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Year 2 LCRS Pharmacology > All of Pharmacology (1-10) > Flashcards

All of Pharmacology (1-10) Flashcards

1
Q
A
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2
Q

What are the principal target organs of the ANS?

A
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3
Q

Name two examples of organs/systems that are only innervates by the sympathetic Nervous system

A

E.g.

  • Blood vessels
  • Skin
  • Liver
  • Kidneys
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4
Q

Name one example of and organ that is innervated by both, sympathetic and parasympathetic NS and describe their respective effect

A

Pupils

  • SNS: dilation
  • PNS: Constriction

Trachea:

  • SNS: dilation
  • PNS: constriction

GI:

  • SNS: inhibitory (less motility and secretion)
  • PNS: exitory (more motilty and secretion
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5
Q

What are the neurotransmitters of the parasympathetic NS? Which receptors do they bind to?

A

PNS uses Acetlycholine (ACh) as transmitter

  1. Binds to nicotinic receptors after (long) pre-ganglionic fibre
  2. Binds to Muscarenic receptors after post-ganglionic fibre in target organ

(First Nicotin than mucus)

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6
Q

What type of receptor is the nicotinic receptor?

A

They are Ionotropic (Type 1) receptors

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7
Q

What is an Ionotropic receptor?

A

A receptor that opens/closes an ion chanel as reaction to a ligand binding

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8
Q

What type or receptor is a muscarenic acetylchline receptor?

A

It is G-Protein coupled (Type 2)

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9
Q

Which Neurotransmitters does the SNS use?

A
  1. ACh after (short) preganglionic fibres
    • Noradrenaline
    • Adrenaline / Noradrenaline produced by adrenals
    • (Sometimes ACh e.g. in sweat glands)
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18
Q

Describe the synthesis + degradation of Acetyloecholine

A
  1. Acetyle CoA + Choline combined by Choline acetyl transferase
  2. Packed into vesicles + excreted when Ca2+ influx
  3. Broken down by Acetylecholine esterase in Choline + Acetate
  4. Reuptake into cell
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19
Q

Describe the synthesis of Noradrenaline

A
  1. Tyrosine —> Tyrosine Hydroxilase —>
  2. DOPA —> DOPA decarboxylase —>
  3. Dopamine (transported into vesicles) —> Dopamine ß hydroxylase —>
  4. Noradrenaline
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20
Q

How is Noradrenaline degraded?

A

Reuptaken in pre- or post-synaptic cell, degraded via

  1. Monoamine oxidase A (MAO-A) (in mitochondria)
  2. COMT (Catechol-O-methyltransferase)
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21
Q

Which receptors does the SNS generally uses

A
  1. Nicotinic ACh receptor
    • adrenergic receptors (adrenoceptors) (Noradrenaline/Adrenaline)
    • Muscarenic (when ACh as neurotransmitter at target organ)
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22
Q

Wich sub-types of Muscarenic receptors are there?

Where do they occur and what do they controll?

A

5 Sub-types

  1. M1: Neural (e.g. in Forebrain for memory)
  2. M2: Cardiac (to decrease heart rate and contractility force)
  3. M3: Exocrine + Smooth muscle (decreased SM contration, increases secretion

4+5 less easy to classify

  • M4 – Periphery: prejunctional nerve endings (inhibitory)
  • M5 – Striatal dopamine release
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23
Q

What does the M1 Muscarinic achetylcholine receptor do?

A

Involved in neural parts (e.g. memory in forebrain)

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24
Q

Which sub-type of muscarinic acetylcholine receptor can be found primarily in the Brain?

A

M1

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25
Q

Which sub-type of muscarinic acetylcholine receptor can be found primarily in the Heart?

A

M2

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26
Q

Which sub-type of muscarinic acetylcholine receptor can be found primarily in exocrine glands and Smooth muscle?

A

M3

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27
Q

What type of receptor are adrenoreceptors?

A

G-protein coupled receptors (Type2)

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28
Q

Which questions can be asked to discribe a pharmacodinamic action of drugs?

