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Pharmacology
| Question | Answer |
|---|---|
| Verapamil Mechanism? | Blocks voltage gated L type ca channels (a1) Reduces opening frequency. Decreases ca current (transmembrane). Deceased ca influx. |
| Verapamil effects on heart and smooth mm. | Cvs - reduced contractility/CO, reduces o2 demand. Av node block, reduced coronary artery spasm Smooth mm - relaxation. |
| Adverse effects verapamil | Cvs - bradycardia, av hb, cardiac arrest, heart failure, hypotension Minor - flushing, dizziness, nausea, headaches, peripheral oedema |
| Verapamil indications | Angina, htn, atrial arrhythmias |
| Acetazolamide action | Carbonic anhydrase inhibitor, ciliary body, choroid plexus, prox renal tubule |
| Toxic effects acetazolamide | Hyperchloraemic met acidosis, renal stones (po4, ca), k+ wasting, drowsiness, paraesthesia |
| Frusemide pharmacokinetics | Abs - well, bio 10-100% Onset - 15-30 min (iv), 1-3 hrs (po) Duration - 2-6 hrs (iv - po) T1/2 - 1.5-2hrs Distribution - albumin bound Metab - liver (small) Excretion - renal |
| Adverse effects frusemide | Cvs - hypotension Electrolyte - hyponatraemia, hypokalaemia, hypomagnesia, hyperuricaemia, met alkalosis CNS - ototoxicity, tinnitus, vertigo Git - n, v ,jaundice Blood - thrombocytopaenia Other - rash |
| Frusemide drug interactions | NSAIDs Amino glycosides Anticoagulant Digoxin Lithium, propranolol, probenecid, thiazides, amphotericin b, cisplatin |
| Frusemide mechanism | Selective inhibition Na/K/2Cl transporter in ThAL. Increased Pg synthesis. Increased renal blood flow. Decreased pulmonary congestion. |
| Mannitol mechanism | Osmotic diuretic. Does not cross intact bbb. Draws water out of cells. Reduces intravascular volume. Reduces icp |
| Other effects mannitol | Reduces intraocular pressure Diuresis Hypovolaemia Dehydration Hypernatraemia Hyperkalaemia |
| Mannitol dose in raised icp | 1-2g/kg iv bolus over 15mins (0.25-2g/kg) |
| How are osmotic diuretics handled by kidney | Freely filtered glomeruli. Not reabsorbed. Water retention in permeable section nephron, prox tubule and desc loh |
| Mechanism thiazide diuretics | Inhibit Na/K transporter in dct. Increased nacl excretion. Increased diuresis |
| Indications for thiazides | Htn, heart failure, generalised oedema, cirrhosis, nephrotic syndrome, nephron diabetes insipidus |
| Adverse effects thiazides | Hypotension, hypokalaemia, hypovolaemia, dehydration Hyponatraemia, met alkalosis, hyperuricaemia, hyperlipidaemia, hypercalcaemia, pancreatitis, allergy (sulfonamides) Weakness, fatigue, paraesthesia (cf mannitol) |
| Mechanism aspirin | Irreversible antagonist Cox inhibitor Inhibit thromboxane a2 synthesis |
| Other types antiplatelets | NSAIDs Beta blockers Gp2b and gp3a blockers (abciximab) Adp inhibitors Pde inhibitors (dypridamole) |
| Indications antiplatelets | Ihd, cva/tia, pre-eclampsia prophy, post acs intervention |
| Mechanism clopidogrel | Irreversible Adp pathway inhibitor |
| Pharmacokinetics clopidogrel | Prodrug - metab to both active and inactive metabolites Activated by liver p450 (80% platelet inhibited in 5/24) T1/2 - 0.5-1h Urine excretion 50%, faeces 46% Loading 300-600mg, 75mg daily |
| Adverse effects clopidogrel | Bleeding, rash Git upset (n/v, diarrhoea, abdo pain) Reflux, ulcers CNS - tingling, numbness Rare - pancytopaenia, ttp |
| Heparin mechanism | Binds/enhances endogenous antithrombin 3 (inhibits 2/9/10 activated factors) accelerates inhibition clotting factors by 1000x |
| Adverse effects heparin | Bleeding, allergy, hit Alopecia, osteoporosis, mineralocorticoid deficiency Thrombocytopenia |
| Advantages lmwh over ufh | Equal efficacy, increased S/c bioavailability, less frequent dosing, less monitoring Shorter chain heparin less effect on thrombin (2a) Reduced bleeding risk Lower incidence hit Improved efficacy in acs |
| Heparin reversal agent | Stop drug Protamine (100 units hep = 1mg protamine) Binds to heparin form complex devoid anticoagulant activity Excess protamine anticoagulant effect |
| Mechanism ufh | Binds at3 (inhibits 7/9/10/2 activated factors) |
| What’s different in moa btwn ufh vs lmwh | Lmwh inhibits 10a but less on at3 Don’t need aptt Increased bioavailability s/c Less frequent dosing |
| Rivoroxaban mechanism | Inhibits activated F10 (free and prothrombin bound) |
| Pharmacokinetics rivoroxaban | Oral bioavailability >80% Small vd <50L High protein bound Elimination renal > liver (cyp3a4) Max plasma level 3/24 post ingestion T1/2 5-14h |
| Clinical advantage rivoroxaban over warfarin | Rapid onset/offset Predictable effect Ease dosing, wider therapeutic index Monitoring not required Fewer drug interactions |
| Disadvantages of rivoroxaban versus warfarin | Predominant renal excretion Not suitable for dialysis patient Adjust in renal failure |
| Thrombolytic agent classes | T-pa: alteplase, tenecteplase, reteplase And streptokinase (strep protein) |
| Mechanism t-pa | Enzyme directly converts plasminogen to plasmin Major fibrinolytic enzyme Fibrin digestion Short half life therefore heparin is essential adjunct |
| Adverse effects of t-pa | Bleeding (cerebral, git, wounds) Allergy (esp streptokinase) |
| Clinical uses of t-pa | Ami, unstable pe, acute ischaemic stroke, severe dvt, intro arterial peripheral limbs |
| Mechanism drug interactions with warfarin | Pk Enzyme inhibition - majority Enzyme inducers Plasma protein binding Pd Synergism (impaired haemostasis) Competitive antagonism (clotting factor synthesis/concentration) |
| Drugs that increase INR | Aspirin, heparin, metronidazole, tmt, ceftriaxone, ssri, macrolides, amiodarone, tramadol, fluconazole, sulfamethoxazole, corticosteroids, hyperthyroidism |
| Drugs decrease inr | Phenytoin, barbiturates, rifampcin, carbamazepine, vit k, diuretics, dicloxacillin, St. John’s wart, azt, haloperidol, hypothyroidism |
| Mechanism warfarin | Inhibits reduction inactive vit k epoxide to active hydroquinolone Blocks gamma-carboxylation glutamate residues in factor 2/7/9/10 and protein c and s |
| Why delay in warfarin action | 8-12hr delay due to partially inhibited synthesis and unaltered degradation of 4 vit k clotting factors and depends on degradation t1/2 life in circulation (f7 - 6h, f9 - 24h, f10 - 40h, f2 - 60h) |
| What is used to reverse warfarin? | Vit k, ffp, prothrombinex complex, recombinant f7a |
| Carbimazole action in thyroid disease | Metabolised to methimazole Blocks t3 and t4 synthesis Inhibits thyroid peroxidase |
| Major side effects carbimazole? | Rash, urticaria, pruritus. Bone marrow suppression, neutropenia. Git upset, nausea, vomit. Arthralgia, lupus reaction, vasculitis, jaundice, hepatitis. |
| How is carbimazole different to propylthiouracil | Prodrug, converted to methimazole. Ptu greater inhibition peripheral deiodination t4/t3. Ptu protein bound, pregnancy preferred as not secreted in breast milk. Ptu shorter 1/2 life (1.5h vs 6h) hence ptu qid vs od carbimazole. |
| Mechanism corticosteroids at cellular level | Bound to corticosteroid binding proteins in blood. Enters cell as free molecule. Intercellular receptor bound to stabilising proteins (hsp90). Active transport into nucleus. Binds to glucocorticoid receptor element. Regulates mRNA transcription. |
| How corticosteroids classified | Length of action (hydrocortisone short, Dexa long) Anti inflammatory (hydrocortisone 1, pred 5, Dex 30) Mineral (salt) - fluodrocort 250x hydrocortisone Top vs non top application |
| Side effects corticosteroids use | Short term (<2/52): insomnia, peptic ulcer, pancreatitis, hyperglycaemia Long term: Cushing syndrome, diabetes, myopathy, osteoporosis, adrenal suppression, poor wound healing, immunosuppression |
| Dexamethasone dose for croup | 0.15-0.60mg/kg po single dose |
| How does Dex compare with hydrocortisone for anti inflammatory effect | Dex = 30x hydrocortisone potency and longer acting No salt retaining activity |
| Describe glucocorticoid effects (anti inflammatory and immunosuppressive) | Peripheral leaks (decrease conc, distribution and fn) Suppression inflammatory mediators (cytokines, chemokines) Inhibit macrophage and apc fn Inhibit pla2 - decease pg/lt/paf Inhibit cox2 Decr histamine release (mast) Reduce ab production |
| Clinical uses dexamethasone | Diagnosis (dexa suppression test) Anti inflammatory effect Croup |
| Groups of drugs to treat diabetes | Insulin Sulphonylureas Biguanides Meglitinides D-phenylalanine derivatives Thiazolidinedones (enhance insulin sensitivity) Alpha glucosidase inhibitors (comp inhibitor git alpha glucosidase) |
| Compare mechanism sulphonylureas and biguanides | S: inhibits K channels in extrapancreatic tissue. Increased insulin release. Reduces serum glucagon levels. B: doesn’t need pancreas. Directly stimulates tissue glycolysis. Reduces liver gluconeogenesis. Slow glucose absorption git. Reduce glucagon lvl. |
| Pharmacological effects glucagon | Metabolic: G protein incr camp, catabolism glycogen (liver not mm). Incr insulin (pancreas), catechols and calcitonin. Cardiac: pos inotrope/chronotrope via camp not beta receptor. Smooth mm relax (large dose) |
| Indications glucagon | Severe hypoglycaemia. Beta blocker o/d (5-10mg iv reverse bradycardia/hypotension) Relax intestine (radiology) Dx endocrine disease (t1dm), tumours (insulinoma, medullary carcinoma) |
| Adverse glucagon | Transient n/v Hyperglycaemia |
| Hydrocortisone effects | Physiologic + permissive effects Metabolic Catabolic + anti anabolic Anti inflammatory + immunosuppressive Other: cns, pituitary axis, psych, renal, neonatal lung |
| Mechanism insulin | Promotes glucose uptake by tissues (fat, liver, sk mm) Glycogen synthesis Insulin receptors found on cell membranes |
| What are different insulin formulations | Short: clear, neutral ph, rapid onset/offset (actrapid) Intermediate: turbid, neutral ph, protamine in p04- prolong action (isophane) Long: clear, soluble, slow onset/offset (glargine) |
| Other indications insulin apart from bgl | Hyperkalaemia Ccb o/d Beta blocker o/d |
| How to administer optimise bgl control | Titrations dose to bgl Use appropriate insulin types ie rapid, intermediate, long Mix insulin preparations Continuous s/c insulin infusion Replace basal (50%) and meal (50%) requirements |
| Complications of insulin administration | Hypoglycaemia Allergy Immune insulin resistance Lipodystrophy injection site |
| Describe principles of operation of s/c infusion device | External open loop pump Individualised basal/boils replacement doses based on bgl User programmed Consists: insulin reservoir, program chip, keypad, display screen attached to s/c inserted infusion set |
| Pharmacokinetics of metformin | Well absorbed Not protein bound Not metabolised Elimination 1/2 1.5-3h Excreted kidney unchanged |
| Side effects metformin | Gi (20% - most common) Hagma (lactic acidosis) esp with coexistent renal disease, alcohol, chronic cardiopulmonary disease Decr b12 absorption |
| Mechanism octreotide | Somatostatin analogue Reduces splanchnic and portal blood flow Inhibits endocrine and paracrine factor secretion (insulin, glucagon, gastrin, gh, tsh) |
| Adverse effects octreotide | Anaphylaxis Localised irritation (red, burning) Git (n/v, decr motility, bowel obstruction, cholelithiasis, steatorrhea) Hypo/hyperglycaemia Cvs: sinus bradycardia, conduction disturbances |
| Pharmacokinetics octreotide | Elimination 1/2 80min Metab by liver 30-40% Renal excreted 20% unchanged |
| Clinical uses octreotide | Oesophageal varicose (50mcg bolus, 25-50mch/hr) Sulphonylureas o/d Insulin o/d Hormonal tumours (acromegaly, gastrinoma) Carcinoid tumours |
| Difference between octreotide vs somatostatin | Oct has longer t1/2 (1.5h vs 3h) so given iv infusion or s/c |
| Sulphonylureas mechanism | Binds atp sensitive k+ channel Inhibits k efflux Depolarisation + ca influx Releases insulin Reduces serum glucagon Closes k+ channels in extrapancreatic tissue |
| Pharmacokinetics gliclazide (sulphonylurea) | Good oral bioavailability 80% Vd 20L (protein bound) Hep metab to inactive metab T1/2 12h Renal excretion 80% |
| Calcium preparations (oral) examples | Ca carbonate Ca acetate, ca citrate, ca gluconate |
| Clinical uses oral ca preparations | Hypocalcaemia (hypoparathyroidism, vit d deficiency, chronic renal disease) Antacid |
