Lecture 7 and 8 Flashcards
1
Q
What is Pharmacokinetics?
A
Relationship between the phsycial, chemical and biological sciences applied to drugs, dosage forms and drug actions
2
Q
What is (L)ADME?
A
- Liberation
- Absorption
- DIstribution
- Metabolism
- Excretion
3
Q
What is Bioavailability (F)?
A
The fraction of drug reaching the systemic circulation after adminstration
4
Q
Example of 100% bioavailability?
A
IV injection
5
Q
What factors influence bioavailability?
A
Physical, chemicial and biological processes
6
Q
How to find Bioavailbility (F)?
A
F = (AUC)oral/(AUC)IV x doseIV/doseoral
7
Q
What is the function of a plasma membrane?
A
- Barrier to control transport of molecules
- Strucutre support for the cell
- Receptor cells ites for hormones and extracellular enzymes
- Cell markers for cell recognition
8
Q
What has to occur for a drug to have its desired effect?
A
Needs to reach site of action/receptor in an appropriate form
9
Q
What are the entral routes?
A
- Sublingual
- Buccal
- Oral
- Rectal
10
Q
What are the parenteral routes?
A
- Intravenous (IV)
- Intramuscular (IM)
- Subcutanous (SC)
- Inhalation
- Conjunctival
11
Q
What is Sublingual adminstration?
A
Drug placed under the tongue
12
Q
What is Buccal administration?
A
Drug placed between gums and lips
13
Q
What formulations can be used in the sublingual and buccal administration?
A
Dissolvable tablet, mouthwash, chewing gum, spray
14
Q
What is the effect of sublingual administration?
A
Fast onset of action but short duration
15
Q
What is the effect of buccal administration?
A
Fast onset of action for a moderate duration
16
Q
What is atherosclerosis?
A
Narrowing of the blood vessels to the heart
17
Q
What does Nitrolycerin do?
A
Releases nitrate ions that covert to nitric oxide to diffuse into smooth muscle cells
18
Q
What effect does Nitroglycerin have?
A
- Causes smooth muscle relaxation
- Decreases blood pressure
- DIlates blood vessel
- Decrease vascular resistance
19
Q
Benefit of Nitroglycerin
A
- Fast onset of action
- Drugs are absorbed into sytemic circulation
- Drugs can be given to unconscious patients
- Muscosa is resistant to damage due to rapid turnover
20
Q
Benefit of Nitroglycerin
A
- Fast onset of action
- Drugs are absorbed into sytemic circulation
- Drugs can be given to unconscious patients
- Muscosa is resistant to damage
21
Q
Downside of Nitroglycerin
A
- Rapid elimination of drug
- Interpatient variability is high
22
Q
What formulations are used in rectal route?
A
Suppository, solutions and emulsions
23
Q
What is effected when the rectal route is used?
A
Local effecte
24
Q
Benefits of the rectal route of administration?
A
- Used when oral route is unsuitable (E.g vomiting, unconcious or uncooperative patient)
- Useful when drug causes GIT irritation
25
Downsides of rectal route of administration
- Absorption can be irregular and unpredictable
- Less convenient
- Patient unlikely to accept administration
26
What is chronic asthma?
Intermittent attacks of dyspnoea (difficulty breathing out), wheezing and cough
27
What is bronhical hyper ractivity
Inflammation of the airways
28
What is Allergic asthma?
Asthmatics have activated T-Cells with a T-helper (Th)2 profile of cytokine production in their bronchiole mucosa
29
What is the immediate phase in allergic asthma?
Activation of Th2 lymphocytes causing a cascade of events leading to spasm of the bronchial smooth muscle
30
What is the delayed phase in allergic asthma?
Often nocturnal, inflammation of the bronchioles
31
What are within asthma inhalers?
β2-adrenoreceptor agonists
32
Examples of short acting asthma inahalers
Salbutamol
33
Examples of long acting agents in asthma inhalers?
Glucocorticoids, Salmeterol, Tiotropium
34
What must happen to molecules when inhaling?
Drugs need to be atomised into small droplets to pass throught he trachea into the lungs
35
What is the size needed for particles to reach the alveolar sacs?
0.5 - 1 um
36
What happens in the lungs if particles larger than 1um enters?
Either deposited on the bronhcial airway or exhaled
37
What are the advantages of pMDI inhalers?
- Multi-dose capability
- Unobtrusive
- Inexpensive
- Fast
- Contents protecred from moisture and pathogens
38
What is the disadvantages of using pMDI inhalers?
- Propellants
- Incorrect use
39
What is the advantages of inhalation route of administration?
- Small drug dose
- High blood flow to lungs and large suface areas makes rapid onset
- Local or systemic delivery
- Potential use for delivery of proteins and peptides
40
What is the function of dry powder inhaler?
