A- Main Study Deck COPY Flashcards

Question

Bainbridge reflex

Answer 1

- Sensor/stimulus: Stretch receptors in atria + pulmonary artery measure changes in pressure - Afferent: vagus - Processor: NTS & CVM - Efferent: ○ Sympathetic fibres to heart ○ Vagal efferents to gardiac ganglion - Effects ○ Increased RA pressure produces an increase heart rate

Answer 2

- Sensor/stimulus: Carotid and aortic body detect low PaO2 and/or high PaCO2 - Afferent: glossopharyngeal + vagus - Processor: NTS + Nucleus ambiguus - Efferents/effectors: ○ Sympathetic fibres to heart and peripheral smooth muscle ○ Vagal efferents to cardiac ganglion - Effects: ○ Primary effects - bradycardia, hypertension ○ Secondary effects - increased preload due to increased ventilation, thus activation of Bainbridge --> increased heart rate ○ Activation of pulmonary stretch receptors --> activation of Hering-Breuer reflex --> increases HR

Answer 3

- Sensor/stimulus: intracranial pressure/cerebral ischaemia is detected by some unknown sensor - Afferent: ○ Fibres from the medullary mechanosensory areas, to sympathetic ganglia ○ Fibres from cerebral hemispheres, which exert descending inhibitory control on the medullary vasomotor sensor - Processor: rostral ventrolateral medulla - Efferents/effectors: Sympathetic fibres to heart and peripheral smooth muscle - Effects: ○ Hypertension + tachycardia ○ Secondary - baroreflex mediated bradycardia

Answer 4

- Sensor/stimulus: Multiple and heterogeneous stimuli interact with receptors in all cardiac chambers, including: ○ Mechanical: pressure and stretch (thus, inotropy preload and afterload) ○ Chemical: veratrum alkaloids, ATP, capsaicin, snake venom, other venoms - Afferent: unmyelinated C-fibres of vagus - Processor: NTS - Efferents/effectors: sympathetic fibres to heart and peripheral smooth muscle, vagus via cardiac ganglion - Effects: hypotension (vasodilation) & bradycardia

Answer 5

- Sensor/stimulus: mechanoreceptors on the globe and in facial muscles detect pressure on the globe - Afferent: long and short ciliary nerves to trigeminal nerve (via Gasserian ganglion) to sensory nucleus of TN. From here, short internuclear fibres to NTS - Processor: NTS - Efferents/effectors: vagus nerve via cardiac ganglion to SA + AV node - Effects: bradycardia, if severe, to the point of arrest

Answer 6

- Sensor/stimulus: pain, temperature, chemical and mechanosensitive stretch receptors detect pressure to globe of eye, pain in trigeminal nerve distribution, cold temperature, or noxious stimulus of anterior ethmoidal nerve - Afferent: trigeminal nerve - Processor: NTS (vagal response), Rostral medulla (sympathetic response), ventral response (apnoea) - Efferents/effectors: Vagus nerve via cardiac ganglion to SA, AV nodes; phrenic nerve to respiratory muscles - Effects: bradycardia, cerebral vasodilation + systemic vasoconstriction, apnoea ○ Net effect is to prevent aspiration and maximise blood flow to CNS at the expense of skin, muscle and splanchnic organs

Answer 7

- Sensor/stimulus: Emotional distress/orthostatic changes, increased ITP (eg. Defecation, cough/sneeze, laughter) - Afferent: unknown - Processor: ?NTS/Nucleus ambiguus - Efferents/effectors: vagus & SNS to SA, AV nodes, peripheral smooth muscle - Effects: Vagal - bradycardia, sympathetic - systemic vasodilation

Answer 8

Jugular - 55% Muscles - 72% Renal - 81% IVC - 71% SVC - 79% Hepatic - 66%

Answer 9

40mmHg & 70-75%

Answer 10

1 MET = 3.5 ml O2/kg/minute

Answer 11

* Seen as early as wk 20 * Compression of IVC by gravid uterus - decreases venous return & reduced CO * Blood returns to heart via paravertebral epidural veins draining into azygous * Uterine perfusion diminished secondary to increased uterine venous pressure * Compression of aorta may be present & associated with uterine arterial hypotension + reduced uteroplacental perfusion * Can be relieved by positioning mother to left side

Answer 12

Afterload (reduced) --> TPR decreases by 30% by wk 12& 35% (by 20th wk, then remains at 30% below non-pregnant values) * Vasodilation mediated by progesterone, prostaglandins & downregulation of alpha-receptors * SBP + DBP - decrease (~10%) & reach nadir at 20wks * Vascular system as whole becomes more refractory to vasoconstrictors * Note re: RV afterload □ CVP + PCWP - remain stable throughout pregnancy. PCWP balance by decreased PVR

Answer 13

○ Preload (increased) --> By term, maternal blood volume increased by 35-40% (approx 1-1.5L) § Plasma volume increases by 45% - Na + H2O retention by oestrogen stimulation of RAAS § RBC volume increases by 20% due to renal erythropoietin synthesis § Disproportionate rise in plasma volume vs red cell mass accounts for fall of haematocrit to 33% ("anaemia of pregnancy")

Answer 14

CO increases by 40-45% by 12-28wks, peaks at 50% 32-36wks, then reaches 47% at term - Heart rate: HR increases by 17% at end of first trimester,(increases to 25% at middle of third trimester); - Stroke volume increases by 20-30% (predom in 1st trim)

Answer 15

- Distribution (regional flow changes) ○ Renal blood flow - increases by 80% in first trimester (may fall slightly towards term) ○ Large proportion of blood flow is directed to uteroplacental circulation, that increases its blood flow 10-fold to 750mL/min at term ○ Increased blood flow to breasts, GIT, skin

Answer 16

Physical/mechanical changes: - LV mass increases by 40g by 3rd trimester - Heart is more rotated to left ○ May see Q waves + TWI in inferior leads - Colloid oncotic pressure falls by 14% - may predispose to oedema

Answer 17

- Pressure: ○ Maternal SBP + DBP increase 10-20mmHg during uterine contraction - Volume: ○ Each uterine contraction squeezes ~300mL blood from uterus into central maternal circulation - Cardiac output: ○ CO increases by ~15% during latent phase of labour, by 30% during the active phase & 45% during the expulsive stage ○ Immediately after delivery, CO ~60-80% above pre-labour values as a consequence of autotransfusion & increase venous return associated with uterine involution - CO & SBP/DBP return to non-pregnant values by 2 wks post delivery

Answer 18

After birth: * FRC and RV return to normal within 48h * Vt returns to normal within 5 days

Answer 19

- Compliance ○ increased adipose tissue and breast mass --> decreased chest wall compliance (lung compliance unchanged) - Resistance ○ Increases in early pregnancy - mucosal oedema ○ Progesterone-mediated bronchodilation - decreased resistance in later pregnancy (35%)

Answer 20

1. Storage - Metabolic fuel: Glycogen- ~100g & fat - Fat soluble vitamins ○ Vitamin A → stored in stellate cells --> converted to retinol (active form). Contains 1-2yr supply ○ Vitamin D → ~ 1-4 month supply ○ Vitamin E & vitamin K - minimal - Vitamin B12 + folate (50% of body's storage for both) - Trace elements - iron (as ferritin), zinc, copper, selenium - Blood reservoir - ~ 500mL of blood

Answer 21

Synthetic - Plasma proteins- albumin, α+ β globulins, fibrinogen - Nutrients - glucose, ketones, lipids, cholesterol, amino acids - Regulatory molecules (thrombopoetin, angiotensinogen) - Bile acids → stored in gallbladder

Answer 22

Metabolic - Carbohydrate metabolism ○ Liver is a glucostat --> maintains strict BSL § in conditions of ↑ glucose, glycogenesis & FFA synthesis will normalise BSL § in conditions of ↓ glucose, gluconeogenesis will normalise BSL - Lipid metabolism → free fatty acids (FFA). synthesised & packaged with as lipoproteins be transported to adipose tissue for storage § FFA oxidation will also produce energy. - Protein Metabolism - amino acids can be transaminated, deaminated or decarboxylated to give acetyl- CoA

Answer 23

Detoxification & excretion - Immunological detoxification: ○ Kupfer cells act as scavengers & phagocytes & secrete prostaglandins - Ammonia → urea conversion via urea cycle - Conjugation of bilirubin & excretion in bile - Processing of drugs via: ○ Phase I (oxidation & hydrolysis) and ○ Phase II (conjugation) reactions

Answer 24

Length: 10-16cm Diameter: (internal) 2.5cm Origin: C6 Termination: carina, T4 (sternal angle)

Answer 25

Generation 1-4 - Bronchi (cartilaginous) Generation 5-14 - bronchioles (non-cartilaginous) Gen 15-18 - Respiratory bronchioles (some gas exchange) Gen 23 - alveolar sacs

Answer 26

**Muscles** - various muscles attaching to the various structures. Important movements: * Phonation: cricothyroid (brings cords together by moving thyroid down), interarytenoid (transverse + oblique), vocalis (subset of muscles from thyroarytenoid) - mediates tension in vocal ligament to modulate pitch * Inspiration: + cricoarytenoid (posterior + lateral) - rotate arytenoids outwards * Expiration: thyroarytenoid adduct cords to increase resistance and provide intrinsic PEEP (3-4 cmH2O), which maintains patency of small airways & maintains FRC * Effort closure - aryepiglottic muscles contract strongly to act as a sphincter, allowing airway to withstand up to 120cmH2O pressure

Answer 27

Dalton's Law: * In a mixture of gases, the pressure exerted by each gas is the same as the pressure exerted if the gas was the only gas in that mixture: * PTOTAL = PGas1 + PGas2 + PGas3

Answer 28

Boyle's Law: * For a fixed mass of gas at constant temperature, the pressure (P) and volume (V) are inversely proportional, such that P ×V = k, where k is a constant.

Answer 29

Henry's Law * The amount of a given gas dissolved in a given liquid is directly proportional to the partial pressure of the gas in contact with the liquid: P = Hv × M Where * P is pressure * M is the molar concentration of gas * Hv is Henry's Proportionality Constant

Answer 30

Graham's Law: * The rate of diffusion is inversely proportional to the √MW

Answer 31

Fick's Law of diffusion: * Passive movement of molecule from an area of high concentration to low - There are many different iterations of Fick's Law - V_gas∝A/T D (P_1− P_2) V_gas = Flow of gas D∝ Solubility/√MW MW = molecular weight A = surface area P_1 − P_2= difference between partial pressure in alveolus vs capillary T = diffusion distance (or thickness of membrane)

Answer 32

The pressure of a fixed mass of gas at constant volume is directly proportional to its absolute temperature (P/T = k).

Answer 33

Equal volumes of gases at the same temperature and pressure contain the same number of molecules (6.023 × 1023, Avogadro’s number).