| Adverse effects iv ca | Vein irritation Cardiac arrhythmias Hypercalcaemia |
| How is Hartmann’s different from n/s | Sodium lactate, potassium chloride, calcium chloride Na 131, k 5, cl 112, ca 2, lact 28mmol |
| Advantage of Hartman for resus fluid | Physiological Less hyperchloraemic Effective bicarbonate (slow acidosis) |
| Complications ivf therapy | Fluid overload (Apo) Hypothermia, acidosis, electrolyte abnormalities, infection, haemodilution, cerebral oedema |
| Classes ivf | Colloid (dextran, albumin, gelatin) Crystalloid (isotonic - n/s, Hartman, hypertonic - saline 3%, hypotonic - 0.45% nacl, dextrose 5%) Blood and blood products |
| Indications for mg in pregnancy | Pre eclampsia and eclampsia to treat life threatening seizures |
| Toxic effects mg | Git - n/v Cvs - hypotension, flushing, cardiac arrhythmia CNS - depression, loss reflexes, resp depression, dbl vision Other - mm weakness, renal failure, mm paralysis |
| Uses mg in ed | Anticonvulsant anti arrhythmic Bronchodilator Affects na/k atpase, na channels, k and ca channels |
| Physiological changes elderly | Absorption - nutrition deficit, delay empty (diabetes) Distribution - decr body water, lean body mass, albumin. Incr fat Metabolism - decr hep blood flow, decr phase 1 Elimination - decr kidney creat clear Polypharmacy and drug interactions/toxicity |
| Changes to morphine iv for older patient | Reduce initial dose, longer interval before 2nd iv dose, incr interval between repeat doses Elderly sensitive to resp dep 2nd resp function decline. Incr distribution time to cns 2nd decr CO Elimination t1/2 increased |
| Which drugs in ed altered for elderly | Benzo - liver met/renal fn Opioids - resp effects NSAIDs - gi/renal effects Warfarin - drug interactions Renal excreted drugs - gent, acyclovir Digoxin - decr vd Phenytoin - zero order kinetics |
| Which drugs where hepatic clearance doesn’t change with age | Salicylate, warfarin, ethanol, oxazepam, nitrazrpam, lignocaine, prazosin |
| Difference in pharmacokinetics children | Composition: neonate 75% water Fat: 1% preterm infants Proteins: decr albumin (toxicity of drug protein bound) Metabolism: 50-70% adult, slow clear, long t1/2 Excretion: decr gfr, neonate 30-40%, 3/52 50-60%, 6/12 adult |
| Factors affecting placental drug transfer | Lipid solubility Mol size Protein binding Placental and foetal drug metabolism |
| Foetal therapeutics | Drug administration to pregnant woman but targeting foetus Corticosteroids- lungs Phenobarbitone - induce enzymes bilirubin glucorindation) Antiretrovirals - hiv prevent Anti arrhythmics |
| Factors contribute to drug response variation | Age Gender Body mass Disease states Other drugs administered Tolerance, tachyphylaxis, idiosyncratic reactions |
| Mechanisms involved in drug response variation | Altered drug conc teaching receptors (abs, clear alterations) Variation endogenous receptor Ligands (eg propranolol in elevate catechol) Altered number/function receptors (down reg, tolerance, withdrawal) Change response distal receptor (age, disease) |
| Difference btwn full agonist and partial agonist | High conc full agonist evoke maximal response, partial cannot Partial agonist acts as antagonist if full agonist present (buprenorphine) |
| What is ec50 | Conc at which agonist produces 50% maximal effect |
| What are spare receptors | Conc agonist to produce maximal response may not occupy all receptors |
| What is antagonist? Difference btwn competitive and non competitive antagonists | Antagonists bind to receptors without activating them. Competitive: can be overcome by higher conc agonists Non competitive: covalent bonds, not overcome by incr conc agonists, depends on receptor turnover rate Shifts conc effect curve to right |
| Give examples of competitive and non competitive antagonists | Competitive: Naloxone, flumazenil, propranolol, isoprenaline, naltrexone Non competitive: Maoi, phenoxyenzamine |
| Define potency | Amount of drug required to produce an effect Ec50/ed50: amount drug to produce 50% maximal effect Affected by receptor affinity for drug binding and coupling efficiency |
| Define efficacy | Maximal effect when all receptors occupied irrespective of conc required to produce that response |
| Describe steps in activation 2nd messenger | Drug binds extra cellular receptor Activated G protein. Changes enzyme/ion channel Changes conc of intercellular 2nd messenger Causes response |
| Give example of 2nd messenger and response | Camp via adenyl Cyclase - fat/cho mobilisation, incr inotrope/chronotropy heart, smooth mm relax Cgmp via guanyly cyclase - no binds cytoplasmic guanyly cyclase. Inhibits pde. Incr cgmp. Decr ca influx. Mm relaxation. |
| What is a second messenger | An intracellular substance which has its concentration altered by a process initiated by extracellular ligand. It then acts to initiate intracellular process via 3 steps extracellular process, transmembrane signalling and intracellular process |
| Transmembrane signalling molecular mechanism | Lipid soluble ligand crosses membrane, binds intracellular receptor Transmembrane protein with ligand binding to extracellular domain regulates enzymatic activity Stimulates tyrosine kinase Opens ion channels G protein and intracellular 2nd messenger |
| G protein function | Extracellular ligand binds surface receptor Receptor activates G protein G protein changes activity of effector element (enzyme/ion channel) Changes 2nd messenger concentration |
| G protein example | Beta agonist: beta adrenoreceptor, Gs protein, adenylcyclase, incr camp conc Glucagon, histamine, serotonin, ach, opioids |
| 2 main mechanisms for spare receptor phenomenon | Temporal: prolonged effect after transient binding Numerical: limited substrate with excess receptors |
| Which variables influence rate and extent of drug absorption | Route Nature absorbing surface: cell membrane (single intestinal vs several skin), surface area (Lung, git) Blood flow: increased enhances absorption Drug solubility: lipid drugs Drug formulation: enteric coatings |
| Why aspirin absorption enhanced by low ph | Aspirin pka 2.98 Therefore unionised in stomach and ionised in small intestine |
| Define first pass metabolism | After absorption oral drug, portal blood delivers it to liver Metabolised prior in git wall, portal blood Metabolised in liver, then excreted into bile Reaches systemic circulation |
| How to increase bioavailability | Different route: iv, Im, s/c, s/l, pr (50% bypass liver) Inhalational Transdermal Drug properties: increase absorption (hydrophilic, lipophilic pumped into gut), prodrug, increase dose |
| Factors affect bioavailability | Absorption: too hydro/lipophilic, reverse transporter, gut wall metab 1st pass: liver metab, excreted in bile Rate absorption: depends on site admin and drug formulation |
| What is bioavailability of ibuprofen | High Weak organic acid Well absorbed rapidly Low 1st pass |
| Define bioavailability | Fraction unchanged drug reaching systemic circulation following any route Iv 100% Im 75-100% Oral 5-100% |
| What is drug bio transformation | Process of metabolism to make drugs inactive or by increasing excretion by making them hydrophilic or making them less active |
| What are phase 1/2 reactions | 1: unmask functional gp to be more polar (oxidation, deamination, hydrolysis, reductions) 2: conjugation with endogenous substrate to be more polar |
| Factors responsible for drug metabolism differences | Genetics - enzyme lvl Diet - induce/inhibit enzymes environment - enzyme inducers Age - extremes have decr enzyme activity Gender - male incr bmr Drug interactions - inducer/inhibition Disease states - liver/resp/cardiac Liver size/fn Body temp |
| What is an enzyme induction | Drug causes increased synthesis or decr degradation Results in accelerated substrate metabolism Decreased pharmacological action of inducer or coadministered drug |
| Sites of drug bio transformation | Liver Git - clonazepam, penicillin (gastric acid), insulin (digestive enzyme), catechols (intestinal enzymes) lung, skin, kidneys |
| Phase 1 biotransformation reaction | Oxidation, hydrolysis, reduction, deaminations, desulfurations, dealkylations, dehydrogenations |
| Phase 2 biotransformations | Glucoronidation, acetylation, sulfation, methylation, glutathione conjugation |
| Define drug clearance | Measure of ability to eliminate a drug. Volume of plasma cleared of a drug per unit time. Cl = rate elimination/drug concentration |
| Factors affecting clearance | Concentration of drug: dose/bioavailability Elimination: dependent on organ function, blood flow, protein binding properties of drug Major site of elimination are kidney and liver Other sites: blood, mm and lung |
| Difference between capacity limited and flow dependent elimination | C: is saturable (zero order). Clearance depends on drug clearance (aspirin, phenytoin, ethanol) F: is not saturable (1st order). Clearance depends on rate of drug delivery to organ, ie blood flow (verapamil, lignocaine, morphine, amitriptyline, labetalol |
| Which drugs predominantly renal clearance | Abx: ampicillin, gentamicin, vancomycin Antihtn: enalapril Cvs: digoxin Other: metformin, lithium |
| Define total body clearance | Ability of body to eliminate drug. Theoretical volume of plasma emptied of drug per unit time (L/h). Reflects sum of all clearance processes including renal, liver and other |
| What is t1/2 and its equation | Time to change amount of drug in body by 1/2 during elimination T1/2 = 0.693 x VD/Cl 50% drug after 1 t1/2 >90% drug after 4 t1/2 |
| Define steady state | The dosing rate = elimination rate Adjusted for disease states, ie renal failure, liver failure |
| Role of p450 system | 1. Bio transformation system to detoxify drugs, eg oxidation (phase 1) making more polar metabolite. On smooth we. 2 enzymes - cytochrome p450, cp450 reductase |
| Mechanism cp450 enzyme induction and give examples | Enhanced rate of synthesis (dex, phenobarbitone), reduced rate degradation (ethanol, clotrimoxazole) Cyp450 2b1 - barbiturates Cp450 3a - steroid, macrolides, anticonv Cp450 2e1 - ethanol, isoniazid Cp450 1a1 - tobacco hydrocarbons |
| First order kinetics elimination | Constant fraction/% drug eliminates per unit time Rate elimination proportional to amount of drug in body. Most drugs work this way |
| Zero order kinetics elimination | Constant amount of drug eliminated per unit time. Constant rate elimination independent of drug amount. Saturated in overdose. Capacity limited clearance E.g ethanol, phenytoin, salicylate, theophylline, thiopentone |
| What factors affect rate drug absorption from small intestine | Ionisation status of drug, intestine factors unionised basic drugs (ph 7-8) Intestinal motility (incr motility means reduced transit time and decr drug absorption) Other: Gut surface area, blood flow, drug solubility, drug formulation |
| Disadvantage of rectal drug route | Erratic absorption 2nd rectal contents Drug irritation locally ?drug retention |
| Define Extraction ratio and give formula | Fraction of drug removed from blood by liver, dependent on liver blood flow, uptake into hepatocytes and enzyme metabolic capacity Er = clearance liver/q Q = liver blood flow (90L/h) |
| What disease state affects drug 1/2 | Vd: malnutrition, albumin, mm mass, fat, oedema, ascites, effusions Cl: nutrition, renal disease, liver disease, cvs disease (CO) |
| Define volume of distribution | Volume in which the amount of drug in body would need to be uniformly distributed to produce the observed concentration in blood/plasma/water Vd = amount drug body/conc drug plasma or blood |
| How is it possible for a drug to have a vd of 2500L? | Drug is not uniformly distributed, ie lipid soluble Therefore drug has higher concentration in extravascular tissues than blood Eg morphine, digoxin (500L), beta blockers, diazepam, clonidine, fluoxetine, tricyclics |
| Give examples of low vd drugs | Aspirin, frusemide, abx (gent, Amox, ceph), phenytoin, lithium, warfarin, theophylline, indomethacin Drugs with high vd can’t be dialysed |
| Factors affecting vd | Drug: lipid solubility, pka, ph, protein binding Patient: age, gender, disease state, body composition (fat distribution), blood flow |
