Intro to pharmacology Flashcards
1
Q
Drug harms
A
anaphylactic reactions
side effects
terogenicity (he ability to cause defects in a developing fetus)
dependency
2
Q
what does ADME stand for in pharmacokinetics
A
Absorption
distribution
metabolism
excretion
3
Q
digoxin drug - what its used for etc.
A
slows conduction at cardiac AV node
used for arrhythmia management and heart failure
really excreted
risk of digoxin toxicity in chronic kidney disease (shows as broad complex bradycardia on an ECG)
4
Q
what do beta2 adrenoreceptors do
A
causes bronchial smooth muscle relaxation
5
Q
define pharmacology
A
the branch of medicine concerned with the uses, effects, and modes of action of drugs.
6
Q
define therapeutic
A
the branch of medicine concerned with the treatment of disease and the action of remedial agents.
7
Q
define drug selectivity
A
Selectivity refers to a drug’s ability to preferentially produce a particular effect and is related to the structural specificity of drug binding to receptors.
8
Q
define drug specificity
A
will be used to describe the capacity of a drug to cause a particular action in a population.
9
Q
define drug dose
A
dose refers to a specified amount of medication taken at one time.
10
Q
define drug concentration
A
defined as the amount of drug in a given volume, such. as mg/L: 1-1.
11
Q
drug affinity
A
the extent or fraction to which a drug binds to receptors at any given drug concentration or the firmness with which the drug binds to the receptor.
12
Q
define agonism
A
A molecule that combines with a receptor on a cell to trigger physiological reaction. An example is an acetylcholine being the agonist that combines with the cholinergic receptor.
13
Q
define partial agonist
A
partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist.
14
Q
Define potency
A
potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a given response at low concentrations, while a drug of lower potency evokes the same response only at higher concentrations.
15
Q
define efficacy
A
is the capacity to produce an effect (eg, lower blood pressure).
16
Q
What is the relationship between drug concentration and response?
A
Progressive increases in drug dose (which, for most drugs, is proportional to the plasma drug concentration) produce increasing response but only within a relatively narrow range of dose; further increases in dose beyond this range produce little extra effect.
17
Q
define desensitisation in pharmacology
A
refers to the common situation where the biological response to a drug diminishes when it is given continuously or repeatedly.
18
Q
define drug tolerance
A
Drug tolerance or drug insensitivity is a pharmacological concept describing subjects’ reduced reaction to a drug following its repeated use. Increasing its dosage may re-amplify the drug’s effects; however, this may accelerate tolerance, further reducing the drug’s effects.
19
Q
examples of full agonistic drugs
A
opioids for pain
beta adrenoreceptors for asthma
20
Q
two types of antagonists
A
competitive and non-competitive
21
Q
what is a competitive antagonist
A
competitive antagonist binds to the same site as the agonist but does not activate it, thus blocks the agonist’s action.
22
Q
what is a non-competitive antagonist
A
A non-competitive antagonist binds to an allosteric (non-agonist) site on the receptor to prevent activation of the receptor.
23
Q
how is antagonism measured
A
The potency of an antagonist is usually defined by its half maximal inhibitory concentration (i.e., IC50 value). This can be calculated for a given antagonist by determining the concentration of antagonist needed to elicit half inhibition of the maximum biological response of an agonist.
24
Q
examples of antagonism drugs
A
beta blockers and antipsychotic drugs
25
what is a drug
any synthetic or natural chemical substance that can alter biological function; may be used in treatment, prevention or diagnosis of disease
26
two ways a drug can produce an (adverse) side effect
1) target is too widespread -drug is selective for its target but the target is in part of the body where it can give side effects (e.g. aspirin therapeutically is an anti-inflammatory, antipyretic, analgesic, and anti-platelet aggregation but in toxicity causes GI bleeding)
2) the drug hits other targets - drug is not selective and will bind and activate other targets (e.g. morphine therapeutically is an analgesic, but in toxicity can cause respiratory depression, is addictive, can cause vomiting and constipation)
27
if a drug is hydrophilic what is the best way to administer it?
through IV or orally
28
what are transdermal patches for
for drugs that are not water soluble
| e.g. nicotine patches or HRT
29
6 molecular targets for drug action
receptors (transduce signal from drug)
enzymes (activate or switch off)
transporters (Carry molecules across membranes)
Ion channels (open or close)
nucleic acids (affect gene transcription)
miscellaneous (lipids, metal ions, etc.)
