A- Main Study Deck Flashcards
(160 cards)
1
Q
Re: Providone/Iodine as an antispectic/disinfectant - what are its main action, onset/duration, advantages & limitations and spectrum of activity?
A
Main action: Oxidative damage.
Onset/Duration: Onset: Iodine is bacteriocidal in 1 minute and kills spores in 15 minutes. However in povidine compounding it has a delayed onset/Duration: No sustained effect
Advantages:
1. Sporicidal
2. Cheap
3. Broad spectrum
Most effective for intact skin
Limitations:
1. Hypersensitivity reactions
2. Delayed onset without residual activity
3. Stains clothes and dressings
Spectrum of activity:
- Bacteria (G+ve and –ve and acid fast)
- Sporicidal
- Viruses
- Fungi
Ineffective against:
Prions
Hydrophilic viruses
Other:
Can be used as antiseptics or disinfectants (latter contains more iodine)
2
Q
4 types of lung receptors (peripheral afferents)
Respiratory
A
- Pulmonary stretch receptors - discharge in response to distension of lung & activity is sustained with lung inflation - ie. They show little adaptation
- Irritant receptors - Rapidly respond to airway irritants - eg. Cigarette smoke/noxious gases/cold air
- J receptors - respond to chemicals injected into the pulmonary circulation –> results in rapid, shallow breathing
- Bronchial C fibres - respond to chemical injected into the bronchial circulation –> results in rapid, shallow breathing
3
Q
Hering-Bruer reflex
Respiratory
A
Stimulation of pulmonary stretch receptors results in slowing of respiration due to increase in expiratory time
[Opposite is true for expiration]
4
Q
Normal compliance
Respiratory
A
100mL/cmH2O
* C(lung)= 200mL/cmH2O; C(chest wall) = 200mL/cmH2O
Specific compliance = 0.05/cmH2O
5
Q
Malignant hyperthermia incidence
Pharmacogenetics
A
1:5,000 - 1:50,000
6
Q
What is porphyria?
Pharmacogenetics
A
Mutation of haem synthesis enzymes which causes a build-up of neurotoxic intermediate metabolites (porphyrin precursors) in response to various drugs (anticonvulsants, antibiotics, thiopentone)
○ Autosomal dominant
7
Q
Malignant hyperthermia mechanism
Pharmacogenetics
A
Mutation of the ryanodine calcium channel receptor which causes a hypermetabolic crisis in response to volatile anaesthetics
8
Q
Malignant hyperthermia signs/symptoms
Pharmacogenetics
A
○ Initial - tachycardia, masseter spasm, hypercapnoea, arrhythmia
○ Intermediate - hyperthermia, sweating, combined metabolic and respiratory acidosis, hyperkalaemia, muscle rigidity
○ Late - rhabdomyolosis, coagulopathy, cardiac arrest
9
Q
Malignant hyperthermia Mx
Pharmacogenetics
A
Cease volatile, start TIVA, give dantrolene 2.5mg/kg increments to 10mg/kg, Rx of complications
10
Q
Atypical plasma cholinesterase/pseudocholinesterase
Congenital/acquired/both/neither?
Pharmacogenetics
A
Fails to metabolise suxamethonium and causes “sux apnoea”
○ Congenital - autosomal recessive
○ Acquired - due to loss of plasma cholinesterase. Can occur in pregnancy, organ failure (hepatic, renal, cardiac), malnutrition, hyperthyroidism, burns, malignancy, drugs (OCP, ketamine, lignocaine and ester Las, metoclopramide, lithium)
○ Note: acquired disease will have normal dibucaine no but just decreased quantity of enzyme
11
Q
How to test for atypical plasma cholinesterase/pseudocholinesterase?
