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Sandra Phase 2a > Pharmacology- Introduction to Clinical Sciences > Flashcards

Pharmacology- Introduction to Clinical Sciences Flashcards

1
Q

What is pharmacology

A

Pharmacology is the study of medications, or chemical compounds, which interact with various living systems, from tiny molecules to cells, to tissues and whole organisms, in order to produce a certain effect.

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2
Q

What are the steps involved in drug development?

A

Step 1 is discovery
Step 2 is preclinical research
Step 3 is clinical development

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3
Q

What is referred to as discovery within drug development

A

when a candidate compound is picked out as a possible therapeutic agent for a specific disease

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4
Q

What is referred to as preclinical research within drug development

A

When the compound is tested on cell cultures and animals, like mice and rats, mainly to see if it causes any serious harm to live organisms.

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5
Q

What is referred to as clinical development within drug development

A

Clinical trials are performed.
Tthe compound is tested on humans to see if it’s safe and effective in treating diseases.

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6
Q

What are the 4 phases of clinical Trials

A

Safety, Efficacy, Approval, and Long term

Remember “All medications need the SEAL of approval,”

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7
Q

What is involved in phase 1 of clinical trials

A

Phase I trials test the medication in a small group of healthy individuals to see if it’s Safe for humans.

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8
Q

What is involved in phase 2 of clinical trials

A

Phase II trials aim to discover more about how effective the medication is or how well it works at a certain dose. This is done by testing it on a moderately sized group of individuals affected by the condition in question

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9
Q

What is involved in phase 3 of clinical trials

A

In phase III trials, the new medication is compared to the standard treatment to find out if it’s actually just as good as or even better than the existing one. Phase III trials generally involve a much larger number of individuals. They aim to replicate the exact setting in which the medication will be administered in real life, which will then be used as the basis for Approval by regulatory organizations for the market.

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10
Q

What are the three names of a new medication

A
  1. Chemical: (describing the chemical structure and used in scientific studies)
  2. Generic (shortened version in chemical names and used by health professionals)
  3. Brand/Trade (given by pharmaceutical companies that make the medication)
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11
Q

What is involved in phase 4 of clinical trials

A

final phase of safety surveillance that looks for Long term or rare side effects that might have been missed. If it’s found to be unsafe, a recall and ban might be needed.

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12
Q

Define pharmacokinetics

A

Refers to the movement and modification of the medication inside the body.

In other words, it’s what the body does to this medication.

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13
Q

What happens once the medication is administered regarding pharmacokinetics (ADME)

A
  1. Absorption: Absorbed into circulation
  2. Distribution: Distributed to various tissue
  3. Metabolism: Metabolised or broken down
  4. Excretion: eliminated or excreted in urine or faeces
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14
Q

Define pharmacodynamics

A

What the medication does to the body

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15
Q

What happens once the medication is administered regarding pharmacodynamics

A

Binds to receptors or specialised proteins: surface or inside the cell
It gives rise to a signal cascade resulting in some change in the cell’s function (boosting the production of a particular type of protein or slowing down DNA replication)

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16
Q

What is an ideal medication

A

produces a single beneficial or therapeutic effect for a certain disease state

In reality, most medications produce several unwanted effects (side effects), like nausea or fatigue.

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17
Q

What is the therapeutic index

A

the ratio between the toxic dose and effective dose of a given medication

The larger the therapeutic index, the safer a medication is considered to be.

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18
Q

How do you calculate the therapeutic index

A
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19
Q

What does it mean if medications have a low therapeutic index

A

Narrow margin of safety
Require close monitoring of serum levels

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20
Q

Examples of medications with a low therapeutic index

A

warfarin
lithium
digoxin
gentamicin
phenytoin
theophylline,

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21
Q

What are drug-drug interactions

A

When 2 medications are administered together

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22
Q

What can happen when two drugs are administered together?

A

Pharmacokinetic interactions: 1 medication can alter the absorption, distribution, metabolism or excretion of another. This changes the amount available to produce the desired effect.

Pharmacodynamic interactions: medications influence each other’s effects directly e.g both increase bp

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23
Q

Define enzymes

A

Proteins that play a major role in biochemical reactions
Act as a catalyst

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24
Q

What is an enzyme inhibitor

A

a 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.

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25
Q

Difference between irreversible and reversible inhibitor

A

Irreversible inhibitors – react with the enzyme and change it chemically (e.g. via covalent bond formation)

Reversible 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.

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26
Q

What is non-competitive inhibition?

A

When the inhibitory molecule binds irreversibly to the enzyme’s active site or reversibly to a different place called the allosteric site.

The net effect is that substrates can no longer bind to the active site, and it is as if the number of available enzymes has decreased.

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27
Q

What is competitive inhibition

A

can be used to decrease the affinity of the enzyme
binds to the active site instead of the substrate and usually doesn’t get metabolized - blocking the enzyme.

