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Principles of disease AM > Drugs > Flashcards

Drugs Flashcards

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1
Q

What is absorption?

A

Process of movement of the unchanged drug from the site of administration to the systemic circulation

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2
Q

What is Cmax?

A

Drug concentration peak

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3
Q

What is Tmax?

A

The time at which Cmax us observed

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4
Q

What is bioavailability?

A

The amount of the drug available for action in the systemic circulation

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5
Q

What factors affect bioavailability?

A

Formulation
Ability of drug to pass physiological barriers
GI effects
First pass metabolism

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6
Q

What are some physiological barriers drugs encounter?

A

Lipid solubility
pH
Ionisation

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7
Q

How does ionisation affect drug diffusion?

A

An ionised drug will not cross the cell membrane

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8
Q

What is the Henderson-Hasselbalch equation used to show?

A

The relationship between local pH and the degree of ionisation

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9
Q

What is the Henderson-Hasselbalch equation?

A

pH=pKa+log10([A-]/[HA])

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10
Q

What is the lipid water partition coefficient?

A

The ratio of the amount of drug which dissolves in the lipid and water phase when they are in contact

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11
Q

How does lipid solubility affect diffusion across a membrane?

A

A drug must be lipid soluble to diffuse across a membrane

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12
Q

By what methods can drugs pass across the membrane?

A 
Passive diffusion
Filtration
Bulk flow
Active transport
Facilitated diffusion
Ion pair transport
Endocytosis
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13
Q

What drugs cross the membrane via facilitated diffusion?

A

Monosaccharides, amino acids, vitamins

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14
Q

What is the driving force for filtration, bulk flow and pore transport?

A

The difference in hydrostatic or osmotic pressure

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15
Q

What gastrointestinal factors affect drug absorption?

A

Motility
Food
Illness

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16
Q

What is first pass metabolism?

A

Metabolism of drug prior to it reaching the systemic circulation

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17
Q

What are the 4 primary systems that affect first pass metabolism?

A

GI lumen
Gut wall enzymes
Bacterial enzymes
Hepatic enzymes

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18
Q

What are the benefits of subcutaneous and IM administration?

A

Only a small volume required
Avoids first pass metabolism
Water soluble drugs absorbed well

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19
Q

What are the benefits of buccal and sublingual administration?

A

Avoids first pass metabolism

Enter circulation directly

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20
Q

What are the benefits and disadvantages of suppositories?

A

Avoids first pass metabolism
Can be used for drugs that irritate stomach
Absorption tends to be slow

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21
Q

What are the benefits of inhalation of drugs?

A

Can be used for volatile agents
Relatively rapid action
Can be used for topical or systemic effects

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22
Q

What are the advantages and disadvantages of transdermal administration?

A

Avoids first pass metabolism
Controlled release
Few substances well absorbed
Needs to be nonirritant

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23
Q

What is drug distribution?

A

Reversible transfer of a drug between the blood and extravascular fluids and tissues of the body

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24
Q

What factor affect tissue distribution?

