ICS - Pharmacology and Prescribing Flashcards
(217 cards)
1
Q
Pharmacokinetics
A
How the body affects the drug - absorption, distribution, metabolism, excretion (ADME)
2
Q
Drug interactions - synergy
A
interaction of drugs such that the total effect is GREATER than the individual effects
3
Q
Drug interactions - antagonism
A
A substance that acts AGAINST and blocks an action (i.e. two drugs that oppose each other)
4
Q
Drug interactions - summation
A
different drugs used together to have the same effect as a single drug would
5
Q
Drug interactions - potentiation
A
enhancement of one drug by another so that the combined effect is greater than the sum of each one alone
6
Q
Pharmacokinetics - absorption (variables of)
A
- Motility - if the gut has slowed digestion, the drugs won’t work a well
- Acidity
- Vascularity
- Surface area
7
Q
Pharmacokinetics - distribution
A
Drugs reversibly leave the bloodstream and enter the ECF and tissues, factors affecting e.g. blood flow, capillary permeability
8
Q
First order drug metabolism
A
Rate of metabolism of drugs is proportional to drug concentration, constant half-life of elimination
9
Q
Zero order drug metabolism
A
Rate of metabolism is constant regardless of drug concentration
10
Q
Phase 1 drug reactions
A
CYP450, oxidation, hydrolysis, etc.
11
Q
Phase 2 drug reactions
A
Conjugation reactions, make the drug more hydrophilic, e.g. glucoronidation
12
Q
Pharmacodynamics
A
What the drug DOES to the body
13
Q
Potency
A
measure of how well a drug works
14
Q
Agonist
A
Compound that binds to a receptor and activates it
15
Q
Antagonist
A
Compound that reduces the effect of an agonist, do NOT activate receptors
16
Q
Signal transduction (cell signalling)
A
Transmission of molecular signals from a cells exterior –> interior, initiated by binding of a molecule to a cells surface receptors
17
Q
Cholinergic receptors
A
ACh binding, two types: muscarinic and nicotinic
18
Q
Affinity describes how well a ligand
A
Binds to a receptor
19
Q
Efficacy describes how well a ligand
A
activates a receptor
20
Q
PK - ADME
A
absorption, distribution, metabolism and excretion
21
Q
Drug targets
A
Receptors, enzymes, ion channels, transporters
22
Q
Types of receptor
A
- Ligand-gated ion channels
- G protein coupled receptors
- Kinase-linked receptors
- Cystolic/ nuclear receptors
23
Q
Nicotinic ACh receptors are of what type?
A
Ligand-gated ion channels
24
Q
Beta-adrenoreceptors are of what type?
A
G-protein coupled receptors
25
Kinase-linked receptors are receptors for?
growth factors
26
Cystolic/ nuclear receptors
modify gene transcription
27
Steroid receptors are
cystolic/nuclear receptors
28
Two types of cholinergic receptors?
nicotinic and muscarinic
29
What is meant by EC50
concentration of a drug that gives half the maximal response
30
Signal amplification
To increase the strength of a signal
31
Allosteric modulation
When an allosteric ligand binds to a different site on the molecule and prevents the signal being transmitted
32
Tolerance
The reduction in drug (agonist) effect over time, seen with continuous repeated high concentration use
33
Enzyme inhibitor
Molecule that binds to an enzyme and decreases its activity, it prevents the substrate from entering the enzyme's active site and prevents it from catalysing its reaction
34
Irreversible enzyme inhibitors
react with enzyme and change it chemically
35
reversible enzyme inhibitors
bind non-covalently and different types of inhibition are produced depending on whether these inhibitors bind to the enzyme, the enzyme-substrate complex, or both
36
NSAIDs inhibit which enzyme?
COX
37
COX is responsible for the
breakdown of arachidonic acid to prostaglandin H2
38
Two iso-forms of COX
COX-1 and COX-2
39
How do NSAIDs work?
Preventing arachidonic acid from reaching the active site of the COX enzyme and thus from being broken down into prostaglandin H2 - competitive inhibition
40
How does aspirin affect the COX enzyme?
Irreversibly blocks the active site
41
ACE inhibitor examples
captopril, enalapril
42
How do ACE inhibitors work as antihypertensives?
Inhibit ACE enzyme, thereby preventing the conversion of angiotensin I to angiotensin II, therefore less vasoconstriction and less aldosterone released by the adrenal cortex
43
Drugs that target transporters?