- Powder formulation and large carrier lactose particles
- Small particles are inhaled, larger powder remain in the throat and swallowed
41
What is the advantage of dry powder inhaler?
- No propellant
- Easier to use than pMEDI
42
What is the disadvantage of dry powder inhaler?
Breath-actuated
43
What is a Nebuliser?
Medication that is breathed in as a mist
44
What is the advantage of Nebuliser?
- Large doses can be administered
- Patient compliance
45
What is the disadvantage of Nebuliser?
- Slow
- Patient compliance (mask)
- Requires specialised equipment
46
What is the disadvantage of Inhalation route of administration?
- Irritant effect on airway
- Delivery systems (e.g nebulisers) can be cumbersome and time consuming
- Costly development
- Patiant compliance
- Some inhalers use propellants
47
What drugs are nebulized?
Tobramycin - Cystic fibrosis
Pentamidine - Pneumonia
Albuterol - Asthma
48
What are the advantages of inhalation?
• Drug dose required is smaller vs oral route
– Reduction in side effects
• High blood flow to lungs and large surface area makes it rapid onset
• Can be used for local or systemic delivery
• Current research into use for delivery of proteins and peptides
49
What are the two types of mucus membranes in Nasal delivery?
- Respiratiory mucosa line (Pseudostratified ciliated columnar epthelium, scattered goblet cells)
- Seromucus nasal glands (has mucous secreting cells and serous cells)
50
What is the role of hair in Nasal delivery?
Hair filters course particles (dust and pollen) from inspired air
51
What is the role of mucus?
Traps dust, bacteria and debris
52
What is the role of Lysozyme?
Destroys bacteria
53
What is Mucociliary clearance?
Physical unidirectional movement and removal of deposited particles and gases dissolved in the mucus from the respiratory tract
54
Where does absorption happen?
Through thin mucus membranes lining the nasal passage
55
What drugs are absorbed in nasal delivery?
LIpophilic drugs
56
What molecules are unlikely to be absorbed through the nasal passage
Polar molecules - low bioavailability
57
What alternative passages do polar molecules use?
Polar molcules use paracellular route
Larger molecules use endocytotic transports
58
What are examples of abosrption promoting agents?
Phospholipids and cylodextrins
59
What properties are important for nasal delivery?
Molecular size
Molecular weight
pH
Partition coefficient,
Potency
60
How long will Mucoiliary clearance occur for if formuation isn't mucoadhesive?
15 - 20mins
61
What are the advantages of Nasal route of administration?
Quick onset of action, highly vascularised area
– Non invasive
– Avoids GI tract and first pass metabolism
– Good bioavailability for low Mw drugs
62
What are the disadvantages of Nasal route of administration?
– Can cause irritation
– Patient compliance
– Rapid elimination due to mucociliary clearance
– Only suitable for potent drugs as only a small volume can be administered
63
What doe sthe skin protect the internal body from?
Pollution, Humidity, Temperature radiation
64
How does the skin get damaged?
Mechanically, chemically, biologically, radiation
65
What may cause surface infection?
- Psoriasis
- Eczema
- Scabies
- Bactericides
- Corticosteroids
66
What may cause deep infection?
Allergies, inflammatory conditions (e.g Antibiotics, Antihistamines, Anaethetics)
67
What may cause damage to the skin due to Hair follicles?
Acne, Alopecia, Benzoyl peroxide, minoxidil
68
What does the skin consist of?
Kertinocytes, melanocytes and dendritic cells
69
Where does new cells divide in the skin?
Stratum basale
70
What is the order of the layer in the skin?
Stratum basale -> Stratum spinosum stratum granulosum -> Stratum lucidum -> Stratum corneum
71
Where does absorption through the skin occur in Transdermal delivery?
Via hair follicles and sweat ducts across the contnuous stratum corneum
72
What factors affect the absorption of durgs through the skin in Transdermal delivery?
Site snd condition of the skin
Formulation of the skin
Changes to the stratum corneum
73
What are the strucuture in the Reservoir system?
Backing
Drug reservoir
Membrane
Drug in adhesive
adhesive layer
Liner
74
What is the Backing in the Reservoir system?
Material chosen for atheetics and occulsion (e.g Polyethylene, polyester)
75
What is the Liner in the Reservoir system?
Protective layer rmeoved by patienr prior to application
76
What is the Adhesive layer in Reservoir system?
Secures patch onto the skin
77
What is the Reservoir?
Drug is dissolved/ suspended in liquid/ gel compartment that acts as a reservoir
78
What is the matrix system?
Drug is suspended/dissolved in a semisolid matrix surrounded by an adhesive
79
Why is a drug evenly distributed through the patch in the matrix system?
