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Medicine Phase 2a > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

Give 3 examples of enteral (oral) routes of administration of drugs

A 
Enteric-coated (intestinal absorption e.g. aspirin)
Extended release (slower absorption e.g. metformin)
Sublingual/Buccal (rapid absorption and avoids first pass metabolism)
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2
Q

Give 3 examples of parenteral (systemic circulation) routes of drug administration

A

Intravenous
Intramuscular
Subcutaneous (insulin)

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3
Q

When would you use intramuscular administration of a drug?

A

Anti-psychotics

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4
Q

Give 3 other examples of drug administration that are not enteral or parenteral

A

Inhalation (oral, nasal)
Topical
Rectal

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5
Q

What is Pharmacokinetics

A

The action of drugs in the body including Absorption, Distribution, Metabolism and Excretion
(What the body does to a drug)

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6
Q

What are 4 properties to consider regarding the pharmokinetics of a drug

A

Absorption
Distribution
Metabolism
Elimination

ADME

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7
Q

Give 4 mechanisms of absorption (e.g. across GI mucosa)

A

Passive diffusion
Facilitated diffusion
Active transport
Endocytosis

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8
Q

What variables affect absorption (ADME)

A

pH
Vascularity (e.g. shock reduces SC absorption)
Surface area
Contact time (e.g. with food = slower gastric emptying)

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9
Q

Define bioavailability and equation of it

A

Rate and extend to which an administered drug reaches the systemic circulation (e.g. IV=100%)

AUC oral
——————– x100 = Bioavailability
AUC injected

(auc = area under curve (think))

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10
Q

What factors influence bioavailability

A

Solubility
Chemical instability (e.g. GI enzyme destruction of insulin)
Effect of Hepatic metabolism on drug (hepatic transformation of drug to inactive metabolites)

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11
Q

Define Distribution (Pharmokinetics - ADME)

A

Drug reversibly leaves bloodstream and enters the extracellular fluid and tissues

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12
Q

What 4 factors affect distribution (Pharmokinetics - ADME)

A

Blood Flow (e.g. brain>muscles)
Capillary permeability
Plasma protein binding (e.g. albumin)
Tissue protein binding (e.g. cyclophosphamide accumulating in bladder -> cystitis
Lipophilicity (ability to cross cell membranes)

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13
Q

Define Metabolism (Pharmokinetics - ADME)

A

Process of elimination, mainly through hepatic, renal and biliary routes

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14
Q

What are the 2 rates of metabolism (Pharmokinetics - ADME)

A

First Order - catalysed by enzymes, rate of metabolism directly proportional to drug concentration
Zero Order - enzymes saturated by high drug doses and rate of metabolism is constant

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15
Q

Give examples of chemicals of Zero order metabolism

A

Ethanol

Phenytoin

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16
Q

Describe the 2 phases of metabolism (Pharmokinetics - ADME)

A

Phase 1:
Polarise lipophilic drugs
Catalysed by Cytochrome P450 system
Reduction/Oxidation/Hydrolysis

Phase 2:
Conjugation
Example - glucuronic acid, polarisation of drugs to be excreted by renal or biliary systems

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17
Q

What system catalyses phase 1 metabolism reactions?

A

Cytochrome P450 system

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18
Q

What 3 reactions (and corresponding chemical) are Phase 1 reactions NOT done by P450?

A

Alcohol dehydrogenase
Xanthine oxidase
Amine oxidation

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19
Q

Name 3 problematic drugs for Cytochrome P450

A

Contraceptive pills
Warfarin
Anti-epileptics

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20
Q

Name inducers of cytochrome P450

A 
Anti-epileptics (Phenytoin, Carbamazepine)
Rifampicin
St Johns Wort
Chronic Alcohol intake
Smokers (CYP1A2)
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21
Q

Define absorption in pharmacokinetics

A

The process of transfer from the site of administration into the general or systemic circulation

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22
Q

Give examples of routes of administration

A 
Oral
Intravenous
Intra-arterial
Intramuscular
Subcutaneous
Inhalational
Topical
Sublingual
Rectal 
Intrathecal
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23
Q

What is meant by subcutaneous

A

Situated or applied under skin

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24
Q

Define intrathecal

A

occurring within or administered into the spinal theca

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25
Q

How would you give Diazepam for a fitting child who had no visible veins & jaws clenched tight?

A

Rectal

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26
Q

How would you give Xray dye for looking at coronary blood vessels?

A

Angiogram

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27
Q

How would you give Ondansetron (antiemetic) in a patient having chemo who cant stop vomiting

A

Intra Venous (IV)

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28
Q

How would you give GTN for a patient having an angina attack at home

A

Sublingual

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29
Q

How would you give insulin for a diabetic adult?

A

Subcutaneous

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30
Q

Define sublingual

A

Situated or applied under the tongue

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31
Q

Which 2 routes of drug administration do not cross at least 1 membrane in its passage from the site of administration to general circulation?

A

Intravenous or Intra arterial

drugs acts at intracellular sites must also cross the cell membrane

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32
Q

Describe 4 methods of passage across cell membranes

A

Passive diffusion through the lipid layer
Diffusion through pores or ion channels
Carrier mediated processes
Pinocytosis

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33
Q

Which of these regarding passive diffusion through the lipid layer is false:
Drugs move down concentration gradient
Need to have a degree of water solubility to cross phospholipid bilayer directly

A

Need to have degree of lipid solubility to cross phospholipid bilayer directly e.g. steroids

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34
Q

What factors are proportional to the rate of diffusion

A

Concentration gradient
Surface area
Permeability
..of the membrane

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35
Q

What factor is inversely proportional to rate of diffusion?

A

Thickness of membrane

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36
Q

Does movement through pores or ion channels happen against or down the concentration gradient

A

Down conc gradient

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37
Q

Give an example of a very small water soluble molecule that can diffuse through pores or ion channels

A

Lithium

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38
Q

What molecule provides energy for active transport or carrier mediated transport

A

ATP

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39
Q

What are the family of carriers called that facilitate cell-mediated transport?

A

ATP-Binding Cassette (ABC)

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40
Q

How many ATP-Binding Cassette (ABC)s are there in humans

A

49

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41
Q

What is the ABC known as MDR1 also called and what is it’s function?

A

MDR1 = Multi Drug Resistance
OR => P-gp

It removes a wide range of drugs from the cytoplasm to extracellular side.

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42
Q

How does Verapamil increase extracellular concentration of Chemo drugs?

A

Inhibits P-gp and so increases the concentration of anti-cancer drugs in the cytoplasm

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43
Q

What 2 ways can a molecule be transferred by facilitated transport (by a carrier)

A

Passive diffusion down concentration gradient
Use of theelectrochemical gradient of a co-transported solute to transport the molecule against the concentration gradient

Neither require ATP

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44
Q

What is OAT1, where is it found and what does it secrete?