| Name common antiemetics used in ed and their mechanisms | Ondansetron - peripheral 5ht3 blocker (Vagal/spinal afferent), central 5ht3 (vomit centre, Ctz) Metoclopramide - d2 blocker (ctz), also incr oesophagi motility, incr gastric empty Prochlorperazine - phenothiazine |
| Adverse effects metoclopramide | Cns: Drowsy, insomnia, agitation, anxiety Epse: acute dystonia, akathisia, parkinsonian, tardive dyskinesia (chronic) Other: prolactinaemia - galactorrhea |
| Antiemetic drug classes | 5ht3 antagonist: ondansetron Phenothiazine: prochlorperazine, dopamine block ctz Butyrophenones: haloperidol Benzamides: metoclopramide, dop antag, 5ht4 agon H1 blocker antihistamine: diphenhydramine Antichol: hyoscine Benzo Thc Corticosteroids |
| Adverse effects prochlorperazine | Acute dystonia (dopamine blockade) Sedation (antihistamine) Antichol (antimusc) Allergy |
| Types of laxatives and their mechanism | Stimulants: senna (emodin alkaloids) Bulking: agar, psyllium seed, bran (bloat/flatus) Osmosis: lactulose, mg, sorbitol (nonabsorbable) Softeners: glycerine, docusate (emulsify stool to soften it) (permit water/lipid penetrate) |
| Why is polyethylene glycol safe for endo prep | Balanced (osmotic active sugar with nacl/nahco3/kcl) No sig osmotic shift. Infested rapidly for bowel cleansing |
| Adverse effects ondansetron | Cns: headache, dizzy Git: constipation, diarrhoea Uncommon: prolong qt |
| PPI mechanism | Irreversible inactivated h/k atpase Blocks proton pump, inhibits >90% acid |
| Why is iv infusion preferred to single bolts for ppi | Bolts inactivates active pumps (<10% in fasted) Hence decr acid secretion for a few hrs |
| How to increase bioavailability of ppi | Inactive prodrug to prevent gastric elimination Take empty stomach 1h preprandial, food decr bioavailability Peak dose drug occurs when most pumps active |
| Define passive immunisation | Given preformed antibodies, from animal/human source |
| Indications for passive immunity | Disease prevention when time not allowed for immunisation Treat diseases normally prevented by immunisation Patients unable to form antibodies Treat conditions where active immunisation unavailable (snakebite) |
| Give examples of passive immunisation in ed | Tetanus, measles, rubella, varicella, hep b/a, diphtheria, Rabies, antivenom Rhesus incompatibility |
| Classify h1 antagonist and describe pharmacodynamics | Sedating (1st gen) vs non sedating (2nd gen) Pd: h1 antag, alpha block, antichol, antidopaminergic, na channel block, antiserotinergic Causes sedation and hypotension, seizure, allergy, antimusc effects |
| Clinical use h1 antag | Allergy, rhinitis, urticaria Motion sickness, vestibular disturbance N/v Sedation Serotonin antag (cryptoheptadine) Drug induced parkinsonian |
| What is erythropoietin and what does it do | Glycoproteins produced by kidneys Stimulates rbc precursors to differentiate Used in anaemia of ckd, some marrow failure states (aplastic anaemia, myelodysplastic disorders, multiple myeloma, aids, cancer) |
| Toxic effects of erythropoietin | Related to rapid hb incr (htn, thrombosis) Allergy (infrequent and mild) |
| What otc preparations ingredients causes toxicity and give 1 example for each | Salicylate - coagulopathies Ethanol - drowsiness Sodium La Caffeine - agitation, headaches Antihistamines - drowsiness |
| Use of penicillamine and its adverse effects | Wilson’s disease Copper poisoning Severe ra (occasional) A/e: Git - n/v Allergy - hypersensitivity (esp penicillin allergy), nephrotic Immune - pemphigus, myasthenia, arthropathy Other - optic atrophy, pancytopaenia |
| Advantage eye ointment vs drops | More stable Less absorption into lacrimal ducts Longer retention time on conjunctiva Safer with potent drugs Provide protection and comfort at night |
| List types of drugs used topically in eye | Mydriatics Miotics Decongestants Abx Antivirals Antiseptics Corticosteroids La Stains |
| What is vitamin k | Fat soluble substance in vegetables, usu synthesised by gut bacteria Vit k1 - food Vit k2 - bacteria |
| Clinical indications for vit k | Reversal warfarin Mx warfarin toxicity Vit k deficiency Prevent haemorrhagic disease of newborn Dose: 10mg iv in n/s or glucose |
| Mechanism benzodiazepines | Binds to gaba A receptors (cns) - cl ion channel Positive allosteric bond, enhance gaba effects Incr cl channel opening |
| What are organ level effects of diazepam | CNS: sedation, anxiolytic, psychomotor and cognitive depression, amnesia, hypnosis, anaesthesia (higher doses), anticonvulsant Resp/cvs: depression, decr contractility Uses: sedation, anticonvulsant, etoh/benzo withdrawal, toxidromes (various) |
| Explain benzo use in etoh withdrawal | Alcohol dependence results down regulation gaba receptors leading to gaba deficiency Bzd allosteric bond facilitates gaba binding to gaba a receptors Cl channels opened Overcome gaba deficiency neuroexcitatory symptoms |
| What receptors does carbamazepine affect | Sodium channel blocker, decr high freq repetitive firing Adenosine receptors Anti cholinergic (antimuscuranic) Inhibits uptake and release nadr Doesn’t affect gaba uptake |
| Most common adverse effects of carbamazepine | CNS: nystagmus, diplopia, ataxia (cerebellar), drowsy Cvs: hypotension Antichol: dry mouth, tachycardia, blurred vision, delirium Git: upset Hepatic: dysfunction Blood: dyscrasias Other: hyponatraemia, water intoxication Allergy: rash |
| Drug interactions of carbamazepine | Cyp450 inducer Incr drug clearance Reduces drug blood levels (warfarin, phenytoin, valproate, lamotrigine, diazepam, phenobarbitone) Breakthrough seizures |
| Clinical use carbamazepine | Anticonvulsant (partial/generalised) Bpad Trigeminal neuralgia Na channel blocker - presynaptic synaptic transmission block (cf phenytoin) Inhibits high frequency repetitive neurone firing |
| How is carbamazepine metabolised | Microsomal enzymes Enzyme inducer Active metabolites |
| Pharmacokinetics midazolam | Water soluble hence Po/Im/in route Poor bioavailability High protein bound Crosses bbb at body ph Elimination t1/2 1.5-2.5h Liver metabolism Renal excretion (56%) |
| Pharmacokinetics phenytoin | High bio 90%, poor imi Peak serum conc 3-12h High protein bound 90% Vd 45L Elimination dose dependent (0 order) Low conc 1st order, enzymes saturated Peak 1.5-3h T1/2 12-36h Liver metabolism to inactive Renal excretion <2% unchanged, bile excre |
| Rationale behind phenytoin loading dose | Otherwise need 4 t1/2 lives to reach steady state Reach target conc rapidly if incr dose Dose = vd x target conc |
| Mechanism of phenytoin | Primary na channel blocker Reduce na+ conductance Prolong inactivated state Reduces ca influx Decr glutamate release Enhanced gaba release Inhibits generation repetitive apot Other: alter k and ca conductance |
| Risks with iv phenytoin | Cvs: hypotensio, bradycardia Allergy Local necrosis if extravasation Max infusion rate 50mg/min over 30-60mins |
| Elimination kinetics phenytoin | Dose dependent (0 order) 1st order at low doses Small recurrent dose increases leads to toxicity |
| Acute overdose phenytoin features | CNS: sedation, coma, nystagmus, ataxia, cerebellar toxicity No cardiac toxicity |
| Adverse effects phenytoin | Idiosyncratic: hirsuitism, gingival hyperplasia, acne, facial coarsening, skin rash, sjs, lymphadenopathy Dose related cns: drowsy, dizzy, blurry, hallucinations, slurred speech, confusion |
| Phenytoin dose status epilepticus | Iv 13-20mg/kg diluted in saline (precipitates in glucose) Max adult rate 50mg/min Then 100mg q6-8h |
| Pharmacodynamics sodium valproate | Gaba Increased presynaptically by reduced gaba breakdown Direct inhibition post synaptic na channel, high freq gates and ca+ ?nmda receptor blocker |
| Valproate adverse effects | Git: n/v, upset Liver: toxicity, liver failure Foetus: abnormalities, developmental effects Allergy: hypersensitivity CNS: tremor, nystagmus Blood: ttp Other: pancreatitis, alopecia |
| Pharmacokinetics valproate | Good bio >80% Peak plasma lvl 2/24 (empty gut) 90% protein bound Small vd 0.15L Liver metabolism 95% Renal excreted (5% unchanged) Elimination dose dependent (0 order) T1/2 15h |
| Toxic effects valproate | Git: n/v CNS: coma, cerebral oedema, tremor Electrolyte: hyperNa, hypoCa, hyperAmmonaemia Liver: hepatotoxic (tx iv L-carnitine) Blood: ttp Allergy: rash Other: alopecia, wt gain, foetal malformation |
| Drug interactions other seizure drugs | Phenytoin- inhibits metabolism Phenobarbitone/carbamazepine- inhibit metabolism of these drugs Lamotrigine - decr clearance |
| Pharmacodynamics amitriptyline | Blocks serotonin and nadr reuptake Blocks musc, symph a1, gaba A, na channel and histamine receptors |
| Toxic effects amitriptyline and treatment | Anticho: blurry, dry mouth, tachycardia, urine retention, delirium Antihistamine: sedation Anti symph: hypotension Anti na: wide qrs, bradycardia Seizures (direct central) |
| Mechanism antidepressants | Enhanced amine dependent synaptic transmission (serotonin, nadr) via 1. Inhibit metabolism (maoi) 2. Inhibit re uptake (tax, ssri) 3. Increase release due antagonist of serotonin and alpha2 nadr receptors (mirtazepine) |
| Pharmacokinetics carbamazepine | Well absorbed Peak lvl 6-8h Protein bound 70% T1/2 36h Does not displace other drugs P450 inducer enzyme |
| Adverse effects lithium | CNS: tremor, ataxia, confusion, withdrawal Thyroid: hypothyroidism Renal: polyuria, polydipsia (DI), nephrotic syndrome Cvs: oedema, worst sick sinus Allergy Skin: acneiform eruptions |
| Pharmacokinetics lithium | Oral absorption Peak 0.5-2h Vd TBW (0.5-0.9L/kg) T1/2 20h No protein binding Nil metabolism Excreted renal unchanged Therapeutic conc 0.6-1.4mmol/L |
| How assess lithium toxicity | Measure levels 10-12h post dose >2mmol/L = toxic Tx: supportive, haemodialysis |
| Drug interactions lithium | Thiazides - 25% reduced lithium clearance NSAIDs - similar reductions clearance Neuroleptics/antipsychotic worsen epse |
| Factors influencing lithium excretion | 1. Renal fn (gfr) 2. Water/na status(incr lithium excretion pct in depleted state) 3. Drugs: thiazides, NSAIDs reduce clear 4. Lithium serum concentration |
| Mechanism serotonin syndrome occurs | Excess stimulation cns receptors due to overdose (single or multiple) Drugs work on difft pathways Inhibit serotonin metab (amphetamines) Prevent reuptake (ssri, snri) Serotonin release incr (trytophan, lithium) |
| What therapies reduce tissue distribution for tca toxicity | 1. Alkalinisation (bicarbonate/hyperventilate) Incr plasma protein binding of free drug Removes drug from tissues Reduce toxic effects |
| Pharmacokinetics tca | Oral absorbed Bio 40-50% High 1st pass High protein binding and high lipid solubility Large vd Liver metabolism Active metabolites |
| Toxic effects tca overdose | CNS: sedation, tremor, insomnia Antimusc: blurry, constipation, urinary retention, tachycardia Cvs: alpha blocker (hypotension), na block (arrhythmias) Psych: agitation, we gain, seizures, withdrawal |
| Tca overdose mx | Support: dopamine/nadr for np Cvs: sodium bicarbonate 50-100meq iv, intralipid |
| Mechanism tca | Blocks amine (nadr/serotonin) transporter at presynaptic endings Prolongs neurotransmitter action post synaptic Most non selective |
| Mechanism sumatriptan in migraines | Selective agonist 5HT1d and 5HT1b receptors located cerebral and meningeal vessels Causes vasoconstriction cerebral arteries |
| Pharmacokinetics sumatriptan | Bio 15% (other agents 40-70% same gp) T1/2 2-3h Given s/c, in, po |
| Advantage and disadvantages sumitriptan | Adv: mild side effect (tingling, dizzy, mm weakness, neck pain, effective) Disadvantage: not for ihd due to coronary spasm, short duration (need several doses if prolonged migraine), expensive |
| Drug mx acute migraine | Simple analgesia (Panadol, aspirin, codeine) Metoclopramide Prochlorperazine Ergot alkaloids (+\- caffeine) Triptans |
| Why is levodopa used with carbidopa | Carbidopa is peripheral dopa decarboxylase inhibitor. It doesn’t cross bbb Reduces peripheral metabolism levodopa Incr levodopa levels More levodopa enters brain |
| Adverse effects levodopa | Git: anorexia, n/v (stimulates emetic centre brainstem) Cvs: arrhythmias, tachycardia, Vent ectopic, af, hypotension Dyskinesis Psych: depression, anxiety, agitation Misc: mydriasis, glaucoma, gout, taste/smell |