Since this is a reversible process, adding more substrate makes it possible to eventually outcompete and displace the inhibitor.

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28
Q

What do drug target?

A

receptors
ion channels
enzymes
transporters

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29
Q

What are receptors?

A

a component of a cell that interacts with a specific ligand and initiates a change of biochemical events leading to the ligands observed effects

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30
Q

Where are intracellular receptors located

A

cytoplasm or nucleus of the cell

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31
Q

What do intracellular receptors recognise

A

small, hydrophobic ligands

e.g steroids that diffuse across a phospholipid membrane

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32
Q

Wha happens once intracellular receptors are bound to ligand

A

Receptor-ligand complex attaches to specific DNA sequences that activate or inhibit specific genes.

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33
Q

What are cell-surface receptors

A

Receptors embedded into plasma membrane and bind to ligands too large or hydrophillic

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34
Q

What are the 3 main types of cell surface receptors?

A
  1. Ligand-gated ion channels
  2. G-coupled protein receptor
  3. Kinase-linked receptor
  4. Cytosolic/nuclear receptors
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35
Q

What are the three different protein ports

A
  1. Uniporters – use energy from ATP to pull molecules in
  2. Symporters – use the movement in of one molecule to pull in another molecule against a concentration gradient
  3. Antiporters – one substance moves against its gradient, using energy from the second substance (mostly Na+, K+ or H+) moving down its gradient
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36
Q

Ion channel examples

A
  • Epithelial (sodium) – heart failure
  • Voltage-gated (calcium, sodium) – nerve, arrhythmia
  • Metabolic (potassium) – diabetes
  • Receptor activated (chloride) – epilepsy
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37
Q

What are kinase-linked receptors?

A

Receptors for growth factors

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38
Q

What are cytosolic/nuclear receptors

A

Steroid receptors

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39
Q

When do ligand-gated ion channels open up?

A

Once bound to a specific ligand

ions: chloride, calcium, sodium, potassium passively flow into the cell, down their gradient, and trigger the signalling pathway

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40
Q

What end of the G coupled protein does the ligand bind to?

A

End sitting outside cell

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41
Q

What subunit is present within the G protein-coupled receptor (inside the cell), and what is it bound to?

A

Alpha subunit bound to GDP

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42
Q

What happens when a ligand binds to G protein-coupled receptor

A

G protein changes shape, causing the alpha subunit to release the GDP, allowing GTP to bind.

This causes the alpha subunit to detach and trigger other proteins in the signalling pathway.

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43
Q

Why do medications cause side effects?

A

Because no drug is 100% specific meaning, it could also bind to other receptors that are similar to its intended target,

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44
Q

What are the two main principles of how medication and receptors interact?

A

affinity
intrinsic activity

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45
Q

Define affinity

A

How strongly a medication binds to its receptor

The higher the affinity, the higher the potency (amount of medication needed to elicit an effect)

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46
Q

Define intrinsic ability

A

Ability to activate receptor once the medication is bound to that receptor

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47
Q

Define efficacy

A

the maximal effect the medication can produce

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48
Q

Describe a dose-response curve

A

Amount of medication given (x-axis)
The response produced (y-axis)

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49
Q

Define specificity

A

Specificity refers to a medications tendency to bind to a specific type of receptor.

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50
Q

Generally, a medication with a better affinity for its receptor, has a higher ..

A

Potency

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51
Q

After the medication binds to a receptor, its ability to activate the receptor is called its

A

intrinsic activity

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52
Q

When is maximum efficacy achieved

A

When the dosage is high enough, all available medication receptors are occupied.

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53
Q

What are the two major categories explaining the effect a medication has on its receptor

A

agonists and antagonists

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54
Q

Define agonist

A

a compound that binds to a receptor and activates it

(it essentially mimics the action of the signal ligand by binding to and activating a receptor)

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55
Q

Define antagonist

A

a compound that reduces the effect of an agonist

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56
Q

Agonists have _____ and ______, but antagonists have ______ and ZERO _____-

A

Affinity
Efficacy
affinity
Efficacy

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57
Q

Define signal transduction

A

A basic process involving the conversion of a signal from outside the cell to a functional change within the cell.

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58
Q

Define signal amplification

A

to increase the strength of a signal

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59
Q

What is allosteric modulation

A

When an allosteric ligand binds to a different site on the molecule and prevents the signal from being transmitted

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60
Q

Define ligand

A

A molecule that binds to another (usually larger) molecule

Typically binds to a receptor without activating them, but instead, decreases the receptor’s ability to be activated by another agonist.

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61
Q

What is the maximum effect an agonist (EMax) can produce

A

Determined by the no. receptors bound to an agonist (depending on dose)
Intrinsic ability

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62
Q

How can antagonists be further subdivided

A

competitive antagonists
non-competitive antagonists

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63
Q

What is a competitive antagonist?