Answer 34

The state of a fixed mass of gas is determined by its pressure, volume and temperature (PV = nRT)

Answer 35

VD/VT = (FACO2 - FECO2) / FACO2 Where: VD = dead space volume VT = tidal volume FECO2 = fraction of expired CO2 FACO2 = fraction of alveolar CO2 *Note: Enghoff modification: P_A 〖CO〗_2 is substituted by P_a 〖CO〗_2 as arterial CO2 is measurable (and arterial CO2 is the mixed product of all lung units (theoretically representative of the average CO2 of all alveoli put together))

Answer 36

PAO2 = (FiO2 × (Patm - PH2O)) - (PaCO2 / RQ) Where PAO2= Partial pressure of alveolar oxygen FiO2 = fraction of inspired oxygen Patm = Atmospheric pressure (usually 760 mmHg) PH2O = partial pressure of water vapour at the alveolus (usually 47 mmHg) PaCO2 = Partial pressure of arterial carbon dioxide RQ = respiratory quotient, usually 0.8

Answer 37

(sO2 × ceHb × BO2 ) + (PaO2 × 0.03) Where: ceHb = the effective haemoglobin concentration (conc of hb species capable of carrying & releasing O2) PaO2 = the partial pressure of oxygen in arterial blood 0.03 = the content, in ml/L/mmHg, of dissolved oxygen in blood (for a PaO2 of 100 mmHg, the O2 content is 0.03 × 100 = 3ml/L BO2 = the maximum amount of Hb-bound O2 per unit volume of blood (normally 1.39 of dry Hb, or 1.30 in "real" conditions) sO2 = oxygen saturation:

Answer 38

Qs/Qt = (CcO2 - CaO2) / (CcO2 - CvO2) Where Qs/Qt = shunt fraction (shunt flow divided by total cardiac output) CcO2 = pulmonary end-capillary O2 content, same as alveolar O2 content CaO2 = arterial O2 content CvO2 = mixed venous O2 content

Answer 39

J_v=L_p S [(P_c − P_i) - σ(π_c− π_i) Where: Jv = filtration rate Lp = Hydraulic permeability S = Surface area Pc = Capillary hydrostatic pressure Pi = Interstitial hydrostatic pressure σ = Reflection coefficient (protein permeability, range 0-1) πc = Intracapillary plasma oncotic pressure πi = Interstitial oncotic pressure *Note: LpS = K = kf = capillary filtration constant* **Note2: πi becomes πegl in the revised Starling model to represent the endothelial glycocalyx layer**

Answer 40

○ LpS - surface area ~140m2 (compared to 4000-7000m2 in systemic circulation) ○ Pc = 4-12mmHg ○ Pi = interstitial hydrostatic pressure - essentially equal to alveolar pressure = atm pressure. Increases during PPV § Surfactant decreases hydrostatic pressure by decreasing surface tension ○ πc = 25mmHg throughout circulation; affectd by blood protein count ○ πi = ~3mmHg at alveoli ○ σ= 0.5-0.7 in lung

Answer 41

2mLH2O/L/s

Answer 42

* Bind to 30s Ribosomal subunit, which interferes with protein synthesis by causing misreading and premature termination of mRNA translation. * Diffuse through porin channels in the outer membrane into periplasmic space. Transport through inner membrane is oxygen dependent (/electron dependent). Antimicrobial activity is markedly reduced in anaerobic conditions (eg. Abscess). * Concentration dependent killing - higher the concentration, the greater the rate at which bacteria are killed. * Post-antibiotic effect exists (bactericidal effect persists after conc

Answer 43

- **Disinfectants** are chemical agents or physical procedures that inhibit or kill microorganisms - **Antiseptics** are disinfectants with sufficiently low toxicity to host cells that can be used directly on skin, wounds or mucosa

Answer 44

**Main action:** Likely act by denaturing proteins. Optimal bacteriocidal concentration is 60-90% **Onset/duration** Rapid/ Lack residual action because they evaporate completely **Advantages:** Evaporative effects are useful when sinks with running water are not available **Limitations:** Flammable- must be allowed to dry fully before diathermy or laser surgery 2. Corneal damage; 3. Skin drying; 4. Ineffective against C. Dif spores **Spectrum of activity:** - Gram positives and negatives, Acid fast bacteria are susceptible, - Lipophilic viruses may be susceptible, Many fungi **Ineffective against:** Spores and prions. Hydrophilic viruses are less susceptible

Answer 45

**Main action:**Cationic biguanide -strongly adsorbs to bacterial membranes causing leakage of small particles and precipitation of cytoplasmic proteins **Onset/Duration:** Delayed/Sustained residual activity **Advantages:** Resistant to inactivation by blood and organic material; Low skin irritation **Limitations:** 1. Neurotoxic 2. Delayed effect 3. No direct spore activity 4. Agents in moisturisers, neutral soaps, and surfactants may neutralised its action **Spectrum of activity** - Bacteria (G+ve>G-ve) - Moderate fungal and viral activity - Inhibits spore germination **Ineffective against** Spores and prions Hydrophilic viruses are less susceptible **Other** Can be combined with 70% alcohol Preferred antiseptic for central venous access Not absorbed orally

Answer 46

- Potency is defined as the concentration (EC50) or dose (ED50) of a drug required to produce 50% of that drug's maximal effect/a specified response in 50% of the population ○ Two drugs may have the same efficacy but one may achieve the effect at a lower dose ○ A drug with lower EC50 or ED50 has higher potency

Answer 47

- Efficacy - a measure of the magnitude of the effect once the drug is bound ○ Different agonists produce varying responses, even when occupying the same proportion of receptors ○ Efficacy can be expressed numerically - as a ratio of the drug's maximal efficacy to the maximal efficacy of some known potent agonist (aka intrinsic activity or maximal agonist effect)

Answer 48

A compound that competes with endogenous agonists for the same binding site - it may be reversible or irreversible ○ In the presence of a competitive antagonist, the Emax of the agonist is unaffected, but the potency is reduced

Answer 49

A compound that binds at a different site to the natural receptor and produces a conformational change that prevents receptor activation

Answer 50

The volume of air in the lungs at end of expiration during tidal breathing. It is the point at which alveolar pressure = atmospheric pressure, and is equal to expiratory reserve volume (ERV) plus residual volume (RV).

Answer 51

_Blood supply:_ * **Upper half**: superior branch of the super thyroid artery * **Lower half**: inferior branch of the inferior thyroid artery _Venous drainage:_ * **Upper half**: superior branch of the superior thyroid vein * **Lower half**: inferior branch of the interior thyroid vein --\> brachiocephalic vein _Nerve supply:_ All muscles are supplied by the recurrent laryngeal nerve except cricothyroid muscle, which is innervated by the external laryngeal _Lymphatics_ * Upper and lower groups of deep cervical nodes

Answer 52

* This is specific to laminar flow (fastest velocity at centre of vessel, little to no movement at periphery)

Answer 53

If Re\<2000, flow more likely to be laminar, 2000-4000 = transitional & \>4000 turbulent

Answer 54

* PaO2 = partial pressure of oxygen in arterial blood (measured value, in mmHg) * This is the pressure that 'dissolved' oxygen (ie oxygen unbound to Hb) exerts on the measuring oxygen electrode * Although the pressure of oxygen is an important indicator of Hb saturation and total oxygen content, it is not a measure of content (ie mass or volume) * SaO2 = oxygen saturation (measured value, in %) * This is the percentage of all the heme sites in all the available haemoglobin that is taken up by an oxygen molecule * Similarly to above, this is an important surrogate measure for oxygen availability however is also not a measure of content * CaO2 = blood content of oxygen (can be measured directly, or calculated by the oxygen content equation, in mL of oxygen/100ml or 1000mL of blood - ie mL/dL or mL/L) * This measures total oxygen content (dissolved plus bound)

Answer 55

The maximal volume of gas in the lungs at which small airways begin to collapse in dependent parts of the lung

Answer 56

The heat required to convert a substance from liquid to vapour at a given temperature. Latent heat of vapourisation decreases as ambient temperature increases, and is reduced to zero at the critical temperature of that substance.

Answer 57

* Vapour pressure = pressure exerted by a vapour above the surface of a liquid. * The more solutes you add to a solution, the lower vapour pressure, at any given temp + pressure * Saturation vapour pressure = pressure exerted by a vapour in equilibrium with liquid of the same substance. It is influenced by temperature and pressure * AKA equilibrium vapour pressure. It is the point at which the rate of evaporation = rate of condensation * Substances with a higher vapour pressure is more volatile. (eg. Sevo has SVP of 157mmHg at sea level, room temp vs H2O which is 18.6mmHg) * SVP increases with increasing temp - at body temp, H2O SVP is 47-48mmHg

Answer 58

The temperature at which vapour pressure equals atmospheric pressure. A lower atmospheric pressure will result in a lower boiling point temperature * Note: evaporation different to boiling - evaporation takes place from surface; bubbles form within the liquid when boiling.

Answer 59

* Critical temperature is the temperature above which it is not possible to liquefy a given gas by increasing its pressure * A substance is a gas when it is above its critical temperature, and a vapour when it remains in gaseous phase below its critical temperature * Nitrous has a critical temp of 36.5o and a critical pressure at this temp of 73atm. At 20O (temp of normal operating room), its critical pressure is 55atm

Answer 60

Minimum pressure which would suffice to liquefy a substance at its critical temperature

Answer 61

The point of minimum pressure and maximum temperature at which both a gaseous and a liquid phase of a given compound can coexist

Answer 62

Volume of space occupied by 1kg of a gas at its critical point

Answer 63

* Absolute humidity is the mass of water vapour present in a given volume of air. * Relative humidity is the percentage ratio of the mass of water vapour in a given volume of air to the mass required to saturate that given volume of air at the same temperature

Answer 64

The amount of a substance filtered per unit time

Answer 65

Any weakly ionised acid or base in equilibrium with its fully ionised salt that can resist changes in pH when a stronger acid or base is added.

Answer 66

Bicarbonate Phosphate (note: conc too low) Protein (note: conc too low)

Answer 67

HCO3 Hb Plasma protein Phosphate (note: conc too low)

Answer 68

Urinary: - Phosphate - Ammonia Bone: - Ca carbonate

Answer 69

HCO3 (important as low proteins, & negligible PO4)

Answer 70

RBCs phagocytosed by macrophages in liver or spleen, or haemolysed in circulation. Heme is degraded to bilirubin, Fe 2+ is recycled

Answer 71

Heme synthesised in mitochondria & cytosol of immature RBCs, globin synthesised by ribosomes in cytosol

Answer 72

**Normal range** 10-13s **Therapeutic values** 20-30s (warfarin) **Coagulation pathway assessed** Extrinsic & common **Method** - Sample collected in citrated blood tube & centrifuged (only plasma analysed) - Recombinant tissue factor added **Abnormal in:** ○ Problems with: § Vit-K dependent factor eg.warfarin § FVII eg. haemophilia § Factor Xa eg. apixaban § Thrombin eg. dabigatran

Answer 73

**Normal range** 30-40 sec **Therapeutic values** usually 50-90 or 60-100s **Coagulation pathway assessed** Intrinsic & Common **Method** - Collected + centrifuged as per PT - Phospholipid & negatively charged FXII activator added **Abnormal in:** - Factor deficiency (XII, XI, X, IX, II), heparin therapy, direct thrombin inhibitor therapy, direct Xa inhibitor therapy, antiphospholipid syndrome

Answer 74

**Normal range** 110-130sec **Therapeutic values** 200sec for ECMO, 400sec for bypass **Coagulation pathway assessed** Whole clotting cascade & platelet function **Method** - Whole fresh blood collected - Point of care test - contact activator (eg. Kaolin) added - Endogenous platelets are used as the source of phospholipid **Abnormal in:** Any coagulopathy. Most useful when there is one single predictable source of clotting dysfunction

Answer 75

Cytochalasin D (platelet inhibitor) - isolates fibrinogen testing

Answer 76

tissue factor

Answer 77

Phospholipid & ellagic acid

Answer 78

Ellagic acid & heparinase

Answer 79

- 500IU of Factor IX - 500IU of Factor II (prothrombin) 500IU of Factor X

Answer 80

- Factor VII (will reduce PT) - Factor IX, XI (will reduce aPTT) - Factor X, II 200IU of Factor VIII per adult dose

Answer 81

Adsorption of coagulation factors from plasma onto an ion exchange medium --> selective elution

Answer 82

Separation (by centrifuge) from whole blood, either by donation or by apheresis. Must be prepared within 6-18hrs

Answer 83

25-50IU/kg Warfarin: INR < 2 - 20U/kg, 2-4: 30U/kg, >4: 50U/kg

Answer 84

Glycogen: 100g Fat: 75g

Answer 85

○ Vitamin A → stored in stellate cells --> converted to retinol (active form). Contains 1-2yr supply ○ Vitamin D → ~ 1-4 month supply ○ Vitamin E & vitamin K - minimal

Answer 86

Primary: Formed in liver from cholesterol (by action of cholesterol 7α hydroxylase) □ Cholic + Chenodeoxycholic acid Secondary: formed by bacterial action on primary bile acids □ Deoxycholic + Lithocholic acid

Answer 87

Tolerance is the requirement of higher doses of a drug to produce a given response

Answer 88

- Pharmacokinetic tolerance - Pharmacodynamic tolerance ○ Receptor downregulation ○ Receptor deactivation ○ Receptor subunit modification ○ Second messenger systems ○ Drug target depletion - Physiological tolerance - Learned/behavioural tolerance - Others: ○ Sensitisation ○ Cross-tolerance

Answer 89

Persistent exposure makes drug clearance mechanisms more active; classically by induction of metabolic enzymes (eg. Effect of ethanol on CYP450 enzymes)

Answer 90

Persistent exposure to the drug produces and adaptive homeostatic response that results in a decreased pharmacological effect ○ Receptor downregulation - receptors are inactivated or endocytosed in response to sustained stimulation ○ Receptor deactivation - receptor protein is phosphorylated in response to excess stimulus (eg. Nicotine and nicotinic receptor) ○ Receptor subunit modification - modified receptor complex is selectively expressed, with diminished selectivity for the drug but maintained sensitivity for the endogenous ligand (eg. GABA-A receptor and benzodiazepines) ○ Second messenger systems - deactivation of post receptor second messenger systems (eg. B-agonists) Drug target depletion - some key molecule is used up in the drug action. Subsequent drug dosing will have diminished effect until the key molecule is regenerated (eg noradrenaline depletion due to ephedrine therapy)