Pharmacogenetics
A
○ Measured by dibucaine number. Dibucaine is an amide LA, which inhibits plasma cholinesterase. Greater inhibition indicates a less severe mutation - so normal:normal dibucaine no = 80 (80% inhibited). Dibucaine resistant:resistant has a no of 20 (20% inhibited)
12
Q
G6PD deficiency
Pharmacogenetics
A
Mutation of glucose 6-phosphate dehydrogenase which produces acute haemolysis in response to oxidative stress due to dapsone, methylene blue, fluoroquinolones, antimalarialas and rasburicase
13
Q
Normal cardiac output and cardiac index values
A
CO = 5L/min; CI = 2.5-4L/min
14
Q
LaPlace’s Law (cardiac)
A
sigma = Pr/2h
where sigma = myocardial wall stress
P = transmural pressure
r = radius
h = ventricular wall thickness
15
Q
Features of SA node and ventricular myocyte action potentials: resting, threshold, peak potentials
A
Ventricular myocyte:
* Resting potential: -90mV
* Threshold: -70mV
* Peak: +50mV
SA node:
* Max diastolic (nil real resting potential): -70mV
* Threshold: -40mV
* Peak: +20mV
16
Q
Structure of fast cardiac Na+ channel
A
2xβ subunits
1x α subunit
* Has 4 domains - I-IV
* The N- & C- terminus are both intracellular
* Each domain has 6 transmembrane segments linked by intracellular and extracellular peptides
–Extracellular peptides linking segments 5-6 form the ion pore (responsible for ion selectivity - the Ca channel has similar structure but is Ca selective)
–Domain IV undergoes a conformational change in response to voltage & opens the pores (activation gate - ‘m’)
– The intracellular peptide loop connecting domain III & IV forms the inactivation gate ‘h’
17
Q
What membrane potential does the absolute refractory period of a cardiac action potential go up to?
A
Absolute refractory period is up to ~-50mV. At this value, some fast Na+ channels have recovered from inactivation enough to permit response to stimulation
18
Q
Time constant equation
A
(tau) = compliance x resistance
19
Q
What are the functions of the FRC?
A
- Oxygen reservoir - prevents rapid changes in alveolar oxygen tension and arterial oxygen content by maintaining gas exchange throughout expiration
- Maintenance of small airway patency (N2 splinting)
- Optimising respiratory workload - compliance maximal at FRC, WOB required from FRC is minimal
○ Keeps tidal volume over steep part of lung compliance curve - Minimises pulmonary vascular resistance & hence RV afterload/work/oxygen demand
20
Q
What are the factors affecting FRC
A
21
Q
Normal WOB
A
0.35J/L
22
Q
Oxygen requirement of breathing
A
The oxygen requirement of breathing at rest is 2-5% of VO2 or 3ml/min
(tidal breathing uses <2% of BMR)
23
Q
Normal osmolarity
A
~285mOsm/kg
24
Q
Baroreceptor reflex
A
- Sensor/stimulus: carotid sinus & aortic arch - circumferential and longitudinal stretch receptors detect change in BP
○ Decreased BP decreases firing rate of baroreceptor- Afferent: glossopharyngeal + vagus
- Processor: NTS & Caudal ventral medulla/RVLM
○ Decreased BR firing rate –> decreases GABA secretion from caudal VM. This decreases inhibition of sympathetic output from RVLM (ie SNS activity increased) - Efferent/effectors: vagus nerve + sympathetic chain
○ Peripheral vessels - a1 mediated vasoconstriction
○ Decreased vagal input into SA - Effect: increased HR and BP in response to fall in BP
- Note: Tends to override Bainbridge reflex when it comes to atrial stretch in hypovolaemia (except in spinal anaesthesia, where reverse Bainbridge reflex may predominate)
25
Bainbridge reflex
- 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
26
Chemoreceptor reflex
- 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
27
Cushing reflex
- 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
28
Bezold-Jarisch Reflex
- 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
29
Occulocardic reflex
- 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
30
Diving reflex
- 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
31
Barcroft-Edholm Reflex
- 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
32
SvO2 from tissue beds: jugular, muscles, renal, IVC, SVC, Hepatic
Jugular - 55%
Muscles - 72%
Renal - 81%
IVC - 71%
SVC - 79%
Hepatic - 66%
33
Normal mixed venous PO2 & SvO2
40mmHg & 70-75%
34
Energy consumption of 1 MET
1 MET = 3.5 ml O2/kg/minute
35
Aortocaval compression syndrome
* 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
36
Changes in afterload during pregnancy
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
37
Changes in preload during pregnancy
○ 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")
38
Changes in CO, HR and SV during pregnancy
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)
39
Changes to distribution of CO in pregnancy (regional flow changes)
- 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
40
Physical and mechanical changes to heart during pregnancy
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
41
CVS changes during PARTUITION + Post delivery:
- 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
42
How long after birth do pregnancy-induced respiratory changes settle?