| Drug classes used for mx agitation in ed | Benzodiazepines Antipsych (phenothiazine - chlorpromazine, butyrophenones - haloperidol, atypical - risperidone) Barbiturates - phenobarbitone Serotonin antag (5HT2a) Dopamine (d2) antag |
| Adverse effects atypical antipsych | Epse - less common that typical Tardive dyskinesia Antimusc: dry mouth, urinary retention Ortho hypotension Wt gain Hyperglycaemia Hyperprolactinaemia Agranulocytosis Neuroleptic malignant sydrome Antialpha Antihistamine Jaundice Endocrine |
| How can epse effects be managed | Lower dose Switch to atypical Administer benztropine or diazepam No effective tx for tardive dyskinesia, prevention vital Monitor for signs and reduce/cease asap |
| Pharmacokinetics antipsychotics | Most readily but incompletely absorbed Significant 1st pass metabolism Lipid soluble High protein binding 92-99% Metabolised by liver enzymes (oxidation, demethylation) |
| Define atypical antipsych | Newer agents Less epse Better treats schizophrenia (meg features) Greater ability alter 5HT2a receptor activity than D2 receptor action Eg Olanzapine, clozapine, quetiapine, risperidone |
| Side effects chlorpromazine | Antialpha - hypotension D2 antag (mesolimbic/mesofrontal) Parkinson, akithesia, dystonia D2 antag - lactation Antihistamine - sedation Anti dopamine (medulla ctz) - nms Antimusc - confusion, tachycardia |
| Disadvantage of olanzapine (thienobenzoduazepine -D4, alpha 1, 5ht) | Antichol effects Lowered seizure threshold Weight gain Diabetes Hyperlipidaemia Expensive Medium sedation |
| Pharmacodynamics haloperidol | Butyrophenone class D2 receptor antagonist High epse Low sedation Low hypotension Minimal antichol effects Minimal 5ht and h1 blockade |
| Olanzapine clinical uses | Wide spectrum Autism Delirium Dementia Acute mania Schizophrenia Behavioural emergency |
| What are effects of adr on different tissue and what receptors mediate these | Vascular resistance Cutaneous - a Mucous membranes - a Skeletal mm - b2/a Renal - a/d Splanchnic - a/b Venous tone - a/b |
| Describe adr effects on organs apart from heart | Resp - bronchodilation Eyes - pupil dilation, decr iop, decr aqueous humour Geniturinary - uterine mm relax, bladder relax, sphincter contract, ejac Saliva - decr Liver - glycogenolysis Met acidosis Leukocytosis |
| Adr effects on heart | Pos inotrope/chronotropy Low dose b>a effects - vasodilation (widened pulse pres) High dose a>b effects - vasoconstriction (narrow pulse pres) |
| Side effects adr infusion | General: anxiety, tremor, n/v, pallor Cvs: palpitations, arrhythmias, ami, htn Metabolic: hyperglycaemia, met acidosis, hypokalaemia |
| Difference btwn adr and nadr | Nadr peripheral alpha effects - vasoconstriction Adrenaline- mixed a/b Nadr - less cardiac effects Difft side effect profile (metabolic effects due beta activation) |
| What cellular mechanisms for beta agonist | Bind specific receptor G protein activation Stimulates adenyl cyclase Increased camp Incr free intracellular ca Activated protein kinase |
| Compare adr and dobutamine | Adr: b1/b2/a, pos inotrope/chronotropy, peripheral vasoconstriction b/vessels, vasodilation skeletal mm (b2), reduce tsvr? Dob: selective b1 agonist, incr CO, less tachycardia (less b2) |
| Mechanism amphetamines | Indirect incr catechols release at synapse Competitive inhibits dopamine transport at presynaptic neurone (DAT) |
| Amphetamine effects | Incr catechols: incr arousal, decr sleep, elevated hr, elevated bp (cva) Incr dopamine: euphoria, abnormal movements, psychosis Serotonin: appetite suppressant, hallucinogenic, hyperthermia |
| Mechanism atropine | Competitive reversible musc Ach receptor antagonist Binds musc receptor, prevents ip3/dag release and inhibits adenyl cyclase Equipotent m1/2/3 receptors |
| Organ effects atropine | Eye: mydriasis, cycloplegia Cns: delirium, decr tremor (Parkinson) Cvs: tachycardia, sa/av node/vagus block Resp: bronchodilator, decr secretions Git: decr saliva/gastric acid/mucin Gut: relax ureter/bladder mm, urine retention Skin - decr sweat |
| Use atropine clinically | Brady arrhythmias, bradycardia Eye: for mydriasis purposes Organophosphate poisoning Palliative care Parkinson Motion sickness |
| Pharmacokinetics atropine | Iv/po/neb/top Well absorbed po Wide vd incl cns T1/2 2/24 Metabolised liver 40% Renal excretion unchanged (60%) |
| How does metoclopramide cause dystonic reaction? | Dopamine antagonist Causes imbalance antichol/dopamine transmission basal ganglia |
| Mechanism benztropine | Blocks musc ach receptors (antimusc) Cf atropine |
| Adverse effects benztropine | CNS - drowsy, hallucinations, confusion Pns - dry mouth, blurry, mydriasis, urinary retention, n/v, constipation Cardiac - tachycardia, palpitations |
| Mechanism indirect cholinomimetics | Inhibit acetylcholinesterase Incr endogenous ach Act on nicotinic and musc receptors Act in Nmj end plate and autonomic ganglion cells |
| What types of indirect acting cholinomimetics | Reversible: gp 1 - alcohol (epdrophonium) Gp 2 - carbamates (neostigmine, physositgmine) Irreversible: gp 3 (organophosphate, insecticides) |
| What are cvs effects of indirect acting cholinomimetics | Activates symph and para symph ganglia Para>symph Bradycardia, decr CO, decr contractility, ?decr BP Overdose may cause tachycardia and hypotension |
| Mechanism metaraminol | Direct alpha 1 receptor agonist Some indirect effect through incr nadr |
| Cvs effects of metaraminol | Vaso and arterial constriction in vasc beds Incr BP Hr slow due to vagal feedback CO unchanged or slight decr |
| What receptors do Nadr work on | Mainly a1 (Vasc smooth mm - vasoconstriction) A2 (presynaptic) - inhibits nadr release (-ve feedback) B1/2 - some effect, b1>b2 |
| How does Nadr incr BP | A1 activity - smooth mm vasoconstriction - incr tpr - incr dbp B1 activity - nerve/platelets/lipocytes/smooth mm - incr contractility - incr sbp B1 activity - hear/bra -incr hr but compensatory baro reflex causes bradycardia therefore minimal hr change |
| Pharmacokinetics of ethanol | Rapid git absorption Peak 30mins Vd TBW 0.5-0.7L/kg Liver metabolism (etoh dehydrogenase>microsomal ethanol oxidising system) Zero order Excretion lungs/urine (small) |
| Pharmacodynamics ethanol | CNS: sedation, disinhibition, impaired judgement/motor, ataxia, slurred speech, resp dep Cvs: dep contractility Smooth mm: vasodilator results hypothermia |
| Action dantrolene and uses | Interferes ca release from ser by binding to ryanodine receptor Reduces excitation coupling Affects motor units that contract rapidly Spasmolysis (cerebral palsy, ms, stroke) Malignant hypothermia (1mg/kg IV, repeat prn max 10mg/kg) |
| Pharmacodynamics ketamine | Nmda receptor antagonist Inhibits reuptake catechols and serotonin Short acting sedative, amnesic, analgesic and anaesthestic |
| Systemic effects ketamine | CNS: dissociative anaesthesia, profound analgesia, cerebral vasodilator (incr blood flow/metabolic rate) Cvs: haemodynamically stable, incr hr/bp/CO Resp: intact airway reflex, min dep, laryngospasm kids, bronchodilator Eye: nystagmus |
| Adverse effects ketamine | CNS: emergence phenomenon, dysphoria, hallucinations, seizures Git: n/v Resp: laryngospasm, incr salivation/lacrimation |
| Pharmacokinetics ketamine | Rapid onset High lipid soluble Effect terminated by redistribution to inactive tissue Low protein bind 12% Liver metabolised p450 to norketamine - inactive metabolites (phase 1/2) Excreted renal |
| Ketamine route and dose for procedural sedation | 1-2mg/kg IV 4-10mg/kg IMI |
| Indications ketamine and routes | Induction agent Procedural sedation Analgesia Iv, Im, in, epidural, po, pr, sc |
| Examples Of anaesthetic induction agents | Thiopentone, propofol, ketamine, fentanyl, midazolam, etomidate |
| Compare onset and recovery of propofol and ketamine | Both rapid Ketamine slower recovery and associated with emergence phenomenon |
| Cvs effects of propofol and ketamine | P: decr BP during induction via decr peripheral arterial resistance and venodilation, negative inotrope K: dose related cv stimulation, incr hr/bp/CO - stimulates central sns +\- inhibit nadr reuptake at symph nerve terminals |
| Explain solubility characteristics of NO | Low solubility blood Reaches arterial tension rapidly Rapid equilibrium in brain Fast onset action/recovery |
| Pharmacokinetics propofol | Iv only Rapid onset/recovery due redistribution from brain to skel mm to fat rather than metab Distrib t1/2 2-4mins Elimination t1/2 4-23mins Duration 3-8mins Liver metabolism, some lung Urinary excretion as glucuronides/sulphites, <1% unchanged |
| CNS: analgeisc, amnesic, incr cerebral blood flow Renal: decr gfr, incr filtration fraction, incr renal vascular resistance Cvs: dose dependent myocardial depression Resp: reduced resp response to co2 and hypoxia | |
| Mechanism nitrous oxide? How does no affect gaba | Directly activate gaba a receptors cl channel Gaba mediated inhibition - membrane hyperpolarisation, decr duration opening nicotinic receptor activated channels, decr excitatory effect Ach |
| What is pancuronium | Non depolarising NM blocker Quaternary ammonium compound Potent competitive antag of Ach at nicotinic receptors skel mm Interruption transmission requires >70% occupancy, blockade >95% occupancy |
| Pharmacokinetics pancuronium | Poorly absorbed orally Rapid and wide distribution post iv High water soluble Hepatic metabolism with biliary excretion Rapid elimination t1/2 30mins Urinary excretion unchanged |
| Adverse effects pancuronium | Uncommon Cvs: minor tachycardia, htn, slight incr CO Allergy: anaphylaxis <1:10k |
| Adverse effects propofol | Cvs: hypotension, vaso/venodilation, negative inotrope CNS: apnoea (dose related resp drive depression) Other: pain injection Allergy: soy/egg |
| How to limit adverse effects propofol | Care with Co administration opiates/benzodiazepines Titrate small doses (10-20mg aliquot) to effect Reduce in elderly and poor cvs reserve Caution haemodynamically unstable patients |
| Dose of propofol for induction of GA vs procedural sedation | Procedural sedation: 0.5-1 mg/kg single bolus or titrate in 10-20mg aliquots in conjunction with morphine Induction: 1-2.5mg/kg adults/2.5-3.5mg/kg kids |
| Clinical effects of propofol | CNS: anaesthesia, sedation, resp depression, apnoea Cvs: hypotension (vaso/venodilation) No analgesia Other: allergy with soy/egg, pain injection, met acidosis, antiemetic |
| Organ effects propofol | CNS: sedation, hypnotic, red cbf, red icp, anticonvulsant, nil analgesia Cvs: hypotension 2nd vaso/venodilation, some inhibition baro reflex results small incr HR Resp: resp dep, apnoea, red tidal vol/rate, red response hypercap/hypoxia, red air reflex |
| What is rocuronium | Nondepolarising mm relaxant Steroid derivative |
| Pharmacokinetics rocuronium | Absorption iv bio 1 Dose 1.2mg/kg Onset 45-60secs Duration 20-75mins High ionised Small vd (80-140ml/kg) Liver metabolism Elimination liver 75-90%, kidney rest 25% |
| Difference between sux and roc | Duration sux 5-10mins Difft side effects and contraindications Sux is depolarising mm relaxant + phase 1/2, phase 1 augmented by pseudocholinesterase inhibitors Sux metabolised by plasma pseudocholinesterases Roc antidote - sugammadex |
| Mechanism rocuronium | Non depolarising mm relaxant Low dose - competitive inhibitor Ach at Nic receptors Large dose - enters ion channel pore to incr nm blockade Also block prejunctional sodium channels - interferes Ach mobilisation at nerve endings |
| Mechanism suxamethonium | Depolarising neuromuscular blocker Phase 1 depolarising (reacts with Nic receptors, opens channel, depolarises nm end plate Phase 2 desensitising (cont exposure to sux - endplate depol decr, membrane depolarises but cannot be depolarises as desensitised |
| Pharmacokinetics suxamethonium | Rapid onset 30-60s Short duration 2-8 mins Hydrolysed rapidly by plasma cholinesterase |
| Adverse effects suxamethonium | Cvs: bradycardia CNS: incr intraocular pres Git: incr intragastric pred Malignant hyperthermia Prolonged paralysis (reduces or abn cholinesterase) Potassium release (burns, trauma, stroke) Mm pain fasciculations |
