Misc

Question 1

What is the PK of Paracetamol?

Answer 1

well absorbed by GIT
Bioavailability: 70-90%
Peak Plasma levels 30-60 mins
highly protein bound

Question 2

How is Paracetamol Metabolised?

Answer 2

Hepatic > 95% undergoes glucoronidation + Sulfation
5% metabolism via CYP450 metabolism (phase 1 hydroxylation) to form NAPQI
NAPQI is toxic but usually detoxified by glutathione (glutathione depleted)

Question 3

what is the toxic dose of paracetamol for adults?

Answer 3

150-200mg/kg

Question 4

What is the mechanism of action for paracetamol?

Answer 4

Selective Cox 2 inhibitor

Question 5

Describe the mechanism of paracetamol toxicity?

Answer 5

Zero order toxicities
undergo conjugation with glucoronide and sulfate –> Saturated
increased paracetamol is metabolised by CYP2E1 to NAPQI
(normally NAPQI detoxified by glutathione but depleted = lots of toxic metabolite)

Question 6

How does NAC work in treatment of Paracetamol Overdose?

Answer 6

NAC is a sulphydryl group donor - restores hepatic glutathione or acts as an alternative substitute for conjugation with toxic metabolite

Question 7

What are the PK characteristics of ibuprofen?

Answer 7

Well absorbed, highly protein bound, highly metabolised by Liver (CYP450)

Question 8

What are the Pd characteristics of ibuprofen?

Answer 8

Inhibition of prostaglandin synthesis
NSAIDs are reversible cox inhibitor
1. anti-inflammatory
2. Analgesic
3. Antipyretic

Question 9

What are common side effects of ibuprofen?

Answer 9

GI: ulcers, GI bleeding, Abdo pain
Skin: Rashes
Renal: Renal Failure
CVS: Oedema, HTN, CCF

Question 10

What is the difference between aspirin and NSAIDs?

Answer 10

Aspirin irreversibly inhibits COX, Newer NSAIDs (ibuprofen, diclofenac) reversibly inhibits

Question 11

COX1 vs COX2

Answer 11

COX 1 - expressed on most cells

COX2 - inducible, expression depends on various ?

Question 12

What is the mechanism of action for salbutamol?

Answer 12

Selective Beta 2 Agonist - stimulates cAMP that 1) Bronchodilates 2) inhibit release of bronchoconstricting (something)

Question 13

What are the side effects of salbutamol?

Answer 13

Muscle tremor - beta 2 receptor skeletal muscle
Hypokalaemia
Tachycardia/SVT - atrial beta 2 receptor stimulation
V/Q Mismatch - pulmonary venodilation -> shunting blood to poorly ventilated areas (decrease arterial O2 tension)

Question 14

What are the Pk characteristics of salbutamol?

Answer 14

Metabolism: 50%, 1st pass
Half life - 3-6 hrs
Excretion: (something) in liver and metabolically excreted in kidney

Question 15

What is the mechanism of action for clopidogrel?

Answer 15

Irreversible blockade of ADP receptor on platelet to inhibit platelet aggregation

Question 16

What are the Pk characteristics of Clopidogrel?

Answer 16

Absorption: prodrug, metabolised to pharmacoligcally active metabolite AND inactive metabolites. Activated in liver by CYP 450
Excretion: half life 0.5-1 hr, effect life 7-10 days, urine 50%, Faeces 46%
Dose: Loading 300, daily 75

Question 17

Adverse effects of clopidogrel?

Answer 17

Bleeding, rash, diarrhoea, abdo pain, gastric ulcer

Question 18

What are the Pk characteristics of metformin?

Answer 18

Absorption: well absorbed, not protein bound
not metabolised
half life 1.5-3 hrs
Excretion: kidney

Question 19

What is the mechanism of action for metformin?

Answer 19

biguanide, unclear. not dependent on functioning pancreatic b cells - doesn’t influence insulin release form pancreas

Question 20

What are the side effects of metformin?

Answer 20

GI - diarrhoea

Lactic Acidosis

Question 21

What is the mechanism of action of sulfonylureas?

Answer 21

Sulphonylurea - increase release of insulin from pancreatic beta cells
binds to G receptor - inhibit K efflux throught ATP sensitive K Channels - deplorisation
deplorisation -> opens voltage Ca Channel -> Ca Influx -> insulin release
Long term use -> decrease serum glucagon

Question 22

What are the pharmacokinetics of Glicazide?