Proton-pump inhibitors (PPIs), diuretics, neuronal uptake inhibitors
44
Uniporters
transporters that use energy from ATP to pull molecules in
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Symporters
transporters that use movement in of one molecule to pull in another molecule against its concentration gradient
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Antiporters
transporters that moves one substance against its gradient, using energy from the second substance moving down its gradient
47
Examples of PPIs
omeprazole, lansoprazole
48
Where are PPIs all activated?
In the acidic stomach environment
49
Diuretics act to inhibit?
symporters, can inhibit the NKCC2 pump on the thick ascending part of the loop of Henle, therefore reducing the amount of Na+, Cl- and K+ ions able to move into the medullary interstitium, therefore less water is reabsorbed and more passes out via the urine
50
Ion channels as drug targets
Calcium channel blockers, local anaesthetics
51
Examples of CCBs
amlopidine, verapamil
52
CCBs are used to treat?
hypertension
53
How does amlopidine work?
blocks calcium channels found in cardiac and smooth muscle, thereby preventing an influx of Ca2+, less vasoconstriction
54
Simply, how do local anaesthetics work?
interrupt axonal transmission by blocking voltage gated sodium channels and preventing neurones from depolarising - do not meet threshold and therefore AP cannot propagate
55
Passage of drug across the membrane?
Passive diffusion through the lipid layer, diffusion through pores/ ion channels, carrier mediated processes, pinocytosis
56
Bioavailability
amount of drug taken up as a proportion of the amount administered
57
Drug absorption - oral
Large SA and high blood flow of small intestine can give rapid and complete absorption of oral drugs
58
Obstacles of oral drug absorption
1. Drug structure - drugs need to be lipid soluble and stable at a low pH
2. Drug formulation - must be able to disintegrate and dissolve for absorption
3. Gastric emptying - rate of which determines how soon a drug taken orally is delivered to the small intestine
4. First pass metabolism - drugs taken orally have to pass 4 major metabolic barriers to reach circulation: intestinal lumen, intestinal wall, liver, lungs
59
Intradermal and subcutaneous absorption
- avoids barrier of stratum corneum
- limited by blood flow
- use for local effect
60
Intramuscular absorption
- depends on blood flow and water solubility
| - bioavailability close to 1
61
Inhalational absorption
- Large SA and high blood flow
- Limited by risk of toxicity to alveoli
- Largely restricted to volatile drugs
62
Protein binding absorption
- Many drugs can bind to plasma/tissue proteins
- Common reversible binding to albumin
- Binding lowers the free concentration of the drug and can release the drug when the plasma concentration is low
63
Half life
Time taken for concentration to reduce by half
64
Elimination of a drug is from which compartment?
Plasma
65
Elimination route for most drugs?
Renal/ hepatic
66
Define clearance
Volume of plasma that can be completely cleared of a drug per unit time or per unit plasma concentration
67
Formula for clearance
Rate of appearance in urine/ plasma concentration
68
Marker substance for measuring renal clearance
Creatinine
69
Problem with renal failure and drug elimination?
Patient will not be able to eliminate drug for weeks
70
Criteria for most drugs eliminated by the kidneys?
Water soluble and small
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For patients with renal impairment you might choose drugs which are eliminated by the
liver
72
What is the hepatic extraction ratio (HER)?
Proportion of drug removed by one passage through the liver
73
What is meant by high HER?
high removal of drug by liver, so that clearance is only limited by the hepatic blood flow
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What is meant by low HER?
low removal of drug so the process is slow and inefficient
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How does the liver adapt when exposed to a low HER drug?
produce more enzymes to enable it to increase clearance
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Where do most phase 1 drug metabolism reactions occur?
SER
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CYP 450 is what type of enzyme? Found where? Involved in what reactions?
Microsomal, SER, phase 1
78
Minimal effect of drug metabolism by liver until at least what % of the liver is lost?
70
79
Why are IV infusions used?
Enables steady state plasma levels to be maintained (drug intake is in equilibrium with elimination) and highly accurate drug delivery, quickest administration, 100% bioavailability
80
Limitations of IV infusions?
Require monitoring, potential for calculation errors, dosage based on body mass (problematic with extreme body weights)
81
Pharmacokinetic considerations of a IV drug infusion with a high volume of distribution?
Means there will be a small fraction in the plasma and so it will take a long time to reach a steady state
82
Adherence
Extent to which a patient's actions match agreed recommendations
83
What % of prescribed medicines are not taken per year? (Costing the NHS £12.9 billion a year)
30-50%
84
What is meant by compliance?
Assumes doctor knows best, passive patient, patient follows doctors instructions
85
What is meant by adherence?
