Pharmacology

Question 1

Tranylcypromine

Answer 1

A non-selective MAOI
Prevents breakdown of monoamines
Can precipitate hypertensive crisis due to increased levels of noradrenaline if high dietary intake of tyramine

Question 2

Caudal blocks

Answer 2

Use 0.25% bupivicaine 
Sacral procedures - 0.5ml/kg
Inguinal procedures - 0.75ml/kg 
Lower thoracic procedures - 1ml/kg
Mid-thoracic procedures - 1.5ml/kg
Because of varying degrees of spread of LA required 
Toxic dose 2mg/kg

Question 3

Clozapine

Answer 3

Partial agonist at D2 receptors

Question 4

ED50

Answer 4

Dose of the drug that produces a response that is 50% of maximal response

Question 5

EC50

Answer 5

Drug concentration at which response is 50% of maximal

Question 6

Cyclic AMP

Answer 6

Is a hydrophilic molecule

Question 7

Pindolol

Answer 7

Partial agonist at beta-1 receptors
Non-selective beta blocker
Partial agonist/antagonist at 5HT1A receptors

Question 8

Mixed agonists-antagonists

Answer 8

Mirtazapine 
Pindolol 
Nalbuphine 
Pentazocine 
Buprenorphine 
Xameterol (at beta adrenoceptors)

Question 9

Chemical bonds

Answer 9

Strong —> weak:
Ionic - electrostatic attraction between oppositely charged ions involving loss/gain of electrons
Covalent - sharing of electrons in the outer shells (can increase in strength with double and triple covalent bonding)
Hydrogen bonds - force of attraction between a positively charged H atom and an electronegative atom
Van Der Waals - constant movement of electrons creates temporary dipoles in atoms which cause forces of attraction

Question 10

Adenylate cyclase

Answer 10

Membrane-bound form and soluble cytoplasmic form
Activated by G-protein which is coupled to adrenoceptors
Converts ATP to cAMP

Question 11

Triamterene

Answer 11

A potassium-sparing diuretic
Acts in the DCT to inhibit Na reabsorption in exchange for K (blocks ENaC)
Works in the same way as amiloride

Question 12

CSHT

Answer 12

Context sensitive half time
Time taken for plasma concentration of a drug to fall to 50% after an infusion has finished
A function of the duration of infusion, not concentration

Question 13

Metabolism of volatile agents

Answer 13

Desflurane is a fluorinated ether and is minimally metabolised (0.02%) to produce trifluoroacetate and fluoride ions
Halothane is the only volatile agent to contain Br ions
C-F bond is stronger than C-Br bond
CYP450 enzymes which metabolise Halothane are induced by barbiturate intake
Halothane is 20% metabolised
Enflurane is 2-2.5% metabolised

Question 14

Levorphanol

Answer 14

Pure opioid agonist

Question 15

Phenazocine

Answer 15

Pure opioid agonist

Question 16

Azapropazone and phenylbutazone

Answer 16

pyrazolone derivative NSAIDs

Question 17

Aspirin

Answer 17

Rapidly metabolised by esterases in the intestinal mucosa and liver to acetic acid + salicylate which is conjugated to water soluble molecules and excreted via the kidneys
Aspirin can compete with urate for renal tubular secretion
80-90% plasma protein bound
Largely unionised in the stomach (pH 2) because it is a weak acid with pKa 3.5

Question 18

Hypotensive effects of morphine

Answer 18

Dose-dependent histamine release
Vagal stimulation
Inhibition of central sympathetic activity
Direct vasodilation

Question 19

Pethidine

Answer 19

More lipid soluble than morphine
Chemically related to atropine and has anti-cholinergic effects
Terminal half life is 3-5hrs
Metabolised to active metabolite norpethidine which is excreted via the kidneys
Has some local anaesthetic activity

Question 20

Disopyramide

Answer 20

Class 1A anti-arrhythmic
Negatively inotropic —> reduces BP (but no direct action on bld vessels)
Prolongs duration of AP
May cause VT, VF or TdP

Question 21

Diazoxide

Answer 21

Vasodilator and hyperglycaemic drug
Opens ATP-sensitive K channels in the Beta islet cells and inhibits insulin release
Causes hyperpolarisation via K efflux and decreased Ca influx
Chemically similar to thiazides

Question 22

Sumatriptan

Answer 22

Used in the treatment of migraine
5HT1 receptor agonist
Can cause Brady and tachy arrhythmias
Lipid soluble and can cross BBB

Question 23

Drugs causing uterine relaxation

Answer 23

Indomethacin (NSAIDs)
Nifedipine (CCBs)
Magnesium 
Terbutaline and ritodrine (adrenergic agonists)
Oxytocin antagonists (atosiban)
NO donors e.g. nitroglycerin 
Volatiles

Question 24

Flumazenil

Answer 24

BDZ antagonist with similar structure to BDZs
Low oral bioavailability due to extensive FPM so only give parenterally
Rapid hepatic metabolism results in short DOA
Can be given by continuous infusion
Lack of response to 5mg IV suggests BDZ OD not cause