A

Medication that reversibly binds to the same receptor site where an agonist binds but it does not activate it

The inhibition caused can be overcome when there are more ligands

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64
Q

How do competitive antagonists affect agonists

A

Decrease agonist potency
Do not affect agonist efficacy

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65
Q

What are non-competitive antagonists

A

Bind to the allosteric site, causing the shape or receptor to change so that ligand can no longer recognise it as a bonding site.

Irreversible change or dissociates very slowly

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66
Q

How do non-competitive antagonists affect agonists

A

Decrease agonist efficacy
Do not affect agonist potency

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67
Q

Difference between full agonists and partial agonists

A

Full agonists: produce a maximal response
Partial agonists: produce submaximal response

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68
Q

What happens when there is persistent flooding of receptors with the same agonist at the same dose

A

The ability of the agonist to produce that response drops

Acts as a defence mechanism preventing overstimulation of agonists

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69
Q

Desensitisation vs tolerance

A

Desensitisation or tachyphylaxis
-happens rapidly
-can occur with an initial dose

Tolerance
-happens more gradually
-typically happens with repeated doses

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70
Q

Mechanisms of desensitisation and tolerance

A
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71
Q

Drug administration

A

swallowed by the mouth or orally
injected into a vein or intravenously
injected into a muscle or intramuscularly
inhaled into the lungs
sprayed into the nose or nasally
applied onto the skin or cutaneously

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72
Q

What is absorption

A

process of moving the medication from the site of administration into the circulation

will need to cross one or more cell membranes before it reaches the circulation except intravenously

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73
Q

How can molecules move across cell membrane

A

Passive transport: Subdivided into facilitated and passive diffusion
Active transport
Endocytosis

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74
Q

What does facilitated diffusion transport

A

Larger, water-soluble, and polar medications move across the membrane through transport proteins like channels and carrier proteins.

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75
Q

What does passive diffusion transport

A

small, lipid-soluble, and nonpolar medications move across the membrane, from an area of high concentration to low concentration

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76
Q

What is active transport

A

medication is transported against their concentration gradient

involves specific carrier proteins that use ATP as a fuel to pump medications into the cell

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77
Q

What is endocytosis

A

The cell membrane invaginates and swallows up the medication forming vesicles

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78
Q

What is the rate of absorption vs extent of absorption

A

How quick
How much

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79
Q

What does the rate/extent of absorption depend on?

A

pH of environment
Surface area available
Blood supply to the absorption site
Presence of food or other material in GI tract

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80
Q

Where is weakly acidic medication better absorbed?

A

Better in an acidic environment in the proximal duodenum

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81
Q

Where is weakly basic medication better absorbed

A

Better in an alkaline environment in the distal ileum

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82
Q

What happens when a medication is taken in by mouth

A

Absorbed through the small intestine’s walls and transported into the liver via the portal vein.

Once in the liver, hepatic enzymes work on the medication to metabolize it (first-pass metabolism or first-pass effect)

Enters circulation

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83
Q

What are the four major metabolic barriers when drugs are taken orally

A

 Intestinal lumen
 Intestinal wall
 Liver
 Lungs

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84
Q

What are the problems with the oral administration of drugs?

A

Undergo extensive first-pass metabolism - concentration in the bloodstream decreases, meaning once the site of action is reached won’t produce desired effect.

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85
Q

How can you bypass the first- pass effect

A

Offer alternate routes of administration as medications go straight into systemic circulation

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86
Q

Pros and Cons of Intradermal and subcutaneous absorption

A

Pros:
* Avoids barrier of stratum corneum
* Small volume can be given
* Use for local effect or to deliberately limit the rate of absorption

Con:
* Mainly limited by blood flow

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87
Q

What does intramuscular absorption depend on

A

blood flow and water solubility

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88
Q

Limitations of inhalational absorption

A
  • Large SA and blood flow but limited by risks of toxicity to alveoli and delivery of non-volatile drugs
  • Largely restricted to volatiles such as general anaesthetics and locally acting drugs such as bronchodilators in asthma
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89
Q

Why are asthma drugs given as a powder or aerosol

A

Because its non-volatile

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90
Q

What is a common reversible binding

A

With plasma protein albumin

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91
Q

What drugs can pass from blood to brain easily

A

Lipid soluble

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92
Q

How are drugs removed from the brain?

A

by diffusion into plasma
active transport in the choroid plexus
elimination in the CSF

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93
Q

What does and does not cross the placenta

A

Large molecules do not cross
Lipid soluble drugs cross

  • Foetal liver has low levels of drug-metabolizing enzymes, so relies on maternal elimination
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94
Q

Define bioavailability

A

Bioavailability or F is actually the fraction of an orally administered medication that eventually reaches the circulation in the unchanged form

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95
Q

What is the bioavailability of intravenously administered drugs?