A 
Plasma protein binding
Tissue perfusion
Membrane characteristics
Transport mechanisms
Diseases and other drugs
Elimination
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25
What is the effect of plasma protein binding?
Only unbound drugs are biologically active
26
What factors affect the amount of a drug that binds to plasma proteins?
``` Renal failure Hypoalbuminaemia Pregnancy Other drugs Saturability of binding ```
27
What is the apparent volume of distribution (Vd)?
Theoretical volume that would be necessary to contain the amount of the administered drug at the same concentration as it is in the plasma
28
What is the correlation between Vd and the ability of a drug to diffuse?
The higher the Vd, the better the drug is at diffusing
29
What is clearance?
The theoretical volume from which a set amount of a drug is completely removed over time
30
What is drug clearance dependent on?
Urine flow rate for renal clearance | Metabolism and biliary secretion for hepatic clearance
31
What is half life (t1/2)?
Time taken for the drug concentration in the blood to half
32
What is the half life dependent on?
Volume of distribution and rate of clearance
33
What does prolongation of the half life cause?
Toxicity
34
When is steady state reached in chronic administration?
Usually after approx 4 half lives
35
What is elimination?
Removal of the active drug and its metabolites from the body
36
What are the 3 stages of drug elimination?
Metabolism and excretion
37
Where does most of drug metabolism take place?
Liver
38
What is the primary organ of drug excretion?
Kidneys
39
What are the 3 principle mechanisms of drug excretion?
Glomerular filtration Passive tubular reabsorption Active tubular secretion
40
What drugs are filtered during glomerular filtration?
All unbound drugs, as long as they size, charge or shape are not excessively large
41
What happens in active tubular secretion?
Acidic and basic compounds are actively secreted into the proximal tubule
42
Why is active tubular secretion important?
Eliminating protein bound cationic and anionic drugs
43
What is the process of passive tubular reabsorption?
As the filtrate moves down the renal tubule, any drug present is concentrated and passive diffusion allows some of the drug to diffuse across the membrane back into circulation
44
Where does passive tubular reabsorption tale place?
Distal tubule and collecting duct
45
What is biliary secretion?
Secretion of the drug into the bile where it can then be reabsorbed into the enter-hepatic circulation
46
What does metabolism in the liver lead to and what does this cause?
Conjugation of the drug | Cannot be reabsorbed into the circulation
47
What ways are drugs delivered to patients?
``` Tablets or capsules Solutions or suspensions Ointments and creams Inhalation Injections Suppositories Pessaries ```
48
Why are there different drug formulations?
To allow selective targeting, avoid pre or systemic metabolism, allow for fast or slow release
49
Where are oral medications absorbed?
GI tract
50
Who are solutions or suspensions used for?
Young, old, those with difficulty swallowing
51
What is the rate limiting step in absorption of tablets?
Break down of the tablet
52
What are the advantages of tablets and capsules?
``` Convenient Accurate dose Reproducability Drug stability Ease of mass production ```
53
What are enteric coated tablets?
A drug with a protective coating to protect the drug from the stomach and the stomach from the drug
54
Why are prolonged or delayed release formulations useful?
Most conditions require prolonged therapy Maintains drug levels within therapeutic range Reduces need for frequent dosing Improved compliance
55
What are prodrugs?
Synthesised inactive derivatives of an inactive drug which requires to be metabolically activated after administration
56
What are buccal and sublingual administration ideal for?
Drugs with extensive first pass metabolism
57
Who is the rectal route useful for?
Young, old, patients unable to swallow
58
What can the rectal route be used to treat?
Local conditions, or systemic absorption
59
What are pessaries used for?
To treat local conditions
60
What are the 3 forms of injection based administration?
IV IM Subcutaneous
61
When is IV used?
When rapid onset of action id required Careful control of plasma levels required Drug has short half life
62
How can IV be given?
Rapidly Slowly- to prevent toxic effects Continuoisly- ensure accurate controls of plasma levels
63
What does IM allow for?
More sustained duration of action
64
What are subcutaneous injections used to administer?
Insulin Heparin Narcotic analgesics
65
What are 2 types of subcutaneous administration?
Dermojet | Pellet implantation
66
Why is subcutaneous injection uses?
Bypasses need for venous access | Slow absorption
67
What is transdermal drug delivery?
Adhesive patched containing the drug are applied to the skin, drug crosses the surface by diffusion and goes into systemic circulation
68
What is the benefit of transdermal drug delivery?
Bypasses first hepatic inactivation
69
What can percutaneous drugs be used for?
Local or systemic
70
Give an example of a systemic percutaneous drug?
Transderm-SCOP
71
Give an example of a local percutaneous drug?
Hydrogel transdermal patch
72
How can inhalation drugs be administered?
Pressurised aerosol, breath activated aerosol, nebuliser, dry powder device
73
What are the advantages of inhalation?
``` Delivered directly to site of action Rapid effect Small doses uses Little systemic absorption Reduced adverse effects ```
74
What are the 3 types of carrier based drug delivery?
Monoclonal antibodies Liposomal drug delivery Nanoparticle based drug delivery
75
How do monoclonal antibodies work as a carrier based drug delivery system?
Modified antibodies with attached toxins cytokines etc act directly when binding to a cancer specific antigen and induce immunological response
76
How does a liposomal drug delivery system work?
Allows for drug accumulation at disease sites and avoidance of sensitive sites
77
How do nanoparticles work as a carrier based drug delivery system?
Drug can be targeted to precise location, making the drug more effective and reduce side effects
78
What are the 3 types of nano carriers?
Nanoparticle Nanotubule Nanoshell
79
What are carbon nanotubes used to treat?
Bronchial asthma
80
What are gold nano tubules used to treat?
Chemo
81
What are nanoerythrosomes and what are they used for?
Resealed erythrocytes that carry proteins, enzymes and macromolecules Used in treatment of liver tumour and enzyme and pancreatic diseases
82
What is an adverse drug reaction?
Any response to a drug which is harmful, unintended and occurs in doses used for prophylaxis, diagnosis or treatment
83
What are the classifications of onset of adverse drug reactions?
Acute- within 60 minutes Sub-acute- 1-24 hours Latent- >2days
84
What are the classifications of severity of adverse drug reactions?
``` Mild= bothersome but requires no change in treatment Moderate= Requires change in therapy, additional treatment, hospitalisation Severe= Disabling, life threatening ```
85
What are the classifications of adverse drug reactions?
``` Augmented Bizarre Chronic Delayed End of treatment Failure of treatment ```
86
What is a type A drug reaction?
Augmented Dose related and predictable Resolve when drug is reduced or stopped
87
What causes a type A drug reaction?
Too high a dose Pharmaceutical variation Pharmacokinetic variation Pharmacodynamic variation
88
What is a type B drug reaction?
Bizarre Rare and unrelated to dose Can cause serious illness
89
What causes a type B drug reaction?
Immunological or genetic response
90
When are type B drug reactions more common?
With macromolecules Patients with history of asthma or eczema Presence of leukocyte antigen Sex linked G6P deficiency
91
What is a type C drug reaction?
Chronic Does not occur with single dose Semi predictable
92
What is a type D drug reaction?
Delayed | Occur in children of patients or patients years after end of treatment
93
What are some examples of type D drug reactions?
Second cancers in those treated with alkylating agent or immunosuppressants Graniofacial malformations in children of those treated with isotrtinoin
94
What is a type E drug reaction?
End of treatment | Adverse reaction when treatment is stopped, particularly when it was stopped suddenly
95
What are some examples of type E drug reactions?
Unstable angina or MI when taken off beta blockers | Withdrawal seizures when taken off anti-epileptics
96
What are type F drug reactions?
Failure of treatment Common and dose related Frequently caused by drug interactions
97
What are the 4 steps in diagnosis a type F drug reaction?
Differential diagnosis Medication history Assess time of onset and dose relationship Lap investigations
98
What are the risk factors of adverse drug reactions?
``` Age Multiple medications Inappropriate medication prescribing, use or monitoring End organ dysfunction Altered physiology History of adverse drug reactions Dose and duration of exposure Genetic predisposition ```

Principles of disease AM (16 decks)

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