Pharmacology Flashcards
1
Q
Bioavailability - what is definition and how to calculate it?
A
Bioavailability (F)
- Fraction of drug given by extravascular route (oral, IM, S/C) that is absorbed into systemic circulation
- Comparison of AUC, compared to IV AUC
- High bioavailabilty = 1, low bioavailability = 0
- Bioavailability (F) = AUC oral/AUC IV (* need to use same dose)
- Bioavailability = fraction absorbed x fraction escaping first pass clearance
2
Q
AUC - definition?
A
AUC (Area under curve)
- How much drug patient actually gets, think serum drug presence
- For most drugs - AUC best correlated with effect
- But some drugs eg aminoglycosides- peak
3
Q
DRESS - clinical features, risk medications, time?
A
DRESS - (Drug reaction with eosinophila and systemic Sx)
- Skin eruption, fever facial edema, lymphadenopathy, eosinophilia
- Hepatitis, nephritis, carditis
- Drugs - anticonvulsants - phenytoin, carbamazepine, lamotrogine, allopurinol, sulfonamides, NSAIDs
- HLA-B*58 (Han Chinese) - allopurine, carbamazepine
- Time -2-8 weeks after exposure
- Mx - corticosteroid
4
Q
What are the phases of Clinical trials and main goals?
A
- Phase 1 - (20-100 subjects) - is it safe? Pharmacokinetics?
- Phase 2 - (100-200 subjects) - Does it work in patients?
- Phase 3 - (1000-6000 subjects) - Does it work, double blind?
- Phase 4 - post marketing surveillance
5
Q
Clearance
A
Clearance = VD / Half life
6
Q
What is clockwise hysteresis and anticlockwise hysteresis and causes?
A
Delayed distribution/anticlockwise hysteresis
- Concentration goes up then down but effect at highest
- Delay in reaching effective compartment
- Distribution delay
- Reponse delay
- Active metabolite
- Sensitisation
Clockwise hysteresis/acute tolerance
- Eg amphetamines, cocaine
- Drug concentrations soon after single dose cause greater effect than same concentration as later time
- Mechanisms - tolerance induced metabolite breakdown, minimise response, translocation receptors
- Tolerance
7
Q
What are key CYP450 inducers (increase rate of metabolism?)
A
“COPRs”
- Carbamazepine
- OCP
- Phenytoin, phenobarbitone
- Rifampacin
- Steroid, St John’s wort
8
Q
What are key CYP450 inhibitors (decrease rate of metabolism?)
A
“MACIC”
- Macrolides - Erythromycin, clarithromycin
- Antifungals ‘azoles’ - itraconazole, ketaconazole, fluconazole
- Calcium channel blockers - verapamil, diltiazem
- Isoniazid - TB
- Cimetidine- H2 receptor antagonist, heart burn
9
Q
Key side effects gentamicin
A
- Nephrotoxic - 10-20%
- Ototoxic - cochlear/vestibular
- Can potential blockade of neuromuscular junction
10
Q
Caffeine MOA
A
- Competitively antagonises bonding of adenosine to purine receptor
11
Q
What is pharmacokinetics
A
- How drug moves in and through body - what body does to drug
- Balance between accumulation and elimination
- Factors - absorption, distribution, metabolism, elimination
- Differ in paediatric population
12
Q
What is plasma concentration time curve
A
- Time curve - plasma concentration and time
- Area under this curve - important
- Bioavailility
- Absorption phase
- Distribution
- Elimination phase
- MEC - minimum effective concentration
13
Q
What is pharmacodynamics
A
- Effect a drug has on human body
- Eg - effect on anti-epileptics and antihypertensive on patients
14
Q
What is pharmacogenetics
A
- Genetic factors have major impact on drug metabolism and development of drug receptors
- Cytochrome P450 - complicated by changes in metabolic pathway and changes in development of receptors
15
Q
Absorption - what is it and process
A
Process of absorption
- Taken into blood stream after administration by different routes:
- Oral/buccal/sublingual, IV, IM, percutaneous, rectal
- Move to sites of absorption –> cross mutliple GI membranes before passing into systemic circulation (first pass metabolism)
- Passive diffusion, sometimes due to active
- Factors affecting - pH, gastric emptying
- Different in neonates, older children and adults
- Insufficient in neonates
- Affected by maturation process of organ systems
16
Q
Active vs passive transport (during absorption)
A
Active:
- Drug will require assistance, energy to walk up hill
- Assisted by enzymes
- Lower concentation to higher concentration - getting up hill with everyone else
- Requires energy
- Nutrients, ions in gut
Passive
- Drug molecules transferred
- Higher concentation to lower concentration - paparrazzi, elevator, no energy
- No energy
- Full mature 4 months of age
17
Q
Physiological differences for neonates for absorption
A
Neonates
- Unpredictable response - delayed gastric emptying
- Affected by maturation of organ systems
- Higher gastric pH
- Decreased intestinal motility
- Decreased bile acid synthesis
18
Q
Distribution (volume of)
A
- Volume of distribution = volume that would accommodate all the drugs in the body if the concentration was the same in plasma
- Vd = Dose administered IV/ plasma concentration (Cp)
- Affects efficacy and duration
- Vd changes throughout childhood as stores of fat and water change
- Changes in Vd can alter half life - adjust dosing interval, eg digoxin
19
Q
Factors affecting distribution
A
- Proteins and protein binding affinity
- Albumins
- Unconjugated hyperbili
- Free fatty aids
- Fat vs water content of body
- Lipophilic vs hydrophobic drug
20
Q
Induction agent - most cardiovascular stable?