A

1 or 100%

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96
Q

What is the bioavailability of an oral medication

A
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97
Q

Define distribution

A

movement of a medication from the circulation into the body tissues

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98
Q

What do the rate and extent of distribution depend on

A

Blood supply
Size and polarity
Degree of plasma protein binding
The apparent volume of distribution

99
Q

What is drug ionisation

A

The basic property of most drugs that are either weak acids or weak bases

Essential for the mechanism of action of most drugs as ionic forces are part of the ligand-receptor interaction

Ionized form is regarded as the most water soluble, and un-ionised as lipid-soluble

100
Q

What is the apparent volume of distribution (Vd)

A

the hypothetical volume that accommodates all of the medication in the body, if the concentration throughout was the same as in plasma

We assume that the medication is distributed evenly throughout the body

101
Q

How to calculate Vd

A
102
Q

What is metabolism

A

Process of converting a medication into a less or more active form. These forms are also known as metabolites

103
Q

What is a prodrug

A

Medication that needs to be metabolised into an active form within the body before it can produce the desired effect.

104
Q

Where do the phases of drug metabolism occur

A

Mainly in the liver
It might occur in the lungs, kidneys, and small intestine walls but to a much lesser extent

105
Q

Which enzyme carries out a Phase 1 reaction in the hepatocyte

A

CYP450

106
Q

Where can you find CYP450 enzyme?

A

endoplasmic reticulum
mitochondria.

107
Q

What do the enzymes CYP… do?

A

Converts non-polar, lipid-soluble medications into more polar, water-soluble metabolites via oxidation, hydrolysis or reduction

108
Q

What are Phase 2 reactions

A

Conjugation reactions - when medications or metabolites are joined with another compound: methyl/acetyl/sulfa/glutathione/glucuronic acid.

These reactions create highly polar, water-soluble metabolites that cannot diffuse through cell membranes very easily, so they are trapped in the urine and eliminated by the kidneys

109
Q

Variability in the rate of metabolic reactions

A

Genes
Age
Liver disease
Medications
Foods & Supplements

110
Q

Define elimination

A

Removal of medication from body

Done by either metabolism or excretion
Mostly through urination

111
Q

How can medications be filtered within the kidney

A
  1. Filtered through the glomerulus
  2. Through the proximal convoluted tubule, it gets secreted into the tubular lumen
  3. Travels towards the distal convoluted tubule
112
Q

How do polar (water soluble) medications get filtered in the proximal convoluted tubule of the kidney

A

Active secretion in the proximal convoluted tubule

113
Q

How do non-polar (lipid soluble) medications get filtered in the proximal convoluted tubule of the kidney

A

Passive diffusion in the proximal convoluted tubule

114
Q

How do non-polar (lipid soluble) medications get filtered in the distal convoluted tubule of the kidney

A

Can passively diffuse back into the peritubular circulation

115
Q

How do polar (water soluble) medications get filtered in the distal convoluted tubule of the kidney

A

Get trapped inside the tubular fluid

116
Q

What property of urine affects the elimination

A

Acidity (pH)
Chemical properties of medication

117
Q

Aside from kidneys, where can the excretion of medications take place

A

Bile: absorbed in the GI tract, enter the enterohepatic circulation and leave through faeces

Faeces: Not absorbed from the GI tract and directly passed into the faeces

Exhaled air: inhaled anaesthetics eliminated by the lungs

Also: Breast milk, sweat, saliva, tears

118
Q

What is clearance (CL)

A

Volume of plasma cleared of a medication per unit of time

119
Q

What is total clearance?

A

Sum of various clearance routes

120
Q

What is the rate of elimination determined by

A

Elimination kinetics:
Most eliminated through first-order kinetics

121
Q

What is first-order kinetics?

A

Rate of elimination is directly proportional to the concentration of that medication in the body.

122
Q

What is first-order kinetics?

A

Rate of elimination is directly proportional to the concentration of that medication in the body.

123
Q

What does first-order kinetics also show us?

A

Half-life = Time required for the plasma conc of the medication to be reduced by half

  • T1/2 = 0.693k (0.693=In2)
124
Q

Which medication gets eliminated through zero-order kinetics

A

phenytoin
warfarin
aspirin.

the absolute amount, or milligrams eliminated per unit of time stays the same, but the fraction eliminated changes

125
Q

What are the routes of administration

A

Enteral
Parenteral
Topical

126
Q

What is the most common form of medication being administered?

A

Enteral administration (medication administered through the GI tract)

E.g
peroral administration (mouth)
sublingual administration (under tongue)
buccal administration (between gums and inner lining of cheeks)
rectal administration (rectum)

127
Q

What is parenteral administration

A

Bypasses GI tract (pump medication directly into circulation)

Intravenously
Subcutaneously
Intramuscularly

128
Q

What is topical administration

A

Medication is applied directly upon a particular area of the skin or mucous membrane to achieve a local effect

e.g. antifungal creams to treat athlete’s foot.

129
Q

Choosing the route of administration depends on

A

Chemical properties (stability, ability to cross barriers of absorption)
Urgency of situation

130
Q

What properties of a perorally administered medication need to have

A

Resist tough, acidic conditions within the stomach

Readily pass through the walls of the intestines into the blood.