After birth:
* FRC and RV return to normal within 48h
* Vt returns to normal within 5 days
43
Effect of pregnancy on lung mechanics
- 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%)
44
Storage functions of the liver
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
45
Synthetic functins of the liver
Synthetic
- Plasma proteins- albumin, α+ β globulins, fibrinogen
- Nutrients - glucose, ketones, lipids, cholesterol, amino acids
- Regulatory molecules (thrombopoetin, angiotensinogen)
- Bile acids → stored in gallbladder
46
Metabolic functions of the liver
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
47
Detoxification/excretory functions of the liver
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
48
Length, diameter, origin and termination of trachea
Length: 10-16cm
Diameter: (internal) 2.5cm
Origin: C6
Termination: carina, T4 (sternal angle)
49
Classify generations of bronchial tree
Generation 1-4 - Bronchi (cartilaginous)
Generation 5-14 - bronchioles (non-cartilaginous)
Gen 15-18 - Respiratory bronchioles (some gas exchange)
Gen 23 - alveolar sacs
50
Describe the muscles in the larynx involved with phonation, inspiration, expiration and effort closure
**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
51
What is Dalton's Law
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
52
What is Boyle's Law?
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.
53
Henry's Law
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
54
Graham's Law
Graham's Law:
* The rate of diffusion is inversely proportional to the √MW
55
Fick's Law of diffusion
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)
56
Third gas law (Gay-Lussac's Law)
The pressure of a fixed mass of gas at constant volume is directly proportional to its absolute temperature (P/T = k).
57
Avogadro's Law
Equal volumes of gases at the same temperature and pressure contain the same number of molecules (6.023 × 1023, Avogadro’s number).
58
Universal (Ideal) Gas Law
The state of a fixed mass of gas is determined by its pressure, volume and temperature (PV = nRT)
59
The Bohr equation for measuring dead space
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))
60
Alveolar gas equation
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
61
Oxygen content equation
(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:
62
The shunt equation
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
63
Starling equation
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**
64
Starling forces in lung
○ 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
65
Normal airway resistance
2mLH2O/L/s
66
MoA of aminoglycosides
* 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
67
Define antispectic and disinfectant
- **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
68
Re: alcohol as an antispectic/disinfectant - what are its main action, onset/duration, advantages & limitations and spectrum of activity?
**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
69
Re: Chlorhexidine as an antispectic - what are its main action, onset/duration, advantages & limitations and spectrum of activity?
**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
70
What is the speed of sound in tissue
1540m/s
71
Define potency
| (of a drug)
- 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
72
Define efficacy
| (of a drug)
- 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)
73
What is a competitive antagonist?
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
74
What is a non-competitive antagonist?
A compound that binds at a different site to the natural receptor and produces a conformational change that prevents receptor activation
75
Define FRC
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).
76
What is the blood supply, venous & lymphatic drainage + nerve supply of the larynx?
_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
77
What is the Hagen-Poiseuille equation?
* This is specific to laminar flow (fastest velocity at centre of vessel, little to no movement at periphery)
78
What is Reynold's number
If Re\<2000, flow more likely to be laminar, 2000-4000 = transitional & \>4000 turbulent
79
What is the alveolar gas equation?