Answer 91

Tolerance to the effects of the drug rather than to the drug itself at the receptor level. Physiological adaptive mechanisms may maintain homeostasis. Eg. Vasodilator antihypertensives may be offset by increased heart rate and CO, which maintains BP

Answer 92

The development of learned behavioural adjustments that compensate for the drug's effects

Answer 93

"reverse tolerance" - subsequent dosing increases the drug effect (eg. Amphetamines)

Answer 94

Development of tolerance to multiple drugs belonging to the same class, after exposure to only one of them (eg. Nitrates)

Answer 95

Decreased response to a drug with repeated short-term use. It occurs over minutes-hours & cannot easily be overcome with increase dose

Answer 96

(DR SVC) Diuretics - Carbonic anhydrase Inhibitors - Loop diuretics - Thiazides - K+ sparing diuretics RAAS antagonism - ACE Inhibitors - ARBs - Direct renin inhibitors Sympatholytics - alpha blockers - beta blockers - mixed alpha + beta - centrally acting (eg clonidine) Vasodilators - Arterial - hydralazine - Arterial + venous - nitrates Ca channel blockers

Answer 97

○ 37 kDa proteolytic enzyme with half life 40-120min ○ Produced in and released from juxtaglomerular (granular) cells in juxtaglomerular apparatus Role: ○ Cleaves angiotensiongen into angiotensin-I ○ Rate-limiting step in RAAS

Answer 98

Stimulus for release: ○ ↓ Na delivery to macula densa ○ ↓ blood pressure or renal perfusion pressure (sensed by intrarenal baroreceptors) --> likely cell stretch-mediated mechanism of renin release ○ Activation of β1 receptors on juxtaglomerular cells Inhibits release: ○ Negative feedback: ↑ Renin --> ↑ Angiotensin II (ATII) --> binds AT1 receptors on juxtaglomerular cells --> ↓ renin secretion

Answer 99

* Class/chemistry: Catecholamine/Endogenous sympathomimetic * Preparation/administration: Clear, colourless solution in 0.1mg/ml or 1mg/ml - can be administered IV/subcut; 1% ophthalmic solution; aerosol (280mic/MD)

Answer 100

* Indication/Dose: -- Anaphylaxis - 0.1-0.5mg subcut -- Cardiac arrest - 1mg IV; -- Low CO states: 0.01-0.1mic/kg/min as infusion in shock -- Glaucoma -- Local vasoconstrictor (added to LA solutions to prolong duration)

Answer 101

* Absorption - inactivated with oral administration; slower subcut vs IM. Well absorbed from tracheal mucosa.pKa 9.7 * Distribution - Vd = 0.1-0.2L/kg; 12 % protein bound

Answer 102

* Metabolism - Metabolised rapidly by COMT (liver)--> metadrenaline + noradrenaline; MAO (neurons); final common products (normetadrenaline + VMA) are inactive. * Excretion - urine; half life ¬2min

Answer 103

* Mechanism of action - directly acting sympathomimetic amine. Agonist of α + β adrenoceptors, with ¬equal activity at both. At α1 - results in release of IP3 --> vasoconstriction. β1 + 2 -->cAMP Onset: immediate Duration: 1-5min

Answer 104

* Effects +/- side effects -- CVS - Positive ionotrope + chronotrope. Increases cardiac output, myocardial O2 consumption, coronary blood flow. May result in tachycardia, dysrhythmias, ischaemia -- Resp - mild resp stimulant (increases both tidal volume and respiratory rate). Potent bronchodilator but tends to increase the viscosity of bronchial secretion -- CNS - Increases cutaneous pain threshold and enhances neuromusclar transmission. Little overall effect on CBF. Cerebral haemorrhage may result -- Renal - decreases renal blood flow by up to 40%, but filtration rate remains mostly the same. Inhibits contraction of pregnant uterus -- Metabolic/other - elevated BSL (increases glucagon secretion, stimulates gluconeogenesis, decreases insulin secretion. Plasma renin increased (B1 effect), plasma conc of FFAs increase (activates triglyceride lipase). Increases BMR by 20-30% * Special points: -- Dose decrease with volatile anaesthetics (risk of ventricular dysrhythmias - mainly halothane, enflurane + isoflurane)

Answer 105

Naturally occurring sympathomimetic amine

Answer 106

* Indication/Dose: -- Hypotension occurring in general, spinal or epidural anaesthesia - 3-7.5mg (max 9mg), repeated every 3-4 min to a max of 30mg, titrated to response -- Nasal decongestant -- Other: Nocturnal enuresis, narocolepsy, diabetic autonomic neuropathy, hiccups

Answer 107

* Absorption - rapidly and completely absorbed via all routes * Distribution - rapidly and extensively absorbed. Vd = ~4L/kg. Crosses placenta & excreted to breast milk

Answer 108

* Metabolism - resistant to MAO + COMT metabolism. Small amount metabolised to norephedrine (may produce central stimulant effect) in liver * Excretion - 55-99% excreted unchanged in urine. Half life 6hrs

Answer 109

* Mechanism of action - acts both indirectly (causes release of NA from sympathetic nerve terminals) and directly by stimulating α & β-adrenoceptors Onset: rapid Duration: 1hr

Answer 110

* Effects +/- side effects -- CVS - Similar to adrenaline but more prolonged - positive ionotrope + chronotrope--> increases cardiac output, myocardial work and myocardial oxygen consumption -- Resp - resp stimulant + marked bronchodilation -- CNS - stimulatory effect similar to amphetamine. Increases CBF -- Renal - constricts renal blood vessels - decreases renal blood flow & GFR -- Metabolic - stimulates glycogenolysis, may increase BMR, thermogenesis **Special points:** -- Tachyphylaxis occurs with prolonged use. Dysrhythmias with halothane -- Clonidine premedication enhances pressor effects of ephedrine

Answer 111

Class/chemistry: Catecholamine/endogenous sympathomimetic Preparation/Administration: Clear, colourless liquid containing 2mg/ml. Administered via CVC in 40mic/ml conc infusion

Answer 112

Dose: titrated to effect. Usually 0.1-0.4ug/kg/min Indication: refractory hypotension

Answer 113

Absorption: Undergoes significant first pass metabolism and is inactive when administered orally Distribution: VD 0.1-0.4L/kg; 25% protein bound

Answer 114

Metabolism: Endogenous NA is metabolised via 2 pathways: - oxidative deamination to aldehyde by mitochondrial MAO (in liver, brain, kidney) and - methylation by cytoplasmic catechol-O-methyl transferase(COMT) to normetanephrine. Predominant metabolite is VMA Excretion: half-life is ~2minutes, 5% of dose excreted unchanged

Answer 115

Mechanism of action: non-selective sympathomimetic - acts on α & β adrenoceptors. Effect of action depends on distribution of these receptors throughout the body. It is generally a poor β2 agonist. Adrenoceptors are G-protein coupled receptors (GPCR) and binding causes a chain of downstream effects - Onset: immediate - Duration of action: 5-10minutes; tachyphylaxis with prolonged administration

Answer 116

Adverse effects: (inc toxicity) Link above to organ systems: - CNS - not much change to cerebral blood flow (mildly reduced) + reduction in O2 consumption. ○ Toxicity/Adverse effects: Anxiety, headache, photophobia - CVS - positive ionotrope - works on the β1 receptor in heart to increase contractility, however does not increase HR like adrenaline (reflex vagal stimulation leads to compensatory bradycardia). CO remains the same or decreases slightly ○ Vasopressor effect - α agonist causing vasoconstriction and raised peripheral vascular resistance, causing rise in SBP + DBP ○ Coronary vasodilation (unclear how/why - possibly β2 stimulation mediated, although NA usually poor β2 agonist) ○ Adverse: chest pain - Resp - increased minute volume, very slight bronchodilation - GU - increases contractility of uterus (may induce fetal bradycardia + asphyxia), increases tone of bladder neck, reduces renal blood flow (GFR well maintained) - Skin: significant cutaneous vasoconstriction. Adverse: pallor; Toxicity: Gangrene. Extravasation - sloughing + tissue necrosis *And others:* - Serious cardiac dysrhythmias during halothane anaesthetics - Co-administration with MAOIs or tricyclic antidepressants can precipitate serious hypertensive episodes

Answer 117

- Class/chemistry: Propanedinitrile derivative - Preparation/administration: Clear, yellow or orange solution for injection – 2.5mg/mL in 5 & 1-mL ampoules

Answer 118

Severe decompensated heart failure unresponsive to other therapies. Cardiogenic shock post cardiac surgery in pts with EF <40% Infusion at 0.05-0.2microg/kg/min. Used for ~24/24

Answer 119

- MoA: Increases calcium sensitivity by binding to myocardial troponin C, leading to stabilisation and increased duration of calcium binding. This results in increased myocardial contractility without impairment of myocardial relaxation or increased oxygen demand. Also stimulates ATP-sensitive K+ channels leading to vasodilation

Answer 120

--- CVS – Increases myocardial contractility via increased calcium sensitivity without increased myocardial oxygen demand. Also causes coronary and peripheral vasodilation. Hypotension

Answer 121

- Class/chemistry: Synthetic isoprenaline derivative - Preparation/administration: 12.5mg or 50mg/mL of dobutamine (diluted prior to infusion)

Answer 122

For low cardiac output states eg: acute heart failure & cardiogenic shock. Dose: 2.5-20mic/kg/min (~100-3000mic/min)

Answer 123

Predominately selective β-1 agonist, weak β2 agonist. Acts directly on catecholamine receptors to activate adenylate cyclase, which catalyses the conversion of of ATP to cAMP

Answer 124

--- CVS – activate cardiac β-1-adrenoceptors. SA automaticity increased and AV nodal conduction velocity also increased. Also has activity at α- and β2-adrenoceptors. It decreases LVEDP and SVR --- CNS – stimulation occurs at high dose ranges. Fatigue/nervousness/headache **Other** Should not be used in people with cardiac outflow obstruction. Tachyphylaxis can occur during prolonged infusion

Answer 125

Synthetic sympathomimetic amine

Answer 126

Adjunct in treatment of hypotension. 0.5-2mg bolus dose. Infusion 0.5-10mg/hr

Answer 127

Absorption: - Distribution: Does not cross BBB. Vd = 4L/kg; 45% PB. Distributes into catecholamine storage vesicle - persists for days

Answer 128

Metabolism: Not metabolised Excretion: Eliminated slowly over hrs/days - distribution t1/2 rapid. Half life - minutes

Answer 129

Direct and indirect acting sympathomimetic. Agonist effect at alpha-1 adrenoceptor, but also some beta-adrenoceptor activity. Causes noradrenaline release from intracytoplasmic stores, in addition to causing adrenaline release Duration of action - 20-60min; onset 1-2min

Answer 130

- CVS - Sustained increase in systolic and diastolic blood pressures due to increase in systemic vascular resistance. Reflex bradycardia. Indirect increase in coronary artery flow - CNS - cerebral blood flow decreased - Renal - renal blood flow decreased **Other:** - Excessive hypertension may occur when administered in patients with hyperthyroidism or those receiving MAOIs

Answer 131

Synthetic catecholamine

Answer 132

Complete heart block, bradycardia with haemodynamic compromise 0.5-10mic/min1

Answer 133

Non-selective Beta-adrenergic agonist. Its actions are mediated by membrane-bound adenylate cyclase and subsequent formation of cAMP Onset: immediate DoA: 10-15min

Answer 134

- CVS - Positive ionotrope + chronotrope --> increased CO; decreased, PVR (B2 effect) & DBP * Side effects = tachycardia, hypotension, arrhythmias, angina - Resp - Potent bronchodilator - CNS - CNS stimulant **Other** - Tachyphylaxis may occur with prolonged use

Answer 135

Naturally occurring catecholamine

Answer 136

Low cardiac output states, especially post cardiac surgery. Initial 2-10mic/kg/min; maintenance up to 50mic/kg/min

Answer 137

Stimulates adrenergic and dopaminergic receptors. Lower doses mainly dopaminergic stimulating (renal + mesenteric vasodilation), higher doses both dopaminergic & β1 stimulating, large doses stimulate α-adrenergic receptors Onset: 5 min Duration: <10min