131
Q

What are the benefits of IV administration

A

Allows medications that are less stable to be directly administered into the bloodstream
Medication that has a major first-pass effect can be directly administered into the bloodstream.

132
Q

Peroral medications

A

Take less time to get absorbed in the GI tract
Effect is much slower than IV
Easier to take at home

133
Q

What form of drug administration is preferred in emergency situations and surgical procedures?

A

IV administration

134
Q

What is the dosing regimen

A

Determines the frequency of administration (dosing interval) and the amount administered (dose)

135
Q

What does the dose regimen affect?

A

The onset of action: time it takes for the medication to start working and produce an effect

Duration of action: total length of time medication produces and effect

136
Q

What are the three main types of dosing

A

Single dosing
Continuous infusion
Intermittent dosing regimen

137
Q

What is single dosing

A

Only one dose of a medication is administered

138
Q

What is a continuous infusion?

A

Medication is infused intravenously at a constant rate

139
Q

How is the steady state of medication determined in continuous infusion

A

By half-life (time needed for plasma conc to be reduced by 50%)

4-5 half-lives to reach a steady state

140
Q

What is the maintenance dose for a continuous infusion regimen

A

The dose required to maintain a steady state

141
Q

What is an intermittent dosing regimen?

A

A certain dose of medication is administered at regular time intervals

142
Q

How is the maintenance dose calculated for an intermittent dosing regimen

A
143
Q

What is the loading dose and, when is it given, how is it calculated

A

The large dose is given at the beginning of a treatment course to rapidly reach the peak plasma concentration.

Given in life-threatening situations or medications with long half-lives

The loading dose is then dropped to lower maintenance doses, maintaining the steady-state plasma concentration.

144
Q

What do maintenance dose and loading dose depend on?

A

Clearance rate
Bioavailability
Volume of distribution

145
Q

Define druggability

A

The ability of a protein target to bind small molecules with high affinity (sometimes called ligandability).

146
Q

Define stereoisomers

A

have the same molecule formula and sequence of bonded atoms, but differ in the 3D orientations of their atoms in space

147
Q

Drug development

A
  • Medicines from plants
  • Inorganic elements
  • Organic molecules
  • Bacteria/fungi/moulds
  • Stereoisomers
  • Immunotherapy antibodies: Vaccinations for hep B, influenza, tetanus, mumps
  • Medicines from animals
  • Gene therapy
148
Q

Clinical use of recombinant proteins

A
  • Insulin
  • Erythropoietin
  • Growth hormone
  • Interleukin 2
  • Gamma interferon
  • Interleukin 1 receptor
149
Q

What is gene therapy

A
  • Gene therapy consists of a recombinant nucleic acid used in or administered to a human being to regulate, replace, add or delete a genetic sequence
  • Its effect relates directly to the recombinant nucleic acid sequence it contains or to the product of the genetic expression of this sequence
150
Q

What is the rational drug design, and what does it consist of?

A

Process of finding new medications based on the knowledge of a biological target.

-The drug is most commonly an organic small molecule that activates or inhibits the function of a biomolecule

-Involves the design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and, therefore, will bind to it

-Relies on the knowledge of the 3D structure of the biomolecular target – structure-based drug design

151
Q

Define inverse agonist

A

a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist

152
Q

Define selectivity

A

the degree to which a dose of a drug produces the desired effect in relation to adverse effects

153
Q

What are the different types of drug interactions

A

Synergetic (1+1>2)
Antagonistic (1+1=0)
Summation (1+1=1)
Potentiation (1+1=1+1.5)

154
Q

Define synergy

A

interaction of drugs such that the total effect is greater than the sum of the individual effects (1+1>2)

155
Q

What is antagonism

A

an antagonist is a substance that acts against and blocks an action (2 drugs opposed to each other) (1+1=0)

156
Q

What is summation

A

different drugs used together to have the same effect as a single drug would (1+1=1)

157
Q

What is potentiation

A

enhancement of one drug by another so that the combined effect is greater than the sum of each one alone (1+1=1+1.5)

158
Q

What are the risk factors for drug interactions

A
  • Narrow therapeutic index
  • Steep dose/response curve
  • Saturable metabolism
159
Q

Define drugs

A

a medicine or other substance which has a physiological effect when ingested or otherwise introduced into the body

160
Q

What are some proteins that drugs target

A
  • Receptors
  • Enzymes
  • Transporters
  • Ion channels
161
Q

Name an example of an exogenous receptor.

A

Drugs (extrinsic)

162
Q

Name an example of an endogenous receptor.

A

hormones, neurotransmitters (intrinsic)

163
Q

What are some of the ways by which chemicals communicate via receptors

A

neurotransmitters (acetylcholine, serotonin)

autacoids (cytokines, histamine)

hormones (testosteragonistone, hydrocortisone).

