metab by plasma cholinesterase These two classes of agents are known to cause malignant hyperthermia What are… volatile anaesthetics and succinylcholine – Causes over-release of Ca from SR - Tx with Dantrolene – Genetic susceptibility Basis for emesis due to succinylcholine What is… Increased intragastric psi due to abdominal muscle contraction – Not triggered by CTZ inhalation, local and IV anaesthetics, and aminoglycosides What are… agents that potentiate NMJ blockade Goal of Tx with spasmolytics What is… reduction in tone, without reduction in strength – Useful in CP, MS and stroke Facilitates GABAmediated pre-syn inhibition What are… benzodiazepines (diazepem) – muscle spasms of any origin – marked sedation GABA-mimetic at GABAB receptors What is… baclofen – hyper-polarises pre-syn afferent of reflex arch – decreases transmitter release – works in brainstem – equally effective as diazepam - less sedation spasmolytic with 3 month duration of action What is… botulinum toxin – effective in blepharospasm, dystonia and achalasia – admin by local injection Tuberculosis and Leprosy Guess the first-line drugs for Tx of TB and win the P.R.I.S.E. What is… Pyrazinamide, Rifampin, Isoniazid, Streptomycin & Ethambutol Slow growth, intracellular, resistance What are… Three reasons for difficulty in Tx TB – Combination Tx is often used to ovecome these problems Mechanism of action of the most import drug in the Tx of TB What is… inhibition of mycolic acid synthesis by INH – Pyridoxine congener The dose-limiting toxicity of INH What is… hepatotoxicity – “INH: Injures Neurons and Hepatocytes – peripheral neuritis is easily Tx with B6 - so, technically, not ‘dose-limiting’ – significant (1%) incidence of severe hepatitis; even greater in alcoholics This TB agent is an inhibitor of DNAdep-RNA polymerase What is… Rifampin – Effective in all mycobacteria and many other agents – good CSF penetration exposure/carrier prophylaxis in meningococci and H.flu Rifampin and phenazopyridine have this in common (think back to UTI) What is… colours body fluids RED – 4 R’s – RNA-poly, Reves P450, Red fluid, Rapid Resistance used alone If you took this TB drug, you may not know that your urine was red from rifampin What is… Ethambutol – Causes loss of red-green discrimination – relative contraindication in children – 2nd TB agent that causes hepatitis This TB agent may precipitate gout in susceptible individuals What is… pyrazinamide – Hyperuricemia occurs in all patients, but only some are symptomatic INH, rifampin, pyrazinamide, but not ethambutol or streptomycin What is… First-line TB agents that cause hepatotoxicity – Ethambutol does, not… as may have been stated in class This quasi-first line agent is still used for life-threatening TB What is… Streptomycin – Especially useful in meningitis and milliary TB – some do not consider it 1st-line for TB anymore Mech of act of this primary Tx for Leprosy What is… Inhibition of dihydropteroate synthase by Dapsone – Just like all of the other PABA analogues This dapsone ADR is similar to that seen in the Tx of spirochete infection What is… the Lepra Reaction – somewhat like Jarisch-Herxheimer reaction (erythema nodosum leprosum) – Tx with thalidomide, chloroquine and clofazime (not in G&G) Perhaps the most effective drug in leprosy, it can never be used alone What is… Rifampin – Resistance is a major concern The main ADR of the main Dapsone alternative in resistant Leprosy What is… Skin discolouration – Clofazime is an ‘azo’ dye that discolours the skin Malarial parasites with more than one exoerythrocytic cycle What are… Vivax and Ovale – Falciparum and Malariae have only one cycle before proceeding to RBCs – Basis for dormant infection in V & O Stages of the lifecycle taken up by the mosquito, and later injected, respectively What are… Gametocytes and sporozoites DOC for Tx and prophylaxis of P. falciparum (area without resistance) What is… Chloroquine – often used in combo with pyrimethamine DOC for prophylaxis of P. falciparum, in resistant areas What is… Melfoquine or Chloroquine + pyrimethamine (Depending on your source) – 2nd choice doxycycline, 3rd chloroquine + proguanil (Katzung and G&G agreee) – Can also be used for the other plasmodia too DOC for Tx of chloroquine-resistant P. falciparum What is… Quinine – given with a tetracycline or antifolate – Mefloquine is used in some geographic areas Drug that would have made Dr. McPhearson a millionare, and which was not covered in class! What is… Artemisinin – Effective blood schizontacide in all types of malaria, including resistant P.f. – Not good for prophylaxis – Not available in US… yet. Only drug for eradication of tissue schizonts What is… Primaquine – One of the few indications that is absolute – only required in Ovale and Vivax Enzyme deficiency associated with ADRs in primaquine and quinine What is… Glucose-6phosphate DeHase – Produces hemolysis and methmoglobin - toxic to kidneys Antiviral Pharmacology Amantadine is used in the Tx of: Influenza A, and... What is… Parkinson’s Disease – I hope you didn’t guess Influenza B or C! This drug…. Is an excellent prophylactic for the Flu, but won’t make you feel any better once you get it What is… amantadine or rimantadine – these agents block uncoating of the viral particle in the cytosol, but by the time you feel sick, you already have lots of viral particle in your system These agents limit the abilitiy of viruses to enter cells What are… Gamma-globulins – Temporary, passive immunity – duration about 3 wks Mech of Act of amantadine (for viruses) What is… blocks uncoating of the virus – Raises pH of endosome to alkaline levels – SE are all neuro related (increased release of DA) Agents that require HSV viral thymidine kinase to be effective What are… All of the “__ciclovirs” – Applies to Tx of HSV 1, 2, and 3 (VCV) – acyclovir, famciclovir, ganciclovir, valaciclovir, etc. Key