80
Define PaO2, SaO2 and CaO2
* 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)
81
Recount the following gas laws:
- Boyle's
- Charles'
- Third gas law (Gay-Lussac's law)
- Avogadro's Law
- Universal (Ideal) gas law
- Henrys Law
* (own question)*
82
Write the definitions for flow, pressure, compliance and work of breathing
*(own question)*
83
Recount the following laws:
- Alveolar gas equation
- Oxygen content of blood
- Shunt equation
* (Own question)*
84
Define closing capacity
The maximal volume of gas in the lungs at which small airways begin to collapse in dependent parts of the lung
85
Define latent heat of vapourisation
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.
86
Define vapour pressure & Saturation vapour pressure
* 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
87
Define boiling point temperature
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.
88
Define critical temperature
* 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
89
Define critical pressure
Minimum pressure which would suffice to liquefy a substance at its critical temperature
90
Define critical point
The point of minimum pressure and maximum temperature at which both a gaseous and a liquid phase of a given compound can coexist
91
Define specific critical volume
Volume of space occupied by 1kg of a gas at its critical point
92
Define absolute humidity and relative humidity
* 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
93
Define filtered load
The amount of a substance filtered per unit time
94
Define buffer
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.
95
List the ISF buffers
Bicarbonate
Phosphate (note: conc too low)
Protein (note: conc too low)
96
List the blood buffers
HCO3
Hb
Plasma protein
Phosphate (note: conc too low)
97
List the urinary and bone buffers
Urinary:
- Phosphate
- Ammonia
Bone:
- Ca carbonate
98
List the CSF buffers
HCO3 (important as low proteins, & negligible PO4)
99
How is haemoglobin metabolised?
RBCs phagocytosed by macrophages in liver or spleen, or haemolysed in circulation. Heme is degraded to bilirubin, Fe 2+ is recycled
100
Synthesis of haemoglobin?
Heme synthesised in mitochondria & cytosol of immature RBCs, globin synthesised by ribosomes in cytosol
101
**Prothrombin time:** normal range, therapeutic values, coagulation pathway assessed, method & abnormal in?
**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
102
**APTT**: normal range, therapeutic values, coagulation pathway assessed, method & abnormal in?
**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
103
**Activated Clotting Time (ACT):** normal range, therapeutic values, coagulation pathway assessed, method & abnormal in?
**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
104
What is the activator for Fibtem?
Cytochalasin D (platelet inhibitor) - isolates fibrinogen testing
105
What is the activator for Extem?
tissue factor
106
What is the activator for Intem?
Phospholipid & ellagic acid
107
What is the activator for Heptem?
Ellagic acid & heparinase
108
Contents of prothrombinex
- 500IU of Factor IX
- 500IU of Factor II (prothrombin)
500IU of Factor X
109
Contents of FFP
- Factor VII (will reduce PT)
- Factor IX, XI (will reduce aPTT)
- Factor X, II
200IU of Factor VIII per adult dose
110
How is prothrombinex prepared?
Adsorption of coagulation factors from plasma onto an ion exchange medium --> selective elution
111
How is FFP prepared?
Separation (by centrifuge) from whole blood, either by donation or by apheresis. Must be prepared within 6-18hrs
112
Dose of prothrombinex?
25-50IU/kg
Warfarin: INR < 2 - 20U/kg, 2-4: 30U/kg, >4: 50U/kg
113
How much Glycogen + fat is stored in the liver? (in g)
Glycogen: 100g
Fat: 75g
114
Amount of fat soluble vitamins stored in liver?
○ 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
115
What are the primary and secondary bile acids?
