Pharmacology Flashcards
1
Q
Four main drug targets
A
- Receptors
- Enzymes
- Transporters
- Ion channels
2
Q
T/F most drug targets are carbohydrates
A
FALSE
Most are proteins
3
Q
What is a receptor
A
A cell component that interacts with a specific ligand and initiates a change of biochemical events ➡️ the ligands observed effect
4
Q
Types of ligand
A
- exogenous - drugs
- endogenous - hormones N-transmitters etc.
5
Q
Types of receptors
A
- Ligand gated ion channels
- G-protein coupled receptor
- kinase-linked receptors
- Nuclear receptors [AKA cytosolic receptors]
6
Q
Example of a ligand gated ion channels
A
Nicotine ACh receptors
7
Q
Example of a kinase-linked receptor
A
Receptors for growth factor
8
Q
Example of nuclear receptors
A
Steroid hormone receptors e.g. oestrogen
9
Q
Example of G-protein coupled receptors
A
Beta adrenoceptors
10
Q
What is an ion channel
A
Pore forming membrane proteins that allow ions to pass into the cell and cause a shift in electric charge distribution by diffusion of +ve of -ve ions in or out
11
Q
What is the largest group of membrane receptors
A
G-coupled proteins
12
Q
Describe the structure of a GCPR
A
7 transmembrane helices
13
Q
Examples of GPCR ligands
A
Light energy
Peptides
Lipids
Sugars
Proteins
14
Q
What are G proteins
A
A family of proteins that transmit signals from GPCRs
15
Q
What factors regulate GPCR activity
A
- factors that control the ability to bind and hydrolyse GTP ➡️ GDP
= guanosine triphosphate = guanosine diphosphate
16
Q
Describe the mechanism of action of kinase liked receptors
A
- Kinase enzymes are linked to the receptor and catalyse the transfer of phosphate groups to tyrosine proteins via phosphorylation.
- Transmembrane receptors are activated when an extracellular ligand binds ➡️ enzymatic activity on the intracellular side.
17
Q
Mechanism of action of nuclear receptors
A
Modifies gene transcription by binding to ligand binding site on DNA.
18
Q
Example of a nuclear receptor drug target
A
Tamoxifen acts as aselective estrogen receptor modulator(SERM), or as apartial agonistof theestrogen receptors.
19
Q
Define an agonist
A
a compound that binds to a receptor and activates it
20
Q
Define an antagonist
A
a compound that reduces the effect of at a receptor
21
Q
What is the 2 state model of receptor activation
A
Where a drug activates receptors by inducing or supporting a conformational change in the receptor to switch it on.
22
Q
Define potency
A
- Concentration or amount of a drug that is needed to produce a defined effect
- measured using EC50
23
Q
What is EC50
A
The concentration that gives half the maximal response.
24
Q
What is a full agonist
A
An agonist that ➡️ full activation of the receptor and full response even with few receptors occupied
25
What is a partial agonist
A ligand that ➡️ a sub-maximal response no matter the number of receptors occupied or the concentration of ligand
26
Which compound is more potent and by how much?
Compound B is 30 fold more potent
27
Which compound is more efficacious
Compound A
28
What is intrinsic activity
The efficacy of a drug
29
Define efficacy
The ability of a drug-receptor complex to produce a maximum functional response
30
T/F Agonist and antagonists have efficacy
False only agonists have efficacy
Antagonists have ZERO efficacy
31
Describe the activity of these agonists
Compound D is more potent than compound A
compound A is more efficacious than compound D
32
T/F antagonists can activate receptors
False
33
What type of antagonism does this graph show
Competitive antagonism as it binds to the same site as the ligand which reduced the “potency”
34
What type of antagonism does this show
Non-competitive antagonism as the antagonist prevents the ligand binding to the receptor ➡️ reduced response [efficacy]
35
What are the categories of cholinergic receptors
1. Nicotinic
2. Muscarinic
36
What is a muscarinic receptor agonist
Muscarine
37
What is a muscarinic receptor antagonist
Atropine
38
What is a nicotinic receptor agonist
Nicotine
39
What is a nicotinic receptor antagonist
Curare
40
What happens when H1 receptors are activated
Allergic reactions
41
what happens when H2 receptors are activated
Gastric acid secretion
42
What happens when H4 receptors are activated
- immune system activation
- inflammatory conditions - such as rhinitis, asthma and pruritus
- inflammatory pain
43
What type of receptors are histamine receptors
GPCR
44
2 receptor related factors governing drug action
- affinity
- efficacy
45
2 tissue related factors governing drug action
- receptor number
- signal amplification
46
Define affinity
How well a ligand binds to a receptor
47
T/F affinity is a property shown only by agonists
FALSE
Both agonists and antagonists display affinity
48
T/F partial agonists have a receptor reserve
False
Even at 100% occupancy a maximal response is not seen
49
Define a receptor reserve
The condition where the agonist produces a maximal response by occupying a small fraction of the available receptors, leaving spare receptors as the receptor reserve.