Acknowledges the importance of the patient's beliefs but recognises that the healthcare professional is still the expert in conveying their knowledge
86
Necessity beliefs
perceptions of personal need for treatment
87
Key points about patient-centered approach
- Shift in focus from treatment to process of care (holistic approach)
- Philosophy of care that encourages focus in the consultation on the patient as a whole person who has individual preferences, and also a shared control of the consultation, decisions about intervention
88
Good doctor-patient communication outcomes? (4)
1. better health outcomes
2. higher adherence to therapeutic regimes in patients
3. higher patient and doctor satisfaction
4. decrease in risk of malpractise
89
Improving communication
- adapt consultation style to patient's needs
| - encourage patient to ask questions
90
Increase patient involvement
- Explain condition, pros and cons
- Clarify what the patient hopes to achieve from treatment
- Record the decision if the patient decides NOT to take the medicine
91
Understand the patient's perspective
- Ask what they know and understand about their medicines
| - Raise any concerns
92
Provide information
- Offer thorough and clear information on their condition and treatments
- Offer individualised information that is easy to understand
93
Assess adherence
- Routinely assess adherence in a non-judgemental way whenever you prescribe
94
Review medicines
- Review patient's knowledge, understanding and concerns about medicine
95
Concordance
Thinking about patients as equals in care settings rather than just following doctor's instructions, patients to take part in decisions
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Barriers to concordance - patients
Sometimes makes the patients more anxious, simply want their doctor to instruct where medical decisions are complex
97
Barriers to concordance - doctors
- Relevant communication skills
| - Time constraints
98
Steps in sharing the decision with the patient
1. Define the problem
2. Convey that professionals may not have one set opinion on the best treatment
3. Outline the options - pros and cons of treatments
4. Clarify patient's understanding and explore any concerns
5. Check the patient accepts the decision
6. Review the needs and preferences after the patient has had time for consideration
7. Review treatment decisions over time
99
Morphine is a receptor a______
agonist
100
Oral bioavailability of morphine? Why so low?
50% due to the liver metabolism
101
Naturally occurring opioids from opium?
morphine and codeine
102
Antagonists to opioids?
Naloxone (give tot reverse overdose)
103
Routes of administration for opioids?
oral, subcutaneous, IV
104
If morphine is given intravenously, how long does it take to reach the brain?
5 minutes
105
Diamorphine =
heroin, more potent and faster acting (crosses BBB quickly)
106
How do opioids work?
Use existing pain modulation systems - natural endorphins and enkephalins
107
Opioid receptors are of which type?
G coupled protein
108
Subunits of opioid receptors
G alpha, beta, gamma
109
When an opioid binds to its receptor what happens to the G receptor subunits?
Alpha separates from beta and gamma
110
G beta gamma subunits?
Inhibit Ca2+ voltage gated channels, and stimulate hyperpolarisation by opening of K+ channels, both making an AP more difficult to occur
111
G alpha subunit?
Inhibits cAMP synthesis
112
Opioids inhibit the
pain ascending pathway
113
opioids activate the
pain descending pathway which blocks the pain ascending
114
Opioid receptor for morphone?
mu
115
Where are opioid receptors located?
Midbrain, spine, GI tract, breathing centre
116
Morphine is metabolised into? Is this more or less potent than morphine?
morphine 6 glucoronide, more
117
How is morphine 6 glucoronide normally excreted? What clinical problems does this present?
Renally, patients with decreased renal function may have problems removing
118
Sustained activation of opioid receptors -->
Tolerance and addiction
119
Side effects of opioids (receptors exist OUTSIDE the pain system --> GI tract and respiratory control centre)
respiratory depression, nausea, constipation, itching, etc
120
What to administer if opioid induced respiratory depression
Naloxone
121
Divisions of the autonomic nervous system? what neurotransmitters are used?
parasympathetic and sympathetic, ACh and noradrenaline
122
somatic nervous system uses which NT?
ACh
123
Two types of cholinergic receptors?
Nicotinic and muscarinic
124
Nicotinic receptors (nAChR) are what type of receptors?
ion channels
125
Muscarinic receptors (mAChR) are what type of receptors
G-protein coupled
126
In the parasympathetic NS, ACh acts on which receptors?
Muscarinic ACh receptors (M1, M2, M3)
127
In the sympathetic NS, what mediates the release of noradrenaline?
ACh
128
Noradrenaline activates which type of receptors?
adrenergic (alpha and beta)
129
In the somatic NS, ACh acts on which type of receptors at the neuromuscular junction
nicotinic
130
Where are nicotinic ACh receptors found?
NMJ
131
Enzymes that forms ACh from acetyl CoA and choline in the neurone?
choline acetyl transferase enzyme
132
After ACh is formed in the neurone, what happens to it?
