Pharmacology Flashcards
(188 cards)
1
Q
What is pharmacodynamics?
A
Effect of a drug on the body
2
Q
What is pharmacokinetics?
A
Effect of the body on a drug
3
Q
What are the 4 physicochemical reactions?
A
- Adsorption
- Precipitation
- Chelation
- Neutralisation
4
Q
What is summation?
A
If 2 half doses of drugs are given at the same time, can get a full dose as a result of the combination
5
Q
What is synergy?
A
When a dose is more than expected when a combined dose is given
6
Q
What is potentiation?
A
Drug A stays the same but causes drug B to have an increased effect
7
Q
What are the patient risk factors for drug interactions?
A
- Polypharmacy
- Old age
- Genetics
- Hepatic disease
- Renal disease
8
Q
What are the drug risk factors for drug interaction?
A
- Narrow therapeutic index
- Step dose/response curve
- Saturable metabolism
9
Q
What are the mechanisms of pharmacokinetics?
A
- Absorption
- Distribution
- Metabolism
- Excretion (ADME)
10
Q
What are the mechanisms of pharmacodynamics?
A
- Receptor based
- Signal transduction
- Physiological systems
11
Q
Describe the absorption of IV drugs
A
Starts low then get quick increase in blood concentration of a drug, which exponentially goes down after it peaks
12
Q
Describe the absorption of oral drugs
A
Low peak which is reached slowly but takes longer to get rid of as it is still being absorbed from the gut even as it is being excreted
13
Q
What is bioavailability?
A
How much of a dose of a drug you get
14
Q
What type of drug is given in ICU to increase feed of pt.?
A
Drugs to increase gut motility
15
Q
What effect does changing the pH of a drug environment have?
A
Changes portion of ionised: non-ionised drug
16
Q
What does it mean if there’s a big volume of distribution?
A
Most of the drug will not go to the effector site
17
Q
What happens if there is a low volume of distribution?
A
The drug is fairly targeted to the effector site
18
Q
What happens in enzyme induction?
A
Drug A increases the effect of CYP450 to make drug B more potent
19
Q
What is enzyme inhibition?
A
Drug A reduces the effect of CYP450 to make drug B less potent
20
Q
What is given to overcome aspirin overdose?
A
NaCO3 which causes excretion of aspirin to happen faster
21
Q
What drugs cause AKI?
A
NSAIDs, furosemide
22
Q
What is the effect of grapefruit juice?
A
Affects CYP3A4 to increase bioavailability
23
Q
What are the routes of excretion?
A
Renal, biliary
24
Q
What is a drug?
A
Medicine or other substance which has a physiological effect when ingested or otherwise introduced into body
25
What is druggability?
Ability of a protein target to bind small molecules with high affinity
26
What are the 4 common drug targets?
1. Receptors
2. Enzymes
3. Transporters
4. Ion channels
27
What is a receptor?
A component of a cell that interacts with a specific ligand and initiates a change of biochemical events leading to ligands observed effects
28
What are the 4 common receptors?
1. Ligand-gated ion channels
2. G protein coupled receptors
3. Kinase-linked receptors
4. Cytosolic/nuclear receptors
29
What do the majority of GPCRs interact with?
PLC or adenylyl cyclase
30
What can change the way a receptor responds?
Polymorphisms
31
What happens when a ligand binds a kinase linked receptor?
Causes polymorphism of components which then recruit molecules which only interact with phosphorylated component of receptor to amplify signal on IC side
32
What is a receptor ligand?
A molecule that binds to another molecule
33
What is an agonist?
A compound that binds to a receptor and activates it
34
What is an antagonist?
A compound that reduces the effect of an agonist
35
What is potency?
EC50, concentration that gives half the maximal response
36
What is efficacy (Emax)?
Maximum response achievable from a dose
37
What is intrinsic activity?
Ability of a drug-receptor complex to produce a maximal functional response
38
How do you determine intrinsic activity (IA)?
IA = Emax of a partial agonist ÷ Emax of full agonist
39
What is competitive antagonism?
Directly competes for binding to receptor
40
What is non-competitive antagonism?
Binds to an allosteric site of receptor to prevent activation of receptor
41
What are the 2 categories of cholinergic receptor?
Nicotinic and muscarinic
42
What factors govern drug action?
1. Affinity
2. Efficacy
3. Receptor number
4. Signal amplification
43
What is affinity?
Describes how well a ligand binds to receptor
44
What is efficacy?
Describes how well a ligand activates a receptor
45
What is receptor reverse?
Where an agonist needs to activate only a small fraction of existing receptors to produce a maximal system response
46
What is a signal cascade?
Response following ligand binding a receptor by causing a number of amplification steps
47
What is allosteric modulation?