Answer 22

Absorbed orally, hepatically metabolised
Half life - 8 hrs
Excreted 80% renally

Question 23

What are the side effects of glicazide?

Answer 23

Hypoglycaemia
GI Side effects
Rash
Pruritus

Question 24

What are the pharmacokinetics of Oxycodone?

Answer 24

Good Oral Absorption (something) 1st pass metabolism
High Volume of distribution
Hepatic metabolism by CYP450
Duration of action - 3-4 hrs
Excreted Renally

Question 25

How does Oxycodone produces its analgesic Function?

Answer 25

opioid antagonist acts mainly on mu receptor in brain and spinal cord

Question 26

What analgesia can be used when prescribing oxycodone to decrease dependence?

Answer 26

1. use controlled release preparation 2. smaller doses at longer intervals 3. combine with non-opioid preparation 4. establish goals of tx 5. frequent evaluation of ongoing requirement

Question 27

What is the mechanism of action for insulin?

Answer 27

Promotes glucose uptake from blood into tissues - fat, liver, muscle promote glycogen synthesis

Question 28

What are the types of insulin formulation?

Answer 28

1. Short acting - lispro, actrapid, novorapid 2. Intermediate - aspart 3. Long acting - glargine, determir

Question 29

How are differing preparations used to optimise glycaemic control?

Answer 29

aim to replace basal insulin requirement and meal requirement

Question 30

What are the other uses of insulin in ED?

Answer 30

Hyperkalaemia, CCB, Betablockade

Question 31

How does dexamethasone's anti-inflammatory function compare to hydrocortisone?

Answer 31

30x more potent, longer acting,

Question 32

Explain the anti-inflammatory function and immunosuppression of glucocorticoid

Answer 32

1. Effect of (s.th), distribution, function of peripheral leucocyte 2. suppression of inflammatory mediator cytokines, chemokines 3. inhibition function of macrophage and APC 4. suppress mast cell degranulation

Question 33

What are the side effects of corticosteroids?

Answer 33

Short term: hyperglycaemia, peptic ulcer, | Long Term: immunosuppression, adrenal suppression, DM, Osteoporosis, Cushing Syndrome, poor wound healing

Question 34

What are the pharmocodynamics of Ethanol?

Answer 34

CNS: sedation, disinhibition, slurring of speech, impaired judgement, ataxia, coma, respiratory depression, CVS: decrease contractility Smooth muscle: vasodilation

Question 35

What are the pharmacokinetics of Ethanol?

Answer 35

Rapid absorption from GIT, peak level at 30mins Metabolised - Zero order kinetics via liver (alcohol dehydrogenase) Excreted in lungs and urine

Question 36

What is the mechanism of action for octreotide?

Answer 36

1. Somatostatin analog, decrease splanchnic and portal blood flow 2. Inhibit endocrine + paracrine secretion (Insulin, glucagon, TSH, GH)

Question 37

What are the side effects of octreotide?

Answer 37

Anaphylaxis, local irritation during injection, GIT - N+V, decreased intestinal motility, abdo cramp hypo/hyperglycaemia

Question 38

What are the pharmacokinetics of Octreotide?

Answer 38

Absorption via IV Metabolised 30-40% by liver Half life 80 mins excreted 20% unchanged by kidneys

Question 39

What are the clinical uses of octreotide?

Answer 39

Control of bleeding from varices sulphonylurea overdose decrease symptoms from hormone secretory tumour (acromegaly, carcinoid)

Question 40

What is the mechanism of action for streptokinase?

Answer 40

enzyme that directly converts plasminogen to plasmin | plasmin - major fibrinolytic enzyme

Question 41

What is the mechanism of Pantoprazole?

Answer 41

Irreversibly inactivated H/K/ATPase | blocking PPI >90% acid secretion for up to 24 hours

Question 42

Why an IV infusion is preferred over a single bolus dose?

Answer 42

only inactivated actively secreted acid pumps (<10%) | single dose only decrease acid secretion for few hours

Question 43

What strategies can increase bioavailability of pantoprazole?

Answer 43

1. Take as inactive pro drugs, begins as acid resistant enteric coated to prevent gastric elimination\ 2. Take on empty stomach (weak bases - pass into acidified parietal cells where it binds to H/K/ATPase 3. Take 1 hour prior to meal - peak dose occur when pump most active