A

Organic Anion Transporter
Kidney
Secretes penicillin and uric acid

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45
Q

Name a drug that can block OAT1 and what is the effect of this?

A

Probenicid
Blocks OAT1 causing uric acid to be excreted
(Crystals of uric acid can form in joints to cause gout)

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46
Q

What is pinocytosis?

A

A form of carrier mediated entry into the cytoplasm. It usually involves the uptake of endogenous macro molecules.
(can be involved in uptake of recombinant therapeutic proteins)

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47
Q

Name a drug that can be taken up into liposome(s) for pinocytosis

A

Amphotericin

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48
Q

Give an example of a drug that is a weak acid

A

Aspirin

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49
Q

Give an example of a drug that is a weak base

A

Propranolol

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50
Q

Why are ionisable groups of a drug essential for the mechanism of action of most drugs?

A

As ionic forces are part of the ligand receptor interaction (on cell membrane)

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51
Q

How would you describe drugs with ionisable groupsthat exist between charged (ionised) and uncharged forms

A

Drugs with ionisable groups that exist in equilibrium between..

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52
Q

Which of these is false for drug pharmacokinetics:
The extent of ionisation depends on the strength of the ionisable group and the pH of the solution.
Ionised form regarded as the most lipid soluble
Un-ionised form regarded as lipid soluble

A

Ionised form regarded as most water soluble

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53
Q

What is meant by the pKa of a drug?

A

pH at which half of a substance is ionised and half is unionised
(Dissociation or ionisation constant)

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54
Q

Where are weak acids best absorbed?

A

Stomach

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55
Q

Where are weak bases best absorbed?

A

Intestine

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56
Q

What is the effect on urine from an aspirin overdose?

A

Normally urine has lower pH than plasma so weak acid will be largely un-ionised and will be reabsorbed into plasma.

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57
Q

How can you reduce reabsorption of aspirin into plasma?

A

If alkalinise urine with IV bicarbonate, can reduce reabsorption of aspirin and lead to faster elimination

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58
Q

Which of these regarding oral administration is false:
Easiest and most convenient route for many drugs
Large surface area and high blood flow of small intestine can give rapid and complete absorption of oral drugs
The drug will go straight into systemic circulation

A

There are a number of obstacles for the drug to overcome before it reaches the systemic circulation

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59
Q

What factors affect absorption of an orally administered drug?

A 
Drug structure
Drug formulation
Gastric emptying (rate of this determines how soon drug taken orally is delivered to small intestine)
First pass metabolism
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60
Q

What drugs can not be given orally and why

A

Benzyl penicillin - unstable at low pH

Insulin - unstable in presence of digestive enzymes

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61
Q

What drugs tend to be only partially absorbed and have much of it passed in the faeces?

A

Highly polarised drugs

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62
Q

Why is Olsalazine used to treat Inflammatory Bowel Disease?

A

Olsalazine not absorbed in small intestine (highly polarised)

This therefore reduces systemic side effects

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63
Q

What is required for a drug to be absorbed from the gut without a carrier protein or other?

A

Lipid solubility

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64
Q

What is important for capsulated drugs or tablets?

A

The capsule or tablet must disintegrate and dissolve to be absorbed.

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65
Q

Give an example of modified release drugs formulated to dissolve slowly

A

Modified release = MR

Could have a coating that is resistant to acidity of the stomach in Enteric Coating (EC)

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66
Q

What can slow gastric emptying rate?

A

Food
Trauma
Antimuscarinic drugs (e.g. Oxybutinin)

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67
Q

Give an example of an antimuscarinic drug

A

Oxybutinin

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68
Q

How could gastric emptying rate be increased?

A

Gastric surgery

e.g. gastrectomy or pyloroplasty

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69
Q

In First Pass Metabolism, what 4 major metabolic barriers need to be crossed to reach circulation?

A

Intestinal lumen
Intestinal wall
Liver
Lungs

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70
Q

How can drugs be digested in intestinal lumen

A

Digestive enzymes present that can split peptide, ester and glycosidic bonds
Peptide drugs (insulin) that can be broken down by proteases
Colonic bacteria can hydrolyse or reduce drugs

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71
Q

The walls of upper intestine is rich in cellular enzymes - give example

A

Mono amine oxidases (MAO)

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72
Q

How can Efflux transporters such as P-gp limit absorption of drug in gut?

A

Luminal membrane of enterocytes contains efflux transporters such as P-gp which may limit absorption by transporting drug back into the gut lumen

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73
Q

How can ‘short gut syndrome’ from extensive bowel surgery decrease absorption?

A

poor oral absorption as little surface left and rapid transit time

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74
Q

What circulation delivers blood from gut to liver?

A

Splanchnic circulation

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75
Q

How can you avoid hepatic first pass metabolism

A

Giving drug to region of gut not drained by splanchnic e.g mouth or rectum ( GTN )

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76
Q

How long until an intravenous route takes effect

A

30-60 seconds (quickest method)

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77
Q

What is slowest method of administering a drug?

A

Ingestion (30-90 mins)

Transdermal (variable from minutes to hours)

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78
Q

What properties are required for a drug to be administered via transcutaneous methods?

A

Potent, non-irritant drugs.
(Human epidermis effective barrier to water soluble compounds. Limited rate & extent of absorption of lipid soluble drugs.)

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79
Q

When would you use Transdermal patches? (give example)

A

Slow and continued absorption.
E.g. Fentanyl patch 72
Hourly in chronic parin or palliative care

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80
Q

When/why would you use subcutaneous or intradermal?

A

Use for local effect (e.g. local anaesthetic) or to deliberately limit rate of absorption (e.g. long term contraceptive implants)

Small volume can be given; avoids barrier of stratum corneum; small volume can be given

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81
Q

What can increase removal of intramuscular administered drug from inject site?

A

Increase in blood flow or water solubility

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82
Q

What is meant by a Depot intramuscular injection?

A

Incorporating drug into lipophilic formulation which releases drug over days or weeks (e.g Flupenthixol )

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83
Q

Give features of intranasal administration

A

Low level of proteases and drug metabolising enxymes
Good SA
Local or systemic effects

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84
Q

What is the effect of cocaine on nose for drug administration

A

Cocaine is a vasoconstrictor and can get both local and systmic effects

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85
Q

Give example of intranasal drug with local effects

A

Decongestants

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86
Q

Give example of intranasal drug with systemic effects

A

Desmopressin

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87
Q

What are pros of inhalational administration

A

Large SA and blood flow

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88
Q

What are cons of inhalational administration

A

Risks of toxicity to alveoli and delivery of non volatile drugs

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89
Q

What drugs can be given inhalational

A

Volatiles likeGeneral anaesthetics

Locally acting drugs like bronchodilators (asthma)

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90
Q

Are asthma drugs volatile and how are they given

A

Non-volatile

Inhalational as aerosol or dry powder

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91
Q

Define distribution

A

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.