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
116
Define tolerance
Tolerance is the requirement of higher doses of a drug to produce a given response
117
Classify the mechanisms of tolerance
- 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
118
Describe pharmacokinetic tolerance
Persistent exposure makes drug clearance mechanisms more active; classically by induction of metabolic enzymes (eg. Effect of ethanol on CYP450 enzymes)
119
Describe pharmacodynamic tolerance
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)
120
Describe physiological tolerance
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
121
Describe behavioural tolerance
The development of learned behavioural adjustments that compensate for the drug's effects
122
Describe sensitisation
"reverse tolerance" - subsequent dosing increases the drug effect (eg. Amphetamines)
123
Describe Cross-tolerance
Development of tolerance to multiple drugs belonging to the same class, after exposure to only one of them (eg. Nitrates)
124
Define tachyphylaxis
Decreased response to a drug with repeated short-term use. It occurs over minutes-hours & cannot easily be overcome with increase dose
125
Classify antihypertensives
(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
126
Renin: description, production + role
○ 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
127
Renin: stimuli for release + regulation
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
128
Classify antihypertensives
(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
129
List receptor mediated mechanisms of drug action
- **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
130
List the non-receptor mediated mechanisms of drug action
- **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
131
What does β1 activation result in?
| (systems)
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
132
What does β2 activation result in?
| (systems)
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
133
What does β3 activation result in?
| (systems)
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
134
Adrenergic agonists: General pharmacokinetics
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
135
Non-adrenergic sympathomimetics: kinetics
D - V (0.14) M (liver - not much)
E - Urine
136
Which β-blockers are:
- non selective
- β-1 selective
- combined α+β
- non selective
--> Prop + Sot
- β-1 selective
--> Bisop, Esmo, Aten, Metop, Nebiv
- combined α+β
--> Carvi + labet
137
Which β-blockers have membrane stabilising activity?
PMN
- prop
- metop
- nebiv
138
Which β-blockers have instrinsic sympathomimetic activity?
- labet
- acebut
- pindo
139
Describe the anatomical course of the pulmonary circulation
140
Describe the anatomy of pulmonary vessels
- 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)
141
Normal PA pressures
| (systolic + diastolic)
PA systolic pressure = 18-25mmHg
PA diastolic pressure = 8-15mmHg
142
Normal pulmonary capillary and venous pressures
Pulmonary capillary pressure = 4-12mmHg
Pulmonary venous pressure = 6-12mmHg
143
Define venous admixture
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
144
Venous admixture - normal value
Normal shunt fraction/venous admixture is 3%
145
Berggren equation
| ie. shunt equation
- 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
146
Class IA antiarrhythmic mechanism + example
**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)
147
Class IB antiarrhythmics: mechanism + example
**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)
148
Class IC antiarrhythmics: mechanism + example
**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)
149
Class II antiarrhythmics: mechanism + example
**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
150
Class III antiarrhythmics: mechanism + example
**Mechanism**
Effect on (ventricular myocyte) AP:
- ↑APD, ERP,
Effect on ECG:
- ↑QT interval
**Example**
Amiodarone
Sotalol
| K channel blockers
151
Class IV antiarrhythmics: mechanism + example
**Mechansim**
Effect on (pacemaker) AP:
- ↓conduction velocity, ↑ERP
Effect on ECG:
- ↑PR interval
**Example**
Verapamil
Diltiazem
| Ca channel blockers
152
What is the O2 requirement of breathing?
2-5% of VO2 or 3ml/min (<2% of BMR)
153
What is a buffer?
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
154
Boston Rules: Acute respiratory acidosis
For every 10 mmHg increase in PaCO2, the HCO3- will rise by 1 mmol/L
In other words, expected HCO3 = 24 + ((PaCO2-40) / 10)
155
Boston Rules: Chronic respiratory acidosis
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)
156
Boston Rules: Acute respiratory alkalosis
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)
157
Boston Rules: Chronic respiratory alkalosis
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)
158
Boston rules: Metabolic acidosis
For complete compensation, expected PaCO2 = (1.5 × HCO3-) + 8
159
Boston rules: Metabolic alkalosis
For complete compensation, expected PaCO2 = (0.7 × HCO3-) + 20
160
Classify adverse drug reactions
A - Augmented
B - Bizarre
C - Chronic/Cumulative
D - Delayed
E - Withdrawal (End of use)
F - Failure
