Drug Therapy Flashcards
(146 cards)
1
Q
What factors affect oral absorption bioavailability?
A
Formulation
The ability of drug to pass physiological barriers - particle size, lipid solubility, degree of ionisation
Gastrointestinal effects - gut mobility, food, illness
First-pass metabolism
Transport across membranes - passive diffusion (most important), protein-mediated transport, filtration, bulk flow
2
Q
What is first pass metabolism?
A
A phenomenon of drug metabolism whereby the concentration of a drug, specifically when administered orally, is greatly reduced before it reaches the systemic circulation.
3
Q
What is the most frequent transport mechanism of drugs?
A
Passive diffusion down a concentration gradient
4
Q
How do lipid soluble drugs diffuse?
A
By dissolving in the lipoidal matrix of the membrane
5
Q
Do drugs ionise in water?
A
Most drugs do not completely ionise in water
6
Q
What does the degree of drug ionisation depend on?
A
As most drugs are weak acids or bases the degree of ionisation depends on the pH of the environment
7
Q
In respect to ionisation, what does not cross the membrane?
A
Both ionised and un-ionised forms will be present.
The ionised drug does not cross the membrane
8
Q
What should un-ionised drugs do at the membrane?
A
The un-ionised form should distribute across the membrane until the equilibrium is reaches - an equal concentration at each side
9
Q
What does a drug have to be in order to cross a lipid layer?
A
In solution and lipid soluble
10
Q
What key factors affect passive transport?
A
Molecular size
Lipid solubility
Polarity
Degree of ionisation
pH of environment
11
Q
Where does filtration normally occur?
A
Through channels in the cell membrane
12
Q
What is filtration the normal method for?
A
Water-soluble molecules with a molecular weight of <100
13
Q
Where does bulk flow of liquid occur?
A
Through inter-cellular pores
14
Q
What is active transport?
A
Energy-dependent transport across membranes against a concentration gradient
15
Q
What do drugs must do to undergo active transport?
A
Resemble naturally occurring compounds
The drug is reversibly bound to a carrier system
16
Q
What physiological barrier on the GI tract in necessary for drugs to pass from one side into the other to get into circulation?
A
Lipid membranes that contain receptors, ion channels and a variety of proteins.
17
Q
What does the speed of gastric emptying affect?
A
The speed at which the drug reaches the site of absorption
18
Q
Where are most drugs absorbed?
A
Small intestine
19
Q
How does food impact rate of absorption?
A
Can enhance or impair rate of drug absorption
20
Q
How can malabsorption impact rate of absorption?
A
Can increase or decrease rate of absorption
21
Q
How do migranes impact the rate of absorption of analgesic drugs?
A
Reduces rate of stomach emptying and increase rate of absorption
22
Q
What can knowledge of first pass metabolism assist in?
A
Deciding on doses and dose schedules
23
Q
What routes can be taken to avoid first pass metabolism?
A
Subcutaneous and intra-muscular
Inhalation and nasal
Sublingual absorption - under tongue
Rectal
Transdermal - drug administered via patch or ointment
24
Q
What route can be affected by first pass metabolism?
A
Oral
25
Discuss the stages of first pass metabolism
1. Drug taken orally travels to lumen of GI tract
2. Drug moves to hepatic portal system, consisting of capillary network and hepatic portal vein
3. The hepatic portal vein takes the drug to the liver
4. The liver metabolises the drug and then the drug moves into systemic circulation
5. Remaining amount (often little) travels into systemic circulation
Little amount of drug absorbed
26
What is the main organ of the body that metabolises drugs?
The liver
27
What does the hepatic portal system consist of?
Capillary network surrounding stomach and small intestine
Hepatic portal vein
28
What does the hepatic portal vein do?
Receives blood from the body and transports it into the liver for filtration and processing
29
What is the heavy first pass effect?
Drug taken orally are so substantially removed by the liver that it results in very little of the drug reaching systemic circulation
30
What is bioavailability?
The fraction (or %) of a drug that reaches systemic circulation
31
What is the bioavailability of intravenous route?
100%
32
What is the bioavailability of oral route?
40%
33
What are the benefits of intravenous medication?
Eliminates the process of drug absorption and breakdown by directly depositing it into the blood.
This results in the immediate elevation of serum levels and high concentration in vital organs, such as the heart, brain, and kidneys.
34
What are the benefits of tropical medication?
- Low risk of systemic adverse events and drug interactions
- Higher concentration of the antibiotic when applied to the affected area
- Smaller amount of drug is used
- Lack of effect on intestinal florae
- Low cost
- Ease of administration to a young child
35
What are the benefits of inhaled medication?
Inhaled drugs are localized to the target organ, which generally allows for a lower dose than is necessary with systemic delivery (oral or injection), and thus fewer and less severe adverse effects.