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92
Q

If equilibrium is reached by a drug between 2 sides of a membrane, what happens if a process removes drug from one side

A

Results in movement across membrane to restore that equilibrium (lipid soluble drugs for passive diffusion)

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93
Q

Define absorption

A

The process of transfer from the site of administration into the general or systemic circulation

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94
Q

Describe the distribution of an IV drug after administered

A

IV drug injection:
High initial plasma concentration and drug may enter well perfused tissue such as brain, liver and lungs
The drug will also continue to enter less well perfused tissues, lowering the plasma concentration.
Concentrations in the highly perfused tissues then decrease.

*Important in terminating some drugs given as a bolus

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95
Q

Give an example of terminating a drugs given as a bolus

A

Thiopental
This produces rapid anaesthesia because of initial high brain concentrations, but is short lived as continued muscle uptake lowers the blood concentration & indirectly the brain concentration

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96
Q

What plasma protein is most commonly bound (reversibly) to drugs?

A

Albumin

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97
Q

True or False:
Binding lowers the free concentration of drug and can act as a depot releasing the bound drug when the plasma concentration drops through redistribution or elimination

A

All true and important

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98
Q

Give an example of a drug that can bind irreversibly and therefore cannot reenter the circulation

A

Cytotoxic chemo with DNA

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99
Q

What makes up the blood brain barrier

A

Tight junctions, smaller number and sized pores in endothelium and astrocytes

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100
Q

What do SLC transporters supply the brain with?

A

Carbohydrates and amino acids

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101
Q

Give and example of a drug that uses the SLC transporters

A

L-Dopa for Parkinsons

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102
Q

How are drugs removed from the brain

A

Diffusion into plasma
Active transport in the choroid plexus
Elimination in the CSF

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103
Q

Give an exmaple of a drug that cannot cross the placenta

A

Heparin

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104
Q

Why does the foetus rely on maternal elimination

A

Foetal liver has low levels of drug metabolising enzymes

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105
Q

Give an example of an opiate given during labour which may persist in newborn who has to then eliminate them

A

Pethidine 7

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106
Q

*Define Elimination in pharmacokinetics

A

The removal of a drugs activity from the body.
May involve METABOLISM (transformation of a drug molecule into a different molecule) and/or EXCRETION (the molecule is expelled in liquid, solid or gaseous ‘waste’

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107
Q

Describe process/purpose of metabolism

A
  • Necessary for elimination of lipid soluble drugs.
  • They are converted into water soluble products that are readily removed in the urine. (If stayed lipid soluble, they would be reabsorbed).
  • One or more new compunds are produced which may show differences from the parent drug (e.g. less biological activity)
  • 2 phases
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108
Q

What are Phase 1 metabolism reactions

A

Involve the transformation of the drug to a more polar metabolite. This is done by unmasking or adding a functional group (e.g. -OH, -NH2, -SH).

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109
Q

*What is the most common Phase 1 reaction?

A

Oxidations

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110
Q

What group of enzymes catalyse Oxidation (phase 1) reactions?

A

Cytochrome P450

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111
Q

What is Cytochrome P450

A

Superfamily of membrane bound isoenzymes

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112
Q

Where is Cytochrome P450 mainly found?

A

Smooth Endoplasmic Reticulum

Largely in liver tissue

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113
Q

What is effect of smoking and alcohol on P450 enzymes

A

Can induce P450 enzymes

More rapid drug metabolism

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114
Q

Give example of drug and example of a food that can inhibit P450

A

Cimetidine

Grapefruit

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115
Q

Give an example of a genetic variation in Cytochrome P450

A

CYP2D6 deficiency/slow metaboliser 6-10% population

e.g. for Tamoxifen

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116
Q

What reactions are classed as Phase 1 reactions

A

Reduction
Oxidation
Hydrolysis

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117
Q

*Give examples of Phase 1 reactions that do not involve CYTP450

A

Oxidation ones:

  • Ethanol metabolisation - instead by Alcohol Dehydrogenase
  • Monoamine oxidase -inactivates Noradrenaline
  • Xanthine oxidase - inactivates 6-mercaptopurine

Other:
Some drugs are metabolised in plasma, lung or gut

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118
Q

Give example of drug metabolised in plasma (Phase 1, not CTYP450)

A

Suxamethonium

Plasma Cholinesterase

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119
Q

*Describe Phase 2 reactions

A

Conjugation
Involves formation of a covalent bond between the drug OR its phase 1 Metabolite
and an endogenous substrate

The resulting products are usually less active and readily excreted by the kidneys

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120
Q

Which of these is Phase 1 reaction?
Synthetic reaction
Degradative reaction

A

Degradative reaction

Synthetic reaction is phase 2

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121
Q

Give examples of molecules that a phase 1 metabolite can be conjugated with in phase 2 reactions

A

Glucuronic acid
Sulfate
Acetyl or Methyl groups

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122
Q

Which of these corresponds to phase 2 reactions:
Mainly microsomal
Microsomal, Mitochondrial and Cytoplasmic

A

Mitochondrial, Microsomal,

Cytoplasmic

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123
Q

Where do Phase 1 reactions mainly occur

A

Mainly microsomal

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124
Q

Where can phase 2 reactions occur

A

Microsomal, Mitochondria, Cytoplasm

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125
Q

Describe differences between a phase 1 and a phase 2 metabolite

A

Phase 1 metabolites formed:
Smaller, Polar or Non-polar, Active or Inactive

Phase 2 metabolites:
Larger, Polar, Water Soluble, Inactive
(for excretion)

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126
Q

What is excreted as a fluid?

A

Low molecular weight polar compounds

Urine, Bile, Sweat, Tears, Breast milk

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127
Q

What is excreted as a solid in faecal elimination?

A

High molecular weight compounds excreted in bile

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128
Q

What is excreted as a gas?

A

Volatiles

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129
Q

What is equation to calculate total urine excretion

A

Total excretion = glomerular filtration + tubular secretion -reabsorption

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130
Q

Describe how molecules end up in faecal excretion

A

High molecular weight molecules are taken up into hepatocytes and eliminated into bile.
Bile passes down gut: Some drug may be reabsorbed and re-enter the hepatic portal vein in Enterohepatic Circulation

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131
Q

*Describe the graph seen for a first order reaction (kinetics)

A

Change in concentration (dC/dt)at any time is proportional to the concentration.

Exponential decline:
A constant fraction of the drug is eliminated per unit of time.

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132
Q

Give an example of First Order Kinetics

A

Drug given via IV is rapidly distributed to the tissues. (exponential decline)

By taking repeat plasma samples, the fall in the plasma concentration with time can be measured.

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133
Q

*Describe a zero order reaction (kinetics)

A

The change in concentration per time(dC/dt) is a fixed amount of drug per time, independent of concentration.

If a system that removes a drug is saturated the rate of removal of the drug is constant and unaffected by an increase in concentration

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134
Q

What would a Zero order graph look like?

