Clinical Pharmacology Flashcards
(108 cards)
1
Q
What is a drug?
A
external substance that acts on living tissue to produce a measurable change in the function of that tissue
2
Q
Name 4 types of drugs used in Dentistry?
A
- LA
- Antimicrobials- treat and prevent infections
- anxiolytics - reduce anxiety
- analgesics- reduce postoperative pain
3
Q
What can drugs do?
A
- simulate normal body communications
- interrupt normal body communications
- act on non-host organisms to aid body defences
4
Q
What is host communication? (simple definition)
A
How your body speaks to itself:
= hormone messages - general information to ALL tissues
= neural messages - targeted information for SPECIFIC tissues
5
Q
Give 4 examples of hormone systems in the body. (4)
A
- thyroid hormones ( T3 & T4)
- insulin/glucagon
- cortisol/aldosterone
-sex hormones
6
Q
How to thyroid hormones work?
A
they work to balance the body’s metabolism:
- too little - hyperthyroidism
- too much - hypothyroidism
7
Q
Which drugs can replace the missing active hormone - T3 & T4?
A
thyroxine dose adjusted to correct level gradually
replacement medicine acts directly in the TISSUES
- no direct effect on thyroid gland
8
Q
Where do replacement medicines act? (with regards to thyroid hormones)
A
directly in the tissues, no direct effect on thyroid gland
9
Q
What are the signs of hypothyroidism? (5)
A
- cold intolerance
- coarse skin
- memory loss
- slow pulse
- low metabolism
10
Q
What are the signs of hyperthyroidism? (5)
A
- rapid metabolism
- high pulse rate
- sweating & heat intolerance
- anxiety and agitation
- weight loss
11
Q
What are two divisions of the autonomic nervous system?
A
Sympathetic
parasympathetic
12
Q
Is adrenaline part of the sympathetic or parasympathetic nervous system?
A
adrenaline (epinephrine) is part of the sympathetic nervous system. “the fight or flight response”
13
Q
Is acetylcholine part of the sympathetic or parasympathetic nervous system?
A
Within the parasympathetic nervous system alone, the postganglionic neuron releases acetylcholine as its primary neurotransmitter. Responsible for the ‘rest and digest phase’
14
Q
Give a sympathetic and parasympathetic example for the control of heart rate:
A
= sympathetic- adrenergic stimulation (speeds up the heart via beta- receptors)
= parasympathetic - cholinergic stimulation ( slows the heart via cholinergic receptors)
15
Q
Give 4 examples of ‘autonomic’ drugs?
A
= adrenaline (beta agonist)
= atenolol (beta blocker)
= pilocarpine (cholinergic agonist)
= atropine (cholinergic blocker)
16
Q
Define ‘topical’
A
drug applied to the tissue where it acts
17
Q
define systemic
A
drug applied to the whole organism
18
Q
define parenteral
A
drug administered by injection
19
Q
define transdermal?
A
drug applied to the skin for absorption
20
Q
define subcutaneous
A
drug injected into the tissues of the skin
21
Q
define intramuscular
A
drug injected into muscle
22
Q
define intravenous
A
drug injected into a vein
23
Q
define transmucosal
A
drug applied to the mucosa for adsorption
24
Q
What can go wrong with drug administeration?
A
- allergy - mind
- allergy - severe - anaphylaxis
- drug-drug interactions
- acute toxic reactions
25
How does a drug-drug interaction occur?
One drug interferes with the adsorption, action or metabolism of another
26
Name 2 protein binding drugs?
=Warfarin: a blood thinner used to prevent blood clots, binds to albumin in the blood.
=Aspirin: a pain reliever and anti-inflammatory drug, binds to both albumin and glycoprotein in the blood.
=Diazepam: a benzodiazepine used to treat anxiety and seizures, binds to albumin in the blood.
=Ibuprofen: a nonsteroidal anti-inflammatory drug (NSAID), binds to albumin in the blood.
27
Name three drugs you may be hesitant to prescribe if a patient is taking either warfarin or simvastatin?
- erythromycin
- fluconazole
- carbamazepine
28
Name three examples of acute toxic reactions?
- bone marrow suppression
- hepatotoxicity & biliary stadid
- acute nephrotoxicity
29
Name two subheading of prescribing errors?
= the decision to prescribe
= prescribing the wrong drug
30
Why might a clinician question the decision to prescribe?