36
What are the four basic factors of pharmacokinetics?
Absorption
Distribution
Metabolism
Elimination
37
What is pharmacokinetics?
Describes what a body does to a drug
38
What is Tmax?
Time to peak concentration
39
What is Cmax?
Peak concentration
40
What is AUC?
Area under the drug concentration-time curve
41
What are the phases of metabolism?
Phase one
Phase two
42
What processes take place in phase one metabolism?
Oxidation
Reduction
Hydrolysis
43
What does phase one metabolism provide for phase two metabolism?
Increases the polarity of the compound and provides an active site for phase two metabolism
44
Regarding phase one metabolism:
What are the most important superfamily of metabolising enzymes?
The cytochrome P-450 enzymes
45
Regarding phase one metabolism:
What is drug specificity determined by?
The isoform of the cytochrome p-450 - specificity is relative rather than absolute
46
Regarding phase one metabolism:
What enzyme in the liver contributes to the metabolism of a wide range or drugs?
CYP3A4 - also found in gut and is responsible for the pre-systemic metabolism of several drugs
47
Regarding phase one metabolism:
What are examples of drugs that CYP3A4 metabolises pre-systemically?
Diazepam, methadone, simvastatin, CCBs
48
Regarding phase one metabolism:
What is CYP2D6 responsible for?
The metabolism of some antidepressants, antipsychotics and the conversion of codeine to morphine
49
Regarding phase one metabolism:
What % of the population have reduced or absent expression and what does this mean?
5-10%
Which means they may be immune to the analgesic actions of codeine
50
Regarding phase one metabolism:
What is CYP1A2 induced by and what is it important in?
By smoking and is important in the metabolism of theophylline
Therefore smokers require a higher dose of theophylline than non-smokers
51
Regarding phase two metabolism:
What does phase two metabolism involve?
Conjugation which increases the water solubility and enhances exertion of the metabolised compound
52
Regarding phase two metabolism:
What does conjugation involve?
Conjugation involves the attachment of glucuronic acid, glutathione, sulphate or acetate to the metabolite generated by phase 1
53
Regarding phase two metabolism:
What does conjugation usually result in?
Inactivation however a small number of drug metabolites may be active
54
What are the patterns of drug metabolism?
Parent molecule - Phase 1 metabolsim
Phase 1 metabolite - Phase 2 metabolism
Parent molecule - Phase 2 metabolism
Phase 2 metabolite - Phase 1 metabolism
55
What is cytochrome P450 present in?
Most tissues of the body
56
What does cytochrome P450 play an important role in?
Hormone synthesis and breakdown (including oestrogen and testosterone synthesis and metabolism)
Cholesterol synthesis
Vitamin D metabolism
57
What does enzyme induction involve?
Increased enzyme synthesis and therefore increased activity
58
What are the most common enzyme inducers?
Alcohol and smoking
59
What drugs can induce metabolising enzymes?
Many drugs and herbals such as:
Phenytoin
Carbamazepine
Rifampicin
St John's Wort
60
How long can induction take?
Weeks or even months
61
What are common inhibitors of enzymes?
Cimetidine, valproate, erythromycin, clarithromycin, ketoconazole, CBBs and grapefruit juice
62
What can pharmacokinetics allow?
Safer and more accurate clinical trials can be designed by scientists.
63
What can gene mutations result in?
In excess or deficiencies or complete absence of a particular metabolising enzyme activity
64
What is the purpose of metabolism?
Deactivate compounds and increase water solubility and so aid exertion.
65
Define drug metabolism
Biochemical modification of pharmaceutical substances by living organisms usually through specialised enzymatic activity.
66
What are the effects of drug metabolism?
- Loss of pharmacological activity
- Decrease in activity, with metabolites that sow some activity
- Increase in activity, more active metabolites - activation of a prodrug
- Production of toxic metabolites - direct toxicity, carcinogenic, tetragenic
67
What is the relationship between the number of drugs a patient takes and the frequency of ADRs?
Increasing the number of medications a patient is taking increases the frequency of ADRs.
68
What is the frequency of ADRs for patients on 6-10 meds?
10%
1 in 10
69
What is the frequency of ADRs for patients on 11-15 meds?
28%
70
What is the frequency of ADRs for patients on 16-20 meds?
65%
71
How many people die annually in the US and UK as a result of ADRs?
US - 100,000
UK - 12-15,00
72
What are the classifications of ADRs?
Type A - Augmented
Type B - Bizarre
Type C - Chronic
Type D - Delayed
Type E - End of treatment
Type F - Failure of treatment
73
Define adverse drug reaction
A harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product.