Where antagonist (or ligand) binds to a site which isn't the active site of that receptor
48
What is inverse agonism?
When a drug binds to the same receptor as an agonists but induces a pharmacological response opposite to that of the agonist
49
What is tolerance?
Reduction in agonist effect over time
50
When does desensitisation occur?
When proteins are uncoupled, internalised or degraded
51
What is an enzyme inhibitor?
A molecule that binds to an enzyme and decreases its activity
52
How do enzyme inhibitors work?
Prevent substrate from entering enzyme's active site and prevents it from catalysing its reaction
53
What are the types of enzyme inhibitor?
1. Irreversible inhibitors
| 2. Reversible inhibitors
54
How do irreversible inhibitors bind?
Covalent bond
55
What are the symptoms of Parkinson's?
```
Hypokinesia
Tremor at rest
Muscle rigidity, motor inertia
Cognitive impairment
Degenerative disease of basal ganglia
```
56
What is the pathway for Parkinson's?
Early degeneration of dopaminergic in nigrostriatial pathway leading to autonomic dysfunction and dementia
57
What are the 3 main protein ports?
1. Uniporter
2. Symporter
3. Antiporter
58
How do uniporters work?
Use energy from ATP to pull molecules in
59
How do symporters work?
Use movement in of one molecule to pull in another molecule against a concentration gradient
60
How do antiporters work?
One substance moves against its gradient, using energy from second substance moving down its gradient
61
What is the mechanism of action for furosemide?
Inhibits luminal NKCC co-transporter in thick ascending limb of loop of Henle to cause loss of Na, Cl and K in urine
62
What is ENaC?
An apical membrane-bound heterotrimeric ion channel selectively permeable to Na ions
63
What high affinity diuretic blocks ENaC?
Amiloride
64
Where are voltage gated Ca channels found?
Membrane of excitable cells
65
How do voltage gated Ca channels work?
Ca enters cell, resulting in activation of Ca-sensitive K channels, muscular contraction, excitation of neurons etc.
66
What is amlodipine?
An angioselective Ca channel blockers that inhibits the movement of Ca ions into vascular smooth muscle cells and cardiac muscle celsl
67
How does amlodipine work?
1. Inhibits Ca ion influx across cell membranes with greater effect on vascular SMC.
2. Causes vasodilation and a reduction in peripheral vascular resistance.
3. Lowers BP and prevents excessive constriction in coronary arteries
68
What is the main inhibitory neurotransmitter in the CNS?
GABA
69
What drug inhibits Na/K ATPase?
Digoxin
70
What is a heterodimeric protein?
Where 2 distinct proteins come together and assemble in the membrane
71
What is H/K ATPase responsible for?
Acidification of the stomach, activation of the digestive enzyme pepsin
72
What is the ideal target for inhibiting acid secretion?
Proton pump
73
What are the symptoms of irreversible inhibition of muscarinic receptors?
```
Salivation
Defecation
Urination
Bradycardia
Hypotension
```
74
What are the symptoms of irreversible inhibition of nicotinic receptors?
Twitching
Severe weakness
Paralysis of diaphragm
75
What are the symptoms of irreversible inhibition of the CNS?
Confusion
Loss of reflexes
Convulsions
Coma
76
What are xenobiotics?
Compounds foreign to an organism's normal biochemistry
77
How much oral morphine is metabolised by first pass metabolism in the liver?
50%
78
What method is used for morphine release in palliative care?
MST continus
79
Why is diamorphine more potent and faster acting than morphine?
It crosses the BBB faster
80
What are the practical issues with controlled drugs?
Secure storage, CD books that need 2 signatures, prescription regulations
81
In what proportion of people is codeine not metabolised?
10%
82
What receptor type do opioids act on?
GPCRs via 2nd messengers
83
How do opioids work?
Inhibit release of pain transmitters at spinal cord and midbrain and modulate pain perception in higher centres
84
What are the 4 main opioid receptors?
MOP (mu), KOP (kappa), DOP (delta), NOP (nociception)
85
What is the side effect of activating kappa OP?
Depression instead of euphoria
86
What opioid receptor do all current drugs target?
Mu
87
What is tolerance?
Downregulation of receptors with prolonged use
88
What is dependence?
A psychological response to drugs with cravings and euphoria
89
How long until opioid withdrawal sets in?
24 hours
90
What are the side effects of opioids?
1. Respiratory depression
2. Sedation
3. Nausea and vomiting
4. Constipation
5. Itching
6. Immune suppression
7. Endocrine effects
91
What drug is given as treatment for respiratory repression?
Naloxone
92
What metabolises codeine to work?
CYP2D6
93
Why might someone be at increased risk of respiratory depression with codeine?