50
Define signal transduction
Receptor activation ➡️ a series of molecular events inside the cell ➡️ cellular response
51
Define signal amplification
an increase in the intensity of a signal through networks of intracellular reactions
52
Define inverse agonism
When a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist.
53
What is allosteric modulation
A ligand binding to a separate site to the receptor active site ➡️ a conformational change in the active site ➡️ increased or decreased affinity of the ligand to the receptor
54
What is tolerance
- A reduction in the agonist effect over time
- caused by continuous or repeated high concentrations
55
What is desensitisation
- The rapid duction in response to an agonist.
- a defence mechanism to prevent overstimulation
56
T/F.
Desensitisation is a slow process and tolerance is a rapid one
FALSE
Desensitisation is a rapid process and tolerance is a slow one
57
Define selectivity
The ability to affect 1 subtype of a receptor and not another
- e.g. salbutamol selectively agonises on B2 adrenoceptors
58
What is the bioavailability of morphine
50%
59
Convert a 20mg oral dose of morphine to a parenteral dose
10mg
Half the dose because 50% bioavailability
60
How long does a single dose of immediate release morphine last
3-4 hours
61
How long does it take for IV preparations to take effect
~ 1min because the blood travels around the whole body in about 1 min
62
How long does it take for SC preparations to take effect
~30mins
63
How long does it take for oral preparations to take effect
~ 1 hour
64
Difference between morphine and diamorphine
Diamorphine is a modified version of morphine that is more potent and faster acting as it crosses the BBB faster
65
How do opioids work
By descending inhibition of pain via blocking opioid receptors
66
Types of opioid receptors
- miu - MOP
- kappa - KOP
- delta - DOP
- nociceptin opioid-like receptor - NOP
67
TOLERANCE =
Down regulation of the receptors with prolonged use
Need higher doses to achieve the same effect
68
Dependence =
Psychological - craving and euphoria
Physical dependence
69
Common side effects of opioids
- respiratory depression
- constipation
- sedation
- N+V
- itching
- Immune suppression
- Endocrine effects
70
What is used to treat opioid induced respiratory depression
Naloxone
- IV is fastest
- has a host half life therefore, give depot first in case pt runs off when they come around
71
MHRA advice for prescribing opioids in chronic, non-cancer pain
* Before prescribing opioids, discuss with the patient the risks and features of tolerance, dependence, and addiction - use short term courses
* Agree a treatment strategy and plan for end of treatment
* Warnings have been added to the drug labels and packaging of opioids to support patient awareness
* At the end of treatment, taper dosage slowly to reduce the risk of withdrawal effects - may take weeks
72
What is codeine metabolised into
Morphine
73
Which enzyme metabolises morphine and codeine
CYP2D6
74
What is morphine metabolised into
morphine 6 glucuronide - a more potent drug than morphine
75
How is morphine excreted
morphine 6 glucuronide is renally excreted.
76
What patient factors need to be considered when prescribing morphine
- **renal function**: reduced renal function ➡️ respiratory depression due to build up of morphine 6 glucuronide - a more potent version.
- **pharmacogenetics**: CYP2D6 presence and activity in individuals varies ➡️ reduced or absent responses.
77
What do you prescribe for opioid pain relief in pts with renal function <30%
Morphine cannot be effectively cleared so oxycodone is given instead as its metabolite is weaker than the parent drug and accumulation is not as dangerous
78
Which enzyme breaks down tramadol
CYP2D6
79
Tramadol primary and secondary effects
- primary
- weak opioid agonist
- secondary
- SNRI - serotonin and nor-epinephrine reuptake inhibitor.
80
Define bioavailability
The proportion of a drug that reaches systemic circulation after administration, and is able to have an effect.
81
Define pharmacodynamics
What the drug does to the body.