74
Give an example type A adverse drug reaction
Bradycardia with beta-blockers
Hypoglycaemia with sulphonylureas or insulin
Respiratory depression with opioids
Bleeding with warfarin.
75
Give an example type B adverse drug reaction
Anaphylaxis with penicillin
Skin rashes with antibiotics
76
Define type A ADR
Augmented
Result from an exaggeration of a drug’s normal pharmacological actions
Predicted, management is to reduce dose
77
Define type B ADR
Bizarre
Novel responses that are not expected from the known pharmacological actions of the drug
Not predicted, management is to discontinue therapy
78
Define type C ADR
Chronic/continuing
Persist for a relatively long time
79
Define type D ADR
Delayed
Become apparent some time after the use of a medicine
80
Define type E ADR
End of use
Associated with the withdrawal of a medicine.
81
Give an example of type C ADR
Osteonecrosis of the jaw with bisphosphonates
82
Give an example of type D ADRs
Leucopoenia, which can occur up to six weeks after a dose of lomustine.
83
Give an example of type E ADRs
Insomnia, anxiety and perceptual disturbances following the withdrawal of benzodiazepines.
84
What is the most common ADR?
Type A - 80%
85
What are the features of type A ARDs?
Easily reversible on reducing dose and not usually life threatening
86
What are the two types of Type A ARDs?
1. Augmentation of the primary effect
2. Secondary effects
87
What are the reasons for Type A ADRs?
Too high or too low a dose
Pharmacokinetic variation (ADME)
Pharmacodynamic variation
Last two commonly occur as a result of disease
88
What is pharmacokinetic variation related to?
Related to absorption distribution, metabolism and elimination of drug.
Decreased absorption may occur with food, formulation of drug, GI mobility and first-pass metabolism.
89
What is the result of ARDs that arise through absorption problems?
Result in therapeutic failure - often a failure to achieve proper absorption and proper therapeutic drug levels.
90
What diseases are important when drugs have a narrow therapeutic index?
Liver and renal
91
What are the primary methods of detecting and reporting ARDs?
1. Voluntary organised reporting - Yellow card system
2. Intensive event monitoring system - Green card system
92
Who can use the yellow card system?
Doctors, pharmacists, pharma companies, members of public
93
What is the yellow cards system for?
All drugs including vaccines
94
What does the yellow card system collect information on?
Side effects, medical device adverse incidents
95
What is the advantage of the yellow card system?
Simple
96
What is the disadvantage of the yellow card system?
Under-reporting & reporting bias by "bandwagon" effect.
Only 10% of serious drug reactions are reported.
Bandwagon effect ig if a new med is in the news such as vaccines for babies which were incorrectly linked to autism then the yellow card reports will increase dramatically by several thousandfold.
97
Describe the green card reporting system of ADRs
Very organised and chooses certain populations to be studied for a short time but it will only pick up ADRs for the medicines being studied at the time
98
What are drug interactions and what do they account for?
Drug-drug interactions occur when two or more drugs react with each other.
Drug interactions are common and account for significant patient morbidity and mortality.
99
What is morbidity?
The condition of suffering from a disease or medical condition
100
What is morality?
Death
101
In what groups does the risk of drug-drug interactions increase?
- Elderly
- Very young
- Critically ill
- Patients undergoing complicated surgical procedures
Patients with chronic conditions:
- Liver disease
- Renal impairment
- Diabetes
- Epilepsy
- Asthma
Interactions which are minor in normal patients can be severe in such patients
102
Define DDI
Modification of a drug effect by proper or concomitant administration of another drug, herb, food or drink.
103
What are the types of DDI
Types:
- Drug-drug interactions (DDI)
- Herb-drug interactions
- Food-drink interaction
- Drink-drug interactions
- Pharmacodynamic interactions
All have caused significant patient morbidity and mortality.
104
What factors affect DDIs?
Remember the precipitant (factors):
- Drugs
- Smoking
- Herbs
- Food
- Alcohol
105
In what illnesses do DDIs increase?
- Hypertension
- Ischaemic heart disease
- Parkinsonism with carbidopa and levodopa
106
What are patient specific risk factors of DDIs?
- Advanced age
- Genetic polymorphisms
- Comorbidities
- Polypharmacy
107
What are drug specific factors of DDIs?
- Polypharmacy
- Narrow therapeutic range
- Dose
108
What are other factors of DDIs?
- Multiple prescribing drs
- Self-prescription
- Prolonged hospitalisation
109
What are the aims of therapeutic drug monitoring?
For selected drugs therapeutic drug monitoring aims to enhance drug efficacy, reduce toxicity or assist with diagnosis.
110
What are the four key factors of bioavailability?
Dose of drug
Frequency of administration - less frequent the better
Timing of administration
Desired speed of onset - depends on disease treated
111
What are the ways drugs can be absorbed through the GI tract?