164
Q

List some imbalances of chemicals in the body

A
  • Allergy: increased histamine
  • Parkinson’s: reduced dopamine
165
Q

List some imbalances of receptors in the body

A
  • Myasthenia gravis: loss of ACh receptors
  • Mastocytosis: increased c-kit receptor
166
Q

How are cholinergic receptors activated

A

When they bind to the neurotransmitter acetylcholine (Ach)

167
Q

What are the subtypes of cholinergic receptors

A

Nicotinic
Muscarinic

168
Q

How can the nervous system be subdivided

A
169
Q

What composes the autonomic nervous system relay

A

Includes 2 neurons:
-preganglionic neurons (cell bodies in nuclei throughout the spinal cord)

-postganglionic neurons (cell bodies in ganglia out of the spinal cord)

170
Q

What do preganglionic neurons in the sympathetic nervous system release? What do they bind to?

A

Ach
Nicotinic receptors on the cell membrane of postganglionic cell bodies

171
Q

What do postganglionic neurons in the sympathetic nervous system release? What do they bind to?

A

Release adrenaline/noradrenaline -> Bind to adrenergic receptors on the plasma membrane of the target organ cells.

Sometimes release Ach -> Bind to muscarinic receptors on the plasma membrane of the target organ cell

172
Q

What are adrenaline and noradrenaline collectively known as?

A

Catecholamines

173
Q

What do postganglionic neurons in the parasympathetic nervous system release? What do they bind to?

A

Ach -> Muscarinic receptors on the plasma membrane of target organ cells

174
Q

What do preganglionic neurons in the parasympathetic nervous system release? What do they bind to?

A

Ach -> Nicotinic receptors on postganglionic cell bodies

175
Q

What is a neuromuscular junction

A

The site where a motor neuron axon comes into contact with skeletal muscle fiber

176
Q

In the somatic nervous system, what neurotransmitter is released and what are the receptors involved

A

A motor neuron receives electrical impulses from the brain triggering small vesicles containing Ach into the neuromuscular joint.

These bind to nicotinic receptors on skeletal muscle
This causes skeletal muscle contraction

177
Q

How many main subtypes of muscarinic receptors are there?

A

5
M1, M2, M3, M4, M5

178
Q

What kind of receptors are muscarinic receptors

A

G coupled receptors

179
Q

Where can you find M1 receptors?

A

Mainly in brain

180
Q

Where can you find M2 receptors

A

Mainly in the heart (their activation slows the heart, so we can block these)

181
Q

Where can you find M3 receptors

A

glandular and smooth muscle. (cause bronchoconstriction, sweating, salivary gland secretion

182
Q

How do adrenergic receptors become activated

A

When they bind to the neurotransmitter catecholamine

183
Q

What are catecholamines involved in

A

Trigger fight or flight response
Stimulate our organs by the sympathetic nervous system

184
Q

What does the sympathetic nervous system do?

A

Involved in fight or flight response
Increase heart rate
Increase blood pressure
Decrease digestion

185
Q

What does the parasympathetic nervous system do?

A

“rest and digest”
Slows heart rate
Increases digestion

186
Q

What adrenergic receptors become activated when bound to noradrenaline (norepinephrine)

A

Alpha 1
Alpha 2
Beta 1

187
Q

What adrenergic receptors become activated when bound to adrenaline (epinephrine)

A

Alpha 1 & 2
Beta 1& 2 & 3

188
Q

List the things that cholinergic and adrenergic pharmacology is responsible for:

A
  • Control of blood pressure: raise it in shock, lower it in hypertension
  • Control of heart rate; speed up lethal bradycardias, slow down dangerous tachycardias
  • Anaesthetic agents; muscle relaxants
  • Regulation of airway tone; treat life-threatening bronchospasm
  • Pressures in the eye; prevent glaucoma causing blindness
  • Control of GI function; diarrhoea and constipation
189
Q

Describe parasympathetic ganglia

A

Short postganglionic nerves,
Long pre-ganglionic nerve

190
Q

Describe postganglionic ganglia

A

Short preganglionic nerves,
Long postganglionic nerve

191
Q

How does anticholinergic drug activity affect the brain and other parts of the body

A

Brain: worsen memory and may cause confusion

Other parts of the body: constipation, drying of the mouth, blurring of the vision, worsening of glaucoma

192
Q

Describe the action of alpha agonists

A

Alpha 1 activators raise blood pressure -> vasoconstrict
Alpha 2 activators lower blood pressure -> vasodilate

193
Q

Describe the action of beta-agonists

A

Beta 1 activation will increase heart rate and chronotropic effects and may increase the risk of arrhythmias.

Beta 2 activation is life-saving in asthma and can delay the onset of premature labour

Beta 3 agonists can reduce over-active bladder symptoms.

194
Q

What do beta blockers do?