30
examples of drugs that inhibit enzymes
Cyclooxygenase inhibitors for pain relief (usually arthritis)
HMG - CoA Reductase inhibitors for hypercholesteraemia
(atorvastatin [Lipitor] ; pravastatin [pravachol])
Angiotensin converting enzyme (ACE) inhibitors for high blood pressure, heart failure and chronic renal insufficiency (capatopril [capoten] ramipril [altace])
31
what are Pro-drugs
given as a pharmacologically inactive compound that is then metabolised by the body to produce a pharmacologically active compound
( L-DOPA (pro-drug) to dopamine (drug) used to treat parkinsons)
32
How is drug affinity measured?
Affinity is inversely proportional to the potency of a drug 1 Kd , where Kd is the dissociation constant. The strength of the binding (interaction) of a ligand and its receptor can be described by affinity. The higher the Kd value, the weaker the binding and the lower the affinity.
33
what determines the position of the binding curve along the concentration axis? (drug affinity)
Determined by affinity, efficacy and receptor number
34
what is a receptor reserve
This refers to the condition in a tissue whereby the agonist needs to activate only a small fraction of the existing receptor population to produce the maximal system response.
35
partial agonism by definition
occupy ALL receptors to evoke their maximum response
| partial agonists have NO spare receptors
36
example of partial agonist (think beta 2 adrenergic receptors)
salbutamol
37
4 types of antagonism
competitive
non-competitive
uncompetitive
physiological
38
competitive antagonism
binds at the agonist recognition site preventing access
39
non competitive antagonism
does not bind at the agonist site but inhibits agonist binding in other ways
40
uncompetitive antagonism
this is when binding occurs to an activated form of the receptor
41
physiological antagonism
when the effect of a neurotransmitter or hormone is countered by the action of another neurotransmitter or hormone
42
what equation describes competitive antagonism
Gaddum-Schild [D1]/[D1] = 1 + ([B]/Kb)
where d1/d1 = concentration ratio
[B] = antagonist
Kb = dissociation constant of antagonist
43
examples of competitive antagonists in the clinic
propanolol - beta adrenoreceptor - lowers HR
Haloperidol - dopamine receptor - antipsychotic
Atropine - muscarinic ACH receptor - dilation of pupils, decreases secretions
Ranitidine - histamine H2 receptor - decreases gastric acid secretion
D-tubocurarine - nicotinic Ach receptor - neuromuscular block
44
effect of a competitive antagonist on an agonist concentration - response curve
shifts the agonist dose response curve to the right with no change in the apparent maximum response obtained
45
What does ADME relate to
dose of drug administered and absorbed
drugs in tissue of distribution
drug in systemic circulation
drug metabolised or excreted
46
what does pharmacokinetics relate to
what the body does to the drug
47
what does pharmacodynamics relate to
what the drug does to the body
48
4 reasons why ADME is important
1) important to know if a drug is going to be absorbed if given by a particular route
2) important to estimate accurate plasma concentrations of drug as a function of time -plasma drug concentration is dynamic it changes with time
3) to know where the drug goes once inside the body- how it distributes
4) Drug metabolism - are the metabolites safe?