A
Ketamine
21
Q
Codeine - what CYP type and how works?
A
- CYP 2D6
- Ultra-metabolisers - more metabolism to active metabolite - increased analgesia effects but increased risk of serious adverse effects
- Slow metabolisers - decreased metabolism to active metabolite, less effect,
22
Q
Mycophenolate - MOA and SEs?
A
- Depletes guanine nucleotides in T and B cell lymphocytes, inhibits proliferation - stops cell mediated response and antibody formation
- Side effects:
- GI upset - diarrhoea and vomiting
- Leucopenia (low WCC) - (bone marrow suppression)
- Anaemia
- Infectious
23
Q
Tacrolimus - MOA and SE?
A
- Calcineurin inhibitor - inhibit calcineurin, impair transcription IL2 and others for T cells –> suppress T cells and T cell dependent B cell activation
- Side effects:
- Hyperglycemia/diabetes
- Hypomagnesium
- Neurotoxicity (seizures, tremors)
- CYP450
- Does not increase cholesterol, ?UTD dyslipidemia
Both - Tacro and Cyclosporin
- Nephrotoxicity
- Hypertension
- Diabetes (more with tacro)
- Neurotoxicity
- Hyperkalemia
- Hypomagnesium
- Dyslipidemia
24
Q
Cyclosporin - MOA and SE?
A
- Acts on T helper cells, increased TGF beta
- Side effects:
- Gingival hyperplasia
- Hirsuitism
- Trichosis - hair
Both - Tacro and Cyclosporin
- Nephrotoxicity
- Hypertension
- Diabetes (more with tacro)
- Neurotoxicity
- Hyperkalemia
- Hypomagnesium
- Dyslipidemia
25
Q
Biologics?
A
- Infliximab - TNF alpha - (IT) - SE - TB, Hep B, fungal
- Rituximab - CD20 B/T lymphocytes inhibitor
- Anakinra - IL1 antagonist - SE - pneumonia
- Tocilizumab - IL6 antagonist - SE - TB
- Omalizumab - IgE - inhibits IgE binding (OE)
- Eculizumab - anti C5 (complement)
- Atanercept - TNF blocker
26
Q
Steroids - equivalent dosing?
A
- Dexamethasone - 0.75mg
- Betamethasone - 0.75mg
- Methylprednisolone - 4mg
- Prednisolone - 5mg
- Hydrocortisone 20mg
- Cortisone 25mg
27
Q
What % of drug will be left after each half life, up to 5?
A
- Half life - time for concentration to halve/fall by 50%
- 1st half life - 50%
- 2nd half life - 25%
- 3rd half life - 12.25%
- 4th half life - 6%
- 5th half life - 3%
28
Q
Caffeine - MOA?
A
- Methylxanthines
- Competitive inhibitors of adenosine receptors
- Adenosine inhibits resp drive
- Blockage of adenosine –> increases ventilatory responsiveness to CO, central hypoxic depression, more force of diaphragm, improved pharyngeal tone
- Adult level - half life 4.5 hours - get there by 4 months
- Dependent on CYP1A2 and renal function
29
Q
Diazoxide MOA?
A
- Prevents insulin release - used on hyperinsulinemic hypoglycemia
- Opens ATP sensitive K channels of beta cells pancreas
30
Q
Hydroxychloroquine main SEs?
A
- Rheum, SLE, malaria
- Corneal toxicity - reversible
- Retinal toxicity - irreversible
- Nausea - not GI ulcers
- Dose related (idiosyncratic)
- Long QT