| Describe succinylcholine and it’s metabolism | Depolarising neuromuscular blocking drug Hydrolysed by plasma cholinesterase to succinic acid and choline |
| Adverse effects depolarising nm blockade | Hyperkalaemia - renal failure, Burns, demyelination, spinal cord injury, cva Incr iop Incr intragastric ICP |
| Describe distribution iv thiopentone bolus | To highly vascular tissue Rapidly crosses bbb High lipid Rapid distributed body fat |
| Adverse effects thiopentone | Adv: rapid, controllable, CNS: amnesic, red ICP, anticonvulsant Disadvantage: Cvs: hypotension, venous irritant, myocardial depression, min mm relaxation, analgesia, hepatic metabolism Rare: porphyric crisis by induce ala synthase liver |
| Pharmacokinetics thiopentone | Lipid soluble Crosses bbb rapidly Rapid diffuses out brain to mm/fat Metabolised 12-16% hourly <1% excreted unchanged kidneys |
| Mechanism vecuronium | Non depolarising nm blockade Comp antag ACh at Nic receptor of nm junction Large dose - enter directly ion channel pore incr blockade Blocks Na prejunctional channels - interfere Ach mobilisation at nerve endings |
| Pharmacokinetics vecuronium | Poor git absorbed High polar Onset 1 min Max effect 3-5min Duration 20-35min Short t1/2 Rapid distribution extracellular space Plasma protein binding 60-90% Small vd (blood volume) Liver elimination liver 75-90%, rest kidney |
| Mechanism bupivavaine | Amuse LA Blocks voltage gated Na channels |
| Pharmacokinetics bupivacaine | Duration 4-8hrs Distribution t1/2 28min Elimination t1/2 3.5h 95% protein bound Lipophilic Large vd 72L Liver metabolism |
| Clinical use bupivacaine | Nerve block in low conc 0.25% for local Infil Types : digital ring, femoral, intercostal, intrapleural, epidural, brachial plexus, sciatic and intra articular |
| Toxic effects bupivacaine | CNS: sedation, visual/auditory disturbance, seizure, perioral paraesthesia, resp depression, nystagmus Cvs: cardiac arrhythmia, hypotension, arrest Allergy |
| Mechanism bupivacaine | Blocks voltage gated sodium channels in nerve Threshold for excursion increases, conduction slows, ap rise declines, ap generation abolished |
| How minimise risk LA toxicity in ed | Ask allergy hx Use safe max dose Avoid vessels Use uss guidance Ask Pt notify of symptoms Avoid hypoxia/acidosis |
| What factors affect absorption after LA infiltration | Drug: protein binding, lipophilic nature Tissue: site of injection, blood flow Other: use vasoconstrictors |
| Toxic effects lignocaine | CNS: early - perioral numb, metal taste, sedation; mod - nystagmus, tinnitus; severe - seizures, sedation Cvs: hypotension, bradycardia, arrhythmia, worse ccf Git: n/v Other: methaemoglobinaemia, allergy (PABA) |
| Mechanism lignocaine | Class 1b Blocks na channels (activate and inactive) Less effect in acidic infected tissue |
| Groups of drugs used in asthma, give 1 example of each | Sympathomimetic (salbutamol) Corticosteroids (dexamethasone) Muscarinic antagonist (tiotropium) Methylxanthine (theophylline) Leukotriene antagonist (montelukast) Other: magnesium Anthihistamines (fexofenadine) Cromoglycate (sodium cromolyn) |
| Mechanism corticosteroids in Asthma | Reduce bronchial activity Inhibit lymphocytes and eosinophils Decr airway mucosal inflammation Incr airway caliber |
| Adverse effects inhaled corticosteroids | Oral candiasis Delayed puberty Osteoporosis Cataracts Slow rate of growth in children |
| Mechanism cromoglycate | Mast cell stabilisation Changes function of delayed cl channels Inhibits cellular activation Affects airway neurones, mast cells, eosinophils |
| Clinical uses cromoglycate | Antigen induced, exercise induced, occupational, young children with extrinsic asthma |
| Types of b receptors | B1/2/3 |
| What cellular processes do beta agonist-b receptor coupling initiate | Activation all 3 receptors stimulates adenyl cyclase and incr conversion atp to camp Mediated by Gs protein via GDP/gtp |
| Clinic use b2 selective agonist | Smooth mm: resp/uterine/vascular smooth relax Skel mm: k+ uptake Resp: bronchodilator, incr mucociliary activity Other: inhibit mast cell release |
| Compare salmeterol and salbutamol | Salbutamol: iv/po/inh, short acting 4hrs Salmeterol: long act 12h, high lipid, dissolved smooth mm membrane (partial agonist) |
| Side effects beta 2 agonists | Cvs: tachycardia Mm: tremor Electrolytes: hypokalaemia, lactic acidosis Other: hypoxaemia, tachyphylaxis |
| Cellular mechanisms by which steroids exert effects in asthma | Decr activation lymphoid/eosinophils Decr cytokines production/action Decr production pgs Decr histamine release Decr production IGE and igg |
| Advantages of different methods salbutamol administration | Neb: rapid absorption, no coordination needed, only a little education, no 1st pass metabolism Puffer: effective as neb, lower dose, less side effects Iv: no 1st pass, for severe asthma but requires iv access and incr systemic effects |
| Pharmacokinetics salbutamol | Absorption fast and complete Within 15-30mins for inh, last 3-4hrs 1st pass 50% T1/2 3-6hrs Liver metab (sulphate) Renal excretion (some unchanged) |
| Organ effects theophylline | CNS: mild arousal, incr alertness, decr fatigue, tremor Resp: bronchodilation, Cvs: pos inotrope/chronotrope via adenosine inhibition (symp nerves, incr catechols release) Git: stimulate gastric acid, digestive enzyme secretion Kidney: weak diuretic |
| How do theophylline effects relate to its serum concentration | Narrow therapeutic window 5-20mg/L: improve plum function, anorexia, nausea 15-20vomit, git upset, headache, anxiety >40: seizure, arrhythmia |
| Metabolism methanol | Methanol to formaldehyde (AD) Form to formic acid (FD) Formic acid to CO2 and water (folic acid) |
| How to treat severe methanol poisoning | Fomepizole (ADH antagonist) Correct acid/base status (ph<7 has poor px) Minimise accumulation formic acid (folic acid) Enhanced elimination by folic acid administer Dialysis |
| What modalities for decontamination | Skin: remove clothes, wash skin Git: emesis, gastric lavage, activated charcoal, whole bowel irrigation |
| How does charcoal work and which drugs it doesn’t work on | Adsorption due to large surface area Ions: fe, li, k Alcohols, cyanide Corrosives (acid/alkali) |
| Which drugs requires repeat charcoal doses | Carbamazepine, theophylline, dapsone |
| Mechanism of nac | Paracetamol liver metabolism saturated results in p450 forming Napqi (toxic metabolite) This depletes glutathione stores and hepatotoxicity Nac works by: 1. Incr glutathione avail 2. Direct bind napqi 3. Provides inorganic sulphate 4. Reduce napqi |
| Adverse effects nac | Alllergy: mild anaphylacttoid reaction (15-20%) Mild flushing Rash Angio oedema |
| Mechanism naloxone | Pure opioid antagonist Binds u opioid sites Rapid onset 1-3mins Duration 1-2 hrs |
| Issues with naloxone adminstration | Precipitate opioid withdrawal Resedation Minimise issue by smaller doses, infusion or appropriate route administration |
| Mechanism flumazenil | Antagonist bzd site on gaba a receptor Decr binding gaba Block gaba induced incr cl permeability and influx Causes hyperpolarisation and decr neurone excitability |
| Indications flumazenil | Avoid intubation or icu admission if bzd overdose Reverse bzd sedation Diagnostic role |
| Problems with flumazenil administration | Precipitate seizure in mixed o/d or pts on bzd for epilepsy Precipitate withdrawal symptoms and seizures in bzd dependence Duration 1-3h thus need repeat doses Adverse: headache, visual disturbance, anxiety, nause, light headedness |
| What is antivenom | Immunoglobulin or antibody (Igg fab) produced by another animal in response to venom Used in people iv/Im post envenomation |
| What antivenoms in australasia | Snake: polivalent and monovalent (black,brown, Death adder, tiger, taipan) Stonefish Red back spider Box jellyfish Funnelweb spider |
| Side effects antivenom | |
| Allergy Anaphylaxis Serum sickness | |
| Which animals used in production different antivenom | Horse: snake, stonefish, redback Sheep: box jellyfish Rabbit: funnelweb spider |
| Mechanism gtn | Nitrite converted to nitric oxide (interacts sulfhydryl gp) Activates cgmp, dephosp mlck, red intracellular ca Results smooth mm relaxation (and vasodilation) PgE/prostacyclin involvement |
| Clinical effects gtn | Cvs: venodilation - decr venous return (preload), decr LVEDV, red lv wall tension, red myocard consumption Vasodilation - epicardial coronary arteries, incr coronary collateral flow, decr sbp Adverse - Cvs: hypotension, tachycardia CNS: headache |
| Gtn indications | Cvs: angina, acs, htn emergencies, apo, aortic dissection (with beta blockade) |
| Routes for gtn | S/l, iv, po, bucc, inh, transdermal |
| Define tachyphylaxis and how it relates to gtn | Continuous exposure to nitrates, smooth mm develops tolerance esp iv infusion or long acting preparations Requires drug free interval at least 8/24 btwn doses |
| How does tachyphylaxis occur with gtn | 1. Diminished release nitric oxide due reduced bioactivation secondary depletion tissue thiol cpds/decr sulphydryl gps Incr o2 free radicals and decr cgrp availability 2. Systemic compensation - after >1/7 salt/water retention reverse favourable change |
| Caution with use of gtn in which situations | Hypotension Pt on sildanefil Infr/postr mi/rv infarct Fixed CO (as, tamponade) Incr icp Sig tach/bradycardia Allergy |
| Pharmacokinetics gtn | Low bio (<10-20%) S/l onset 1-3mins, duration 10-30mins Liver metab Renal excretion Tachyphylaxis cont use |
| Adverse effects gtn | CNS: post hypotension, tachycardia CNS: dizzy, headache, flush, blurry, dry mouth Allergy: rash |
| Cellular mechanism gtn | Denitration by glutathione S-transferase Free nitrite ions releases to form no Activates guanyl cyclase to incr cgmp Dephosp mlck Smooth mm relaxation Vasodilation |
| What are the effects nitric oxide? | Main: smooth mm relax, platelet inh, immune regulator, neurotransmitter |
| Potential applications no | 1. Vasc: smooth mm relax, decr bp 2. Htn pregnancy (no and pg replacement) 3. Resp: newborns with pulm htn/weds to decr pulm art pressure/improve oxygenation 4. Sepsis: urinary excretion no3 (bac product) 5. Block ldl oxidation 6. Inh platelet adhes |
| Mechanism adenosine | |
| Acts adenosine receptors Enhances k conductance, inh camp induced ca influx Hyerpolarisation and decr Apot Bolus dose - av node inhibition, incr av node refractory, less effects sa node | |
| Indications adenosine | Svt Unmask aflutter/afib |
| Adverse adenosine | Cvs: av block, afib, hypotension, flush 20%, chest burning CNS: headache, paraesthesia Resp: sob Git: nausea Contra: av block, sick sinus, asthma, no consent |
| How does adenosine work? | Activation inward k rectifier Inh ca current Marked hyperpolarisation Suppress Apot Direct inh avnode Incr av refractory Interrupts re entry pathway via avnode |
| Pharmacokinetics adenosine | Rapid metabolism adenosine deaminase (rbc) Short elimination t1/2 10secs Duration 30s Given iv bolus |
| Amiodarone effects on heart | Incr Apot duration due block delay K current Chronic use blocks slow k rectifier Prolongs qt Blocks na channels (inactivated) Weak beta blocker and ca channel blocker |
| Indications amiodarone and adverse rhythm caused | Af Vt/vf Svt (reentrant or accessory) Adverse rhythm: tdp |
| Adverse effects amiodarone | Acute: bradycardia, hb, hypotension, neg inotrope Chronic: pulm fibrosis, deranged lft, hepatitis, skin deposits (grey-blue), hypo/hyperthyroidism |
| What antiarrythmics for mx af | Beta blocker: class 2 Ccb: class 4 Na blocker (flecainide): 1c K blocker: amiodarone class 3 Digoxin: class 5 Other: mg |
| Drug interactions with amiodarone | Warfarin (inh metab result incr inr) Digoxin (incr conc result toxicity, incr conc) Incr cardiac effects other anti arrhythmic Phenytoin (incr plasma conc) |
| Cardiac effects amiodarone cellular level | Prolong ap duration (k block) Block inactive na Mild beta block (non competitive) Weak adrenergic blocker (slow hr, av conduction) Weak ccb Inh abnormal automaticity Slow sinus rhythm Incr pr interval |
| Mechanism drug interactions with amiodarone | 1. Inhibits liver cytochrome enzymes (incr drug lvl) - dig, warfarin 2. Cimetidine (decr liver clear) - amio tox 3. Interacts with statins (use pravastatin) 4. Incr conc drugs - phenytoin, anaesthetics, theophylline, procainamide, flecainide |