Answer 138

- CVS - Dose dependent - increased ionotropy, CO, coronary BF (beta effects); increased vasoconstriction, SBP (alpha effects) - Resp - may decrease ventilatory response to hypoxia - CNS - Nausea (direct stimulation of CTZ). Does not cross BBB - Renal - in low doses, marked reduction in renal vascular resistance --> increases flow. Diuresis via D1 receptors at luminal and basal membranes of PCT **Other** - Reduce dose in people who have taken recent MAOIs

Answer 139

Synthetic sympathomimetic amine

Answer 140

hypotension, nasal decongestant, mydriatic agent. 50-100microg bolus doses

Answer 141

Direct acting selective alpha-1-adrenoceptor agonist (nil B-effects) Duration of action 15-20min IV; onset immediate

Answer 142

- CVS - rapid increase in SBP + DBP, SVR. Reflex brady - may reduce CO - CNS - mydriasis - Renal - RBF decreased

Answer 143

(Argipressin is synthetic compound which is identical to endogenous human vasopressin) **Class/chemistry:** - Naturally occurring nonapeptide prohormone produced in posterior hypothalamus **Preparation/Administration:** Available in 3 synthetic analogues: (all clear, colourless liquids) - Argipressin in 20IU/mL (SC/IV or IM) - draw up into 20U/20mL - terlipressin - desmopressin in oral, IV, IN | (Note - analogues L2)

Answer 144

- Management of catecholamine-refractory shock: Argipression is 0.6-2.4IU/hr - Cranial diabetes insipidus & Management of polyuria/polydipsia post hypophysectomy: 100mic TDS desmopressin, adjusted to response - Bleeding oesophageal varices: terli: 0.5mg/hr for 48/24 - Perioperative/trauma management of people with haemophilia and VW disease

Answer 145

Absorption: desmopressin - 0.08-0.16% of dose is absorbed via PO route; 10% via IN route Distribution: Argi: Vd = 0.14L/kg, not protein bound. Largest is terlipressin: 0.5l/kg

Answer 146

Metabolism: Endogenous vasopressin metabolised by vasopressinases (endothelial peptidases). Argi = 35% metabolised, desmo - minimal, terli - completely metabolised Excretion: Endogenous vaso has a half life of 10-35 minutes; argi is shorter (10-20), terli is longer (50-70), desmo is 2-3hrs. 65% of argi and desmo is unchanged in urine

Answer 147

Act on GPCR vasopressin receptor - V1 = GqPCR - act via PLC --> IP3 + DAG --> increase IC Ca - V2 = GsPCR - activated AC --> cAMP --> increase IC Ca Onset 1-2min Duration up to 20min

Answer 148

- CVS: V1 receptors in smooth muscle - activation causes vasoconstriction (via increased intracellular calcium) - increases MAP + SVR. At very low doses, causes vasodilation of pulmonary artery - GU: reduction in urine output and resolution of polydipsia in DI (V2 in DCT + CDs), activation leads to aquaporin-2 trafficking from intracellular vesicle membranes within renal epithelial cells into apical cell membrane --> water resorption - Endo: release of ACTH from pituitary

Answer 149

* Class: Ionotrope * Chemistry: Bypyridine molecule * Preparation/Administration: Clear, colourless solution for injection in 10-20mL glass ampoules (1mg/mL)

Answer 150

* Severe treatment-resistance congestive cardiac failure * Low cardiac output states following cardiac surgery (loading dose 50mic/kg over 10min; infusion between 0.375-0.75mic/kg/min titrated to response)

Answer 151

* Absorption: - * Distribution: Vd = 0.3-0.4L/kg; 70-80% protein bound

Answer 152

* Metabolism: 12% glucuronidated in liver; Mostly cleared renally - unchanged * Excretion: Mostly cleared renally - unchanged; half life 2.3hrs in patients with heart failure, longer in renal dysfunction

Answer 153

* Mechanism of action: Selective inhibition of type III cAMP PDE in cardiac + vascular muscle (PDE responsible for cAMP catabolism) --> increased intracellular Ca --> increased contractility in cardiac; decreased vascular contraction

Answer 154

* CVS: positive ionotropic effect --> CI increases by 25-30%, decreased SVR + MAP. May increase AV nodal conductance (may lead to increase in ventricular response in pts with atrial flutter or AF) * Renal: u/o + GFR may increase due to increased CO **Other** - Decrease infusion rate in renal failure

Answer 155

(mnemonic: DR SVC) - Diuretics (see renal) - RAAS antagonists - ACE inhibitors - ARBs - Direct renin inhibitors- eg.Aliskiren - Sympatholytics - B-blockers - A-blockers - Mixed A + B - Centrally acting (eg clonidine) - Vasodilators - Arterial - Arterial + venous - Ca- Channel antagonists

Answer 156

- Indications: Hypertension, HFrEF, Post MI, diabetic nephropathy - Examples: - Captopril (dose range 6.25mg-max 150mg/24hrs. Usually 12.5mg BD for HTN), - perindopril (2.5mg arginine = 2mg erbumine. Usually 4-5mg (max 8-10mg daily)), - ramipril dosing same as perindopril arginine

Answer 157

ACEIs: Blocks ACE which catalyses conversion of angiotensin I--> angiotensin II ARBs: Block AT1 receptor (10000-fold more selective for AT1 than AT2). Inhibits biological effects of AngII, similar to ACEIs

Answer 158

Organ effects: - CVS: ↓vasoconstriction & ↓hypertrophic remodelling (less ATII) & ↑ bradykinin levels (decrease breakdown) --> stimulates PGs --> vasodilation - Renal: ↑ natriuresis Adverse effects: - Hypotension, - cough (accumulation of lung bradykinin), - hyperkalaemia (in pts taking K+ sparing diuretics) - Note: ARBs: ARF, less cough Contraindicated in pregnancy (teratogenesis, fetal hypotension, anuria, renal failure)

Answer 159

Hypertension, some ACEs approved for diabetic nephropathy, valsartan for HF Dose: - Irbesartan (150mg daily - max 300mg) - candesartan (4mg daily to max 32mg) - telmisartan (40mg - max80mg)

Answer 160

- **Alter ion permeability** - act on ligand gated ion channels (membrane spanning complexes that can form a transmembrane channel for ions). Types: -- *Pentameric* -> 5 membrane spanning units (eg, nicotinic Ach receptor at NMJ - Na+ flux, GABA A receptor - Cl- flux)   -- *Ionotropic glutamate* -> NMDA, AMPA and kainate iontropic ligand gated ion channels. They form Na, K and (NMDA only) Ca channels when glutamate binds    -- *Purinergic receptors* -> activated by purines such as adenosine & ATP. Permeable to Na, K and Ca - **Produce intermediate messengers** - act on membrane bound systems which transduce signal from an extracellular ligand to an intracellular signal transmitted by intermediate messengers. Eg: ○ *G proteins* (most common) - eg, Nad and Adr    ○ *Tyrosine kinase* - eg, insulin    ○ *Guanylyl cyclase* - Membrane bound - eg. atrial natriuretic peptide on its receptors - Soluble - eg. NO  - **Regulate gene transcription**  ○ Steroids & thyroid hormones act on intracellular receptors to alter the expression of DNA and RNA  

Answer 161

- **Physiochemical properties** ○ Antacids - neutralise gastric acid    ○ Chelating agents (eg, resonium - on gut K)    - **Enzymes** ○ Concentration of the substrate normally metabolized by the enzyme is increased, and product of reaction is decreased    ○ Eg, ACE inhibitors (captopril, enalapril) prevent the conversion of ACEI to ACEII & bradykinin into its breakdown fragments    - **Voltage gated Ion channels** ○ Involved in the conduction of action potentials in excitable tissues    ○ Eg, local anaesthetics (eg, lignocaine) block Na channels, calcium channel blockers (eg, diltiazem) acts on vascular smooth muscle ion channels   - **Alteration on transport proteins** - eg. Frusemide on NKCC2   - **Prodrugs** ○ Require conversion to activated form by a metabolic pathway Eg. Levodopa --> dopamine

Answer 162

Class: Organic nitrate Chemistry: Ester of nitric acid

Answer 163

- Stable, unstable, variant angina Dose: 0.3mg s/l; 0.4-0.8mg s/l buccal spray; 5-10mg/24 transdermal; - LV failure secondary to MI - Perioperative control of BP Start 5-10mic/min. Increase up to 200microg/min IV infusion (sometimes up to 400mic/min)

Answer 164

**Absorption:** Rapid + efficient s/l (40%). POBA 3% **Distribution:** PB 60% Vd ~2L/kg

Answer 165

**Metabolism:** by liver + RBCs to mono- & di-nitrates + nitrites - all have lower activity than parent **Excretion:** 80% urine. T1/2 1-3min

Answer 166

Metabolised to NO --> stimulates guanylate cyclase in vascular smooth muscle --> increased cGMP--> phosphorylation cascade--> relaxation **Onset:** 1-3min s/l or ~100s IV **Duration:**15-30min s/l or 3-5min IV

Answer 167

**CVS:** at low doses, venodilation --> veno + arterial at higher doses. Decreases afterload, decreases myocardial O2 demand, increases myocardial oxygen supply. Reflex tachycardia in normal individuals **CNS:** ICP may increase due to cerebral vasodilation **Other:** 40-80% of IV GTN adsorbed onto plastic giving-sets (needs non-PVC)

Answer 168

Class: Inorganic nitrate Chemistry: Central Fe atom with 5 cyanide groups + 1x NO

Answer 169

Absorption: - Distribution: Vd up to 0.2L/kg (EC space)

Answer 170

IV infusion 0.5-6microg/kg/min - Hypertensive crisis - Aortic dissection prior to surgery - LV failure

Answer 171

**Metabolism:** * Rapid non-enzymatic hydrolysis in RBCs --> 5x cyanide ions per molecule of SNP * --> 1x cyanide reacts with methaemoglobin --> cyanomethaemoglobin * --> 4x cyanides enter plasma --> 80% react with thiosulfate --> thiocyanate (catalysed by hepatic rhodanese). Remainder of cyanide reacts with hydroxycobalamin to form cyanocobalamin **Excretion:** Metabolites excreted unchanged in urine. T1/2 2 min (thiocyanate 2 days)

Answer 172

Interacts with sulfhydryl groups on smooth muscle membrane --> releases NO --> vasodilation **Onset:** 1-2min **Duration:** 3-7min IV

Answer 173

**CVS:** decreases SBP, CO well maintained. Decrease Myocardial O2 consumption. Causes both veno - and arterio dilation **Resp:** attenuates HPV in lungs **CNS:** cerebral vasodilation, increased ICP. Shifts autoregulation to left **Other** Can be removed by haemodialysis Needs to be protected from light Can get cyanide toxicity

Answer 174

Antihypertensive Pthalazine derivative

Answer 175

- acute severe hypertension - Pre-eclampsia IV 5-10mg, administered slowly. May repeat 20-30min later. IVI initially 200-300microg/min, maintenance 50-150microg/min - chronic moderate to severe hypertension - PO 50-200mg daily in divided doses

Answer 176

Activates ATP sensitive K+ channels --> inhibits opening of voltage gated Ca channels by hyperpolarising membrane --> electromechanical decoupling + inhibition of contraction **Onset:** 5-20min when given IV **Duration:** 2-6hrs

Answer 177

**CVS:** predominately arteriolar vasodilation --> decreases SVR. Compensatory tachycardia **CNS:** CBF increases **Metabolic:** increases plasma renin **Other:** Additive hypotensive effects with volatiles

Answer 178

Antihypertensive Aniline derivative

Answer 179

0.05-0.6mg PO (max 900microg/day), IV 0.15-0.3mg - Hypertension - Migraine - Chronic pain, opiate and alcohol withdrawal - premedication in anaesthesia

Answer 180

Stimulates alpha 2 (200:1 ratio alpha 2:alpha1 affinity) receptors (pre-synaptic) --> decreases NAd release --> decreased sympathetic tone. GiPCR--> decrease cAMP --> dec Ca2+ influx & Ca-mediated NAd release Analgesic effect - activation of alpha 2 R in dorsal horn of spinal cord (inhibits neurotransmission) **Onset:** Within 5min IV **Duration:** 3-7hrs when given IV

Answer 181

CVS: transient increase in BP (stimulation of alpha1), then sustained decrease. SVR decreased with long term treatment CNS: Decreases cerebral blood flow + IOP. Depressant effect on spontaneous sympathetic outflow & afferent A delta- & C-fibre mediated somatosympathetic reflexes Sedation Analgesia