82
Define pharmacokinetics.
What the body does to the Drug.
- Absorption
- Distribution
- Metabolism
- Elimination / excretion.
83
What is an irreversible inhibitor
A molecule that binds to the active site of an enzyme and changes it chemically eg by covalent bonds.
84
What is a reversible inhibitor
A molecule that binds non-covalently and produce different types of inhibition based on whether these inhibitors bind to:
- the enzyme
- the enzyme-substrate complex
- both
85
Define active transport.
- Movement of ions from low concentration to higher concentration.
- needs energy to work.
- needed for cells to get ions, glucose, amino acids etc.
86
Types of protein ports
- **uniporters**: use ATP to pull molecules in
- **symporters**: the movement in of one molecule to pull in another molecule against a concentration gradient.
- **antiporters**: one substance moves against its gradient, using energy from the second substance one substance moves against its gradient, using energy from the second substance
87
Where can you find symporters?
Give an example
In organs that secrete fluids
NKCC - Na-K-Cl cotransporter in kidney
88
What are the main drug targets in the body
1. Receptors
2. Enzymes
3. Transporters
4. Ion channels
89
Where can opioid receptors be found
- CNS
- GIT
- respiratory system
90
How does naloxone work
A competitive opioid receptor inhibitor
91
Why are ADRs concerning
1. Adversely affect patients' quality of life
1. Increase costs of patient care
1. Preclude use of drug in most patients, although they may occur in only a few patients
1. May mimic disease
1. Very common cause of death, behind heart disease, cancer and stroke
92
What is an ADR
- An unwanted or harmful reaction following administration of a drug or combination of drugs under normal conditions of use and is suspected to be related to the drug.
- Has to be noxious and unintended
93
Difference between ADR and side effects
- ADRs are unexpected and harmful
- Side effects are minor, predictable and can be beneficial
94
How do toxic effects occur
- dose too high
- drug interactions
- reduced excretion due to renal or hepatic impairment
95
3 broad ADR risks
1. Patient risk
2. Drug risk
3. Prescriber risk
96
Examples of patient risk factors for ADRs
Gender (F>M)
Elderly
Neonates
Polypharmacy (21% 5 or more drugs)
Genetic predisposition
Hypersensitivity/allergies
Hepatic/renal impairment
Adherence problems
97
Examples of drug risk factors for ADRs
- low therapeutic index
- commonly causes ADRs
- steep dose-response curve
98
T/F
All ADRs occur immediately
False
- ADRs can occur rapidly, late, delayed or intermediate.
99
What is the Rawlings Thompson ADR classification system
- **Type A**: Augmented pharmacological
- **Type B**: Bizzare or idiosyncratic
- **Type C**: Chronic
- **Type D**: Delayed
- **Type E**: End of treatment
- **Type F**: Failure of therapy
100
What is a type A ADR
Augmented pharmacological
- A predictable, dose dependent common ADR
- Accounts for ~80% of all ADRs
101
What is a type B ADR
Bizzare
- not predictable and not dose dependent
- e.g. anaphylaxis with penicillin
102
What is a Type C ADR
Chronic
- e.g. osteoporosis caused by steroid use
103
What is a type D ADR
Delayed
- e.g. malignancies after immunosuppression
104
Type E ADRs
End of treatment
- occur after abrupt withdrawal of meds
- e.g. opiate withdrawal syndrome
105
What is a type F ADR
Failure of therapy
- Failure of oral contraceptive pill in presence of enzyme inducer
106
What does DoTS stand for
* **Do**se relatedness (toxic, collateral or hypersusceptibility)
* **T**iming eg fast infusion of frusemide hearing loss and tinnitus
* Patient **s**usceptibility eg patient factors
107
How do Type A ADRs present
- an extension of primary effects - e.g. hypoglycaemia and insulin
- a secondary effect of the drug - e.g. bronchospasm with beta blockers
108
Features of type B ADRs