49
most common route of drug administration
oral
50
2 examples of drugs that are administered sublingually
GTN spray
| ondansetron (for migraines)
51
why are drugs administered sublingually
rapid onset
| only suitable for drugs that are lipid soluble so they can cross the membrane
52
why are drugs administered rectally
in order to be absorbed into general systemic system or localised
usually give diazepam rectally if patient is unconscious or seizing or for a small child whose veins might be too small
53
what does enteral mean in terms of drug administration
it means that it is via the GI tract
54
What does parenteral mean in terms of drug administration
that it does not go via the GI tract
55
What does bolus mean
all at once
56
what does infusion mean
over a length of time (usually hours or days)
57
Benefits/downfalls of IV
rapid and can be given over a long period
(also associated with drug abuse)
(can cause an air embolism)
58
Benefits/downfalls of IM
released in an aqueous vehicle to allow for rapid distribution
59
```
Fluphenazine (drug)?
what type of administration is used
used to treat what
dissolved in what
released how
```
depot injection - used to treat schizophrenia
dissolved in an oily vehicle
released slowly into blood from muscle over a few weeks
60
Enteral routes of drug administration
oral
sublingual
rectal
61
parenteral routes of drug administration
```
IV
IM
Subcutaneous
Intradermal
Intranasal
Inhalation
Epidural
Transdermal
Topical
```
62
examples of drugs administered intravenously
thiopentone (barbiturate, used to help you relax before you receive general anesthesia with an inhaled medication.)
Vanomyocin (antibiotic medication used to treat a number of bacterial infections.)
63
examples of drugs administered intramuscularly
morphine (pain medication of the opiate family)
fluphenazine (high-potency typical antipsychotic medication)
64
examples of drugs administered subcutaneously
insulin ( any pharmaceutical preparation of the protein hormone insulin that is used to treat high blood glucose. )
Humira (is a prescription medicine used to treat moderate to severe Crohn's disease (CD) in adults and children 6 years of age and older.)
65
examples of drugs/things administered intradermally
flu vaccine
| allergy testing
66
examples of drugs administered intra-nasally
sumatriptan (medication used to treat migraine headaches and cluster headaches, serotonin agonist)
beclometasone (for hay fever and cold-like symptoms caused by common allergies (rhinitis))
67
examples of drugs administered through inhalation
isoflurane (can be used to start or maintain anesthesia, however other medications are often used to start anesthesia rather than isoflurane, due to airway irritation with isoflurane)
salbutamol (brand name Ventolin among others, is a medication that opens up the medium and large airways in the lungs. It is a short-acting β₂ adrenergic receptor agonist which works by causing relaxation of airway smooth muscle.)
68
examples of drugs administered through epidural
bupivacaine (medication used to decrease feeling in a specific area. In nerve blocks, it is injected around a nerve that supplies the area, or into the spinal canal's epidural space)
69
examples of drugs administered transdermally
nicotine - patches
Buprenorphine (opioid used to treat opioid use disorder, acute pain, and chronic pain.)
70
examples of drugs administered topically
latanoprost (brand name Xalatan among others, is a medication used to treat increased pressure inside the eye)
Steroid cream - hydrocortisone
71
what is oral bioavailability
the fraction of the oral dose that reaches the systemic circulation
72
give an example of a drug with high oral bioavailability and one with low
high - diazepam
low - morphine
(Bioavailability refers to the extent and rate at which the active moiety (drug or metabolite) enters systemic circulation, thereby accessing the site of action. )
73
3 factors affecting the oral bioavailability of a drug
1) poor absorption from the gut
2) breakdown of drug in gut
3) first pass effect
74
what is the first pass effect of drugs
phenomenon in which a drug gets metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation
75
Describe the use of pro-drugs in medicine
can be used to improve drug delivery or pharmacokinetics, to decrease toxicity, or to target the drug to specific cells or tissues. Ester and phosphate hydrolysis are widely used in prodrug design because of their simplicity, but such approaches are relatively ineffective for targeting drugs to specific sites.
76
why might a pro-drug be used for a patient
may be used to improve how selectively the drug interacts with cells or processes that are not its intended target. This reduces adverse or unintended effects of a drug, especially important in treatments like chemotherapy, which can have severe unintended and undesirable side effects.