| What is digoxin mechanism in heart failure | Blocks na/k atp block Na inside cells drives na/ca exchanger Ca incr inside Incr contraction strength Incr sv/CO Decr hr (pns and av node effects) |
| Why are ccf Pt prone to dig toxicity | 1. Poor renal function due low CO 2. Dehydration and other drug interactions (acei, arb, diuretics, ccb) 3. Effects on VD 4. Low K from meds 5. Poor cardiac output, alter dig handling, altered fluid distribution |
| Features of dig toxicity | 1. High k (strong mortality association) 2. Git: n/v/d 3. Cvs: arrhythmia, av node block, severe hb, hypotension, incr automaticity 4. Cns: lethargy, headache, paraesthesia, confusion, agitation, visual disturb |
| Factors predispose towards dig toxicity | Electrolyte imbalance: hypokalaemia, hypercalcaemia, hypomagnesaemia Organ disease: renal impair, hypothyroidism Other drugs: amiodarone, ccb, k deplete drugs |
| Actions of dig on heart at therapeutic lvl | Mech: na/k atpase Elec: direct - alt apot, indirect - pns effects predominant, baroreceptors sensitisation, central vagal stimulation, facilitation musc transmission |
| Are pns effects uniform in the heart | No Affects atrial/at node > vent/purkinje mm |
| Non cardiac effects of dig toxicity | Git: n/v/d, anorexia CNS: disorientation, hallucinations, visual disturb, agitation, convulsions Other: gynaecomastia, hyperkalaemia |
| Pharmacokinetics digoxin | Good oral absorb 10-20% pop with enteric bacteria reduce oral bioavailability 20-40% protein bind Mid VD 6.3L/kg Not extensively metabolism Excreted renal (2/3rd unchanged) |
| Flecainide mechanism | Class 1c Na blocker Inhibit fast na channels Minimal effect Apot duration No effect in qt interval Decr rate rise apot |
| Pharmacokinetics flecainide | Well oral absorb T1/2 20hrs Peak plasma lvl 3/24 VD 5-13.4L/kg Liver metabolism Renal excreted (30% unchanged) |
| Which patient is flecainide contraindicated | Hypotension LV dysfunction |
| What distinguishes lignocaine from other class 1 drugs | Does not prolong Apot duration Dissociates from channel with rapid kinetics No effect on normal cells |
| Describe pharmacodynamics propranolol make it useful in thyrotoxicosis | Non selective competitive beta blocker Cvs: neg inotrope/chronotrope, decr catechols effects (prominent in hyperthyroid) Other: inhibits peripheral Cjmc ersion t4 to t3 Na channel blocker to aid membrane stabilisation |
| Adverse effects of propranolol | CNS: sedation, depression, seizure, delirium, toxicity - coma Cvs: hypotension, bradycardia, worsen ccf, qrs widening, arrhythmias Resp: worse asthma/cops Other: fatigue, decr libido, impotence, mask hypoglycaemia symptoms |
| Pharmacodynamics sotalol | Non selective beta blocker - Class 2 Prolong plateau phase - class 3 |
| Main side effects sotalol | Cvs: ccf, pro arrhythmia (qt prolong), tdp, avn block Resp: asthma |
| What drug interactions with sotalol prolong qt? | Phenothyazines, macrolides (erythromycin), quinolone, antidepressant, tdp Drugs cause incr k: hypomagnaesia, (increases risk tdp) Myocardial depressant drugs - once LVF Ccb, class 1a - incr refractory time and contraction |
| Mechanism acei | Competitive block a1 to a2 Decr vascular tone (no atII effects) Inh aldosterone secretion (red Na and water resorption) therefore decr bp |
| Adverse effects acei | CNS: dizzy, headache, weakness, loss taste Cvs: hypotension Git: n/v/d Resp: cough Renal: hyperkalaemia, arf Allergy: rash Other: fever, joint pain |
| Describe pharmacodynamics drugs modulate angiotensin | 1. Acei - bind ace reversible prevent a1-a2 Inh RAAS Stimulate kallikrein-Kinin system 2. Arb - A2 inh in don’t result in bradykinin production therefore decr incidence cough and angioedema Greater effect as other enzymes then ace can generate a2 |
| Sites of action of different antihtpertensives | Vasomotor - clonidine, methyldopa Sym ganglia - trimethaphan Sym nerve terminal - reserpine Beta receptors heart - bb At2 receptor- arb Alpha receptors - prazosin Vasc smooth mm - hydralazine, ccb, gtn Beta cells juxtaglomerular - beta blockers |
| Mechanism captopril | Acei Inh hydrolysis a1 to a2 Decr pvr and bp Inh bradykinin inactivation to cause vasodilation |
| Adverse effects captopril | Cvs: hypotension, angio oedema Resp: cough Renal: hyperkalaemia, arf (with bilateral arf), anuria Other: alters taste Allergy: rash, drug fever (10%) Foetal: malformation, death |
| Drugs interact with captopril | K supps K sparing drugs NSAIDs impair bp reduction |
| Clinical uses captopril | Cvs: chf, post mi (preserve lvf) Endo: diabetic neuropathy (decr proteinuria, stable renal function) Htn |
| List drugs used in hypertensive emergency | Gtn Nifedipine Hydralazine Nitroprusside Esmolol Labetalol |
| Pharmacokinetics sodium nitroprusside | Iv route Onset mins Peak effect mins T1/2 2mins (thiocyanate 3/7) Duration 1-10mins Elimination - rbc to cyanide Liver to thiocyanate Renal excretion |
| Toxicity na nitroprusside | Cyanide toxicity: hypotension, met acidosis, punk skin, tachynoea decr reflexes, dilated pupils, coma Thiocyanate toxicity: ataxia, blurry, headache, n/v, tinnitus, delirium, unconsciousness |
| Mechanism prazosin | Selective alpha 1 blocker in arterioles and venules Red art press by dilation resistance and capacitance vessels Alpha 1 block means unopposed negative feedback by alpha 2 receptors |
| Other effects of prazosin | CNS: dizzy, syncope, headache Cvs: hypotension, reflex tachycardia, palpitations Gu: red prostrate smooth mm tone alleviating prostatic obstruction Other: decr ldl/triglycerides, incr hdl |
| Pharmacokinetics ramipril | Inhibit peptides dipeptidase (a1-a2) Stops inactivation bradykinin (vasodilator) Inh RAAS Stimulates kallikrein-kinin system Decr proteinuria and stabilises renal function |
| How is ramipril eliminated and the significance? | Eliminated by kidneys. Reduce dose in renal impairment |
| Pharmacokinetics beta blockers | Well absorbed Low bioavailability Large VD Liver metabolised |
| How does carvedilol differ from propranolol | C: no LA action, beta > alpha 1 block |
| Pharmacodynamics propranolol | Non selective beta blocker Membrane stabilising Antagonises renin release from symp nerves Competitive pure antagonist Stimulation lipolysis Inh liver glycogenlysis Red aqueous humour production Incr vldl, decr hdl Block b2 receptors incr resis |
| Pharmacokinetics metoprolol | Well absorbed Bio 50% Large VD >200L T1/2 3-4h Liver metabolism |
| Cardiovascular effects metoprolol | 1 neg inotrope/chronotrope 2. Slow a-v node conduction, incr pr 3. Decr bp |
| How does metoprolol differ from propranolol on their action on beta receptors | B1 equipotent B2 50-100x less potent Ie metoprolol is b1 specific Metoprolol at high doses less specific |
| Effects of ccb on smooth muscle | Relax smooth mm esp vascular Arterioles more sensitive than veins Does effect bronchiole GIT and uterine |
| What mechanism do ccb control angina | Decr myocardial contractility Decr o2 demand Decr afterload Relieve and prevent coronary artery spasm |
| Why is verapamil more effective than dihydropyridines in tx arrhythmias | Block L channels in tissues firing frequently More effect on tissues dependent on ca channnels for activiation, sa/account nodes More marked on tissues less polarised at rest |
| Mechanism ccb | Bind to receptors on a1/a2/gamma/delta subunits of L type ca channels Decr frequency opening ca channels Decr transmembrane ca current Decr ca influx Vasc smooth mm relax Decr contractility cardiac mm Decr sa rate Decr Av node conduction velocity |
| What are the differences in pharmacokinetics of dihydropyridines and other ccb | Dihydropyridines are vasc smooth mm selective Verapamil have effect in cardiac/conducting tissue |
| What are the different side effect profile between. Dihydropyridines and other ccb | Dihydropyridines: flush, headache, tachycardia Other: bradycardia Both: hypotension |
| What are indications for acyclovir in ed | 1. HSV: encephalitis, vzv, hiv, genital herpes - vzv: within 24h varicella, 72h zoster |
| Describe mechanism of action of acyclovir | Inhibit viral DNA synthesis 1. Irreversible bind viral DNA polymerase 2. Incorporate into viral DNA with termination 3. Specific for thymidine kinase |
| Pharmacokinetics of acyclovir | 1. Short 1/2 life 2.5 hrs (5x dosing) 2. Low oral bio 3. Excrete urine (unchanged) 4. Wide distribution |
| Name side effects of acyclovir | 1. CNS: tremor, delirium, seizure, headache 2. Git: n/v/d 3. Renal: reversible toxicity |
| List some anti influenza agents | Zanamavir Oseltamivir Amantadine Rimantadine |
| What is mechanism of action of zanamivir (relenza) and oseltamivir (tamiflu) | Neuraminidass inhihitor (glycopeptide) - disrupt viral replication and release - against influ a/b |
| What are indications for anti influenza drugs | 1. Uncomplicated influenza 2. 5/7 course within 36-48h onset sx = shorten severity/duration illness 3. May decr incidence resp complications |
| What is relevance of anti influenza drugs to Ed practice | 1. Higher risk groups (indigenous, pregnant, older, immunocompromised 2. Vaccination preferred 3. Used at early phase pandemic to limit spread |
| What classes of antibiotics used to treat staph infections | 1. Beta lactam -ve: - Pen - 1st gen ceph 2. Beta lactam +ve: - methicillin - 1st gen ceph - aug df (clavulanic a) - vancomycin - aminoglycosides - macrolides |
| What is mechanism resistance of mssa | 1. Pen bind prot low affinity bind beta lactam 2. Can overcome if high conc abx - not clinically achievable |
| What are adverse effects of vancomycin | 1 local phlebitis 2. Chills/fever 3. Flush (histamine release - red man) 4. Ototoxic/nephrotoxic |
| In treatment of Tb what are important drug use principles | 1. Multiple drugs initially (usu. 4) to ensure efficacy 2. Prolong course >6/12 3. Close supervision = Compliance and detect adverse effects |
| Describe pharmacology rifampcin | 1. Good oral absorb 2. Lipid soluble - wise tissue distribution 3. Liver metab, excrete faeces 4. Induce p450 enz = incr drug interact 5. Discolour body fluids (orange) 6. Use in prophylaxis |
| What class antibiotic is azothromycin | Macrolide |
| What is it’s mechanism of action | 1. Inhibits protein synthesis 2. Bind ribosomal rna 50s 3. Blocks aminoacyl translocation and formation initiation complex (transpeptidation) 3. Bactericidal high conc |
| What organisms does azithromycin target/cover | 1. Haemophilus influenza 2. Chlamydia 3. Mycobacterium about complex 4. Staph 5. Strep 6. Mycoplasma 7. Legionella 8. Neisseria |
| What is an important cardiac effect of azithromycin | Prolong qt interval |
| How does azithromycin differ from other macrolides? | 1. Higher tissue penetration 2. Longer elimination t1/2 (2-4d) vd 2-5h 3. Single daily dosing 4. More effective against haemophilus 5. Highly effective against chlamydia 6. Less effective staph/strep 7. Food impedes absorp 8. Excreted unch wee |
| What kind of antibiotic is ceftriaxone | 3rd generation cephalosporin Beta lactam antiobiotic |
| What is mechanism action of ceftriaxone | 1. Bactericidal 2. Kills growing bacteria 3. Inhibits transpeptidation reaction bacterial cell wall synthesis 4. Halts peptidoglycan synthesis = inh growth = death |
| Explain microbiological spectrum of ceftriaxone activity | 1. Not degraded by beta lactamases 2. Broad spectrum activity 3. Expanded gram -be cover 4. Crosses bbb 5. Targets: haemophilus, neisseria, pen resist pneumococcus 6. No action against pseudomonas |
| What is ceftriaxones plasma half life | T1/2 = 7-8hrs May be administered daily at 15-50mg/kg |
| How are cephalosporins classified | 1: - gram +ve (gpc/e coli/k pneumonia/proteus) 2: - add gn cover + 1 (klebsiella, some anaerobe) 3: - expand -ve + cross bbb, less staph, against beta lactamase (haemophilus/neisseria) 4: - enteric gnr, pseudomon, staph aureus, enterobact, s pneum |
| What is relationship between penicillin and cephalosporin allergy | 5-15% cross reactivity with penicillin allergy |
| Are there any bacteria responsible for cns infection not covered by cephalosporins | 1. Listeria 2. Resist pneumococci need vancomycin 3. Resist E. coli 4. Pseudomonas need gentamicin |