A

Concentratrion (y axis) and Time (x axis)

Constant gradient down (diagonal line going down)

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135
Q

Give example of zero order kinetics

A

Ethanol follows zero order kinetics once alcohol dehydrogenase has been saturated
(However up to this point, it is presumably first order)

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136
Q

Give the equation for a zero order kinetics graph

A

dC/dt = -k where k is reaction rate constant or gradient
units often mg/min

dC/dt = change in concentration per time

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137
Q

Give equation for a first order kinetics graph

A

dC/dt = -kC where k is the reaction constant

dC/dt is change in concentration per time

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138
Q

If plotted a logarithm (e.g.lnC) of concentration against time for first order kinetics equation, what would graph look like

A

Straight line with slope -k and intercept gives concentration at time zero (lnC x o)

(Diagonal straight line going down)

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139
Q

*What is half-life

A

Period of time required for the concentration or amount of drug in the body to be reduced by one-half.
(usually consider the half life of a drug in relation to the amount of the drug in plasma)

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140
Q

*What is bioavailability

A

The fraction of the administered drug that reaches the systemic circulation un–altered (F).

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141
Q

What is the bio-availability of IV drugs

A

1

as 100% of the drug reaches the circulation

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142
Q

Why may oral drugs have a bio-availability of <1

A

If they are incompletely absorbed or undergo first pass metabolism

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143
Q

How would you determine the oral bioavailability of a drug

A

AUC IV

AUC = area under the curve

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144
Q

What would it mean if a drug has an oral bioavailability of 0.1

A

The oral dose will need to be 10x IV dose

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145
Q

What is meant by the distribution of a drug

A

Rate and extent of movement of a drug into and out of tissues from blood

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146
Q

What determines the distribution of water soluble drugs

A

Rate of passage across membranes

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147
Q

What determines the distribution of lipid soluble drugs

A

Blood flow to tissues that accumulate drugs

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148
Q

Why is the extent of distribution of a drug important clinically

A

As this determines the total amount of drug that has to be administered to produce a particular plasma concentration

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149
Q

*What is equation to measure the apparent volume of distribution (Vd)

A

Vd = total amount of drug in body (dose)/plasma concentration

(*Remember APPARENT volume)

150
Q

What is the apparent volume of distribution if give 50 mg of drug and find plasma concentration is 1mg/L

A

Vd= 50mg/1mg/L

=50L

151
Q

What would a low apparent volume of distribution suggest?

A

Suggests drug may be confined to circulatory volume

152
Q

What would a high apparent volume of distribution suggest?

A

Suggests drug may be distributed in total body water

153
Q

*What is meant by Clearance

A

The volume of blood or plasma cleared of drug per unit time

e.g. if 10% of a drug (carried to liver) is cleared at flow rate of 1000ml/min
The clearance would be 100ml/min

154
Q

If 5% of a drug (carried to liver) is cleared at flow rate of 1200ml/min, What is clearance?

A

60ml/min

155
Q

If drug has a high Vd, would concentration in plasma be higher or lower

A

Lower plasma conc

156
Q

If a drug has a high Vd and therefore a lower plasma conc, what would this mean for for rate of elimination.

A

Rate of elimination is inversely proportional to Vd

157
Q

How would you calculate the rate constant of elimination?

A

k=CL/Vd
k is the rate constant of elimination
CL is clearance
Vd is apparent volume of distribution

158
Q

What would it mean if the clearance of a drug was zero?

A

The drug would not be removed and plasma concentration would remain at equilibrium indefinitely (AUC would be indefinitely large)

159
Q

How is clearance of IV drug determined?

A

Clearance is usually determined using the AUC after an IV dose
CL=Dose/AUC for IV drug

160
Q

How is clearance of an oral drug determined?

A

CL= Dose x F/AUC for oral drug with bioavailability of less than 1

F is bioavailability
/ means or

161
Q

When are repeated drug doses used

A

To maintain a constant drug concentration in the blood and at the site of action for therapeutic effect

162
Q

*What is Steady state

A

Css

It is a balance between drug input and elimination

163
Q

With IV infusion, how long would it take to reach 95% of Css (steady state)

A

Approx 4-5 half-lives

164
Q

What is effect on time taken to reach Css (steady state) for a drug with a slower elimination

A

Will take a long time to reach steady state and it will accumulate high plasma concentrations before elimination rate rises to match drug infusion/input

165
Q

Other than a slow elimination rate, what else can delay reaching a steady state

A

High Vd

as t1/2 or half life is also dependent on Vd (t1/2 = 0.693xVd/CL )

166
Q

What is equation to calculate half life or t1/2

A

t1/2 = 0.693Vd/CL

167
Q

How is Css achieved in IV infusion?

A

Css is achieved when the rate of elimination equals the rate of infusion

168
Q

How would you calculate steady state for IV infusion

A

Css = Rate of Infusion/CL

169
Q

How would you calculate plasma clearance for IV infusion

A

CL=rate of infusion/Css

170
Q

How is rate of elimination calculated for IV infusion

A

Rate of Elimination = CL x Css so at steady state the rate of infusion also equals this

171
Q

By what route is most long term drug administration

A

Oral route

172
Q

On graph where have intermittent doses, what will be effect on concentration in plasma

A

Fluctuating

Peaks and troughs

173
Q

How does rate of absorption affect the profile of oral administration graph?

A

Rapid rate of absorption - exaggerated peaks

Slow rate of absorption - flatter peaks

174
Q

How would you correct a (oral) dose for bioavailability?

A

D x F/t
F is bioavailability
t is time interval between doses

175
Q

Give final equation to calculate Css

A

Css = (D x F)/(t x CL)

Css - steady state
D - dose
F - bioavailability 
t - time interval between doses
CL - clearance
176
Q

Explain how reach this for steady state:

Css = (D x F)/(t x CL)

A

When steady state is reached, the rate of administration is equal to the rate of elimination
which is CL x drug conc between peaks and troughs

Therefore D x F/t = CL x Css
So Css = (D x F)/(t x CL)

177
Q

Using this equation:
Css = (D x F)/(t x CL)
What factors affect plasma steady state?

A

Dose (D) or time interval between doses (t)

178
Q

*What is a loading dose?

A

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.

179
Q

Why would you use a loading dose?

A

Shortens the time taken to reach a steady state.
e.g. if a drug has a long half life, it would take a long time to reach a steady state

if takes 4-5 half life to reach steady state and half life is 24 hours, means it would take 4-5 days to reach a steady state

180
Q

How would you calculate Loading Dose?

A

Loading dose = Css x Vd

181
Q

After you have reached the steady state by giving a loading dose, what would you given to maintain steady state

A

Maintenance dose

182
Q

How would you calculate maintenance dose to keep steady state

A

Css = (D x F)/(t x CL)

(Css x t x CL) / F = D

183
Q

In shock, what needs to be done to control BP

A

Increase BP

e.g. with Adrenaline

184
Q

In hypertension, what needs to be done to control BP

A

Lower BP

e.g. beta blockers

185
Q

What is bradycardia?