1 = would a different treatment be a better option
= most common dental prescribing error
2= prescribing the wrong drug
=ADR
= ineffective
=less effective
3= incorrectly completing the prescription
31
What 8 things should be on a prescription form? (9)
= patient's name, address, age (under18)
= patients identifier - DoB, CHI number
= number of days treated
= drug to be prescribed
= drug formulation and dosage
= instructions on quantity to be dispensed
= instruction to be given to patient
= signed- identifier to prescriber
32
What 3 things ensure prescription validity?
= six months from date issues
= more than one item on a script
= more than one repeated dispensing occasion (useful when patient is getting a medication over several months0
33
What are the advantages of written instructions?
= stressed patient may not remember instructions
= language issues may prevent proper understanding - multilingual options, large print options
= contact number for patient issues with the medicine
= legal protection is post-treatment course questioned
34
What advice should you give to patients about taking prescribed medications?
= take drugs at correct time and finish the course
= unexpected reactions: STOP and contact prescriber
= known side- effects should be discussed e.g. metronidazole and alcohol
= keep medicines safe: especially from children
35
What are the 4 main modes of action for drugs?
= activation or blocking of receptors
= activating or blocking enzyme function
= opening or blocking ion channels
= facilitation or blocking transport systems
36
In a receptor, what do agonists and antagonists do?
= agonist is a drug which causes a reaction to happen
= an antagonist prevents the action from happening
37
How do ion channels open?
through their natural activity
38
Give 1 example of ion channels being opened?
through electrical nerve conduction and change the polarity of the membrane
39
How can ion channels be blocked?
Ion channels can be blocked by molecules moving into the channel or through modulators which work within the channel itself to increase or decrease the opening
40
How to enzymes work as a method of drug action?
= enzymes are proteins which will act upon a substrate to produce a metabolite or a selection of metabolites or perhaps several metabolites as part of their normal action -> they then return to their original state ready to carry out that action again.
41
How do transport systems work?
Transport systems work by moving drugs from one part to another and these can be interfered with by inhibitors or false substrates
42
What must happen after a drug/receptor interaction has taken place?
some mechanism within the cell must exist to change that receptor binding into an action within the cell (often through proteins called G-proteins which will then couple receptor to ion channel or enzyme)
43
What will allow change to happen in the cell membrane?
action of receptor being changed in shape, cascades through to g protein in cell to allow change to happen in cell membrane
44
What is causing the changes which take place post drug/receptor interaction?
they happen because of conformational changes in the systems (receptors) which are often trans-membrane proteins and these will affect changes within the cell.
45
Drugs bind to and release from the receptors constantly: In drug-receptor interactions, when is the receptor activated?
Only when the drug is bound
46
What things affect the drug response in a drug-receptor interaction?
= drug receptor interaction
- affinity: the tightness of the drug binding to the receptor
- occupancy: how much time the drug spends on the receptor
= drug induced response
- efficacy: how effective the drug is at producing a response from the receptor
47
In drug- receptor interactions : what happens when the drug is an agonist and provide an example.
agonist is a chemical that when bound to receptor produces the expected change in the receptor and consequently they expect an action in the body system: e.g. adrenaline
48
With regards to agonist/partial agonist response to stimulation: how will acetylcholine react in response to stimulation?
ACh is a normal drug agonist for receptor, it will give characteristic logarithmic response - rapid change in efficacy with concentration
49
With regards to agonist/partial agonist response to stimulation: how will propionylcholine react in response to stimulation?
PCh will achieve the same result but requires a much more concentrated solution of drug to achieve same maximal response
50
With regards to agonist/partial agonist response to stimulation: how will Butyrylcholine react in response to stimulation?
BCh even with much greater conc, the maximal receptor response will not be obtained
51
What will a drug in the vicinity of a receptor obey?
law of mass action
52
What is the effect on the receptors if there is a higher drug concentration?
if there is more drug available for the receptors there is more chance that at any one time the receptors will be occupied by a drug molecule.
-the lower the concentration the less chance there is that at any time there will be a certain proportion of receptors occupied
53
What is a linear response to a drug-receptor interaction?
receptor occupancy follows drug effect, so in some cases when half of the receptors are occupied half of the clinical response is achieved
54
What is a non-linear response to a drug-receptor interaction?
maximal response will happen at fairly low percent of receptor occupancy and this can be very important where small changes in concentration may make a big difference to how a body system works
55
What are the differences between agonists and partial agonists?