Oral
Sublingual
Buccal - placing a drug between your gums and cheek
Rectal
112
What is an example of a drug administered via buccal and sublingual routes?
GTN
113
How do buccal and sublingual drugs work?
- Small and dissolve slowly under the tongue or in the buccal cavity
114
What is the ideal method for drugs that have extensive pre-systemic or first pass metabolism?
Buccal or sublingual
115
In what cases would drugs be administered rectally?
- Treat local conditions such as proctitis
- To achieve systemic absorption (benzodiazepines)
- Useful in the young or old
- Patients unable to swallow
- By-pass pre-systemic metabolism
116
What are examples of medications taken orally?
- Tablets
- Capsules
- Solutions & Suspensions
- Modified release tablets
117
Features of solutions and suspensions
- Useful in the young, elderly and patients who can't swallow
- It May be given via nasogastric or PEG tube
- Absorbed very quickly
- Absorption depends on gastric emptying and is most rapid in the small intestine
118
What is the rate limiting step in absorption?
Dissolution of tablet/capsule breakdown
119
What are advantages of tablets and capsules?
- Convenience
- Accurate
- Reproducibility of dose
- Drug stability
- Ease of mass production
120
Why are some drugs coated?
Protect drug from stomach acid (omeprazole)
Protect the stomach from the drug (aspirin)
121
What do modified tablets-enteric coated delay?
Delays disintegration of the tablet until it reaches small intestine
122
Discuss percutaneous absorption
- Creams, ointments and skin patches
- Achieve local effect however the steroid will still be absorbed and may produce systemic effects
123
What do skin patches allow?
Allow release of drug from a reservoir into the skin and then into the systemic circulation
124
What are possible to obtain via skin patches?
Controlled, sustained blood levels of the drug such as nicotine, nitroglycerin, GRT, contraception
125
What are transdermal drug delivery systems?
Adhesive patches containing the drug are applied on the skin
126
How do drugs work in transdermal delivery systems?
Adhesive patches containing the drug are applied on the skin
127
What do transdermal delivery systems bypass?
First pass hepatic metabolism
128
What is inhalation of drugs used for?
To deliver drugs directly to lung for local effect (eg salbutamol) or to achieve a systemic effect (eg inhaled anaesthetics)
129
How are inhaled drugs delivered?
Medicine administered via a pressurised aerosol, breath-actuated aerosol, nebuliser or dry powder device
130
What are the advantages of inhaled drug delivery?
- Drug delivered directly to site of action
- Rapid effect
- Small doses used
- Little systemic absorption
- Reduced adverse effects
131
What are the disadvantages of inhaled drug delivery?
Patient education is essential
132
What is meant by error?
Any error in the prescribing, dispensing or administration of a drug, irrespective of whether such errors lead to patient harm
133
Define medication
A drug or other form of medicine that is used to treat or prevent disease.
134
Define prescribing error
Incorrect drug selection for a patient
135
What are the cons of prescribing errors?
- Patient safety
- Collegues
- Unprofessional
- Legal issues
- Bad publicity for healthcare if gone public
136
What is a medication error?
Mistakes may be defined as errors in the planning of an action
137
How can a medication error be made?
Knowledge based
Rule based
138
What is a rule based medication error?
Misapplication of a good rule (eg injecting a medication into a non-preffered site) or the application of a bad rule or the failure to apply a good rule such as using an excessive dose of a drug
139
What is a knowledge based medication error?
Giving a medication without having established whether the patient is allergic to that medicine
140
What is a slip?
An erroneous performance
Writing up the incorrect medicine
141
What is a lapse?
An erroneous memory
Giving a drug that a patient is already known to be allergic to
142
What is a prescribing error?
Incorrect dose, quantity, indication or prescribing of a contained drug
143
What can lead to a prescribing error?
- Illegible handwriting
- Inaccurate medication history taking
- Confusing with drug name
- Inappropriate use of decimal points
- Use abbreviations (eg AZT has lead to confusing between zidovudine and azathioprine)
- Use of verbal orders
144
What factors contribute to prescribing errors?
Lack of knowledge on of the prescribed drug, its recommended dose and patient details
Tired
145
What can minimise the occurrence and impact of medication/prescribing errors?
Before prescribing consider:
- Patient's medication history
- Other factors that might alter the benefits and risks of treatment
- Select effective, safe and cost-effective medicines
individualised for the patient
- Adhere to national guidelines and local formularies
- Monitor the beneficial and adverse effects of medicines
- Communicate and document prescribing describing
- Prescribe within the limitations of your knowledge, skills and experience
146
What is the major mechanism through which drugs cross the capillary walls?
Bulk flow of liquid