A

Slow heart rate

186
Q

What is tachycardia?

A

Fast HR

187
Q

Give examples of multiple effects drugs could have

A

A drug to lower blood pressure will slow the heart

A drug to relax the airways may raise pressures in the eye

188
Q

What does autonomic NS do?

A

Conveys all outputs from the CNS to the body, except for skeletal muscular control

189
Q

What does the autonomic NS regulate?

A 
Vascular, airway and smooth muscle
Exocrine secretions (sweat)
Control of Heart Rate
Energy metabolism in the liver
Links to immune system
190
Q

Give examples of actions of the Parasympathetic division of the autonomic NS

A 
Constricts pupils
Stimulates tear glands
Strong stimulation of salivary flow
Slows heart rate
Constricts bronchi
Stimulates digestive juice secretion
Stimulates intestinal motility
Contracts bladder
Stimulates erection
191
Q

Give examples of actions of the Sympathetic division of the autonomic NS

A 
Dilates pupils
Tear glands moisturise
Inhibit excess salivary secretion
Accelerates heart rate and constricts arterioles 
Dilates bronchi
Inhibits stomach motility and secretion
Inhibits pancreas (and adrenals?) 
Inhibits intestinal motility
Relaxes bladder
Stimulates ejaculation
192
Q

What neurotransmitter acts on adrenergic receptors

A

Noradrenaline

193
Q

What are two types of adrenergic receptor

A

Alpha

Beta

194
Q

What type of receptor would you find in both parasympathetic and sympathetic fibres

A

nicotinic receptor

Between pre and post ganglionic fibre

195
Q

What chemical can be given to mimic the effects of the sympathetic NS

A

Adrenaline

e.g. in anaphylactic shock

196
Q

Give examples of organs with dual parasympathetic and sympathetic innervation (with opposing roles)

A

Gut
Bladder
Heart

197
Q

Give examples of parts of body that only have sympathetic innervation

A

Sweat glands

Blood vessels

198
Q

Give example of part of body that only has parasympathetic innervation

A

Bronchial Smooth Muscle

199
Q

What are two main neurotransmitters that can be targeted by therapeutic innervation

A

Acetylcholine

Noradrenaline

200
Q

What neurotransmitter is released by post-ganglionic sympathetic fibres and what receptor does this act on

A

Noradrenaline

Acts on alpha and beta adrenoreceptors

201
Q

What is only exception to post-ganglionic sympathetic fibres releasing Nad onto adrenoreceptors

A

Sweat Glands

Release ACh to stimulate muscarinic receptors

202
Q

What neurotransmitter is released by post-ganglionic parasympathetic fibres and what receptor does this act on

A

ACh

muscarinic receptors

203
Q

What neurotransmitter is released by pre-ganglionic sympathetic fibres and what receptor does this act on

A

ACh

nicotinic receptors

204
Q

What neurotransmitter is released by pre-ganglionic parasympathetic fibres and what receptor does this act on

A

ACh

nicotinic receptors

205
Q

What are NANCs

A

Non-Adrenergic, Non-Cholinergic Autonomic transmitters

206
Q

What system used NANCs

A

Enteric NS

Autonomic NS divisions

207
Q

Give examples of NANCs

A

Nitric oxide and Vasoactive Intestinal peptide (parasympathetic)
ATP and Neuropeptide Y (sympathetic)

208
Q

What ganglia are stimulated by nicotine

A

All autonomic ganglia via specific ganglionic nicotinic receptors
activating both parasympathetic and sympathetic NSs

209
Q

*What can activate muscarinic receptors

A

ACh
Muscarine (from poisonous mushrooms)

these receptors also susceptible to drug targetting

210
Q

What breaks down ACh

A

Acetylcholinesterases

211
Q

How many muscarinic receptors are there in the human body?

A

M1-5 (so 5)

212
Q

*Where is M1 (muscarinic receptor) mainly found

A

Brain

213
Q

Where are M2 receptors (muscarinic) mainly found

A

Heart

214
Q

What results from activation of M2 receptors

A

Slows the heart

215
Q

What can be given to block M2 receptors and what is the result of this

A

Atropine
(e.g. for life-threatening bradycardia and cardiac arrest)
Speeds up heart rate

216
Q

Where are M3 (muscarinic) receptors found?

A

Glandular and smooth muscle

217
Q

What results from activation of M3 receptors

A

Bronchoconstriction
Sweating
Salivary gland secretion

218
Q

Where are M4/5 receptors mainly found?

A

CNS

219
Q

What is Pilocarpine and what is it’s function

A 
Muscarinic agonist (stimulates)
Stimulates salivation (useful after radiotherapy or in Sjorgens syndrome)
Activates parasympathetic NS
220
Q

What can muscarinic agonists be used for in terms of eye disease

A

Glaucoma

by facilitating drainage of aqueous humour

221
Q

What is a side effect of muscarinic agonist

A

Slow the heart

222
Q

Give examples of Muscarinic ANTAgonists

A

Atropine

Hyoscine

223
Q

What are uses of muscarinic antagonists like atropine

A

Prevent bradycardia and BP drop, dry secretions perioperatively
Treat bradycardia induced by excessive doses of beta blockers
Treat bradycardia in cardiac arrest

224
Q

*How is bronchoconstriction treated?

A

Drugs that block M3 receptor

Anti-cholinergics or Anti-muscarinics

225
Q

Give an example of a short-acting Anti-cholinergic/anti-muscarinic (e.g. bronchoconstriction)

A

Ipratropium bromide (Atrovent)

226
Q

Give example of a long-acting anti-cholinergic/anti-muscarinic (e.g. bronchoconstriction)

A

LAMAs such as Tiotropium, Glycopyrrhonium

227
Q

How can you increase selectivity in treatment of bronchoconstriction?

A

Choice of drug delivery mechanism e.g. inhalers

Receptor selectivity e.g. tiotropium relatively selective for M3 receptors

228
Q

What can anti-cholinergic be used for?

A

Treating bronchoconstriction

Overactive bladder e.g. Solifenacin

229
Q

How can you open up pupil to allow eye examination

A

Short acting anticholinergic

230
Q

What can be used to treat irritable bowel syndrome

A

Mebeverine

Acts on parasympathetic fibres in intestinal colic and spasm also

231
Q

Why do anticholinergics worsen memory

Therefore what can be used for dementia treatment

A

ACh signalling involved in memory

Acteylcholinesterase inhibitors may be useful for treatment of dementia

232
Q

What can hyoscine be used for

A 
Palliative care
Travel sickness (anti-emetic actions)
233
Q

What is the major neurotransmitter innervating skeletal muscle

A

ACh

234
Q 
True or False:
Botulinum toxin (botox) prevents NAd release
A

False

prevents ACh release

235
Q

What are uses of botulinum toxin (botox)

A

Cosmetic

Anti-spasmodic (inhibiting ACh release to inhibit muscle activity

236
Q

What are uses of nicotinic blockers

A

induce relaxation in surgery

237
Q

Give example(s) of nicotinic blocker

A

Pancuronium

Suxamethonium

238
Q

What happens in myasthenia gravis

A

Autoimmune destruction of nicotinic ACh receptors which results in muscle weakness

239
Q

What can be given in myasthenia graves to increase signalling?