A

Lower blood pressure (reduction in cardiac output reduction in central sympathetic outflow activity),

Reduce cardiac work

Treat arrhythmias

195
Q

Uses of beta blockers

A

Angina
MI prevention
High blood pressure
Heart failure

196
Q

What are the side effects of beta blockers

A
  • Tiredness
  • Bronchoconstriction
  • Bradycardia
  • Cardiac depression
197
Q

Define potency

A

whether a drug is ‘strong’ or ‘weak’ relates to how well the drug binds to the receptor, the binding affinity

198
Q

Define efficacy

A

the concept of full or partial agonists

199
Q

Define tolerance

A

Down-regulation of the receptors with prolonged use. Need higher doses to achieve the same effect

200
Q

Define dependence

A

psychological – craving, euphoria

201
Q

When does opioid withdrawal

A

starts within 24 hours, lasts about 72 hours

202
Q

What % of oral morphine is metabolised by the first-pass metabolism

A

50%
Halve the dose is given IM/IV

203
Q

What are three controlled drug (CDs) legislation

A
  1. Misuse of drugs act 1971
  2. Opioids - class A drugs
  3. Practical issues :
    - secure storage
    - CD books - two signatures needed
204
Q

How do opioids work?

A
  • Descending inhibition of pain
  • Part of the fight or flight response
  • Never designed for sustained activation
  • Sustained activation leads to tolerance and addiction
205
Q

Opioids and pharmacodynamics

A
  • Review of pain pathways – opioid drugs simply use the existing pain modulation system
  • Natural endorphins and enkephalins
  • G protein-coupled receptors – act via second messengers
  • Inhibit the release of pain transmitters at the spinal cord and midbrain – and modulate pain perception in higher centres – euphoria – changes the emotional perception of pain
206
Q

Side effects of opioids (9)

A
  • Opioid receptors exist outside the pain system e.g. digestive tract, the respiratory control centre
  • We can sometimes deliver opioids epidurally, but for the most part, we have to give them systemically
  • Respiratory depression
  • Sedation
  • Nausea and vomiting
  • Constipation
  • Itching
  • Immune suppression
  • Endocrine effects
207
Q

What is morphine metabolised into

A

Morphine is metabolized to morphine 6 glucuronide

208
Q

What can morphine lead to and why?

A
  • Morphine is metabolized to morphine 6 glucuronide, which is more potent than morphine and is renally excreted. With normal renal function, this is cleared quickly
  • In renal failure, it will build up and may cause respiratory depression
209
Q

When do you have to be careful when administering morphine
- How do you overcome this?

A

If patients have <30% renal function (creatinine clearance <30).

-Reduce dose and timing interval.

210
Q

What are the 4 key takeaway points from administering opioids which you have to be made aware of?

A
  1. Oral bioavailability – 50% oral morphine
  2. Titrate the dose to suit the patient
  3. Potential for respiratory depression
  4. Potential for addiction – be very careful before starting strong opioids for chronic backache etc.
211
Q

Define allergy

A

an abnormal response to harmless foreign material

212
Q

What are the clinical indications related to allergy (5)

A
  • Epithelial – eczema, itching, reddening
  • Excessive mucus production
  • Airway constriction
  • Abdominal bloating, vomiting, diarrhoea
  • Anaphylaxis
213
Q

What are the cells involved in an allergic reaction

A

o Mast, eosinophil, lymphocytes, dendritic
o Smooth muscle, fibroblasts, epithelia

214
Q

What are the mediators involved in an allergic reaction

A

o Cytokines, chemokines, lipids, small molecules

215
Q

What kind of reaction is a hypersensitivity type 1-3 reaction

A

antibody-mediated reaction

216
Q

What reaction is an allergic reaction

A

Type 1 hypersensitivity reaction

217
Q

What does an allergic reaction involve?

A

Involves recognition of an antigen by primed IgE immunoglobulin on mast cells.

218
Q

How do plasma cells become primed specifically towards a particular allergen (sensitised towards particular allergen)

A

Involves first contact or first exposure to a particular benign antigen such as pollen, food, drugs

The antigen is picked up and expressed by APC on the cell surface.

The APC will carry the allergen to nearby lymphoid tissue, where sensitisation begins. APC presents to T helper cell.

T helper cells activate B cells to differentiate into plasma cells via IL-21

IL 4 stimulates the B cells to class switch from IgD to IgE. Causes plasma cells to become IgE-secreting plasma cells primed specifically towards the particular allergen

IgE sits on the receptors of mast cells containing histamine and basophils

219
Q

When does sensitisation regarding an allergic reaction begin?

A

When there is an initial exposure to an antigen

220
Q

What happens to subsequent exposure to an allergen in an allergic reaction (early phase)

A

Bound IgE on mast cells and basophils will recognise the allergen. The allergen cross-links IgE on mast cells.

This activates cells to degranulate, releasing granules of histamine.

Results in vasodilation and increased vascular permeability causing oedema and erythema to local tissues

Increased vascular permeability allows the extravasation of neutrophils and other acute inflammatory cells.