Answer 182

0.5mg -1mg BD or TDS initially. Maintenance 3-20mg in divided doses - Hypertension - CCF - Raynauds (1-2mg BD) - BPH

Answer 183

Inhibits post synaptic alpha1 receptors --> GqPCR --> inhibits PLC --> decreased IP3 + DAG --> decreased intracellular {Ca2+] **Onset:** 30-90minutes **Duration:** 10-24hrs

Answer 184

CVS: decrease in SVR without reflex tachycardia Genitourinary: Improvement in urinary flow Adverse: orthostatic hypotension, rarely tachycardia

Answer 185

β1 receptors: * Distribution: mostly cardiac * Effects: ○ CVS § ↑ SA node firing rate, ↑ HR § ↑ contractility § ↑ conduction velocity § ↑ AV node automaticity ○ Renal § ↑ renin secretion by the kidney ○ GI § ↓motility and tone of the stomach

Answer 186

β2 receptors: * Distribution: Smooth muscle * Effects: ○ Resp: § Bronchodilation ○ CVS: § Vasodilation of vascular beds (coronary arteries, arteries of abdo viscera, renal arteries) § Mild cardiac effects – β2 receptors make up 25% of total cardiac β receptor population ○ GI: § ↓motility + tone of stomach, intestine § Gallbladder relaxation ○ Skeletal muscle effects: § Increased K+ uptake § Glycogenolysis à Hyperlactataemia ○ Metabolic/endocrine § ↑glycogenolysis & gluconeogenesis in liver, insulin secretion, lipolysis, thermogenesis

Answer 187

β3 receptors: * Bladder (detrusor) relaxation * ↑ water & solute resorption at the kidney * ↑ lipolysis and thermogenesis at the adipocyte * Modulation of cardiac contractility * Relaxation of uterine contractions

Answer 188

A - no available or inactivated PO (brush border COMT) D - 0.1-0.2L/kg (Except aramine & ephedrine 4L/kg M - COMT & MAO (aramine & ephedrine not metabolised) E - urine

Answer 189

D - V (0.14) M (liver - not much) E - Urine

Answer 190

- non selective --> Prop + Sot - β-1 selective --> Bisop, Esmo, Aten, Metop, Nebiv - combined α+β --> Carvi + labet

Answer 191

PMN - prop - metop - nebiv

Answer 192

- labet - acebut - pindo

Answer 193

B-blocker/ antihypertensive Racemic mixture of 4 stereoisomers

Answer 194

Dose: 100-800mg PO BD; 5-20mg bolus IV or titratable infusion 20-160mg/hr - Hypertensive emergencies - All grades of hypertension

Answer 195

A: Rapidly absorbed but extensive FPM. BA 10-90% D: 50% PB; Vd up to 15L/kg

Answer 196

M: Metabolized by the liver via CYP3A4 and CYP2D6 – inactive compounds E: Elimination half-life of 5-8 hours. Excreted in the urine and feces.

Answer 197

Non selective B-blocker with α1 blockade. Has some intrinsic sympathomimetic activity. Alpha:beta 1:3 PO or 1:7 IV Onset: IV – 5-30min Duration: IV – 50min

Answer 198

CVS: beta-1 & beta-2 blockade in cardiac tissue à decreased HR & contractility Alpha-1 block à vasodilation à 20% decrease BP Decreases HR + CO by ~10% Renal: decreased renal VC à increased RBF à GFR unchanged

Answer 199

- Hypertension - PO initial 12.5mg daily --> 25mg (max 50mg) Chronic heart failure with reduced ejection fraction - initial 3.125mg BD to max 25mg BD

Answer 200

Non selective B-blocker with α1 blockade, No ISA. Onset: 30-60min Duration: Long (t1/2 = 7-10hrs)

Answer 201

CVS: ↓CO, ↓HR, ↓ reflex orthostatic tachycardia, vasodilation, ↓PVR, ↑ANP Renal: ↓renal VC, ↓ plasma renin

Answer 202

- Pulmonary arteries can be classified: ○ Elastic (large, contain elastin) ○ Transitional (increasing amounts of circumferential muscle fibres) ○ Muscular (enough muscle to allow vasoreactivity) ○ Non-muscular (small endothelial vessels) ○ Capillaries (form a vascular sheet) - Pulmonary veins - thinner walled, contain more collagen + less elastin - Pulmonary arteries and veins travel with bronchi (+ nerves + lymphatics) in bronchovascular bundles (à peribronchial cuffing)

Answer 203

PA systolic pressure = 18-25mmHg PA diastolic pressure = 8-15mmHg

Answer 204

Pulmonary capillary pressure = 4-12mmHg Pulmonary venous pressure = 6-12mmHg

Answer 205

A volume of blood that needs to be added to pulmonary end capillary blood to explain the observed difference between pulmonary end capillary oxygen content and arterial oxygen content

Answer 206

Normal shunt fraction/venous admixture is 3%

Answer 207

- Shunt fraction --> ratio of venous admixture to total cardiac output ○ Q_s/Q_t = ((Cc_(O_2 ) −Ca_(O_2 )))/((Cc_(O_2 )− Cv_(O_2 ))) Where: § Q_s= shunt blood flow § Q_t = cardiac output (so Qs/Qt = shunt fraction) § Cc_(O_2 ) = pulmonary end-capillary blood O2 content § Ca_(O_2 ) = arterial O2 content § Cv_(O_2 ) = mixed venous blood O2 content

Answer 208

- Iodinated benzofuran derivative (Class 3 antiarrhythmic) - PO tablets 100mg or 200mg; IV 30 or 50mg/ml amiodarone hydrochloride

Answer 209

- tachydysrhythmias resistant to other treatment + related to WPW syndrome Initial loading dose 5mg/kg in 250mL 5% dextrose. Maintenance 15mg/kg/day. PO dose initially 200mg TDS, which is reduced to 100-200mg daily after 1/52 - cardiac arrest: shockable rhythm. 300mg IV every 3 cycles

Answer 210

- Absorption: bioavailability of 22-86% (Smith) or 35-65% (Katzung) - Distribution: 96-98% protein-bound in plasma; VD is 1.3-65.8L/kg, according to dose

Answer 211

- Metabolism: largely in liver, to desethyl-amiodarone (has anti-arrhythmic properties and is cumulative) - Excretion: 1-5% in urine, mostly in bile + faeces T1/2 variable - up to 60days

Answer 212

prolongs cardiac action potential & delays refractory period. - partial antagonism of alpha- and beta- agonists by reducing number of receptors or by inhibiting the coupling of receptors to the regulatory subunit of the adenylate cyclase system - Delays K+ efflux, depresses Na+ influx & depresses Ca2+ influx - Onset: within 1hr IV, PO 2-3days-weeks - Duration after discontinuation can be weeks to months. Half-life (elimination half-life has slow (3-10days) and rapid (weeks) components)

Answer 213

CVS - marked prolongation of the action potential duration (and QT interval on the ECG) by blockade of intracellular K. ○ Sinus rhythm is slowed secondary to reduction in the slow diastolic depolarisation in nodal cells. Automaticity is depressed and AV nodal conduction is slowed by 25% - Other: Contraindicated in porphyria

Answer 214

○ Hypotension - Vasodilation w ↓ SVR (due to polysorbate 80) ○ ↓ CO - Decreased cardiac contractility ○ May get bradycardia/complete HB resistant to atropine, Ad & NAd

Answer 215

○ Pulmonary fibrosis § Tends to occur during chronic therapy § May be rapidly progressive and fatal § Risk factors: underlying lung disease, high doses, recent pulmonary insults (e.g. pneumonia) § Rx: Withdrawal of drug; high dose glucocorticoids [MIMS]

Answer 216

○ Peripheral: - Peripheral neuropathy [MIMS] □ Typically exposure-dependent (long term; high dosage) □ Sensory > motor neuropathy (glove and stocking paraesthesia; disequilibrium) □ Incomplete resolution on drug withdrawal ○ Central effects: § Tremor § Dizziness § Vertigo **Ocular:** ○ Corneal microdeposits (almost ubiquitous, but usually asymptomatic) [Katzung, Goodman and Gilman’s] § Occasional visual changes (e.g. halos in peripheral visual fields) [Katzung, Goodman and Gilman’s] ○ Optic neuritis w blindness [Katzung, Goodman and Gilman’s]

Answer 217

* Musculoskeletal system: ○ Proximal myopathy [MIMS] * Cutaneous: ○ Photodermatitis (photosensitivity) [Katzung] ○ Grey-blue discolouration in sun-exposed areas [Katzung] * Thrombophlebitis

Answer 218

* Endocrine effects: ○ Blocks peripheral de-iodination of T4 to T3 [Katzung] ○ Hyperthyroidism ○ Hypothyroidism (Wolf-Chaikoff effect) ○ Amiodarone-induced thyroiditis (types 1 and 2)

Answer 219

* Pharmacokinetic interactions: § Enzyme inhibition: □ CYP3A4 □ CYP2C9 § Efflux pump inhibition (PGP): * Pharmacodynamic interactions: § Negative chronotropes/dromotropes: risk of bradyarrhythmias § Synergistic QTc prolongation with other agents

Answer 220

○ Nausea and vomiting ○ Hepatic: ○ Drug-induced liver injury § Δ AST, ALT, ALP § Rarely, acute liver failure ○ Hypersensitivity hepatitis [Katzung]

Answer 221

**Mechanism** Effect on (ventricular myocyte) AP: - Moderate ↓ in phase 0 slope, ↑ APD, ↑ ERP Effect on ECG: - ↑ QRS + QT interval **Example** Quinidine Procainamide | Na channel blockers (moderate)

Answer 222

**Mechanism** Effect on (ventricular myocyte) AP: - Small ↓ in phase 0 slope, ↓ APD, ↓ ERP. Effect on ECG: - minimal Preferentially affects ischaemic or depolarised Purkinje and ventricular tissue **Example:** "I'd buy Liddy's Mexican Tacos" Lidocaine, mexiletine Phenytoin | Na channel blockers (weak)

Answer 223

**Mechanism** Effect on (ventricular myocyte) AP: - Significantly ↓ Phase 0 slope; No effect on ERP or APD in Purkinje and ventricular tissue Effect on ECG: - Significant ↑ in QRS duration, therefore ↑ Qtc - Significantly prolongs ERP in AV node + accessory bypass tracts, therefore ↑ PR interval **Example** "Can I have fries please" Flecainide, propafenone | Na channel blockers (Strong)

Answer 224

**Mechanism** Effect on (pacemaker) AP: - ↓ SA & AV nodal activity (↓cAMP & Ca2+ currents) - Suppress abnormal pacemakers - ↓ slope of phase 4 Effect on ECG: - AV node particularly sensitive - ↑ PR interval **Example** Metoprolol | B-blockers

Answer 225

**Mechanism** Effect on (ventricular myocyte) AP: - ↑APD, ERP, Effect on ECG: - ↑QT interval **Example** Amiodarone Sotalol | K channel blockers

Answer 226

**Mechansim** Effect on (pacemaker) AP: - ↓conduction velocity, ↑ERP Effect on ECG: - ↑PR interval **Example** Verapamil Diltiazem | Ca channel blockers

Answer 227

**Class/chemistry** Sodium channel blocker Tertiary amine pKa 7.9, ionisation 25% **Administration/preparation** - Multiple routes - IV, S/c, IT, epidural, topical - 1-2% IV solution for injection, topical gel - Combined formulations with adrenaline

Answer 228

- Local anaesthetic (3mg/kg to max 200mg) - Class Ib antiarrhythmic - Rx for ventricular tachydysrhythmias - IV bolus 1mg/kg over 2 min, Inf 20-50mic/kg/min

Answer 229

**Absorption** Absorption of LAs related to site of injection, dose, VCs (delay absorption) **Distribution** ~ 70% PB (alpha-1 glycoprotein); VD = ~1L/kg

Answer 230

**Metabolism** Liver with multiple metabolites. Some lower seizure threshold, some with antiarrhythmic properties **Elimination** Half life ~100min <10% in urine

Answer 231

Diffuse into cells in unionised form, combine with H+ --> enters internal opening of Na+ channel and combines with receptor --> decreases Na+ conductance --> prevents depolarisation of cell membrane Acts on Nav1.5 subunit of fast voltage gated Na channels Onset: 1-5min local infiltration; rapid IV Duration: ~1-2hrs local (increased with adrenaline); 10-20min IV