77
6 factors affecting drug absorption at a membrane
1) pKa of a drug (pH at which is it 50% ionised)
2) pH at absorbing site
3) Drug preparation
4) area of absorbing surface
5) Rate of blood flow to other side of absorbing surface
6) presence of food, drugs that can affect stomach emptying/gut motility
78
pH of stomach
2
79
pH of plasma
7.4
80
pH of small intestine
8
81
what is ion trapping
ion trapping is the build-up of a higher concentration of a chemical across a cell membrane due to the pKa value of the chemical and difference of pH across the cell membrane.
82
why is pH and pKa important in drugs
because many drugs are either weak acids or weak bases, and so can exist in ionised or un-ionised forms depending on pKa of drug or pH of solution
If membrane is present which separates different pH solutions it can lead to ion trapping
83
define drug distribution
penetration of a drug into tissues and organs from the blood
84
what does the degree of drug distribution depend on
lipid solubility
plasma protein binding (like albumin)
rate of blood flow
85
How can drug distribution be measured
by apparent volume of distribution (Vd) - volume of water in which drug would have to be distributed to give its plasma concentration
also written as (amount of drug in body/Cp)
where Cp is plasma concentration
86
can volume of Vd (apparent volume of distribution of a drug) exceed the total body water content
yes
87
two uses of Vd (apparent volume of distribution of a drug)
partly determines plasma half-life of the drug
used in pharmacokinetic calculations to determine dosing schedules
88
what is plasma drug binding important for?
distribution
as drugs that are bound to plasma proteins (such as albumin) cannot leave the blood
drugs that are tightly and extensively bound to plasma proteins tend to have a small Vd (drugs like anticoagulant warfarin)
89
how does drug redistribution work in the body
extent of drug distribution into tissues depends on the degree of plasma protein and tissue binding. In the bloodstream, drugs are transported partly in solution as free (unbound) drug and partly reversibly bound to blood components (eg, plasma proteins, blood cells).
90
what is elimination of a drug
overall removal of drug from the body, can be done by excretion or metabolism
91
what is excretion of a drug
movement of a drug or metabolite from inside to outside the body
92
what is metabolism of a drug
chemical change of drug structure
93
5 main excretive methods of drugs
urine, faeces, milk, bile, vomit
94
4 main organs for drug metabolism
liver
kidney
lungs
blood plasma
95
what is plasma half-life of a drug (T0.5)
time it takes for plasma concentration (Cp) to fall to half its initial value
96
what does a short drug half life mean
that the body eliminates the drug quickly and that oral doses have to be given more often than drugs with longer half lives
97
give an example of a drug with a very short, short, medium, long, and very long half -life
very short - remiphentanil (15 mins), patient-controlled analgesia (PCA)
Short - proprananol (beta-blocker, 3-4 hrs), medication of the beta blocker class.
medium - tetracycline (antibiotic) (10hrs)
long - amphotericin (anti-fungal) (18hrs)
very long - digoxin (40hrs)
98
equation for rate of elimination of a drug
rate of elimination = clearance x Cp
99
what is clearance of a drug
equal to the amount of plasma which is cleared of its drug content in a unit time
100
as the rate of drug absorption decreases what 3 things happen (think graph)
peak Cp decreases
time to peak increases
drug persists in body longer
101
which drugs are excreted by the kidney
drugs that are not lipid soluble
102
how can changes in urinary pH alter drug excretion
for a weak acid, urinary excretion can be increased by making the urine more alkaline (e.g. with sodium bicarbonate)
for a weak base, urinary excretion can be increased by making urine more acidic (e.g. with ammonium chloride)
103
explain first order drug elimination
occur when a constant proportion of the drug is eliminated per unit time. (key here is proportion of drug not amount)
104
explain zero order drug elimination
a constant amount of drug is eliminated per unit time
| key here is amount not proportion
105
difference between IV bolus and IV infusion
bolus achieves a very high peak which only lasts 5–6 hours. The infusion achieves steady levels after an initial delay. An infusion produces a steady level which can be varied and is exactly what is needed, for example during and after surgery.
106
what is a loading dose in comparison to a maintenance dose
a loading dose is an initial higher dose of a drug that may be given at the beginning of a course of treatment before dropping down to a lower maintenance dose. A loading dose is most useful for drugs that are eliminated from the body relatively slowly, i.e. have a long systemic half-life.