Overactive CYP2D6
94
What builds up to cause respiratory depression when taking morphine with renal failure?
Morphine 6 glucuronide
95
What alternative to morphine is used in patients with renal failure?
Oxycodone
96
What is the secondary effect of tramadol?
Serotonin and noradrenaline reuptake inhibitor
97
What does tramadol interact with?
SSRIs, tricyclic antidepressants, MAOIs
98
Why can nicotinic receptors not be targeted for the nervous systems?
It is used in both sympathetic and parasympathetic pathways
99
What pathway does cholinergic pharmacology target?
Parasympathetic
100
What does nicotine stimulate?
All autonomic ganglia via specific ganglionic nicotinic receptors
101
What does muscarine activate?
Muscarinic receptors of parasympathetic nervous system
102
What is targeted in cholinergic pharmacology?
Muscarinic receptors
103
What are the muscarinic receptors?
M1-5
104
Where is M2 found?
Heart
105
What are drugs which target M2 used for?
Life-threatening bradycardia, cardiac arrest
106
Where are M3 found?
Glandular and smooth muscle
107
What do M3 cause?
Bronchoconstriction, sweating, salivary gland secretion
108
What is hyoscine used for?
To reduce respiratory secretions in palliative care
109
Give 5 side effects of anti-cholinergic drugs
1. Confusion
2. Constipation
3. Dry mouth
4. Blurred vision
5. Glaucoma
110
Give 4 side effects of cholinergic drugs
1. Muscle paralysis
2. Twitching
3. Salivation
4. Confusion
111
Which receptors is NA the agonist for?
Alpha 1, Beta 3
112
Which receptors is Adr the agonist for?
Beta 2
113
Which receptors are NA and Adr the agonists for?
Alpha 2, Beta 1
114
What is the mechanism of alpha 1?
Increases intracellular Ca, Gq signalling
115
What is the consequence of alpha 1?
Contracts smooth muscle
116
What is the mechanism of alpha 2?
Gi signalling, inhibition of cAMP generation
117
What is the consequence of alpha 2?
Mixed effects on smooth muscle
118
What is the mechanism of the beta receptors?
Gs, raises cAMP
119
What is the consequence of beta 1?
Chronotropic and inotropic effects on heart (increase strength and stroke volume)
120
What is the consequence of beta 2?
Relaxes smooth muscle (premature labour, asthma)
121
What is the consequence of beta 3?
Enhances lipolysis, relaxes bladder detrusor
122
Name a drug control-indicated in asthma which blocks beta 1/2
Propranolol
123
Give 5 uses of beta blockers
1. Angina
2. MI prevention
3. High BP
4. Anxiety
5. Arrhythmias
6. HF
124
Give 5 side effects of beta blockers
1. Tiredness
2. Cold extremities
3. Bronchoconstriction
4. Bradycardia
5. Hypoglycaemia
6. Cardiac depression
125
What % of hospital admissions do adverse drug reactions account for?
5%
126
What is an adverse drug reaction?
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 drug
127
What are the requirements for an adverse drug reaction?
Noxious and unintended
128
What is a side effect?
An unintended effect of a drug related to its pharmacological properties and can include unexpected benefits of treatment
129
What causes adverse drug reactions (ADRs)?
1. Toxic effects
2. Collateral effects
3. Hypersusceptibility effects
130
When can toxic effects occur?
1. If dose is too high
2. If drug excretion is reduced
3. Interaction with other drugs
131
What is a type A ADR?
Augmented pharmacological - predictable, dose dependent, common
132
What is a type B ADR?
Bizarre or idiosyncratic - not predictable and not dose dependent
133
What is a type C ADR?
Chronic
134
What is a type D ADR?
Delayed
135
What is a type E ADR?
End of treatment - occur after abrupt drug withdrawal
136
What is a type F ADR?
Failure of therapy
137
What is DoTS in relation to ADR causes?
Dose relatedness, Timing, patient Susceptibility
138
What are 5 patient risk factors for ADRs?
1. Female
2. Elderly
3. Polypharmacy
4. Genetic predisposition
5. Renal impairment
139
What are 3 drug risk factors for ADRs?
1. Steep dose-repense curve
2. Low therapeutic index
3. Commonly causes ADRs
140
What are the main causes for ADRs?
1. Pharmaceutical variation
2. Receptor abnormality
3. Abnormal biological system unmasked by drug
4. Abnormalities in drug metabolism
5. Immunological
6. Drug-drug interactions
7. Multifactorial
141
What is idiosyncrasy?
Inherent abnormal response to a drug
142
When should an ADR be suspected?