Answer 232

CVS: decreases rate of rise of phase 0 of ventricular AP, slows AP propagation + reduces automaticity. In toxicity, it decreases PVR & contractility --> hypotension + CV collapse Resp: Bronchodilation. Resp depression in toxicity CNS: biphasic effect - excitation then depression **Other** Not removed by dialysis

Answer 233

**Class/chemistry** Antiarrhythmic Class 1c **Dose/indication:** PO 50-100mg BD (max 400mg daily) IV 2mg/kg (max 150mg) - SVT - Suppression of irritable foci eg. ventricular tachycardia + ectopics - In treatment of re-entry dysrhythmias eg WPW - In treatment of pAF

Answer 234

Sodium channel blocker. Reduces maximum rate of depolarisation --> slows conduction. Has greatest effect on His-Purkinje system + ventricular myocardium

Answer 235

CVS: markedly slows phase 0 of action potential, but decreases ERP - may be proarrhythmogenic. Increases QRS duration, PR prolongation CNS: may have visual disturbances **Adverse effects** May exacerbate heart failure, ventricular dysrrhythmias, increases non-fatal cardiac arrest

Answer 236

HTN, angina 2.5-5mg daily (max 10mg daily)

Answer 237

Class IV antiarrhythmic Non-dihydropyridine/phenylalkylamine

Answer 238

240-480mg BD-TDS; - Hypertension - Angina - pSVT, AF, flutter - 2.5-10mg IV

Answer 239

Competitive blockade of slow Ca2+ channels, leading to decrease Ca2+ influx into vascular smooth muscle and myocardium Onset: PO 10-20min; IV 3-5min Duration: PO 6-8hrs; IV 0.5-6hrs

Answer 240

CVS: decreases automaticity and conduction velocity, increases refractory period. Decreases SVR, potent coronary artery vasodilator CNS: cerebral vasodilation **Adverse effects** Dizziness, flushing, nausea, first or second degree heart block **Other** Avoid co-administration with dantrolene

Answer 241

Ca2+ channel blocker - dihydropyridine

Answer 242

IV infusion and tablets (30mg) **D/I** - Prevention of cerebral vasospasm secondary to subarachnoid haemorrhage - Dose: 60mg Q4H; IV 1mg/hr for first 2hrs -->2mg/hr 5-14 days - Migraine - Drug-resistant epilepsy

Answer 243

CNS: headache, cerebral vasodilation, increased CBF CVS: hypotension, bradycardia GI: nausea

Answer 244

**Absorption** Rapidly and well absorbed, significant FPM - BA low (30%) **Distribution** Highly protein bound, large Vd (1-2L/kg)

Answer 245

**Metabolism** Liver **Excretion** Urine t1/2 up to 6hrs

Answer 246

Modulates opening of Ca2+ channels on vascular smooth muscle (?preferential action on cerebral vasculature) --> prevents Ca2+ influx --> vasodilation

Answer 247

B-blocker/antiarrhythmic

Answer 248

Usually ~80mg BD initially - AF, maintenance of sinus rhythm - SVT Ventricular arrhythmias

Answer 249

Non-selective B-blocker - prolongation of atrial action potentials. K+ channel blocker - prolongs phase 3 of ventricular AP Onset: 1-2hrs PO

Answer 250

CVS: slows heart rate, decreases AV nodal conduction, increased AV nodal refractoriness, prolongation of atrial and ventricular action potentials **Adverse effects** Bradycardia, chest pain, palpitations, dizziness, fatigue, headache, dyspnoea

Answer 251

Cardiac glycoside. Contains steroid nucleus

Answer 252

Doses - loading dose 250-500microg every 4-6hours to effect (max daily dose 1.5mg). Then maintenance at 125-250microg daily Indication - use in AF + Flutter, heart failure, prevention of supraventricular dysrhythmias post thoracotomy

Answer 253

- Direct action - binds to & inhibits Na+/K+ ATPase in sarcolemma cell membrane--> ↑ intracellular Na+ & ↓ intracellular K+. ↑Na/Ca exchange via INCX - ↑ intracellular Ca-->ionotropy. Decreased K+ leads to slowed AV conduction & ↓ pacemaker cell action - Indirectly modifies autonomic activity & ↑ efferent vagal activity **Onset:** PO 1-2hrs; IV 5-60min **Duration of action:** 3-4 days; Half life: 36-48hrs

Answer 254

- CVS - ↑ ionotropy. ↓ HR (depression of SA node discharge, AV node conduction), ↑ AV nodal refractory period & indirect vagal effect. Rapid IV administration may cause vasoconstriction, leading to HTN & ↓ CBF. ECG changes - prolonged PR, ST depression, T wave flattening & shortened QT ○ (toxicity) - any dysrhythmia - esp junctional brady, ventricular bigemini, 2nd/3rd degree HB. Reverse tick on ECG - Renal - mild intrinsic diuretic effect - GI - (toxicity): anorexia, nausea, vomiting, diarrhoea, abdo pain Neuro - (toxicity): headache, drowsiness, confusion, visual disturbances, muscular weakness, coma

Answer 255

Toxicity - Therapeutic range is 0.6-1.0nmol/L (=0.25 ng/mL) digoxin-specific antibody fragments can treat toxicity. They form complexes with dig molecules then are excreted in urine. ○ Indications for treatment: life-threatening arrhythmia, cardiac arrest, K>5.0 ○ Consider treatment when: end organ dysfunction, mod-severe GI symptoms, serum dig >12ng/mL (25nmol/L), significant features of dig toxicity with serum dig > 4nmol/L ○ Formulation - 40mg reconstituted in 4mL. Response in ~20min (0-60) **Other specifics** ○ Increased risk of dysrhythmias with concurrent sux/pancuronium or B-agonists ○ Increased likelihood of toxicity with: low K, Hyper Na, Hyper Ca, Low Mg, acid-base disturbance, hypoxaemia and renal failure ○ Increased plasma dig levels with coadmin of verapamil, nifedipine, amiodarone, diazepam ○ Cannot be removed by dialysis

Answer 256

Naturally occurring nucleoside Clear, colourless solution 3mg/mL

Answer 257

- Diagnosis and treatment of paroxysmal SVT. Initially 3-6mg IV, followed by 12mg at 1-2min intervals until effect observed

Answer 258

Metabolism - absorbed from plasma into RBCs --> phosphorylated to AMP or deaminated to inosine. T1/2 <10sec

Answer 259

Direct agonist at A1 and A2 receptors. Adenosine activates acetylcholine sensitive K+ current in the atrium and sinus & AV nodes - shortens APD, hyperpolarisation + slowing of normal automaticity **Onset** 10 seconds **Duration** 10-20 seconds

Answer 260

CVS: depression of SA & AV nodal activity; coronary vasodilation - endothelial A2 receptors Resp: increase in depth + rate of respiration. May induce bronchospasm CNS: infusion results in increased CBF **Adverse effects:** Facial flushing, dyspnoea, chest discomfort

Answer 261

Mg2+ 2nd most abundant intra-cellular cation Mg2+ oxide, chloride, sulphate PO & IV IV MgSO4 (50% Mg & inorganic sulphate, 40mmol/100ml), ampoule 10mmol/5ml

Answer 262

Dose: depends on Mg2+ level, 10-20mmol over 20/60 Eclampsia & pre-eclampsia Premature labour Low Mg2+ Ventricular dysrhythmias incl TDP Asthma

Answer 263

**Absorption:** BA: 25-65% **Distribution:** ECF: 1% (0.7-1mmol/L) Bone: 60% ICF: 39% (15-20mmol/L) 30% bound to albumin

Answer 264

**Metabolism** Dissociates into active Mg2+ No metabolism Bound to bone or filtered into kidneys **Elimination:** Renal 90% reabsorbed in TAL LOH

Answer 265

Same role of endogenous Mg2+ Multiple mechanisms * Reduces membrane excitability e.g. muscle & nerve * Reduces NT release cholinergic & adrenergic synapses Ca2+ antagonist -> relax smooth muscle Onset: immediate after IV

Answer 266

- CVS: Direct vasodilator - ¯ SVR, ¯ BP, ¯ cardiac conduction & force of contraction, ¯ HR, ¯ catecholamine release - Resp: Bronchodilator - CNS: ¯ catecholamine from adrenal medulla & adrenergic nerve terminals, CNS depressant, Anti-convulsant, Cerebral vasodilator - GIT: Osmotic laxative -> diarrhoea - GU: Renal vasodilator, Diuretic - O&G: ¯ uterine tone & contractility

Answer 267

N&V, facial flushing, CNS depression, areflexia, respiratory depression. Reverse with Ca2+ Plasma level (mmol/L) Effect <0.7 Arrhythmia 4-6 Nausea, ¯ reflexes, speech impaired 6-10 Muscle weakness, resp depression, ¯ HR >10 Cardiac arrest

Answer 268

**Class**: Anticholinergic **Chemistry**: Racemic mixture of D- and l-hyoscyamine (l- form is active) **Prep/admin**: Clear, colourless solution for injection in 0.5/0.6mg/mL and 3mg in 10mL

Answer 269

- Bradycardia with haemodynamic compromise - 0.5-1mg - repeat 3-5minutely - Counter the muscarinic effects of anticholinergic agents - During CPR - treatment of organophosphate poisoning, tetanus

Answer 270

A: Well absorbed IM D: 50% PB; Vd = 2-4L/kg. Crosses BBB & placenta

Answer 271

M: Hydrolysed in liver and tissues to tropine + tropic acid E: T1/2 = 2.5hrs, excreted in 24hrs in urine

Answer 272

Competitive antagonism of acetylcholine at muscarinic receptors (GPCR) Onset: immediate

Answer 273

CVS: tachycardia, increased CO. Decreases AV nodal conduction time Resp: Bronchodilation, secretions reduced, RR increases CNS: CNS excitation or depression can occur GI: antiemetic, decreases gastric motility Metabolic: reduces sweating, BMR increases, suppresses ADH secretion

Answer 274

Class: sedative/anxiolytic Chemistry: Imidazobenzodiazepine Preparation: Vials 5mg/5ml Administration: IV + IM

Answer 275

- Induction of anaesthesia - 0.15-0.2mg/kg - Sedation in ICU- 0.03-0.2mg/kg/hr - Termination of seizures

Answer 276

A: Poor bioavailability 44% D: 96% protein bound (albumin) with Vd = 0.8-1.5L/kg

Answer 277

M: Extensively hepatic (CYP3A4). Hydroxylated and forms many active metabolites E: Renally excreted as hydroxylated metabolites T1/2 = 2hrs; CSHT 70-80min post 8hr infusion

Answer 278

Targets (between α & γ subunits) GABA-A receptors in CNS -- enhances inhibitory effect of GABA (increased permeability to Cl-) Different receptor subtypes are responsible for the nuances in effects of the different benzos Onset: IV 1-5min; Duration: ~1hr for sedation

Answer 279

- CNS: sedation, hypnosis, anterograde amnesia. CMRO2 & CBF decrease - CVS: decrease in SVR, decrease in BP with compensatory increase in HR - Resp: Can cause apnoea, impairs ventilatory response to hypercapnoea

Answer 280

**Class**: Anticonvulsant/Hydantoin. **Chemistry**: Little difference in activity between isomers Fosphenytoin is the water-soluble prodrug pKa 8 **Admin/prep: ** PO - 25/50/100/300mg capsules, syrup of 6mg/ml IV - clear, colourless solution 50mg/mL

Answer 281

1. Prophylaxis and treatment of GTC + partial epilepsies - Status: IV 15-20mg/kg with additional 5mg/kg post 12hrs if needed - 4-5mg/kg (usually 200-500mg) in 1 or 2 doses in epilepsy 2. Arrhythmias (especially from dig toxicity) - 3-5mg/kg 3. Trigeminal neuralgia Onset: 0.5-1hr IV; PO 2-24hrs

Answer 282

A: Absorption is slow via PO + IM routes. (Note IM may cause muscular damage) Bioavailability is 85-95% D: 90-93% protein bound in plasm - Vd = 0.5-0.7l/kg Crosses BBB + placenta

Answer 283

M: In liver. Large genetic variation in rate of metabolism. - Hydroxylated derivative --> conjugated to glucuronide - Exhibits zero order elimination just above therapeutic range E: 70-80% renally excreted by active tubular secretion as the major metabolite, 5% unchanged - t1/2 = 9-22hrs in the first-order kinetics range - plasma concentration increases disproportionately with increased dosage