107
what are the different types of metabolites formed from drug metabolism
Two different phases:
phase I: by oxidation, reduction, or hydrolysis
phase II: by conjugation (joining together) species formed in Phase I with polar molecules, making metabolite less lipid soluble, and hence easier to excrete in urine
108
how does enzyme induction affect how drugs are metabolised
refers to an increase in the rate of hepatic metabolism
this leads to a decrease in the concentrations of drugs metabolised by the same enzyme
109
how does enzyme inhibition affect how drugs are metabolised
reduces metabolism
110
genetic polymorphism
are defined as the occurrence of multiple alleles at a locus, where at least two alleles occur with a frequency greater than 1%.
example is blood groups - ABO
111
how does genetic polymorphism affect how drugs are metabolised
it varies - it can affect the gene that metabolises drugs
| known to cause people variations
112
describe the toxicity of paracetamol in overdose
may cause varying degrees of liver injury over the 2 to 4 days following ingestion, including fulminant hepatic failure. Rarely, massive overdose may initially present with coma and severe metabolic acidosis.
113
What is an adverse drug reaction
unintended, harmful events attributed to the use of medicines – occur as a cause of and during a significant proportion of unscheduled hospital admissions.
114
1mM in M
1 x 10-3 M
115
1nM in M
1 x 10-9M
116
1µM in M
1 x 10 - 6 M
117
1pM in M
1 x 10 - 12 M
118
• 300µg/ml with initial volume of 0.5ml, diluted to final volyme of 10ml. Concentration?
○ 15µm/ml
| C1V1=C2V2
119
• 1ml stock volume diluted to 20ml. Final solution has concentration of 20µg/ml. concentration?
○ 400µg/ml
120
liquid drug calculations ( how to do them)
○ Volume needed=mass needed x (mass/volume)
○ Need 500mg dose of Y
§ Y comes in 250mg/50ml
§ 500mg x (50ml/250mg) = 100ml
121
Drug C comes in 15% w/v how much solution is needed to provide 30g of C?
200ml
| 30/0.15
122
Drug C comes in 15% w/v how much solution is needed to provide 22.5g of C?
150ml
| 22.5/0.15
123
Drug C comes in 15% w/v how much solution is needed to provide 90g of C?
600ml
| 90/0.15
124
Patient has been taking 2 tablets per day of clarithromyocin, each tablet contains 250mg. They are switched to liquid form of the drug which is 5% (w/v). How much liquid do they need to take per day.
500mg in g is 0.5g
0.5/0.05 = 10
so answer is 10ml
125
Patient takes 20ml of 2% (w/v) solution of drug x. They are switched to taking tablets that are 200mg of drug. How many tablets do they need to take a day.
0.4g a day
0.4 g to mg is 400mg
so 2 tablets a day
126
Patient needs 20µg/kg of drug Y. They weigh 80kg. Tablets contain 0.4mg of drug Y. How many tablets do they need?
80 x 20 = 1600
1.6 mg
4 tablets
127
What is meant by Kd
the equilibrium dissociation constant -
| Think of equation P = [D]/([D] +KD)
128
opioid toxidrome definition
opioid agonism leading to pinpoint pupils (miosis) and CNS and respiratory depression
129
sedative hypnotic toxidrome
group of drugs that cause CNS depression
benzodiazepines and barbiturates are most commonly used
130
serotenergic toxidrome
a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system (CNS). It is seen with therapeutic medication use, inadvertent interactions between drugs, and intentional self-poisoning
131
anticholingeric toxidrome
results from competitive antagonism of acetylcholine at central and peripheral muscarinic receptors. Central inhibition leads to an agitated (hyperactive) delirium - typically including confusion, restlessness and picking at imaginary objects - which characterises this toxidrome.
132
cholinergic toxidrome
represents the acute phase of cholinesterase inhibitor poisoning. It results from the accumulation of excessive levels of acetylcholine in the synapses, glands, smooth muscles, and motor end plates where cholinergic receptors are found.