This all happens within minutes of exposure to the allergen

221
Q

What happens to subsequent exposure to an allergen in an allergic reaction (late phase)

A

Occurs hours after exposure to the allergen

Other mediators are synthesised after the cells degranulate

These mediators cause the following :
-increased vascular permeability
-bronchospasm
-attracts eosinophils to tissues immediately

222
Q

List 5 allergic diseases

A
  • Anaphylaxis
  • Allergic asthma
  • Contact dermatitis
  • Insect venom
  • Food allergies
223
Q

What is anaphylaxis

A

acute allergic reaction to an antigen to which the body has become hypersensitive

a most severe form of type 1 hypersensitivity

224
Q

What are some symptoms of anaphylaxis?

A

Hypotension
Oedema of the lips and neck
Severe bronchoconstriction
Tachycardia

225
Q

Management of anaphylaxis

A
  • Commence basic life support
  • Adrenaline – IM 500µg
  • High-flow oxygen
226
Q

What does adrenaline do once administered regarding anaphylaxis

A
  1. Vasoconstriction – increase in peripheral vascular resistance, increased BP and coronary perfusion
  2. Stimulation of beta1-adrenoceptors positive ionotropic and chronotropic effects on the heart
  3. Reduces oedema and bronchodilates via beta2-adrenoceptors
227
Q

What are the clinical criteria for allergy to the drug

A

It does not correlate with the pharmacological properties of the drug

No linear relation with dose (a tiny dose can cause severe effects)

Reactions similar to those produced by other allergens

The induction period of primary exposure

Disappearance on cessation

228
Q

Define atopy

A

immediate hypersensitivity reactions with both an environmental trigger and a strong familial predisposition

229
Q

What are the potential reasons leading to atopy (4)

A
  1. Dysfunction of barrier leading to enhanced antigen exposure
  2. Increased uptake and presentation
  3. T-cell dysregulation
  4. Hyperesponsive to tissue mediators
230
Q

Define adverse drug reaction

A

unwanted or harmful reactions following the administration of drugs or combination of drugs under normal conditions of use and is suspected to be related to the drug

231
Q

Define side effects

A

an unintended effect of a drug-related to its pharmacological properties and can include unexpected benefits of treatment

232
Q

What is the severity of adverse drug reactions

A
  • Can be mild e.g. nausea, drowsiness, itching rash
  • Can be severe e.g. respiratory depression, neutropenia, catastrophic haemorrhage, anaphylaxis
233
Q

What is an example of an adverse drug reaction

A
  • Beta-blockers
  • Bradycardia and heart block are the primary adverse effects
  • Bronchospasm is a secondary pharmacological adverse effect
234
Q

Adverse drug reactions – Rawlins Thompson classification

A

Type A – (augmented pharmacological) – predictable, dose-dependent, common

Type B – (bizarre or idiosyncratic) – not predictable and not dose-dependent

Type C – (chronic) – osteoporosis and steroids

Type D – (delayed) – malignancies after
immunosuppression

Type E – (end of treatment) – occurs after abrupt drug withdrawal.

Type F – (failure of therapy) – failure of the oral contraceptive pill in the presence of enzyme inducer

235
Q

What are the causes of an adverse drug reaction

A
  • Pharmaceutical variation
  • Receptor abnormality
  • Drug-drug interactions
236
Q

When do you suspect an adverse drug reaction

A
  • 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
237
Q

Common side effects of an adverse drug reaction

A
  • Confusion
  • Nausea
  • Balance problems
  • Diarrhoea
  • Constipation
  • Hypotension
238
Q

What is the Yellow card Scheme

A

The first ADR reporting scheme

Collects spontaneous reports

Acts as an ‘early warning system’ for the identification of previously unrecognised reactions

Provides information about factors which predispose patients to ADRs

Continual safety monitoring of a product throughout its life span as a therapeutic agent

239
Q

What are the four critical pieces to include on a yellow card

A
  1. Suspected drug
  2. Suspect reaction
  3. Patient details
  4. Reporter details
240
Q

Mechanism of a paracetamol overdose

A

Hepatic mechanism to N -acetyl-p-benzoquinone-imine (NAPQI) - highly toxic

In normal doses, NAPQI combines with thiols to produce nontoxic metabolites

In overdose, thiol stores are depleted and NAPQI accumulates

241
Q

What is the clinical effect of paracetamol (acetaminophen) overdose

A

hepatic injury and potentially fulminant liver failure

242
Q

What is the antidote to a paracetamol overdose?

A

Give N-acetyl-cysteine (NAC)

-Detoxifies and decreases the production of NAPQI
-Very effective when given early -within 8 hours of ingestion

243
Q

What are anticoagulants and antiplatelet drugs supposed to treat?

A

Thrombotic disorders or unwanted clots inside a blood vessel leading to a heart attack or stroke

244
Q

Name a platelet aggregation inhibitor.

A

Aspirin

Sandra Phase 2a (17 decks)

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