Question 25

Diamorphine

Answer 25

3,6-diacetylmorphine Di-ester of 1 molecule of morphine with 2 molecules of acetic acid Metabolised to 3 and 6-monoacetylmorphine which is active (diamorphine has no affinity for opioid receptors) and morphine Requires a free -OH gp at position 3 More rapid onset and shorter duration of action than morphine when give epidurally due to greater lipid solubility

Question 26

Propranolol

Answer 26

Half life 4hrs Metabolised to 4-hydroxypropranolol which has some activity Oral bioavailability 30% Lipid soluble therefore can cross the BBB and cause central effects e.g. sleep disturbance

Question 27

Tetracyclines

Answer 27

Have a wide spectrum of anti-bacterial activity | Prevent bacterial proteinsynthesis by binding to ribosomes and preventing translation of mRNA

Question 28

Side effects of oxytocin

Answer 28

Transient hypotension if given rapidly Sinus tachycardia Nausea and vomiting Water intoxication (due to ADH-like activity)

Question 29

Noradrenaline

Answer 29

Presented only as the L-isomer because the D-isomer is much less potent

Question 30

Opioids

Answer 30

can stimulated 5HT3 receptors and cause N&V

Question 31

Buprenorphine

Answer 31

Partial agonist with high affinity for mu opioid receptors Elimination half life of 3-4hrs but much longer DOA Extensive FPM 30x more potent than morphine

Question 32

Induction doses of IV agents

Answer 32

Etomidate: 0.3mg/kg Thiopental: 3-5mg/kg Ketamine: 1-2mg/kg Propofol: 2mg/kg

Question 33

Thiopental

Answer 33

Causes respiratory depression via direct action on medullary respiratory centre 80% plasma protein bound at pH 7.4 Highly lipid soluble Distributes rapidly into well perfused tissues (water compartments) Slowly metabolised in the liver (low HER)

Question 34

Ester LAs

Answer 34

Include amethocaine and cocaine | Highly protein bound

Question 35

Atropine

Answer 35

Less potent than glycopyrrolate Presented as a racemic mixture of D- and L-hyoscyamine Causes mydriasis and raised IOP Decreases GI motility and secretions Causes bronchodilation and increased physiological dead space Non-selective mAChR antagonist

Question 36

Protein binding

Answer 36

Acidic and neutral drugs bind to albumin: - phenytoin, diazepam, NSAIDs, propofol Basic drugs bind to alpha1 acid glycoprotein: - LAs, opioids

Question 37

Bioavailability

Answer 37

``` Aspirin 65% Oramorph 25% Paracetamol 90% Ibuprofen >80% Diclofenac 50% ```

Question 38

Cisatracurium

Answer 38

3-4x more potent than atracurium Predominantly metabolised by Hoffman degradation Metabolism unaffected by renal function

Question 39

Ester LAs

Answer 39

Highly protein bound

Question 40

Fade in NMB

Answer 40

Caused by blockade of pre-junctional nAchRs which normally provide positive feedback during high stimulation

Question 41

Heparin

Answer 41

Does not cross the placenta as low lipid solubility so does not affect the foetus Causes hyperkalemia by inhibiting aldosterone

Question 42

Ketamine

Answer 42

Indirect positive inotropic effect via catecholamine release Direct negative inotropic effect

Question 43

Etomidate

Answer 43

Broken down by Ester hydrolysis | 10-20x more potent than thiopental

Question 44

Alfentanil

Answer 44

90% unionised at pH7.4 90% protein bound (more than other opioids) Lower clearance but smaller Vd than morphine and fentanyl 10x less potent than fentanyl

Question 45

Sevoflurane

Answer 45

BP 58’C | Causes dose dependent resp depression

Question 46

Thiopental

Answer 46

``` Sulphur analogue of pentobarbital Forms a sodium salt Weak acid with pKa 7.6 Forms an alkaline solution in water Acid may precipitate out of solution so sodium carbonate is added and it is stored in vials with N2 80% ionised at physiological pH Rapid onset due to high lipid solubility Rapid emergence due to redistribution Contraindicated in porphyria ```

Question 47

Xenon

Answer 47

3x denser and twice as viscous as nitrous oxide

Question 48

Systemic absorption of LAs

Answer 48

``` In order of increasing absorption: Subcutaneous Femoral Brachial plexus Epidural Caudal Intercostal Poor absorption when injected subcut or around plexi/large veins ```

Question 49

LAs

Answer 49

Most have vasodilator effects at low conc and vasoconstrictor effects at high conc Cocaine is a pure vasoconstrictor

Question 50

Drugs undergoing zero order kinetics

Answer 50

``` Phenytoin Ethanol Salicylates Thiopental Theophylline “PESTT” ```

Question 51

Inodilators

Answer 51

Improve cardiac contractility and vasodilation Reduce preload and afterload Include dopexamine (acts via dopamine and B2 receptors) PDE3 inhibitors e.g. milrinone and enoximone Theophylline is NOT an inodilator Levosimendan is NOT an inodilator (calcium sensitiser)