A

Anti-acetylcholinesterase

to increase amount of ACh in the body

240
Q

Add to drug formulary: Suxamethonium

A

Broken down by acetylcholinesterase and so contraindicated in patients with low level of this enzyme.
Contra-indication of anti-acetylcholinesterase

241
Q

Give side effects of anti-cholinergics

A

In brain they can worsen memory snd may cause confusion

Peripherally - can get constipation, drying of the mouth, blurring of vision, worsening of glaucoma

242
Q

Give examples of anti-cholinergics

A

Tricyclic antidepressants
Some early antihistamines
Some anti-emetics (prochlorperazine)

243
Q

Give examples of cholinergics

A

Organophosphate insecticides and Nerve gas

244
Q

Give side effects of cholinergics

A 
Irreversible acetylcholinesterase inhibitors and so can cause:
Muscle paralysis
Twitching
Salivation
Confusion
245
Q

Define catecholamines

A

Hormones produced by the adrenal glands

246
Q

What are 3 main catecholamines of body

A

Adrenaline
Noradrenaline
Dopamine

247
Q

What is the precursor of adrenaline and noradrenaline

A

Dopamine

noradrenaline -> adrenaline

248
Q

Where can noradrenaline be used in management

A

Management of shock in the intensive care unit

249
Q

What factors determine the outcome of a signalling pathway

A

Which receptor
Which cell its on
Which G protein (7 transmembrane GPCR)

250
Q

What are 5 main adrenergic receptors

A

Alpha 1 and 2
Beta 1 2 and 3

All G-coupled protein receptors

251
Q

*What are effects of alpha 1 agonist

A

Vasoconsriction

particularly in skin and splanchnic (abdominal) beds (less so in brain, lungs and heart)

252
Q

What are uses of alpha agonist

A

Treatment of Septic Shock

Topical alpha activation in Nasal Decongestion (Xylometazoline)

253
Q

Name an Alpha 2 agonist

A

Clonidine

lowers blood pressure

254
Q

Name Alpha Blockers/Antagonists

A

Doxazosin - blocks alpha 1 to lower blood pressure
Tamsulosin - help treat prostatic hypertrophy, via alpha 1A subtype in prostate
(no useful alpha 2 blockers)

255
Q

*What are effects of Beta 1 agonists

A

Increase HR and chronotropic effects

May increase risk of arrhythmias

256
Q

What are effects of Beta 2 agonists and what is use

A

Muscle relaxation

Asthma and can delay onset of premature labour

257
Q

Which Beta agonists affect carbohydrate and lipid metabolism

A

1 and 3

258
Q

What are general side effects of beta agonists

A

May affect glucose metabolism in liver

Tachycardia

259
Q

What are Beta 3 agonists used for

A

Reduce Over-active bladder symptoms

260
Q

Name 2 beta blockers

A

Propranolol

Atenolol

261
Q

What adrenergic receptors are blocked by Propranolol

A

Beta 1 and 2

262
Q

What are effects of Propranolol

A

Slow Heart rate
Reduce tremor
May cause wheeze

263
Q

What adrenergic receptor is blocked by Atenolol and where are main effects of drug

A 
Beta 1 (selective)
Main effects on heart
264
Q

How do beta blockers work

A

Lower blood pressure (by reduction in cardiac output and gradual reduction in central sympathetic outflow activity)
Reduce cardiac work
Treat arrhythmias

265
Q

What are uses of beta blockers

A 
Angina
MI prevention
High blood pressure
Anxiety
Arrhythmias
Heart failure
266
Q

**Side effects of beta blockers

A 
Tiredness
Cold extremities
Bronchoconstriction
Bradycardia
Hypoglycaemia
Cardiac depression
267
Q

What are less direct effects of beta blockers

A

Methyldopa can be used as a last resort antihypertensive - useful in eclampsia or preeclampsia that blocks NAd synthesis

Monoamine oxidase inhibitor (MAOIs) used as antidepressants by preventing NAd breakdown

268
Q

Patient with cardiac disease (angina and occasional atrial fibrillation) - what would you give

A

Beta 1 blocker e.g. Atenolol

269
Q

What would you give for this patient with:
COPD
Prostatic hypertrophy
Bladder instability

A 
COPD (M3 antagonist, B2 agonist) - would hopefully send them home on inhaler 
Prostatic hypertrophy (Alpha agonist)
Bladder instability (B3 agonist)
270
Q

Patient admitted with pneumonia and septic shock and get wheezy

A

NAd for septic shock

Beta agonist for wheezy

271
Q

Patient is penicillin allergy and gets anaphylaxis

A

Adrenaline

272
Q

Patient has cardiac arrest

A

Atropine

for bradycardia

273
Q

What proteins are Alpha-1 adrenoreceptors coupled with?

A

Gq protein

Phospholipase C

274
Q

What proteins are Alpha-2 adrenoreceptors coupled with?

A

Gi (i=inhibit) protein

in turn inhibits Adenyl cyclase when NAd binds

275
Q

What are effects of alpha-1 adrenoreceptors

A

Vasoconstriction
Pupil dilation
Bladder contraction

276
Q

What are effects of alpha-2 adrenoreceptors

A

Presynaptic inhibition of NAd (-ve feedback)

i.e. when blood sugar is low then alpha-2 in pancreas will be stimulated to reduce NAd release, thereby reducing insulin levels being released from the pancreas

277
Q

What proteins are coupled with Beta-adrenoreceptors

A

All beta-adrenoreceptors use pathway:
Gs protein
Adenyl cyclase

278
Q

What are effects of Beta-1 adrenoreceptor activation

A 
Increased FORCE of heart contraction (+ve inotropic effect)
Increased Heart Rate
Increased electrical conduction in heart
Increased RENIN release from kidney
=Increased Blood Pressure
279
Q

What are effects of Beta-2 adrenoreceptor activation

A

Bronchodilation
Vasodilation
Reduced GI motility

280
Q

What are effects of Beta-3 adrenoreceptor activation

A

Increased lipolysis

Relaxation of bladder

281
Q

*Define Adverse Drug reaction

A

Unwanted or harmful reaction following administration of a drug or combination of drugs under normal conditions of use and is suspected to be related to the drug.