difference in phosphorylation of Ganciclovir What is… phosphorylated by CMV-specific kinase – uses regular thymidine kinase for HSV, but a different one in CMV Mech of Act of acyclovir What is… comp inhibit viral DNA polymerase & causes chain termination – May cause some renaldysfxn, but generally well tolerated Key indication for use of Ganciclovir What are… CMV retinitis, pneumonitis, esophagitis, and colitis – SE: reversible neutropenia and renal dysfxn Spectrum of action of inhaled Ribavirin What is… RSV, Influenza A & B Spectrum of action of oral/IV Ribavirin What is… Lassa fever – HCV effects are debatable – many more SE when given systemically - cytopenias and suppressoin Mech of Act of Ribavirin What is… Inibits RNA-depRNA polymerase – May interfere with GTP synthesis and the cap on mRNA as well – effective in BOTH DNA and RNA viruses Phosphorylated by Host cell kinases What are… Idoxuridine, cytarabine, Vidarabine, Trifluridine – Inhibit viral DNA poly – too toxic for systemic use, except Vidara for neonatal herpes in immunocompromised HSV /VCV drug requiring no host or viral kinase activity What is… Foscarnet – Inhibits viral DNA & RNA poly AND HIV reverse transcriptase Key uses of Foscarnet What are… • AIDS-related CMV • Acyclovir resistant / thymidine kinase def HSV • Gancicovir-resistant CMV – Limited resistance has been observed 3 mechanisms of action of interferons What are… • synth of protein kinases to inhibit further protein synth • oligoadenylate synthase activates RNAase • PDE degrades tRNA Major indications for interferon Tx What are… • Pv disseminated HSC, relapse CMV, and trigeminal HSV • Hep B & C • Kaposi’s and warts ...to name a few Major SE of interferon Tx What is… Constitutional symptoms – Fever, malaise, chills, etc. Type of kinases used on 5 out of 6 HIV reverse transcriptase inhibitors What are… Host cell kinases – All 3 phosphorylation steps, c.f. just the last two step for antiherpes drugs Primary means of resistance to AZT, et al What is… mutation of RT gene – Much more common in mono Tx and in advanced disease Basis for selective toxicity of the RT inhibitors What is… our cells do not have RT! – Simple point, but commonly overlooked Indications for AZT What are… • CD4 count < 200 (500 w symptoms) • 3rd trimester (with 3TC) • Prophylaxis for needle stick Major toxicity of AZT What is… Bone marrow suppression – increased by Rx that undergo glucuronidation, and decerased by rifampin Two RTI’s that cause pancreatitis What are… ddI and ddC – More common in alcoholics – also cause peripheral neuropathy Claim to fame of Nevirpapine What is… NON-nucleoside RTI – potentiallife threatening rash The function of HIV aspartate protease What is… Final protein cleavage into mature, infectious particles – SE: kidney stones and unconjugated hypernilirubinemia General formulae for HIV Tx What is… AZT + 2nd RTI + Protease inhibitor Hypertension Long term Mech of Act of diuretics What is… Reduction in Na altering vascular tone – Volume reduction occurs early, but is abated over 6-8 weks in mild essential HTN Location and Mechanism of Action of Clonidine What is… Central and peripheral alpha-2 sympathomimetic – blocks NE release – SE: sedation and dry mouth Major caution in clonidine use What is… withdrawal syndrome – Rebound HTN, tachcardia, sweating – As little as one or two missed doses – Tx with alpha and beta blockers Direct vasodilators must be used with these drugs What are… Beta blockers – No sympathoplegia, so reflex response to a decreased BP is still present Orally active direct vasodilators What are… Hydralazine and minoxidil – work through opening K channels and hyperpolarises arteriolar SMCs Fast acting, IV arteriolar and venous dilator What is… Na Nitroprusside – high dose > 1 hr assoc w cyanide toxicity – onset in 1-10 minutes – activate guanylyl cyclase - not a K channel agent The other IV only direct vasodilator What is… Diazoxide – much longer acting means less precise control – inhibits insulin release 1st-line Tx in an elderly, black patient with CHF and CRF What is… A loop diuretic – Without the RF (GFR < 30 ml/min) a thiazide would be first choice – beta blockers have little efficacy in black patients Anti-HTN agent contraindicated in pregnancy What is… ACE-I and AgII receptor blockers – fetal hypotension and risk of malformation Rationale not to use direct dilators or alpha blockers in coronary artery disease What is… Coronary steal – provokation of angine Patients in who you should not use amiloride or ACE-I for HTN Whe are… Patients in renal failure – both tend to exacerbate hyperkalemia Drugs not to be used for HTN in diabetes What are… thiazides and nonselective beta blockers Tx of HTN assoc with kidney stones What is… Analgesia and hydration – Different stories in different small groups – Texts indicate no benefit of diuretics or anti-spasmodics Management of HTN crisis What is… decrease psi by < 25%, and diastolic not less than 100110 – according to Katzung BP at which to initiate Drug Tx What is… 140/90 (open for discussion) – For stage I patients, after 6-12 months of lifestyle change Why hydrochlorothiazide and alphamethyldopa are used in preg assoc HTN What is… “fetal friendly” – May not be the best agents, but there are proven safe. – Hard to test new Rx on mothers. Basis for pulmonary edema in our case study What is… Albuterol activates RAS via beta-2 receptors & the ‘infusion’ may have volume overloaded the patient – Discussion…. – MgSO4 may have been better, but fetus old enough to deliver Two causes for red urine in our case study What are… Hemorrhagic cystitis & doxorubcin die effect Two causes of the erythematous response at the injection site What are… extravasation of vesicant antineoplastics & the “Adriamycin-flare” Best of Luck to you All! Slides available at sguweb.tripod.com