| What are the adverse effects of cephalosporins | 1. Allergy: anaphylaxis, fever, rash 2. Haem: granulocytopenia, haemolytic anaemia, decr prothrombin, bleeding 3. Renal: interstitial nephritis, toxicity, atn 4. Local: pain imi, thrombophlebitis iv 5. Other: disulfiram rn with etoh |
| What are adverse effects of chloramphenicol | 1. Git: n/v/d 2. Haem: bm suppress, rbc suppr, aplastic anaemia 3. Neonatal: gray baby syn 4. Drug interact: phenytoin, warfarin (prolong t1/2 and incr conc) |
| Which bacteria does it effect | - Aerobic/anaerobic gram +ve/-ve - rickettsia - NOT chlamydia |
| What is mechanism action of chloramphenicol | Inhibits protein synthesis via bind s50 subunit of bact ribosome. Inhibits peptidyl transferase. Bacteriostatic. |
| What is an antiseptic | Chemical disinfectant applied to livin tissue to decrease number organisms by killing/removing/diluting with low toxicity to tissues |
| Describe the actions and uses chx | 1. Low skin sensitising or irritation 2. Oral toxicity low (poor git ansorb) 3. Active against bacteria (gram pos cocci, mycobacterium, moderate against fungi/virus 4. No inhibition by blood/organic products |
| When is chx contraindicated | 1. Middle ear surgery (sensorineural deaf) 2. Nsx as neural toxicity 3. Allergy |
| Describe pharmacokinetics of ciprofloxacin | Po/iv (500mg bd/300mg bd) - good bio 80% - protein bound 20-40% - elimination t1/2 3-5h - renal elimination (adjust dose if crcr <50ml/min |
| Describe its mechanism of action | 1. Blocks DNA synthesis 2. Inhibits topoisomerase 2 (dna gyrase) and 4 3. Prevent transcription and replication 4. Excellent gram -ve/mod gram +ve activity 5. S aureus, mycoplasma, chlamydia, legionella, pseudomonas, mycobacterium, anthrax |
| What is mechanism action doxycycline | 1. Protein synthesis inhibitor - bind reversible 30s subunit ribosome (bacteriostatic) 2. Active against malaria parasites schizonts 3. For prophylaxis (malaria), but not single agent as not active against liver stages |
| Side effects doxycycline | 1. Git: n/v 2. Eyes: photosensitive 3. Liver: hepatotoxicity 4. Bones: discolour teeth/bone 5. Candida vaginitis |
| Indications for doxycycline | 1. Malaria 2. RTI 3. STI (chlamydia, syphilis) 4. Skin infect - acne 5. Rickettsia (q fever) 6. Vibrio sp (cholera) 7. Anthrax 8. Antihelminthic |
| What is mechanism of erythromycin | Inhibits rna protein synthesis 1. Bind 50s ribosome subunit 2. Bacteriostatic (cidal at high conc) |
| What is mechanism for drug interactions associated with erythromycin and give examples | 1. Inh cyp3a4 2. Inh metab other drugs causing incr activity Eg. Benzo, carbamazepine, digoxin, warfarin, theophylline, cyclosporine, tacrolimus |
| Adverse effects erythromycin | 1. Git: abdo cramp, n/v/d 2. Candida 3. Rate: hsr, hearing loss, pancreatitis, hepatotoxic 4. Rapid iv: ventricular arrhythmia |
| Mechanism flucloxacillin | 1. Beta lactam 2. Inhibits bact growth 3. Binds active site pbp 4. Interfere transpeptidation cell wall synthesis 5. Cell death (bactericidal) |
| What organisms susceptible to flucloxacillin | 1. Staph incl beta lactamase 2. Streptococci 3. NOT mrsa, enterococci, anaerobes, gram -ve |
| Important side effects flucloxacillin | 1. Allergy/anaphylaxis 2. Gut: n/v 3. Liver: cholestasis 4. Renal: interstitial nephritis 5. Haem: neutropenia/thrombocytopenia |
| Why is oral flucloxacillin given before meals | 1. Acid labile (inactivated by gastric acid) 2. Binds to food proteins (disrupt absorption) |
| What are the mechanisms of resistance to fluoroquinones? | Resistance due 1+ point mutations in quinolone binding region of target enzyme or change in permeability of organism |
| What are potential adverse effects fluoroquinolones | 1. Prolonged qt 2. Git: n/v/d 3. Allergy: rash 4. Haem: abn lft 5. Eyes: photosensitive 6. Growing cartilage damage 7. Hyperglycaemia (diabetics) 8. Avoid pregnancy/lactation |
| What are used of ciprofloxacillin | 1. Uti 2. Bact diarrhoea (salmonella, shigella, E. coli 3. Rti 4. STD (gonococcal, chlamydia) |
| How does antibacterial activity of norfloxacin compare to that ciprofloxacin | 1. Ciprofloxacin has greater activity (4-8x lower mic) against gram -ve, greater activity against gram +ve |
| What is mechanism of gentamicin | 1. Binds 30s subunit bact ribosome 2. Inh prot synthesis 3. Bactericidal 4. Gram negative 5. Conc dep killing (incr conc = kill more bact at rapid rate) 6. Post abx effect (last longer than serum lvl) |
| Pharmacokinetics gentamicin | - iv/Im/top - small vd (<10% prot bound) - NOT metab - renal elimination - t1/2 2-3hrs, once daily dosing - outpatient therapy possible |
| Advantages of single daily dosing regimen due gentamicin | 1. Decr toxicity time and conc dependent killing 2. Less time above toxic threshold 3. Cost effective 4. Nephrotoxic 5. Ototoxic 6. Prolong nm blockade 7. Obtain serum lvl if use >4-5d |
| Which organisms are targeted by gentamicin | 1. Gram neg bact (e coli, pseudomonas, proteus, klebsiella) 2. Gram pos (staph, strep w beta lactamase) 3. No anaerobic activity |
| How do penicillins enhance efficacy gentamicin | 1. Low ecf ph and anaerobic conditions inhibits transport 2. Transport enhanced by cell wall active drugs (eg penicillin) |
| What is mechanism of action of gentamicin and how does resistance develop | 1. Aminoglycoside binds 30s bacterial ribosomes and inhibit protein synthesis 2. Resistance: - transferase inactivates drug, from plasmids - inspired cell entry (cell wall) - altered ribosomal receptor proteins |
| Outline pharmacokinetics gentamicin | 1. Poor oral absorb 2. Given iv/im 3. Highly polar, does not enter cells well 4. Water soluble 5. Not metabolised 6. T1/2 2-3h 7. Dose adjust renal impair 8. High renal excretion |
| Name some macrolide antibiotics | Erythromycin Azithromycin Clarithromycin Roxithromycin |
| Describe mechanism macrolides | 1. Inhibits bacterial protein synthesis 2. Binds 50s subunit bacterial ribosome rna 3. Blocks aminoacyl translocation reaction and formation initiation complexes (transpeptidation) 4. Bactericidal at high concentrations otherwise bacteriostatic |
| What organism are macrolides effective against | 1. Gram pos - pneumococci, streptococci, mycobacterium, legionella, chlamydia, listeria, some mycobacteria 2. Gram neg - neisseria, bordatella pertussis, treponema pallidum, campylobacter sp, bartonella, less susceptible haemophilus |
| What are adverse effects of erythromycin | 1. Git: anorexia, n/v/d 2. Liver: toxicity, cholestatic hepatitis 3. Allergy: fever, eosinophilia. Rash 4. Drug interactions (inh cytochrome p450) |
| By what mechanism can bacteria be resistant to beta lactam antibiotics | 1. Inactivation via beta lactamase (commonest) 2. Modification of pbp (pen bind prot) - mrsa, pneumococci, enterococci 3. Impaired cell wall penetration (gram neg only - outer cell wall membrane) 4. Efflux pump (gram neg only) |
| What circumstances encourage development of bacterial resistance to anti microbial agents | Resistance due natural selection via spont mutations or DNA exch (direct plasmid, indirect bacteriophage) 1. Nosocomial (multiple bact sp. collaborating) 2. Antibiotics partially treat infection (inadequate dose, potency or duration) 3. Overuse abx |
| Describe pharmacokinetics metronidazole | - Well oral absorb - Iv/po/pr - 99% bio - liver metab - renal excrete - low protein bind (10-20%) - t1/2 7.5h |
| Adverse effects metronidazole | 1. Git: n/v/d, dry mouth, metal 2. Cns: headache, paraesthesia, dizziness 3. Other: thrombophlebitis, disulfiram like effect (avoid etoh), potentiate warfarin (incr inr)/lithium, teratogenic (mice) but unproven humans |
| Describe the mechanism of action of penicillins | 1. Inhibition cell wall synthesis 2. Interefere with transpeptidation 3. Covalent bond to pbp (important for cross linking) 4. Bactericidal but only kills growing cells |
| What is the anti microbial spectrum of penicillin g | 1. Gram pos - strep, staph, enterococci, clostridium 2. Gram neg - meningococci 3. Other - treponema pallidum |
| Describe the pharmacokinetics penicillin | 1. Oral absorb impaired by food 2. Wide distribution 3. Renal excretion 4. Tubal secretion |
| What are clinical manifestations of penicillin allergy | 1. Anaphylaxis 2. Fever 3. Skin (maculopapular rash)/urticaria skin rash/exfoliative dermatitis 4. Serum sickness 5. Sjs 6. Other: - renal failure, seizure (high dose), git dusturb, candida infection, hepatitis (flucloxacillin/oxacillin) |
| How does probenecid alter elimination of some penicillins | Inhibits secretion weak acids from the proximal tubules |
| Describe the mechanism of sulphonamides | Reversible blocks folic acid synthesis thus inhibiting bacterial growth |
| Why is trimethoprim co administers with sulfamethoxazole | 1. Anti bacterial synergism = enhanced effect 2. Block sequential steps in folic acid dep purine synth 3. Bactericidal (static if use alone) - inh dihydropteroate synthase - convert paba to dihydrofolic acid 4. Sulfonamides = struct analogue paba |
| How do tetracyclines exert their antimicrobial activity | 1. Bacteriostatic 2. Binds reversible 30s subunit bacterial ribosome 3. Blocks binding tRNA to mRNA ribosome complex 4. Stop addition amino acids to peptides |
| Describe the pharmacokinetics of tetracycline | 1. Variable oral absorb usu >60% 2. Absorb impair by food/ca/dairy/alkaline ph 3. Protein bound large 40-80% 4. Widely distribution except csf 5. Cross placenta, chelate ca (teeth/bone) 6. Bile/urine excrete (enterohep circ) 7. Doxy no renal elim |
| Are their any groups where tetracycline contraindicated and why | 1. Pregnant 2. Children <8 3. Breast feeding - crosses palcenta - present in breast milk - teratogenic - stains teeth/bone |
| How does resistance to doxycycline develop | 1. Decr intracell accumn - impair influx - incr efflux by active transp prot pump (encode on plasmid) - drugs interact: aminogly, sulfon 2. Ribosome protect: bact proteins interfere tetracycline ribosome bind 3. Enzyme inactivation of tetracycline |
| What are the clinical uses of doxycycline | 1. RTI - atypical 2. STDs 3. H pylori infection 4. Acne |
| Describe the mechanism of trimethoprim | 1. Selective inhibit bacterial enzyme (dihydrofolic acid reductase) which is needed for covert dihydrofolic acid to tetrafolic acid 2. Inhibits purine and dna synthesis |
| What is the mechanism of vancomycin | 1. Glycopeptide - inhibit cell wall synthesis - bind to peptidoglycan pentopeptide - inhibits transglycosylase - prevents cross linking and weakening cell wall/membrane |
| What are target organism for vancomycin | 1. Gram pos - staph (incl mrsa, enterococci) 2. Gram pos anaerobes - C. difficile |
| What clinical condition requires dose adjustment | 1. Renal impairment 2. Morbid obesity |
| Outline mechanism of action of aspirin | 1. Irreversible non selective Cox inhibitor - in platelets: inh cox1, red txa2, red platelet aggreg for lifespan platelet 10dy - in tissues: inh cox2, anti inflam, analgesia, antipyretics |
| Describe pharmacokinetics aspirin | 1. Rapid absorb git 2. Hydrolysed (esterase) to salicylic acid in plasma/blood 3. Peak plasma lvl 1-2h 4. T1/2 15 mins 5. Low prot bind, small vd 6. When saturated 1-0 order kinetics 7. Urinary alkalisat incr excretion salic/conjug 8. Pka 3.5 |
| Adverse effects aspirin | |
| Git: gih (gastritis/ulcer), n/v Liver: toxic, abn lft, liver fail Haem: incr bleed time, thrombocytopen, neutropenia, aplastic anae Allergy: asthma, angioedema, rash CNS: tinnitus, dizzy, headache Cvs: fluid retent, oedema Renal: fail, hyperk, prot | |
| What are therapeutic indications for aspirin | 1. Tia 2. Acs 3. Pre thrombolysis 4. Anti inflam 5. Analgesia 6. Antipyretics |
| Describe the mechanism of action of colchicine. What effect does it have on uric acid? | 1. Anti inflammatory effect - binds to tubulin, inh wbc migration and phagocytosis - inh formation leuk b4 (ltb4) - no effect on uric acid metabolism |
| What are the indications and dosage of colchicine | 1. Acute gout episode (0.6-1.2gm q12h until pain resolve or diarrhoea, 8mg fatal) 2. Prophylaxis recurrent episodes (0.6mg od-tds) 3. Prevent Mediterranean fever, treat sarcoidosis arthritis/hepatitis cirrhosis |