= agonists bind to a receptor and cause an effect (Adrenaline)
= partial agonists (Bch) are more difficult to produce the drug/receptor effect than with an agonist
= increase partial agonist concentration will improve eficacy for some
=not for others
56
Describe what happens when a drug such as adrenaline binds to the receptor vs how partial agonists work
=we have a drug such as adrenaline binding to the receptor
= when the drug binds to the receptor the signal is transmitted through the membrane to the cell and an affect will happen
= when we have a partial agonist it may well still bind to receptor site but it is not as good at promoting change within cell, it may be 100% of the total is enough (partial agonist is present but may be less???)
57
Describe what happens when an antagonist binds to a receptor site?
= an antagonist is a drug which will bind to receptor site but will not produce conformation change needed to give message to cell systems
=for example, 'atenolol' (beta-receptor blocker) that will the action of adrenaline by competing with it for adrenergic receptor and where you have your blocking drug on the protein, it meant the adrenaline can no longer cause an effect inside the cell
58
What two types of antagonist exist?
= competitive and competitive
59
Within the subheading of compititive and non-competitive antagonists, these can either be reversible or irreversible: define each of these and provide an example..
= Reversible
- antagonist effect reduced by increasing the concentration of the agonist
-EXAMPLE: atenolol (Beta blocker)
= Irreversible
-Bind and reduces available receptors for the agonist
- EXAMPLE: phenoxybenzamine (alpha 1 blocker)
60
Drugs can change enzyme action by:
- substrate antagonism: - competitive
- non- competitive substrate inhibition
61
What 2 things can change due to ion channel effects?
= cell electrical activity
= ion influx
62
Where else can ion channels be found apart from the cell membrane?
= cell organelles (for example endoplasmic reticulum or golgi aparatus)
63
In summary: name 3 things that drugs act through:
- Receptors on cells
- influencing enzyme action
- disruption of ion conduction channels
64
In summary: What is the difference between agonist and antagonist?
- agonists bind to receptors and cause an effect
- antagonists bind to receptors and don't cause an effect
(both can be competitive)
65
What two things can affect drug efficacy?
occupancy and affinity affect drug efficacy
66
What stages do drugs in the body go through? (6)
= administration
= absorption
= transport
= clinical effect
= metabolism
= excretion
67
What is the difference between pharmacokinetics and pharmacodynamics?
= pharmacokinetics : the study of how a drug is absorbed, distributed, metabolized, and eliminated from the body.
= pharmacodynamics : the study of how a drug interacts with the body at the molecular, cellular, and organ level to produce its effects.
68
What does the old terminology 'enteral' mean?
via the gut
69
Name the route of administration which enters the body via the gut ?
Oral
70
What does the old terminology 'parenteral' mean?
not via the gut
71
Name 6 routes of administration not via the gut?
= transdermal
= transmucosal
= intravenous (iv)
= intramuscular (im)
= subcutaneous (sc)
= inhalation
72
What are the advantages of oral drug administration?
=socially acceptable
= drug formulation can change onset and duration of action
73
What are the disadvantages of oral drug administration?
= slow onset
= variable absorption ( food interactions in the GI tract/ GI disease/ gastric acid may destroy drug)
= 'first-pass' metabolism
74
What is first pass metabolism?
First-pass metabolism refers to the initial processing that a drug or other substance undergoes in the liver after it is absorbed into the bloodstream from the digestive system. During this process, enzymes in the liver break down the substance into smaller molecules, which can affect its effectiveness and potency. This can lead to a reduction in the amount of active substance that reaches the rest of the body, as well as changes in its chemical structure. First-pass metabolism can therefore have significant implications for the effectiveness and safety of medications and other substances.
Simple definition: orally administered drugs can reach systemic circulation after passing through the liver once: alters drug concentration
75
In detail describe how first pass metabolism works: all blood from the GI tract...
= all blood from the Gi tract drains into the hepatic portal vein (except sublingual and rectal veins)
= Hepatic portal vein drains to the LIVER
- liver metabolises the contents
- drug only reaches systemic circulation AFTER passing through the liver once
=Can inactivate or activate a proportion of the drug
- will vary with liver disease
76
Give an example of first pass metabolism
= Liver metabolises drug
- inactivated drug (more needed by oral route to get desired clinical effect, glyceryl trinitrate)
- activates drug (makes an active form of an inactive drug, less needed by oral route, valaciclovir aciclovir)
77
what is glyceryl trinitrate used for ?
management of angina
78
What are the advantages of IV & IM routes of administration?