Less risk of overdoese
80
What is the effects of the first generation system of patches?
Low Mw, lipophilic, efficaious at low doses
81
What is the limitations of the first generation system of patches?
Limited by the stratum corneum
82
What is the targeted delivery for first generation of patches
Larger molecules
83
What is the alterative to first generation system of patches?
Liquid spray for testosterone
84
How is second generation of patches different from the first?
Enhances skin permeability without damage by external forces (e.g iontophoresis, ultrasound)
85
How is the third generation of patches different to the second generation?
Targets stratum corneum
- More effective transdermal deliery - hydrophilic drugs / macromolecules
- Destruction of the skin is minimised - rapid recovery
86
What is the frequency for Radiofrequency ablation for localised heating of the outer skin layer?
100 - 500 kHz
87
What is Sonophoresis?
Use of ultrasound to heat and drive molecules into and across skin
88
What is the benefits of microneedles?
- Easy to use
- Less painful
- Controlled and sustaiend release of drugs
89
What is the structure of microneedles?
- Solid
- Surface coated
- Dissolvable
- Hollow - shaped
90
How is the fourth generation different to the third?
- Controlled and feedback - induced TDD
- Wearable deivce, complete feedback loop
91
How is personalised therapy used in patches?
Contorl of dose - accurate real time obsevration of the patient physicological parameters
92
What are soft Bioelectronics?
Bioelectronic devices in a skin-mounted patch
93
What is the role of Actuators in 4th generation of patches?
Transfer energy to drug-laden patch
94
What are the advantages to Transdermal delivery? (TDD)
Avoids first pass effect of the liver, Zero order kinetics can be produced
• Advantages c.f injections, painful, generate medical waste, - disease transmission
• Non-invasive – generation dependant
• Self administered –generation dependant
• Can provide release for long periods of time
• Generally inexpensive
• Could eliminate pulse entry, peaks in plasma concentrations often produce undesirable effects and troughs are sub-theraputic.
95
What are the disadvantages to Transdermal delivery? (TDD)
- Dosage trans-dermally is often imprecise
- Body absorbs drugs slowly through the skin
- Drug can be lost by washing, adherence to clothes, shedding with skin cells
96
Why is Oral administration used?
- Capacity to prevent complete absorption (induce vomiting, stomach pump)
- Intended for systemic action of the drug
97
What are the four layers in the Gl tract?
- Mucosa
- Submucosa
- Muscularis externa
- Serosa
98
What is the Mucosa?
Moist epithelial membran lining the alimentary canal
99
What are the main functions of mucosa?
- Secrete mucus, digestive enzymes and hormones
- Absorb digested products into the blood
- Protect against disease
100
What are the main functions of mucus?
- Protects organs from digestive enzymes
- Eases food passage along the tract
101
What is the structure of Oesophagus?
Composed of a thick muscular layer, ~250mm long, 20mm diameter, connects the mouth to the stomach
– Squamous epithelium mainly protective function
102
How are materials moved through the Oesophagus?
Swallowing
103
What is the function of the stomach?
Acts as a temporary reservoir for ingested food, delivering to the duodenum in a controlled manner
104
What provides high surface area for absorption in the small intestine?
CIrcular folds, cili, mircovilli
105
What are the different parts in the small intestine for digestion and absorption?
Duodnum, jejunum and ileum
106
What is the function of the colon?
- Absoprtion of sodium, choride ions and water
- Storage and compaction of faeces
107
What is sodium, choride ions and water exchanged for in the colon?
Potassium and bicarbonate
108
What are involved in the movement of materials in Gl tract?
- Gastric emptying
- Small interstinal transit
- Colonic transit
109
What are the challenges to oral delivery?
- Presence of physical, physiological, and biochemical barriers of the intestinal mucosa
- Unfavourable physicochemical properties of drugs
110
What molecule weights does mucus filters?
600 - 800 Da
111
What is Fick's first law of diffusion?
dC/dt = kΔC
112
What is the K in Fick's first law?
Rate constant (energy difference between the two concentration states)
113
What does each letter mean in the equation: K = DA/h
D = diffusion coefficient of the drug in the GI membrane
h = thickness of the membrane
A = surface area of the membrane
114
How does Dissolution rate increase by?
increasing A (surface area/particle size of the drug)
– Increasing ΔC (concentration difference across the boundary layer)
– Increasing k (rate constant)
– Decreasing h (thickness of the oundary layer)
115
What does the coefficient between the membrane phase and aqueous phase allow?
Measure of the lipophilicity of a molecule
116
What is Chirality?
Mirror-image, non-superimposable molecules
117
Are Enantiomers considered as 2 seperate drugs?
Yes