| What adverse effects associated with use of cox2 inhibitors | 1. Renal toxicity 2. Git but ?less than non selective Cox inh 3. Possible incr cvs thrombotic events |
| Describe the mechanism of fentanyl | Synthetic opioid acting on mu receptors |
| Describe the pharmacokinetics fentanyl | 1. High 1st pass metabolism 2. Duration 1-2h 3. Liver metab (p450 cyp3a4), no active metabolites 4. Transdermal/mucosal/im/iv/in/sc/sl/buccal routes 5. High lipid 6. T1/2 5mins |
| Describe fentanyl potency compared to morphine | 100x more potent. 0.1mg fentanyl = 10mg morphine |
| List adverse effects of fentanyl | 1. Resp: depression, cough 2. Git: n/v 3. Cns: dysphoria, sedation 4. G-u: constipation, urine retention 5. Allergy: itch, urticaria 6. Other: chest wall/laryngeal rigidity |
| What is dug potency | Dose or concentration to achieve 50% maximal effect - ec50 or ed50 |
| What is bioavailability | The fraction of unchanged drug reaching the systemic circulation following administration by any route |
| What factors affect bioavailability | 1. Absorption - too hydrophilic/lioophilic (decr) - reverse transporter (p-glycoprot) pumps back to lumen (decr) - git wall metab (decr) 2. 1st pass - liver metab - small effect if biliary excr 3. Rate absorb - determine by site admin + drug form |
| What is bioavailability of ibuprofen | 1. High 2. Weak organic acid 3. Well absorb rapid 4. Minimal 1st pass metab |
| What is mechanism of action of morphine | 1. Act on mu/delta/kappa receptors 2. Reduce presynaptic neurotransmission (esp glutamate) 3. Inhibit post synaptic neurons 4. Central (thalamic action) |
| Why do opiates cause respiratory depression | 1. Inhibition of brainstem respiratory controls - less response to hypercapnea |
| How is morphine metabolised | 1. Liver conjugation (phase 2) to: - morph-3-glucuronide (most - neuroexcitation) - morph-6-glucuronide (10%, 4-6x I increased analgesic potency) - renal excretion |
| What are the possible acute adverse reactions with morphine? Why are we more cautious in using morphine in renal failure patients? | 1. Cns: sedation, respiratory depression, dysphoria 2. Git: nausea, vomiting 3. Cvs: hypotension 4. Allergy: pruritus 5. Other: histamine release, biliary colic. Renal excretion - cause seizure or prolonged analgesia if patient has renal failure |
| Describe the cns and pns effects of morphine? | CNS: - Main: analgesia, euphoria, sedation, respiratory depression - other: cough suppression, miosis, n/v Pns: - Main: cvs (neg inotrope/chronotrope), gi constipation - other: pruritus, renal (seizure/prolong in failure) |
| Describe the effect of morphine on the different opioid receptors | 1. Full mu rc agonist (analgesia/sedation/decr git motility/modulate hormone/neurotransmitter release) 2. Delta rc (analgesia/mod horm/neurotransmim rel) 3. Kappa rc (analgesia/psychomimetic effects/decr git motility) |
| Describe effects of morphine on different organ systems? | CNS: analg/euphor/sedation/resp dep/miosis/hypertherm - stim adh/prolactin/somatotrophin Resp: depress, cough suppress Cvs: bradycardia Git: constipate, contract biliary sm mm, n/v Renal: depress fn Gynae: decr uterine tone Skin: pruritus,urticaria |
| What is mechanism of morphine at cellular level | 1. Binds specific G protein coupled rc in brain/spinal cord 2. Decr ca influx presynaptic nerve terminal 3. Decr transmitter release 4. Hyperpolarise postsynaptic neurones by incr k conductance 5. Inhibits postsynaptic potential |
| Describe the pharmacokinetics ibuprofen | 1. Well absorbed 2. Food doesn’t change bioavailability 3. Highly protein bound 4. Liver metab cyto p450 |
| Describe pharmacodynamics ibuprofen | 1. Reversible Cox inhihitor 2. Inh pg synthesis 3. Anti inflam (cox2)/analgesia (Cox 2)/antipyretic (pge1/2) 4. Other: - inh chemotaxis - downreg il-1 prod, decr free rad production, interfere ca med intracellular events 5. Anti platelet (txa2) |
| What are side effects of nsaids | CNS: headache, tinnitus, dizzy CVS: fluid retent, htn, oedema, (rare - ami/ccf) Git: n/v, ulcer/bleed, dyspep, pain Renal: fail, hyperk, proteinuria Haem: thrombocytopen, aplastic a, neutropen Liver: abn lft, fail Resp: asthma Skin: rash, urtic |
| How does aspirin differ from their NSAIDs in its action on cox | 1. Aspirin = irrev inh Cox, nsaids = rev cox inh 2. 2 types cox: - cox 1 - most cells, - cox 2 - inducible 3. Selective Cox 2 inh: - don’t affect platelet fn at usual dose, other nsaids do inhihit platelet aggregation |
| What specific side effects occur with aspirin | 1. Salicylism (n/v, tinnitus, hear loss, vertigo) 2. Exac asthma 3. Histamine jnduexed flushing 4. Irrev platelet inhib 5. Raised lfts |
| Mechanism action nsaids | 1. Antipyretic (pg e1/2) 2. Anti inflam (cox 2) 3. Analg (Cox 2) 4. Rev anti platelet (txa2) 5. Inh gastric cytoprotect (pg e1) 6. Renal impair (pge1/2, pgi2 - incr gfr via vasodil) 7. Smooth mm eff (inh vasodil - bronchodil) 8. Close pda (pge1/2) |
| Name some drugs used in treatment of opiate addiction | 1. Methadone 2. Buprenephine 3. Clonidine 4. Naltrexone 5. Naloxone |
| Outline the principles of how drugs against opiate addiction work | 1. Meth: - longer act, antag, oral, to stabilise then grad w/d, addict 2. Bup: - part antag, daily, low dose detox, high maintain 3. Clon: - a2, help sns w/d 4. Naltr: - long act oral, antag, detox b4 5. Nalox: - rapid antag, short t1/2, prec w/d |
| Describe clinically important pharmacological difference between morphine and fentanyl | 1. Morph (phenanthrene) nat, fent (phenylpiperidine) syn 2. Rc: - both strong ag - potency fent > morph 3. Absorb: - both low oral:parenteral ratio 4. Elim: - elim t1/2 morph > fent |
| How does methadone differ from morphine and fentanyl? | Pd: - meth blocks Nmda rc and mao reuptake Pk: - meth has high oral:parent ratio - elim: t1/2 meth > morph > fent Other: - meth highly variable pk between individuals |
| What advantages and disadvantages might buprenorphine have in treatment of heroin addiction compared with methadone | 1. Bup is partial agonist at mu rc, long action duration due slow dissociation from mu rc. 2. Equal effective in detox/main as meth 3. Lower fatalities due part agonist 4. Slow rc dissociation = resist nalox reverse, + prevents act other opioid analg |
| Describe the pharmokinetics oxycodone | 1. Good oral absorb 2. High vd 3. Low 1st pass metab 4. Duration 3-4h, longer for mr 5. Liver metab p450 6. Kidney excrete 7. 10mg morphine = 4.5mg endone |
| How does oxycodone produce analgesic effects | 1. Act mainly mu rc in brain and spinal cord, also outside cns |
| What strategies may be used when prescribing oxycodone to reduce development dependence | 1. Establish goals at start of Rx 2. Combine with non opioid analgesics 3. Smaller dose longer intervals 4. Use controlled release preparations 5. Frequent evaluation of ongoing requirements |
| Describe pharmacokinetics oral paracetamol | 1. We’ll absorb git 2. Peak plasma 0.5-1h 3. Slight protein bound 4. T1/2 2-3h; incr 6h liver disease 5. Liver metab >95% glucuronidation/sulfation; 5% metab cyp 450 - phase 1: hydroxylation = napqi (toxic), usu detox by glutathione |
| What is toxic dude paracetamol | 150-200mg/kg in adult >7gm = adult |
| How does paracetamol cause toxicity | 1. In od: - glucuron/sulf path saturate (0 Oder kinetics) - paracetamol brkdwn by phase 1 reaction (napqi) - incr napqi consume glutathione - glutathione consumes, napqi hepatotoxic |
| Describe pharmokietics paracetamol | 1. Rapid absorb 2. Good bio 70-90%, vd 1L/kg tbw 3. Peak .5-1h 4. Part metab liver microsomal enz to paracetamol glucuronide/sulphate (90%), 5% hydrox/conj with glutathione/cysteine via p450 5. 1st order kin 6. T1/2 2-3h 7. <5% excrete unchanged |
| What are clinical manifestations of toxicity? | 1. Cns; coma 2. Git: n/v, pain 3. Renal: atn, fail 4. Liver: toxic, fail 5. Electrolyte: hagma |
| What is antidote for paracetamol toxicity | N acetyl cysteine - glutathione substitute - binds to toxic metabolite (act as substrate) - antioxidant |
| Describe mechanism of liver damage caused by paracetamol toxicity | Nac benzoiminoquinone reacts with sulphydryl group on proteins. Prevented by using nac. |
| Outline clinical features of salicylate toxicity | 1. Salicylism: hearing loss, tinnitus 2. Cns: coma 3. Git: disturb 4. Haem: coagulopathy 5. Renal: fail 6. Electrolyte: resp alk/met acid/hypoglycaemia |
| Describe enhanced elimination strategies in managing patient with salicylate overdose | 1. Ph manipulation via urinary alkalinisation 2. Forced diuresis 3. Dialysis - Pd - hd - haemoperfusion |
| During clinical drug trials, what factors might confound the results? What are some of the host factors/observer factors? Why do you blind trials? | 1. Variable natural history of most diseases 2. Presence of other diseases and risk factors 3. Subject/observer bias |
| What can be done to minimise the confounders? | 1. Large pop over sufficient time, cross over trials 2. Exclusion criteria/randomisation/cross overs 3. Placebo controls, blinding, cross overs |
| What is erythropoietin and what are it’s clinical applications? | Glycoprotein produced by kidney 1. Stim rbc precursor prolif/differentiate 2. Release reticulocyte (bm) 3. Used anaemia crf where erythropoietin prod impaired 4. Help in some marrow fail (aplastic a, myeloprolif dys disorder, mult myeloma, aids, cax) |
| What toxic effects with increased erythropoietin | 1. Toxicity due rapid hb rise - htn - thrombosis 2. Allergy: infrequent and mild |
| Name ingredients in otc preparations that may cause toxicity and give 1 example. | 1. Ethanol (drowsy) 2. Antihistamines (drowsy) 3. Salicylates (Reyes - kid, pud, coag) 4. Caffeine (agitate, headache, nephritis) 5. La 6. Sodium 7. Sympathomimetics (t1dm, htn, asthma, hypothyroidism) |
| What are the therapeutic uses of penicillamine | 1. Copper poison 2. Wilson diseases 3. Severe rheumatoid arthritis (occasionally) |
| List adverse effects d-penicillamine | 1. Git: n/v 2. Cns: optic atrophy 3. Allergy: hsr (if pen allergy) 4. Renal: nephrotic syn 5. Haem: pancytopen 6. Autoimmune; myasthenia, arthropathy, pemphigus |
| Describe phases of testing new drug | 1. In vitro animal 2. Human phase 1-4 |
| Please describe ways in which new drugs might be discovered or produced | 1. Chemical modification 2. Random screening 3. Gene methods 4. New drug target identification 5. Rational designs |
| What are medical uses of St. John wort and it’s important drug interactions | Depression 1. Pk: - cyp inducer (decr drug effect) 2. Pd: - inh catechol reuptake (potentiate some drug effects) |
| List the advantages of eye ointments over eye drops | 1. More stable 2. Less absorption into lacrimal ducts 3. Longer retention time over conjunctival surface 4. Safer with potent drugs 5. Ointment base provides protection and comfort at night |
| List by action the types of drugs used topically in the eye | 1. Mydriatics 2. Miotics 3. Cycloplegics 4. Decongestants 5. Antibiotics 6. Antivirals 7. Antiseptics 7. Corticosteroids 8. La 9. Stains, fluorescein |
| List the ideal properties of an ocular la | 1. Quick onset (10-20s) 2. Good duration action (10-20m) 3. No obvious effects on function or healing 4. No interactions with drugs used concurrently |
| What is vitamin k | 1. Fat soluble substance (leafy vegetable - vit k1) 2. Usu synthesised by gut bacteria (vit k2) |
| Describe vit k mechanism of action in reversal of warfarin anticoagulation | 1. Warfarin (coumarin) prevent reduct metab inactive vit k to active vit k 2. Produce biolog inact 7/9/10/prothrombin/prot c/s 3. Vit k1 confers biological activity on above by participate in post ribosome modification 4. Onset action 6h, complete 24h |
| What methods are available to reverse warfarin induced anticoagulation? How does vit k reverse warfarin | 1. Cease warfarin 2. Vit k oral/iv 1-10mg 3. +\- ffp or prothrombinex 4. Interact with warfarin to reduce inr by re establish normal activity clotting factors (2/79/10 vit k dep) |
| What are clinical indications for prescribing vit k | 1. Reverse oral anticoag effect 2. Mx warfarin toxicity or supratherapeutic warfarin 3. Vit k deficiency 4. Prevent/treat haemorrhagic disease newborn |
Created by:
Chi Le
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