Stored in a vesicle ready for release
133
ACh is broken down in the synaptic cleft after use by what enzyme? what are the products?
acetylcholinesterase, into choline and acetate
134
where are M1 receptors found?
mainly brain
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where are M2 receptors found?
mainly in the heart, activation SLOWS the heart
136
where are M3 receptors found?
glandular and smooth muscle, causes bronchoconstriction, etc.
137
where are M4 receptors found?
mainly in the CNS
138
Muscarinic agonist?
Pilocarpine
139
PS agonistic action of pilocarpine
1. Stimulates salivation
2. Contracts iris smooth muscle - pupil constriction
3. Side effects of slowing the heart
140
Treatment of bronchoconstriction?
Drugs that do this in the airway block the M3 receptor and are called anti-cholinergics or anti-muscarinics
141
Drugs such as solifenacin that treat overactive bladders?
Anticholinergics
142
Anti-cholinergic side effects
In the brain may worsen memory and may cause confusion
Peripherally, may cause constipation, drying of the mouth, blurring of the vision
143
Botulinum toxin (botox) has both cosmetic and anti-spasmodic uses - how does it work put simply?
Prevents ACh release
144
Precursor of catecholamines
Dopamine
145
Adverse effects of muscarinic agonists (DUMBELS)
Diarrhoea, urination, miosis (excessive pupil constriction), bradycardia, emesis (vomiting), lacrimation, salivation
146
Noradrenaline is a __________, adrenaline is a ___________
neurotransmitter, hormone
147
Synthesis of adrenaline beginning with tyrosine?
Tyrosine, DOPA, dopamin,e noradrenaline, adrenaline
148
Classes of alpha adrenergic receptors?
alpha 1 and 2
149
Classes of beta adrenergic receptors?
beta 1, 2 and 3
150
Effect of alpha-1 adrenoreceptors?
vasoconstriction, pupil dilation, bladder contraction
151
Effect of alpha-2 adrenoreceptors?
Presynaptic inhibition of noradrenaline
152
Alpha-1 adrenoreceptor activators act to? whereas alpha-2 act to?
Raise BP, lower BP
153
Why might you block alpha-1 receptors?
Lower BP (e.g. doxazosin)
154
Alpha-1 blocker which lowers BP drug?
doxazosin
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Effect of beta-1 adrenoreceptors?
Increased cardiac effects
156
Effect of beta-2 adrenoreceptors?
Bronchodilation
157
Effect of beta-3 adrenoreceptors?
- increased lipolysis
| - relaxation of the bladder
158
Key adrenergic agonist
adrenaline
159
What is meant by adrenaline being a non-selective agonist?
Works on any alpha and beta adrenoreceptor
160
Uses of adrenaline has an adrenergic agonist?
anaphylaxis, cardiac arrest, acute hypotension
161
What happens when adrenaline binds to beta-2 receptors?
bronchodilation
162
Activation of which adrenergic receptors can be life saving in asthma?
Beta-2
163
Activating alpha-1 adrenergic receptors causes?
vasoconstriction
164
Activating beta-1 adrenergic receptors causes?
increased force of heart contraction
165
Beta-3 agonists reduce symptoms of an?
Over-active bladder
166
Beta blockers
Lower BP, reduce cardiac work, treat arrhythmias
167
What patients would you not prescribe beta blockers to? Why?
Asthmatics, since already on beta-2 agonists
168
Side effects of beta blockers?
tiredness, bronchoconstriction, bradycardia, cardiac depression
169
Clinical indications relating to allergy?
1. Epithelial - eczema, itching, reddening
2. Excessive mucus production
3. Airway constriction
4. Abdominal bloating
5. Anaphylaxis
170
Ab involved in allergic phenomena?
IgE
171
Low affinity IgE receptor expressing cells
B cells, T cells, monocytes, platelets, neutrophils
172
High affinity IgE receptor expressing cells
eosinophils, mast cells, basophils
173
Mast cells
- IgE mediated immunity
- primary role in innate and acquired immunity
- only circulate in their immature form
174
What mAKES an allergen?
Particulate delivery of antigens, presence of weak PAMPs resulting in weak innate immunity activation
175
Complications of anaphylaxis?
- Mast cell/ basophil activation
- Vasodilation
- Increased vascular permeability
- Lowered BP
- Mucus production
- Rash
- Swelling
176
Allergy treatments - immunotherapy
Increasing dose of antigen via sub-lingual or subcutaneous, usually only used for very serious conditions
177
Allergy treatments - reducing mast cell products
Histamine receptor antagonists, prostaglandin antagonists
178
What is meant by druggability?