Answer 284

- Blocks voltage and use dependent Na+ channels. Also delays outward K+ flux & Ca2+ flux - High affinity binding site for phenytoin in CNS, so likely endogenous binding site

Answer 285

CNS - stabilises the seizure threshold by preventing the speed of seizure activity, rather than abolish a primary discharging focus. Tonic phase can be abolished, but clonic seizure may be exaggerated/prolonged. Toxicity - nausea/vomiting, drowsiness, behavioural difference, tremor, ataxia, nystagmus, paradoxical seizures, peripheral neuropathy + cerebellar damage CVS - class IB antiarrhythmic properties + enhances AV nodal conduction. Hypotension may complicate rapid IV administration of the drug; complete heart block, VF & asystole Metabolic/other -Hyperglycaemia, hypocalcaemia + LFT derangement (suppresses ADH secretion) Haem - megaloblastic anaemia (folate deficiency with chronic use)

Answer 286

**Drug interactions** - Increase phenytoin toxicity: metronidazole + isoniazid - Reduces effect of benzodiazepines, pethidine + warfarin. May also decrease the MAC of volatiles - May enhance CNS toxicity of Las **Therapeutic drug monitoring** Limited correlation b/w therapeutic efficacy and plasma conc but may be useful to confirm toxicity or compliance

Answer 287

1. Single agent (or adjuvant) for seizures (myoclonic, partial, generalised epilepsy) - 250mg BD, then increase to 500mg in 2/52 (titrate to max 1.5g BD) - Loading dose in status 60mg/kg (to max 4.5g)

Answer 288

Not well understood - interact with SV2A (synaptic vesicle protein) to decrease release of neurotransmitters Peak effect ~ 5-30min IV

Answer 289

**CNS:** Sedation, anticonvulsant **Adverse effects:** - Ataxia, fatigue, dizziness, somnolence - Psychiatric disturbances - aggression, paranoid **Other:** - Does not interact with CytP450 - Dose reduce in renal failure

Answer 290

1. Primary generalised seizures - Initially 600mg daily in 2 doses. Maintenance 20-30mg/kg in 2 doses(max 2.5g daily) 2. Chronic pain of non-malignant origin - 200-400mg BD for migraine prevention 3. Bipolar disorder. Dosing similar to epilepsy

Answer 291

Inhibits GABA transaminase + succinate semialdehyde dehydrogenase (enzyme that metabolise GABA) Blocks voltage-gated ion (Na+, K+ & Ca2+) channels

Answer 292

**CNS:** anticonvulsant, minimal sedation **Metabolic:** infrequently, hyperammonaemia **Toxicity:** liver dysfunction, decreased GCS, thrombocytopaenia, coagulation dysfunction **Adverse effects:** weight gain, oedema, coagulation dysfunction, hepatic impairment, pancreatitis

Answer 293

Partial and generalised seizures - initial 25mg --> 100-200mg/day

Answer 294

Inhibits voltage gated Na+ channel & reduce release of glutamate

Answer 295

**CNS:** Anticonvulsant **Adverse:** Headache, nausea, diplopia & tremor, rarely aseptic meningitis, HLH, SJS

Answer 296

1. Epilepsy - PO 60-240mg daily nocte 2. Status epilepticus - 10-20mg/kg (max 1g) infused at <60mg/min. Repeat after 6hrs if needed

Answer 297

Enhance the binding of GABA to GABAA receptors. Extends the amount of time the chloride ion channel is open by interacting with GABAA receptor subunits.

Answer 298

CVS: can cause bradycardia,hypotension, syncope CNS: CNS depression, confusion, dizziness, drowsiness GI: constipation, nausea, vomiting Resp: can get apnoea (especially with rapid IV use), hypoventilation, respiratory depression **Other:** Concentration monitoring 10-40mg/L or 24-180micrmol/L Previously used as anaesthetic - but now rare use due to haemodynamics

Answer 299

Class: Sedative/hypnotic Chemistry: Alkylphenol derivative. 2,6-diisopropylphenol

Answer 300

Not well understood. Potentiates inhibitory neurotransmitters (GABA + glycine) - presumably GABA-A agonism

Answer 301

Opaque, white liquid. 1% liquid emulsion (1mg/mL). Excipients include: - soy bean oil, Egg lethicin - NaOH (to adjust pH) - EDTA (disodium edetate), which retards bacterial growth - glycerol Administered IV

Answer 302

1. Induction + maintenance of general anaesthesia 1.5-3mg/kg bolus, followed by 4-12mg/kg/hr - 50% dose increase for children, and dose reduce for elderly 2. Sedation in ventilated ICU patients - 1-3mg/kg/hr (max 4mg/kg/hr) 3. Intractable nausea + vomiting in chemotherapy patients 4. Termination of status epilepticus

Answer 303

A: 98% protein bound in plasma with VD = 4L/kg. Highly lipophilic. pKa ~11 D: Short distribution half life. Has initial effect (alpha phase) before distribution to tissues.

Answer 304

M: There are 2 metabolic pathways - glucuronide metabolite (inactive) by liver - hydroxylated metabolite (quinol) which is sulfated and glucuronidated by cyt P450 Extrahepatic metabolism (40%) Inter-individual variability effects which pathway it is metabolised. E: Metabolites are renally excreted. Quinol metabolite can cause green discolouration of urine + hair. Maximal CSHT ~20min

Answer 305

**CVS:** Bradycardia, decreases cardiac output by 20% (decreases systemic vascular resistance due to production and release of NO & blunts baroreceptor reflex) **CNS:** Causes hypnosis/sedation. Some people may have initial jerking movements (? Imbalance in subcortical inhibitory/excitatory centres), anticonvulsant, decreases CBF, ICP, CMRO2, antiemetic **Resp:** Causes decrease in tidal volume, apnoea, decreased response to hypercarbia + hypoxia, decreases laryngeal reflexes **Other:** Toxicity - propofol infusion syndrome - rhabdo, renal failure, multi-organ failure

Answer 306

**Class: **Sedative **Chemistry: **Phencyclidine derivative. Racemic mixture (S-enantiomer more potent). Soluble in water **Preparation/ Administration: ** 50, 100mg/ml IV, IM, IN, Oral (lozenges)

Answer 307

**Induction: **1-2mg/kg **Procedural sedation: **0.2-0.5mg/kg every 5-10minutes **Analgesia:** 0.25-0.5mg/kg bolus, then 0.05-0.25mg/kg/hr

Answer 308

A: BA (oral 25%), nasal (50%), IM (93%) D: 20% PB, Vd = 3L/kg

Answer 309

M: CYP450 - Norketamine (25% activity of parent) E: Elim half life 2hr; 90% in urine

Answer 310

NMDAR non-competitive antagonist at NMDAR Inhibition of glutamate Onset: 1min; Duration 10-15min

Answer 311

**CVS: **Stimulates SNS, increases HR, CO, BP - however is a direct myocardial depressant. S-ketamine - less myocardial depressant effect **CNS: **Dissociative anaesthesia, analgesia. May increase CMRO2 **Resp: **Bronchodilation, respiratory rate. Airway reflexes intact **AS: **increases salivation **GI: **causes nausea + vomiting

Answer 312

Class: Sedative Chemistry: Imidazole derivative IV formulation. Nil additives

Answer 313

Dose 0.2-1mic/kg/hr - Procedural sedation - Sedative in ICU

Answer 314

- 94% PB; VD = 1.3L/kg

Answer 315

M: Hepatic via CYP & glucuronidation, inactive metabolites E: Urine; t1/2 - large variation in CSHT (~4min after 10min infusion - 2-3H post 8 hr infusion) T1/2 elimination = 2hrs

Answer 316

Selective alpha2 adrenoceptor agonist Sedative actions primarily post synaptic alpha2 adrenoceptors Inhibition of NAd release in locus ceruleus

Answer 317

CNS - sedation, easily roused. Decreases cerebral VO2, blood flow, ICP CVS - Higher doses cause peripheral alpha2 effects - decreased sympathetic output

Answer 318

Class: sedative/anxiolytic Chemistry: Benzodiazepine Preparation/administration: Tablets - 2mg, 5mg, oral liquid 1mg/mL IV solution 5mg/mL (2mL)

Answer 319

- Short term treatment of anxiety - 2-5mg - Alcohol withdrawal - individualised - Muscle spasm in tetanus or other spastic conditions

Answer 320

A: Rapidly absorbed. BA 86-100% D: 99% protein bound; Vd = 1L/kg

Answer 321

M: Liver. Major active metabolite = desmethyldiazepam (t1/2~100hrs). Other active metabolites - oxazepam + temazepam -formed by oxidation & further undergo glucuronidation. Low HER E: T1/2 20-40hrs

Answer 322

Targets (between α & γ subunits) GABA-A receptors in CNS -- enhances inhibitory effect of GABA (increased permeability to Cl-) **Onset: **IV 4-5min; **duration: **hours

Answer 323

**CVS:** Transient decrease in BP + CO **Resp:** respiratory depression in large doses **CNS:** anxiolysis, sedation, hypnosis, anticonvulsant properties, anterograde amnesia

Answer 324

Class: Sedative Chemistry: Thiobarbituate. pKa 7.6, 61% unionised at pH 7.4 High lipid solubility Preparation/administration: (hygroscopic) yellow powder, stored under atmosphere of nitrogen. Reconstituted with water which is stable in solution for 24-48hrs

Answer 325

Induction of anaesthesia: 2-6mg/kg Management of status epilepticus Neuroprotection (raised ICP): 1.5-3.5mg/kg intermittent bolus dose

Answer 326

A: Is absorbed PO and PR D: PB 80%, Vd = 2L/kg

Answer 327

M: Liver - oxidation to pentobarbital & cleavage to urea + 3-C fragments. 15% dose metabolised/hr E: Elim half life - 3-22hrs. CSHT variable

Answer 328

- Prolong GABAA receptor opening duration, direct activation at higher doses - Primarily act at synapses by depressing post-synaptic sensitivity to NTs and impairs pre-synaptic NT release - Multisynaptic pathways depressed preferentially (eg. Reticular System) - Membrane stabilising effects - ↓s Na+ + K+ conductance

Answer 329

**CNS:** anaesthesia, CBF, ICP, IOP ↓. Anticonvulsant **CVS:** negative ionotrope, ↓ CO, SVR **Resp:** Potent respiratory depressant, ↓ in ventilatory response to hypercapnoea. Laryngeal spasm occasionally seen, may get bronchoconstriction Other: contraindicated in porphyria

Answer 330

Class/chemistry: Typical antipsychotic/1st generation antipsychotic/ Butyrophenone Preparation/ Administration: PO tablets, capsules, syrup,, solution for injection, depot

Answer 331

IV 1-5mg; Po dose 1-15mg - Schizophrenia/psychoses - Nausea + vomiting - Acute confusional states + delirium - Premedication - Palliative care

Answer 332

- Central dopaminergic (D2) blockage --> increased threshold for vomiting at CTZ - Post synaptic GABA antagonism

Answer 333

CVS: some alpha2 antagonism - may have hypotension CNS: Neurolepsis, raises seizure threshold Metabolic: may cause hyperprolactinaemia Other: May produce extrapyramidal symptoms, including NMS

Answer 334

Class/chemistry: 2nd generation/atypical antipsychotic/ thienodiazepine PO, IM

Answer 335

Varies 5-10mg - Agitation/aggression (organic + psychiatric causes) - Delusional disorders - Schizophrenia - Huntington associated chorea

Answer 336

- Potent antagonism of 5HT2A +2C, D1-4, H1, alpha1-adrenergic receptors

Answer 337

CVS: orthostatic hypotension GI: constipation Metabolic: increased cholesterol

Answer 338

2nd generation/atypical antipsychotic/ dibenzothiazepine PO

Answer 339

Varies 25-100mg - Agitation/aggression (organic + psychiatric causes) - Delusional disorders - Schizophrenia - GAD

Answer 340

- 5HT2 + D2 antagonism with H1 + alpha effects - Nil cholinergic/benzo effects

Answer 341

CVS: increased BP, tachycardia Metabolic: cholesterol CNS: may cause EPS

Answer 342

Chemistry - 3-ring central structure plus side chain. Most have pKa ~8.5 § Tertiary amines have 2 methyl groups at the end of the side chain. They are generally more potent in blocking 5-HT over NE (amitriptyline, doxepin, imipramine) § Secondary amines have one methyl group at the end of the side chain. They are more potent in blocking NE (nortryptiline, desipramine) Preparation: most available in oral forms only Dose/Indication - Major depression. Dose is started at 25-75mg for all, with titration ever 2-3 days to 75-150mg - Clomipramine used in OCDs + cataplexy with narcolepsy - Imipramine can also be used for nocturnal enuresis