= very rapid onset
= predictable plasma levels
=no first pass metabolism
79
What are the disadvantages of IV & IM routes of administration?
= allergic reactions more severe
= short duration of action
= access difficulties/ self-medication
= drug cost higher
80
What are the advantages of Transdermal and SC routes of administration?
= no first pass metabolism
= allergic reactions often very localised
= prolonged action - can be days with transdermal patches
81
What are the disadvantages of Transdermal and SC routes of administration?
= very slow onset
= self-medication possible
= drug cost higher
= effect will vary from person to person and site to site
82
What does bioavailability mean?
Proportion of an ingested drug that is available for clinical effect
83
What can bioavailability be modified by?
= dosage form & route of administration
= destruction in the gut
= poor absorption
= first pass metabolism
84
What does the speed of diffusion into tissues from the blood depend on?
= the blood flow to the area
= the blood wall vessel barrier
= active secretion of the drug into the tissue
85
During drug distribution, after the drug is dissolved in the blood what happens next...
It is transported bound to carriers (usually plasma proteins- albumin)
86
What happens during drug binding to plasma proteins?
= bound drug is inactive- can act as a reservoir
= drug interactions possible by competitive binding - warfarin and aspirin
87
Do drugs distribute themselves evenly throughout the body?
NO
88
Planning drug use is based on the idea of "......... ......."
Body compartments
89
What is the difference between single compartment model and two compartment model?
= single compartment model - drug behaves as if it is evenly distributed throughout the body
= two compartment model- drug behaves as if it is in equilibrium with different tissues in the body
90
With regards to drug distribution: different parts of the body may receive different drug levels compared with plasma - 'compartment model'. (Vascular, tissues, CNS). What might drug selection depend on?
= drug selection may depend upon the 'preference' of some drugs for some areas of the body
=some drugs actively secreted into tissues or fluid rather than simple diffusion.
91
What is drug distribution affected by?
=lipid binding: slow release from accumulation- prolonged effect
= drug binding to plasma proteins (bound drug is inactive)
92
Give an example of drugs which have significant lipid binding in the tissues?
the anaesthetic gasses- halothane and isofluorane
93
What does 'volume of distribution' mean?
how much of the body the drug is diluted in (different compartments)
94
What is drug metabolism ?
preparing the drug from elimination from the body
95
What is the phase 1 reactions for drug metabolism?
= inactivates drug
= oxidation, reduction, hydrolysis
96
what is the phase 2 reactions for drug metabolism?
= prepared for removal/removes from body
= conjugation (sulphation, methylation, acetylation, glucuronidation)
97
Where is the majority of drugs metabolised?
liver mostly : and excreted by the kidneys (through urine) : EXAMPLE LA: Most local anesthetics are administered by injection or topically, but some can also be given orally for certain procedures. Once absorbed into the bloodstream, oral local anesthetics are carried to the liver, where they are metabolized into inactive compounds that are then excreted by the kidneys.
98
How to the police test for drugs?
= any body fluid will eliminate most drugs
99
Where does the most extensive excretion occur through?
= renal excretion of water soluble metabolites- urine
= liver metabolism and excretion- bile
= lungs - inhaled gases and volatile fractions of other drugs
100
Where can small proportions of drugs be excreted through?
= sweat
= saliva
= tears
101
Which 2 diseases can interfere with normal function of main excretory organs?
= renal disease
= liver disease
Drug doses must be reduced for both
102
What must you always do when prescribing a drug for a patient with renal or liver disease?
must always seek advice from a patient's doctor about how much to reduce a drug use in an individual case
= will depend on liver/renal function
= will depend on the drug being used
103
Name 3 modes of drug clearance kinetics...
= Plasma half life
= first order kinetic
= zero order kinetics
104
What does plasma half-life mean?
= time taken to eliminate half of the drug
105
What is first order kinetic?
= drug metabolism increases as drug concentration increases
= excretion is by PASSIVE DIFFUSION only
106
What is zero order kinetics?
= drug metabolism is at a FIXED rate- ACTIVE process
= irrespective of drug concentration
= can lead to the drug accumulation if saturation exceeded
107
With regards to drug accumulation, what will happen if a dosing is too frequent?
will result in plasma levels that may be toxic - depends upon the drug's therapeutic index
108
What happens with regards to drug accumulation and dosing if drug is administered too infrequently?
will result in sub-therapeutic plasma levels and no clinical effect