Ability of a protein target to bind small molecules with high affinity
179
Penicillin was developed using?
fermentation
180
Stereoisomers of a molecule affect its biological activity, which form of the isomer do biological systems use?
L-amino acids (R form)
181
Recombinant proteins in clinical use?
Insulin, EPO, growth hormone, interleukin 2, gamma interferon
182
What is meant by rational drug design?
Process of finding new medications based on the knowledge of a biological target
183
Evolution of insulin as a therapy:
- Extracted from beef/ pork pancreas
- engineering insulin
- second generation insulin
184
Gene therapy in drug development
Delivery of a nucleic acid polymer to the cell, DNA is delivered using a viral vector, therapeuric gene administered to treat effects of mutated gene, suppresses mutated gene gene expression
185
Adverse drug reactions
response to a drug which is noxious and unintended
186
Adverse drug reactions - facts
- 5% of hospital admissions
- 10-20% occur in hospital inpatients
- 60% are preventable
- 5th most common cause of hospital death
- Patients lose confidence in their doctors
187
Types of adverse drug reactions (ADRs)? - ABCDE
Augmented, bizarre, chronic, delayed, end of use
188
Side effects (as opposed to ADRs)
an unintended effect of a drug related to its pharmacological properties and can include unexpected benefits of treatment
189
adverse drug reactions - beta blockers
Bradycardia and heart block are primary adverse effects. Bronchospasm is a secondary pharmacological adverse effect
190
ADR - augmented
- commonest, extension of clinical effect
- predictable
- dose-related
191
ADR - augmented examples
Diuretic causing dehydration, drug for hypertension causing hypotension, anticoagulant causing bleeding
192
ADR - bizarre
- unexpected and unpredictable
- unrelated to dose
- mostly immunological mechanisms
- hypersensitivity
193
ADR - chronic
- occurs after long term therapy, e.g. osteoporosis and steroids
194
ADR - delayed
after long term treatment, e.g. malignancies after immunosuppression
195
ADR - end of treatment
After abrupt drug withdrawal
196
Susceptibility to ADR?
elderly, female, pregnant, diseased (liver or renal), genetics
197
Causes for ADRs
- Pharmaceutical variation
- Receptor abnormality
- Drug-drug interactions
198
When to suspect an ADR?
Symptoms after: a new drug, dosage increase
199
Commons ADRs?
confusion, nausea, balance problems, diarrhoea, constipation, hypotension
200
DoTS (ADR)
1. Dose relatedness
2. Timing
3. Susceptibility
201
Most common drugs to have ADRs?
antibiotics, CDV drugs, NSAIDs, anti-neoplastics
202
Name for the ADR reporting scheme?
Yellow card scheme
203
Advantages of the yellow card scheme?
- identifies adverse reactions
- readily accessible
- cheap to operate
- acts as an early warning system
204
Information to include on a yellow card? (4)
1. Suspected drug
2. Suspect reaction
3. Patient details
4. Reporter details
205
Weaknesses of yellow card?
- Relies on ADR being recognised
| - Bias due to promotion and publicity
206
What does the black triangle mean?
Indicates a medicine is undergoing additional monitoring e.g. contains a new active substance
207
clinical criteria for allergy to drug
- no correlation to dosage
- no correlation to pharmacological drug properties
- disappearance on cessation
208
Main features of anaphylaxis
1. Exposure to drug - immediate rapid onset rash
2. Swelling of the face, lips, oedema
3. Hypotension
4. Cardiac arrest
209
First step in the management of anaphylaxis?
Commence basic life support - airway, breathing, circulation (ABC)
210
Effect of adrenaline in management of anaphylaxis?
1. vasoconstriction
2. bronchodilation
3. increased cardiac output
211
Medicine risk factors for drug hypersensitivity
1. Protein base macro molecules e.g. penicillin
| 2. Monoclonal antibodies can cause reactions
212
How does adrenaline cause vasoconstriction in the treatment of anaphylaxis?
via alpha 1 adrenoreceptors
213
How does adrenaline cause increased CO in the treatment of anaphylaxis?
stimulation of beta-1 adrenoreceptors - positive ionotropic and chronotropic effects on the heart
214
How does adrenaline reduce oedema in the treatment of anaphylaxis?
stimulation of beta-2 adrenoreceptors
215
What is non-immune anaphylaxis?
Type of anaphylaxis that does not involve the immune system, rather the direct stimulation of mast cell degranulation, some drugs are recognised to cause this
216
Drug interaction of avocado
Reduces the effectiveness of warfarin, thus could increase the risk of blood clots
217
Drug interaction of grapefruit juice
Increases effectiveness of calcium channel blockers