Answer 343

- Inhibit both NE + serotonin uptake - Also block cholinergic, histaminergic, alpha1-adrenergic and (inhibit fast Na channels in His-Purkinje system & myocardium --> similar to Class 1A antiarrhythmics)

Answer 344

- CVS - alpha1 blockade can cause orthostatic hypotension, QT prolongation, and other conduction delays - CNS - can lower seizure threshold - Anticholinergic - blurred vision, constipation, dry mouth, urinary retention - Antihistaminic - Increase appetite, cause sedation

Answer 345

-Delayed Absorption (dec. gut motility - anticholinergic); acidaemia- dec glycoprotein binding (incr free drug) Signs/symptoms - CNS - mental state changes (agitation, delirium), decreased GCS, seizures (? GABAA antag) - CVS - Hypotension (peripheral vasodilation - alpha1 blockage). Tachycardia (vagolysis) + reflex tachy. Can have arrhythmias. --> ECG: widened QRS (>100ms), QT prolongation - Anticholinergic (hyperthermia, flushing, dilated pupils) Management - Decontamination, Supportive care - Antidote: NaHCO3 - cardiac toxicity (QRS >100msec) --> Plasma alkalinsation (improves protein binding) --> Intracellular alkalosis (increases the unbinding rate of TCAs from Na+ channel receptor + favours the non-ionised state of the TCA) --> Sodium load

Answer 346

Chemistry: Hydrazine + non-hydrazine compounds Preparation: Mostly oral formulations Dose/Indication: (moclobemide 150mg starting dose) ○ Major depression (third line) ○ Some anxiety disorders/panic disorder

Answer 347

Inhibit MAO-A & MAO-B (located in the mitochondria and metabolise monoamines). MAO-A metabolises dopamine, NE, serotonin; MAO-B metabolises dopamine. Both enzymes exist in the brain + are distributed differently throughout the body

Answer 348

- CNS: increased NTs (5-HT, NE)--> improves postsynaptic NT binding. Supratherapeutically: seizures, mania, serotonin syndrome, restlessness, agitation, nausea, insomnia - CVS: MAO-A + B metabolise dietary tyramine --> inhibition of metabolism --> release of tyramine into general circulation --> triggers release of NE. May precipitate hypertensive crisis - Hepatic: can cause hepatotoxicity, hypoglycaemia Other specifics - Irreversible MAOIs will bind for the life of the MAOs (~2/52)

Answer 349

SSRI: initially block reuptake of 5-HT via SERT & result in increased length of time that serotonin is available in synapse, increasing postsynaptic receptor occupancy - They are 10x more selective for SERT than NET - Initial increase in synaptic serotonin eventually leads to increased production of neuroprotective proteins such as BDNF + Bc1-2 SNRI: inhibit SERT & NET

Answer 350

Class: Opioid analgesic Chemistry: Naturally occurring phenanthrene derivative. Weak base (pKa 8). 23% ionised at pH 7.4 Preparation/administration: - PO formulations various strengths - 5/30mg suppositories - IV 10/15/30mg/mL of morphine sulfate - Preservative free formulation needed for epidural/spinal injection . Routes: PO, IV, IM, S/c

Answer 351

Dose generally titrated to effect. Initial dose 0.1-0.2mg/kg s/c or 0.05-0.1mg/kg IV - Pre-mediation - Pain relief in terminal care - Treatment of ACS/LV failure

Answer 352

A: BA 30% (extensive FPM) D: 20-40% PB; VD ~ 4L/kg

Answer 353

M: Liver - Morphine-3glucuronide(60%-arousal), morphine-6-glucuronide (5-10% analgesic-13x more potent than parent), normorphine E: Urine, small percentage of metabolites in faeces. Half-life ~4hrs, accumulation of M6G in renal failure. Maximal CSHT 20min (regardless of duration of infusion)

Answer 354

Agonist at MOP & KOP. At pre-synaptic MOP: GiPCR --> inhibition of adenylate cyclase --> decreased cAMP --> decreased Ca2+ influx --> decreased Ca2+ mediated NT release - Post synaptic MOP: increases K+ conductance and hyperpolarisation of excitable cell membranes **Onset:** 5-10min, 30min PO; Peak: 20min **Duration:** 3-5hrs IV

Answer 355

**CVS:** may cause some histamine release - decreases SVR, may cause orthostatic hypotension **Resp:** respiratory depression, may cause bronchoconstriction in high doses **CNS:** potent analgesic. Euphoria **GI:** decreases GI motility, increases CBD pressure (spasm of sphincter of Oddi). N/v/constipation **Renal:** increases tone of ureters, bladder - retention **Endo:** morphine increases ADH Caution in hepatic/renal failure. Dependence is an issue pruritis may occur from eipdural/spinal admin

Answer 356

2-5% of VO2 or 3ml/min (<2% of BMR)

Answer 357

Class/chemistry: Opioid analgesic. Tertiary amine (synthetic phenylpiperidine derivative) pKa 8.4, 9% unionised at pH7.4. Preparation: Available PO, IV, S/L, IN, TD, IM. 15 & 50microg/mL

Answer 358

Dose titrated to effect. - analgesia during GA - 50-100microg IV - premedication - Palliative care Epidural (50-100mic), Spinal (up to 25mic)

Answer 359

A: BA 33% D: 90% PB; VD ~4L/kg. Octanol:water partition coefficient 717. High pulmonary uptake (partly due to active transport)

Answer 360

M: Liver - N-dealkylation --> norfentanyl, then further hydroxylation to hydroxypropionyl derivatives. CYP 3A4 plays predominant role in metabolism. Metabolites not pharmacologically active E: 10% of drug excreted in urine. Elimination half-life ~2hrs. Maximum CSHT of 5hrs.

Answer 361

Highly selective MOP agonist (GiPCR) (pre-synaptic) --> inhibition of AC --> reduced cAMP, closure of voltage-gated Ca channels Onset: <1-2min; Peak: 3-5min Duration: 30-60min

Answer 362

**Effects/Side effects** **CVS:** bradycardia (vagal); CO, MAP, SVR, PVR unaffected. Obtunds CV response to laryngoscopy and intubation **Resp:** potent respiratory depressant - decreases RR & tidal volume. Decreased ventilatory response to hypoxia and hypercapnia. Chest wall rigidity **CNS:** 50-80x more potent than morphine. Little hypnotic/sedative effect. Potent antitussive **GI:** decreases GI motility & gastric acid secretion. Spasm of sphincter of Oddi **Other** Secondary peak in plasma fentanyl concentration due to elution from muscle

Answer 363

Class/chemistry: Opioid analgesia. Synthetic phenylpiperidine derivative. pKa 7.1; 68% unionised at pH7.4 Admin/prep: White lyophilised powder to be reconstituted. 1/2/5mg vials. IV only

Answer 364

Titrated to response. 0.0125-1mic/kg/min infusion or 1mic/kg bolus dose over 30s - Analgesia in GA - Analgesia during labour - Analgesia/sedation during 'awake' fibreoptic

Answer 365

A: Given IV only D: 70% PB. VD (ss)= 0.3L/kg

Answer 366

M: Rapidly hydrolysed by non-specific plasma and tissue esterases --> remifentanil acid (4600x less potent) E: CSHT - fixed 4-5min. Elimination half life 10min

Answer 367

Pure MOP agonist (pre-synaptic Gi) Peak effect 1-3min Duration ~4min

Answer 368

**CVS:** decreases MAP + HR **Resp:** Potent respiratory depressant. May get chest wall rigidity similar to fentanyl **CNS:** analgesic potency similar to fentanyl. Centrally mediated vagal activity, miosis (EW nucleus) **GI:** decreased GI motility. Relatively low n+v

Answer 369

Any weakly ionised acid or base in equilibrium with its fully ionised salt that can resist changes in pH when a stronger acid or base is added

Answer 370

Class/chemistry: Opioid analgesic. Semi-synthetic phenanthrene. pKa 8.5 Preparation: Available PO (immediate + slow release; in combination with naloxone) + IV (10mg/mL & 50mg/mL)

Answer 371

Moderate-severe pain, initial dose 5mg PO Q4hr

Answer 372

A: BA 80% D: 45% PB; VD 2.5L/kg. Penetrates placenta, and is found in breast milk

Answer 373

M: Hepatic. 3A4 --> noroxycodone; 2D6 --> oxymorphone (both active) E: Renal. Half-life 3hrs (controlled release 4.5hr)

Answer 374

Agonist at MOP, KOP, DOP. GiPCR Onset: 10-15min PO; Peak 30-60min Duration: 3-6hrs

Answer 375

CVS: minimal, some orthostatic hypotension Resp: respiratory depression, antitussive CNS: drowsiness, relief of anxiety, euphoria, miosis GI: decreases GI motility. N/v/c Renal: urinary retention Should be used with caution in hepatic failure as it may precipitate encephalopathy

Answer 376

Opioid analgesic. Synthetic phenylpiperidine derivative. pKa 6.5; 90% unionised at pH7.4

Answer 377

Adjunct for intubation - 25-100mic/kg Pain during anaesthesia

Answer 378

MOP agonist. Onset: <1min; Peak <2min Duration: <15min

Answer 379

CVS: decreases MAP + HR Resp: Potent respiratory depressant CNS: ~5-6x less potent than fentanyl GI: decreased GI motility

Answer 380

Opioid analgesic. Diphenylheptane derivative. pKa 9.2; 1% unionised at pH 7.4

Answer 381

Dosing regimen highly individualised - based on percentage of daily baseline oral morphine dose - Opioid use disorder - Opioid withdrawal Chronic pain

Answer 382

Metabolised in liver to multiple inactive metabolites; 40% excreted unchanged in urine (enhanced in acidic conditions) - renal clearance becomes more important in higher doses

Answer 383

Agonist at MOP & may have activity at NOP(unclear if partial agonist vs antagonist). May be an antagonist at NMDAR - this thought to be especially beneficial in treatment of certain neuropathic pain otherwise resistant to typical opioids Onset: 10-15min; Peak 30-60min Long duration of action

Answer 384

CVS: decreases MAP + HR Resp: Respiratory depressant GI: decreased GI motility CNS: benefits in tolerance and addiction

Answer 385

Class: Opioid analgesic. Chemistry: Synthetic derivate of alkaloid thebaine. pKa 8.5 Admin/prep: Clear colourless solution containing 300mic/mL, 200/400microg tablets and various strengths of transdermal patches, epidural

Answer 386

Mod-severe pain - 0.2-0.4mg s/l

Answer 387

Extensive FPM --> given s/l (44-94%) High PB & VD Liver - norbuprenorphine (active) Mostly excreted in faeces unchanged,metabolites in urine. Elimination half life - 5hrs

Answer 388

Partial agonist at MOP. Affinity for KOP (but low intrinsic activity here). Dissociates slowly from receptor - reason for prolonged analgesic effect Onset: <15min S/l, <30min t/d; Peak 60-90min, hrs t/d Duration: up to 72hrs s/l or 96hrs t/d

Answer 389

CVS: HR, SBP decrease Resp: respiratory depressant + antitussive, can increase PVR (histamine + tryptase release from lung parenchymal mast cells) CNS: 25x more potent than morphine. Decreases cerebral glucose metabolism by 30%, miosis Other: Naloxone does not completely reverse respiratory depression, but doxapram will. Partial agonism precipitates abstinence syndromes in opioid-dependent subjects

Answer 390

For every 10 mmHg increase in PaCO2, the HCO3- will rise by 1 mmol/L In other words, expected HCO3 = 24 + ((PaCO2-40) / 10)

Answer 391

For every 10 mmHg increase in PaCO2, the HCO3- will rise by 4 mmol/L In other words, expected HCO3 = 24 + (4 × (PaCO2-40) / 10)

Answer 392

For every 10 mmHg decrease in PaCO2, the HCO3- will fall by 2 mmol/L In other words, expected HCO3 = 24 - (2 ×(40-PaCO2) / 10)

Answer 393

For every 10 mmHg decrease in PaCO2, the HCO3- will fall by 5 mmol/L In other words, expected HCO3 = 24 - (5 ×(40-PaCO2) / 10)

Answer 394

For complete compensation, expected PaCO2 = (1.5 × HCO3-) + 8

Answer 395

For complete compensation, expected PaCO2 = (0.7 × HCO3-) + 20

A- Main Study Deck COPY Flashcards

(425 cards)