282
Q

How much do ADRs cost NHS annually

A

£466 million

283
Q

How many hospital admissions are caused by ADRs

A

1 in 20

284
Q

Define a side effect (different to ADR)

A

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

285
Q

What is different between each of these:
Side effects
Toxic effects
Hypersusceptibilty effects

A 
Side effects (therapeutic range)
Toxic effects (beyond therapeutic range)
Hypersusceptibilty effects (below therapeutic range)
286
Q

Give examples of mild ADRs

A

Nausea
Drowsiness
Itching
Rash

287
Q

Give examples of severe ADRs

A

Respiratory depression
Neutropenia (low neutrophils)
Catastrophic haemorrhage
Anaphylaxis

288
Q

What % of ADRs occur in hospital inpatients

A

10-20%

289
Q

What % of ADRs are preventable according to WHO

A

60%

290
Q

What are social and economic effects of ADRS

A

Adversely affect patient’s quality of life
Cause patients to lose their confidence in drs
Increase costs of patient care
ADRs can mimic disease

291
Q

Give example of primary and secondary ADRs

A

B-blockers:
Primary adverse effects = Bradycardia and heart block
Secondary pharmacological adverse effect = Bronchospasm

292
Q

What can be used to classify ADRs

A

ABCDE Rawlins-Thompson

293
Q

What does each letter stand for in ABCDE Rawlins-Thompson

A 
Augmented
Bizarre
Chronic
Delayed
End of use
294
Q

What is most common type of ADR in Rawlins-Thompson

A

Type A - Augmented

295
Q

Describe type A adverse drug reaction (Rawlins-Thompson)

A

Augmented

An extension of the clinical effect
Predictable
Dose-related
Self-limiting

296
Q

Give examples of Type A reactions (Rawlins-Thompson)

A

Diuretic causing dehydration
Anticoagulant causing bleeding
Drug for hypertension causing hypotension

297
Q

What groups are at increased risk of Type A reaction (Rawlins-Thompson)

A

Those with renal or hepatic impairment due to elimination difficulties i.e. have high blood plasma levels of the drug for longer
Elderly (above 65) - decreased glomerular filtration and hepatic impairment etc

298
Q

Describe type B adverse drug reaction (Rawlins-Thompson)

A

Bizarre

Unexpected
Unrelated to dosage and not expected from known pharmacological action
Unpredictable
Mostly immunological mechanisms
Hypersensitivity
Can be seen in drugs that inhibit certain metabolic pathways
Genetically linked

299
Q

Give example of type B ADR (Rawlins-Thompson)

A

Heparin causing hair loss

300
Q

What groups at at increased risk of type B ADR (Rawlins-Thompson)

A

Those with predisposing factors such as

history of allergy, asthmatics and some family history

301
Q

Describe type C ADR (Rawlins-Thompson)

A

Chronic

Occurs after long term therapy
May not be immediately obvious with new medicines

302
Q

Give example of type C ADR (Rawlins-Thompson)

A

Diabetes that result from

Steroids that predispose to hypoglycaemia

303
Q

Describe type D ADR (Rawlins-Thompson)

A

Delayed

Also occurs after a long period of time (many years) after treatment
Common to see patient having treatment then after 20-30 years they suffer an ADR

304
Q

Give examples of type D ADR (Rawlins-Thompson)

A

Teratogenesis (congenital malformations in foetus) after taking thalidomide
Neoplasia

305
Q

Describe features of type E ADR (Rawlins-Thompson)

A

End of use

Relatively long term use (days/weeks)
Withdrawal reactions
Serious complication of stopping related to clinical effect

306
Q

To identify Type A ADR, what would you ask yourself

A

Augmented
Is it predictable from the mechanism of action?
Does it seem does-related?

307
Q

To identify Type B ADR, what would you ask yourself

A

Bizarre

Is there a history of allergy?

308
Q

To identify Type C ADR, what would you ask yourself

A

Chronic

Has the patient been using the medication for a long time?

309
Q

To identify Type D ADR, what would you ask yourself

A

Delayed

Has the patient uses a drug in the past that could be causing a problem now?

310
Q

*To identify Type E ADR, what would you ask yourself

A

End of use

Is the patient withdrawing from a medicine?

311
Q

*In general what makes someone more susceptible to an ADR

A 
Age - elderly
Gender - more common in females
Pregnancy - negative effect on baby etc
Disease - liver or renal in particular
Drug interactions
Diet or alcohol intake changes
Genetics
Hypersensitivity
312
Q

*What is Type 1 Hypersensitivity

A

IgE-mediated drug hypersensitivity

ANAPHYLAXIS

313
Q

*What is Type 2 hypersensitivity

A

IgG-mediated cytotoxicity

314
Q

*What is Type 3 hypersensitivity

A

Immune-complex deposition

315
Q

*What is Type 4 hypersensitivity

A

T-cell mediated

usually substance containing metals

316
Q

Through what type of hypersensitivity can some drugs cause renal failure?

A

Type 2

IgG-mediated cytotoxicity

317
Q

What type of hypersensitivity involves reaction with antibiotics

A

Type 3 (immune-complex deposition)

318
Q

Briefly describe process of acute anaphylaxis

A

Prior exposure to antigen (drug)
Virgin B lymphocyte activation to IgE producing plasma cells
IgE become attached to mast cells, expresses cell surface receptors

319
Q

Define idiosyncrasy

A

Inherent abnormal response to a drug

320
Q

What are causes of idiosyncrasy

A

Genetic abnormality, enzyme deficiency

May be due to abnormal receptor activity

321
Q

What is name for an inherent abnormal response to a drug

A

Idiosyncrasy

322
Q

Describe process of idiosyncrasy from receptor abnormality

A

Malignant hyperpryrexia (high fever) with general anaesthetics
Sudden huge rise in calcium concentration
Increase in muscle contraction
Increase in metabolic activity
Rise in body temperature

323
Q

Give example of idiosyncrasy as result of enzyme deficinecy

A

X-linked enzyme deficiency:
Glucose 6 phosphate dehydrogenase (G6PD) enzyme deficiency and give primaquine (drug for malaria).
Primaquine should not be given as leads to haemolytic and haemolytic anaemia.

324
Q

What are most common drugs to have ADRs

A 
Antibiotics
Anti-neoplastics
Cardiovascular drugs
Hypoglycaemics
NSAIDs
CNS drugs
325
Q

What systems are most likely to be affected by an ADR

A 
GI
Renal
Haemorrhagic
Metabolic
Endocrine
Dermatologic
326
Q

*Give 6 examples of common ADRs

A 
Confusion
Nausea
Balance problems
Diarrhoea
Constipation
Hypotension
327
Q

What % of ADRs are avoidable

A

30-50%

Inappropriate or Unnecessary medication

328
Q

*What is the MHRA

A

Medicines and Healthcare products Regulatory Agency

(Government agency) Responsible for approving medicines and devices for use

329
Q

*What is the yellow card scheme

A

-ADR reporting scheme
Voluntary
-Collects spontaneous reports and suspected adverse drug reactions
-Introduced in 1964 as worlds first ADR reporting scheme

330
Q

What are strengths of Yellow card scheme

A
  • Can work rapidly and is readily accessible.
  • *Continual safety monitoring of a product throughout its life span as a therapeutic agent.
  • Fairly cheap to operate
  • Acts as ‘early warning system’ for identification of previously unrecognised reactions
  • Provides information about factors which predispose patients to ADRs
  • Allows comparisons of ADR ‘profiles’ between products within same therapeutic class
331
Q

What are weaknesses of yellow card scheme

A
  • *Not all ADRs are reported (only 10% of serious reactions reported)
  • Cannot provide an estimate of risk as true number of cases is underestimated and total number of patients exposed is unknown
  • Relies on ADR being recognised
  • May be stimulated by promotion or publicity
  • Reporting high for newly marketed drugs and falls off over time
332
Q

What is meant by the Black Triangle with regards to a drug

A

Indicates a medicine is undergoing ‘additional monitoring’

333
Q

Why are ADR reporting rates low?