- unpredictable and not related to pharmacology
- not dose dependent
- cannot readily be reversed
- less common but more serious and can be life threatening
- low morbidity and high mortality
- can be caused by allergy/ hypersensitivity
109
What is idiosyncrasy
- An inherent abnormal response to a drug. Caused by:
- genetic abnormality ➡️ enzyme deficiency
- abnormal receptor activity, e.g. Malignant hyperpyrexia with general anaesthetics
- rare but serious
110
How does one develop an allergy / hypersensitivity reaction
1. Antigen/antibody reaction
1. First dose acts as antigen
1. Antibody produced
1. Second dose causes antibody-antigen reaction
111
What are the types of hypersensitivity reactions
* **Type 1:**immediate anaphylactic IgE eg penicillin allergy
* **Type 2:** cytotoxic antibody IgG, IgM eg methyl dopa and haemolytic anaemia
* **Type 3:** immune complexes eg procainamide induced lupus
* **Type 4:** delayed hypersensitivity T cell eg contact dermatitis
112
Features of a type C ADR
- **chronic** [continuous]
- uncommon
- related to cumulative dose
- time related
- e.g. steroid use ➡️ osteoporosis. Colonic dysfunction due to laxatives
113
Features of a type D ADR
- **delayed**
- usually dose related
- uncommon
- shows itself some time after the use of the drug
- e.g. teratogens is and carcinogenesis
114
Features of a type E ADR
- **End of drug use **
- uncommon
- occurs soon after drug is withdrawn
- E.g
- Opiate withdrawal
- Glucocorticoid abruptly withdrawn leads to adrenocortical insufficiency
- Withdrawal seizures when anticonvulsants are stopped
115
Features of Type F ADRs
- **Failure**
- common
- dose related
- often caused by interactions
- e.g: failure of oral contraceptive pill with an enzyme inducer
116
When should you suspect an ADR
- Symptoms soon after a new drug is started
- Symptoms after a dosage increase
- Symptoms disappear when the drug is stopped
- Symptoms reappear when the drug is restarted
117
What actions should be taken if an ADR is suspected
1. Assess if urgent action is required
1. Take a history
1. Review medication history
1. Review the adverse effect profile of suspected drug
1. Modify dose, stop or swap
1. Report
118
What are the most common systems to be affected by ADRs
- GI
- Renal
- Haemorrhagic
- Metabolic
- Endocrine
- Dermatological
119
6 common ADRs
1. Confusion
1. Nausea
1. Balance problems
1. Diarrhea
1. Constipation
1. Hypotension
120
T/F
Reporting ADRs is a legal requirement
FALSE
It is good practice
121
What do you report on a yellow card
- **All suspected reactions for**
* herbal medicines
* black triangle ▼ drugs
- **All *serious* suspected reactions for**
* established drugs, vaccines and contrast media
* drug interactions
122
What does the ▼ Black Triangle mean?
The black triangle ▼ indicates a medicine is undergoing ‘additional monitoring’
123
Which preparations are given a black triangle
1. New active substances
2. Biological meds or anything derived from plasma
3. Anything given conditional approval
4. Anything that requires additional studies e.g. for side effect monitoring
124
Who can report on a yellow card
- Doctors, dentists, coroners, pharmacists, nurses, including midwives and health visitors, radiographers, optometrists.
- pts, parents or carers since 2005
125
4 key bits of info to put on a yellow card
Suspected drug(s)
Suspect reaction(s)
Patient details
Reporter details
ALSO: Additional useful information
126
Draw out the structure of the nervous system
127
What does the somatic nervous system innervate and what is the result of its activation
The skeletal muscle
Activation ➡️ muscle excitation
128
How many neutrons lie between the CNS and the skeletal muscle in the somatic nervous system
1
129
How many neutrons lie between the CNS and the target organs in the autonomic nervous system
2 neutron chain with a ganglion in between
130
What does the autonomic nervous system innervate?