1. Symptoms soon after a new drug is started
2. Symptoms after a dosage increase
3. Symptoms disappear when drug is stopped
4. Symptoms reappear when drug is restarted
143
Give 5 common symptoms of ADRs
1. Confusion
2. Nausea
3. Balance problems
4. Diarrhoea
5. Constipation
6. Hypotension
144
What is the yellow card scheme?
ADR reporting scheme
145
Give 2 advantages of the yellow card scheme
1. Early warning system for identifying reactions
| 2. Provides info about what factors predispose patients to ADRs
146
Give 2 disadvantages of the yellow card scheme
1. Not all ADRs are reported
| 2. Relies on ADR being recognised
147
What is a black triangle drug?
A medicine which is undergoing additional monitoring
148
What is hypersensitivity?
Objectively reproducible symptoms or signs, initiated by exposure to a defined stimulus at a dose tolerated by normal subjects and may be caused by immunologic or non-immunologic mechanisms
149
What are 5 symptoms of anaphylaxis?
1. Rash
2. Oedema/swelling
3. Shortness of breath
4. Hypotension
5. Cardiac arrest
150
What causes non-immune anaphylaxis?
Direct mast cell degranulation
151
How much adrenaline is given in anaphylaxis?
500 mcg
152
How does adrenaline work?
Stimulates Beta1-adrenoceptors to give positive ionotropic and chronotropic effects on heart
153
What are the actions of drugs in the body?
1. Absorption
2. Distribution
3. Metabolism
4. Excretion
154
What is absorption?
The process of transfer from the site of administration into the general or systemic circulation
155
How can drugs cross membranes?
1. Passive diffusion
2. Diffusion through pores or ion channels
3. Carrier mediated
4. Pinocytosis
156
What is required to passively diffuse over the lipid bilayer?
Degree of lipid solubility
157
What is pinocytosis involved in?
Uptake of endogenous macromolecules, can be involved in uptake of recombinant therapeutic proteins
158
Why are ionisable groups essential for most drug mechanisms?
Ionic forces are part of ligand receptor interaction
159
What does the extent of ionisation depend on?
1. Strength of ionisable group
| 2. pH of solution
160
What affects the speed of oral absorption?
1. Drug structure
2. Drug formulation
3. Gastric emptying
4. First pass metabolism
161
What metabolic barriers must drugs taken orally pass to reach circulation?
1. Intestinal lumen
2. Intestinal wall
3. Liver
4. Lungs
162
How can hepatic first pass metabolism be avoided?
Give drug to region of gut not drained by splanchnic
163
How are inhalation drugs limited?
1. Risks of toxicity to alveoli
| 2. Delivery of non-volatile drugs
164
What is distribution?
The process by which the drug is transferred reversibly from the general circulation to the tissues as the blood concentration increases and then returns from the tissues to the blood when the blood concentration falls
165
What type of drugs easily pass from blood to brain?
Lipid soluble drugs
166
What protects the brain by returning drug molecules to the circulation?
Efflux transporters
167
What is elimination
Removal of drugs activity from body
168
What may elimination consist of?
Metabolism and excretion
169
What is metabolism re. drugs?
Transformation of drug molecule into a different molecule
170
What is excretion re. drugs?
Molecule is expelled in liquid, solid or gaseous waste
171
What does phase 1 of drug metabolism involve?
Transformation of drug to a more polar metabolite by unmasking or adding a functional group
172
What catalyses most phase 1 reactions?
Cytochrome P450
173
What can induce P450?
Smoking and alcohol
174
What can inhibit P450?
Drugs and food e.g. cimetidine and grapefruit
175
What does phase 2 drug metabolism involve?
Formation of covalent bond between drug or its phase 1 metabolite and an endogenous substrate
176
What are the processes in renal drug processing?
1. Glomerular filtration
2. Tubular secretion
3. Reabsorption
177
What is zero order kinetics?
The change in concentration per time is a fixed amount of drug per time, independent of concentration
178
What is first order kinetics?
Change in concentration at any time is proportional to the concentration
179
What is half-life?
Time taken for a concentration to reduce by one half
180
What is half-life used for in practice?
Elimination rate from plasma
181
What is bioavailability?
The fraction of the administered drug that reaches the systemic circulation unaltered
182
What is the bioavailability of IV drugs?
1 (100%)
183
What is distribution?
Rate and extent of movement of a drug into and out of tissues from blood
184
What does drug distribution determine?
Total amount of drug that has to be administered to produce a particular plasma concentration
185
What is clearance?
Volume of blood or plasma cleared of drug per unit time
186
What are repeated drug doses used to maintain?
A constant drug conc. in the blood and at the site of action for therapeutic effect
187
What is steady state?
Balance between drug input and elimination
188
How can plasma steady state be altered in oral drugs?
Change dose or interval