A

Ignorance - not sure how to report
Diffidence - I may appear foolish about reporting a suspected ADR
Fear - may expose myself to legal liability by reporting ADR
Lethargy - too busy to report ADRs
Guilt - I am reluctant to admit I may have caused harm
Ambition - I would rather collect cases and publish them
Complacency - only safe drugs are marketed

334
Q

What are reasons to report ADRs

A

Important for patient safety
To identify ADRs not identified in clinical trials
To identify new ADRs asap
To compare drugs in the same therapeutic class
To identify ADRs in ‘at risk’ groups

335
Q

Whats meant by a serious reaction

A 
Reaction that..
..is fatal
is life threatening
is disabling or incapacitating
results in hospitalisation
prolongs hospitalisation
336
Q

Who can report on a Yellow card

A 
Patients
Doctors
Dentists
Coroners
Pharmacists
Nurses (incl midwives and health visitors)
Radiographers
Optometrists
337
Q

What pieces of information are needed on Yellow Card

A 
Suspected drug(s)
Suspected reaction(s)
Patient details
Reporter details
Additional useful information
338
Q

True or False:

All suspected ADRs for new medicines should be reported

A

True

339
Q

True or False:

All ADRs in children should be reported

A

True

340
Q

What is mast cell degranulation

A

Cross-linking of IgE receptors releasing acute inflammatory mediators

341
Q

What acute inflammatory mediators are released in mast cell degranulation

A

Histamine
Thromboxanes, prostaglandins
Tumour Necrosis Factor (TNF)

342
Q

*Describe non-immune anaphylaxis

A

(Anaphylactoid reactions)

Not caused by IgE antibodies
Due to direct mast cell degranulation

Some drugs are recognised to cause this
No prior exposure
Clinically identical to immune anaphylaxis

343
Q

**Describe the main features of anaphylaxis

A 
Exposure to drug, immediate rapid onset
Rash with characteristic blotches
Swelling of lips, face, oedema, central cyanosis (go blue/purple)
Wheeze
Hypotension (anaphylactic shock)
Cardiac arrest
344
Q

*Give an alternative presentation of anaphylaxis

A

Cardiorespiratpry arrest

No skin changes

345
Q

*Describe management of anaphylaxis

A 
Commence basic life support (A airway, B breathing, C circulation)
Specific treatment:
-STOP DRUG if Infusion
-Adrenaline
-IV Anti-histmine
-IV Hydrocortisone (100 to 200mg)
346
Q

What are effects of adrenaline (given in management of anaphylaxis)

A

Vasoconstriction
Bronchodilation
Increased cardiac output

347
Q

What is needed to get drugs circulating if cardiac arrest?

A

Cardiac massage

348
Q

True or False:

IV hydrocortisone is likely to cause harm in excess

A

False

Iv hydrocortisone unlikely to cause harm in excess so can’t really give too much

349
Q

What dosage of adrenaline is given in management of anaphylaxis

A

Adrenaline 1mg (10mls of 1:10,000 (IV)), 1ml IV increments

350
Q

Give an example and dose of IV anti-histamine used for management of anaphylaxis

A

Chlorphenamine (10mg)

351
Q

Give medicine risk factors for drug hypersensitivity

A
  • Protein or polysaccharide based macro molecules e.g. penicillin
  • Mono-clonal antibodies (proteins) can cause reactions
352
Q

Give host risk factors for drug hypersensitivity

A

More common in females compared to males

Immunosupression

353
Q

Give genetic risk factors for drug hypersensitivity

A

Certain HLA groups (gene that encodes major histocompatibility complex MHC)

354
Q

*Is Type A ADR a form of allergy

A

IgE mediated but NO
However some people can be more sensitive to Augmented hypersensitivity e.g. more likely to develop hypotension with anti-hypertensives

355
Q

If suspect ADR, what is procedure

A

Elicit a full medication history and previous reactions
Check useful sources to find if ADR is described e.g. BNF, eMC, Medicine Information Centres and MHRA
Identify markers

356
Q

What are markers that can be identified for Type A ADR

A

serum concentration - plasma monitoring

357
Q

What are markers that can be identified for Type B ADR

A

Tryptase - only released from mast cells

Urine Methylhistamine - breakdown product of histamine

358
Q

What is the best test to confirm allergy based ADR

A

Tryptase test

359
Q

If a patient has an ADR, what can be done to prevent further ADR in patient

A

Continue drug but manage the ADR by other means
Reduce dose of the drug
Stop the drug

360
Q

*Describe management specific to Type A ADRs

A

Dose-related
May respond to dose-reduction or temporary withdrawal
Severe reactions may require active treatment

361
Q

*Describe management specific to Type B ADRs

A

Not usually dose-related
SHOULD USUALLY WITHDRAW THE MEDICINE IMMEDIATELY
Give supportive treatment if reaction is severe (e.g. anaphylaxis)

362
Q

*How would you report an ADR

A

MHRA Yellow-card scheme

363
Q

True or False:

All suspected ADRs for new medicines should be reported

A

True

364
Q

True or False:

All ADRs in children should be reported

A

True

365
Q

What is difference between Pharmacodynamics and pharmacokinetics

A

Pharmacodynamics - effect drug has on body

Pharmacokinetics - what body does with the drug

366
Q

*Pharmacodynamics: what is a summative reaction

A

Effect of 2 drugs added together

1 + 1 = 2

367
Q

*Pharmacodynamics: what is a synergistic reaction

A

1 + 1 > 2

Sum of drugs greater than what expect when individually add them together

368
Q

Give examples of synergistic reaction

A

Clavulanic acid and Amoxil to make Augmentin

Paracetamol and Codeine to increase analgesic effect

369
Q

*Pharmacodynamics: what is Antagonism

A

1 + 1 = 0

370
Q

Give example of antagonism (Pharmacodynamics)

A

Morphine and Naloxone

371
Q

*Pharmacodynamics: what is potentiation

A

1 + 1 = 1 + 1.5

Drug A makes Drug B more powerful, but Drug B is not made more powerful by Drug A

372
Q

Give example of Potentiation

A

Probenicid then Penicillin (increased penicillin in blood)

Medicine Phase 2a (22 decks)

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