- Smooth muscle
- cardiac muscle
- glands
- GI neutrons
131
What is the result of autonomic system activation
Leads to excitation or inhibition
132
Fight or fight is associated with the
Sympathetic nervous system
133
Rest and digest is associated with which nervous system
Parasympathetic
134
Which nervous system has an autonomic ganglion adjacent to the spinal cord
Sympathetic
135
Which nervous system has an autonomic ganglion near the effector organ
Parasympathetic
136
What neurotransmitters does the somatic nervous system use
Acetylcholine
137
What neurotransmitters does the parasympathetic nervous system use
Acetylcholine
138
What neurotransmitters does the sympathetic nervous system use
Acetylcholine and noradrenaline
139
Types of acetyl choline receptors and which systems they are found in
- nicotinic - found in somatic nervous systems
- muscarinic - found in parasympathetic nervous systems
140
Which nervous system and neurotransmitter are responsible for sweat glands
ACh released at sympathetic post ganglion if termini
141
Which nervous system and neurotransmitter are responsible for blood vessels
Nitric oxide released from the Parasympathetic postganglionic termini
142
Nicotine stimulates which nervous systems
Parasympathetic and sympathetic
143
Muscarine stimulates which nervous systems
Parasympathetic
144
How many muscarinic receptor types are there and where are they found
M1: Brain
M2: Heart
M3: All organs with parasympathetic innervation
M4: Mainly CNS
M5: Mainly CNS
145
What type of receptor are muscarinic receptors
GPCR
146
Effect of activation of M2 on heart SA node
Decreases the heart rate
147
Effect of activation of M2 on heart AV node
- Decrease in conduction velocity
- induces AV node block
148
Type of muscarinic receptor found in the respiratory system AND effect of stimulation
- **M3**
- produces mucus in the airways and nasopharynx
- induces bronchoconstriction - smooth muscle contraction
149
Type of muscarinic receptor found in the GIT system AND effect of stimulation
- **M3**
- Increase saliva production
- Increases gut motility
- Stimulates biliary secretion
150
Type of muscarinic receptor found in the skin, which nervous system is responsible AND effect of stimulation
- M3
- **sympathetic** system releases ACh
- stimulates the sweat glands to release sweat
151
Type of muscarinic receptor found in the urinary system AND effect of stimulation
- **M3**
- Contracts detrusor muscle
- Relaxation of internal urethral sphincter
152
Type of muscarinic receptor found in the eye AND effect of stimulation
- **M3**
- Causes myosis
- Increases drainage of aqueous humour
- Secretion of tears
153
symptoms of Muscarine poisoning
- blurred vision
- hypersalivation
- bronchoconstriction
- bradycardia
- diarrhoea
- polyuria
- hyperhidrosis
154
T/F ACh is implicated in memory and can contribute to memory problems
True
155
Cause of myasthenia gravis
Blockage of normal ACh transmission ➡️ skeletal muscle weakness, especially on repeated attempts on movement.
156
Myasthenia gravis treatment
Anticholinesterase to increase availability of ACh at the NMJ.
- e.g.
157
Where is noradrenaline released from
From the sympathetic nerve fibre
158
Where is adrenaline released from
Adrenaline glands
159
Alpha 1 receptor agonist
Noradrenaline and adrenaline
NAd>Ad
160
Alpha 1 receptor is found where
AND what are the results of activation
- found in blood vessels
- results in smooth muscle contraction in pupils and blood vessels and skin
161
Alpha 2 receptor agonists
Noradrenaline and adrenaline
162
Result of alpha 2 receptor activation
Mixed effects on vascular smooth muscle
Also found in the brain
163
Beta 1 receptor agonists
Noradrenaline and adrenaline
164
Effects of activation of receptor activation
Chronotropic and ionotropic effects on the heart
165
Beta 2 receptor agonists
Adrenaline and noradrenaline
Ad> NAd
166
Effects of beta 2 receptor activation
Relaxes smooth muscle in the lungs and uterus
167
Beta 3 receptor agonist
Noradrenaline and adrenaline
NAd> Ad
168
Consequences of beta 3 receptor activation
- Enhances lipolysis
- relaxes bladder debris or
169
Alpha 1 blocker uses
- lower BP
- phaeochromocytoma
- BPH
170
Clinical uses of alpha 2 blockers
Trick question there aren’t any
171
Beta 1 receptor locations
- heart
- kidney
- fat cells
172
Effect of beta 1 receptor agonism
- tachycardia
- increase in stroke volume
- renin release to increase vascular tone
- lipolysis and hyperglycaemia
173
Beta 1 receptor blockers effects
- reduced heart rate
- reduced stroke volume
- Reduce stroke volume
- Reduce myocardial oxygen demand and help remodelling in heart failure or post-myocardial infarction
174
What do you use for beta blocker poisoning and why
- **glucagon**
- used because glucagon increases the heart rate and myocardial contractility regardless of the presence of beta blockers as it bypasses the beta-adrenergic receptor site
175
5 locations of beta 2 receptors and the effect of their agonism
176
Uses of beta 2 receptor agonists
- asthma
- COPD
- Tocolysis - delaying preterm labour
177
Side effects of beta 2 receptor agonists
- tremor
- tachycardia
- hyperglycaemia - due to glucagon release