A
  1. What is the drug target?
    * e.g. a1 adrenergic receptor
  2. Where is the drug target?
    * on SM tissue
  3. What is the end result of the interaction?
    * Vasoconstriction
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29
Q

Describe the synthesis + degradation of Acetyloecholine

A
  1. Acetyle CoA + Choline combined by Choline acetyl transferase
  2. Packed into vesicles + excreted when Ca2+ influx
  3. Broken down by Acetylecholine esterase in Choline + Acetate
  4. Reuptake into cell
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30
Q

Describe the synthesis of Noradrenaline

A
  1. Tyrosine —> Tyrosine Hydroxilase —>
  2. DOPA —> DOPA decarboxylase —>
  3. Dopamine (transported into vesicles) —> Dopamine ß hydroxylase —>
  4. Noradrenaline
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31
Q

How is Noradrenaline degraded?

A

Reuptaken in pre- or post-synaptic cell, degraded via

  1. Monoamine oxidase A (MAO-A) (in mitochondria)
  2. COMT (Catechol-O-methyltransferase)
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32
Q

What does Pharmacokinetics discribe?

A

What the body does to/with the drug

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33
Q

Wht does Pharmacodynamics discribe?

A

What the drug does the the body (what the effect is)

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34
Q

What are the prinicpal target sited of drugs?

A

Proteins:

  • Receptors
  • Ion channels
  • Transport systems
  • Enzymes
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35
Q

Which signals does a receptor respond to?

A
  • Neurotransmitters
  • Hormones
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36
Q

Where are receptors located

A

Type 1-3: in cell membrane (usually)

Type 4: intracellular steroid receptors

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37
Q

Which Sub-Types of Receptors are there?

A
  1. Type 1: ionotropic (ion channel linked)
  2. Type 2: G-protein coupled
  3. Type 3: Kinase linked
  4. Type 4: intracellular steroid receptors
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38
Q

What are the characteristics of a Type 1 receptor?

A

Ionotropic receptors (ion channel coupled)

  • very fast response (milli sec.)
  • e.g. nAChR, GABA
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40
Q

Whar are the characteristics of a Type 2 receptor?

A

G-protein coupled –> set off intracellular messenger system

  • seconds of response
  • e.g. ß1 adrenergic receptor in heart
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41
Q

What are the characteristics of a Type 3 receptor?

A

Kinase linked

  • response within minutes
  • e.g. insulin, Growth factor
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42
Q

Whar are the characteristics of Type 4 receptors?

A

Intracellular steroid hormones

  • regulate DNA transcription
  • response within hours
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44
Q

Which type of receptor is an ionotrypic receptor?

A

Type 1

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48
Q

Which signals does an ion chanel respond to?

Which example drugs target ion channels?

A
  1. Change in voltage (voltage gated)
  2. Receptor binding (Receptor linked)

e.g. Local Anesthetics, Calcium channel blockers

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49
Q

How can transport systems be exploited as drug target?

A

By blocking transport systems that transport substanced against their concentration gradient ( are specific for substance + ATP dependant)

  • e.g. Neurotransmitter uptake (blocking of reuptake of Noradrenaline used in antidepressants)
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50
Q

In which ways can drugs target Ezymes?

A
  1. Enzyme inhibitors
    • inhibit enzyme action and slows reaction down
  2. False substrate
    • Derivate von enzym substaten lassen “False transmitters” entstehen (e.g. Methylnoradrenaline from Methyldopa which has a less powerful effect)
  3. Produgs
    • umwandlung des Medikaments durch Enzym
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51
Q

What is a False transmitter? What is a true transmitter?

A

False transmitter: Transmitter that closely immitates the action of a transmitter but act a bit different

  • e.g. Methyldopa (False transmitter) giving Methylnoradrenaline binding weaker to target –> causing muscle relaxation
  • DOPA would be the true transmitter
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52
Q

What are Non-specific drug actions?

A

Drugs that work via theit physiochemical properties

  • anitacids (bases)
  • osmotic purgatives (abführmittel)
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53
Q

What is an agonist?

A

Something that enhances receptor action

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54
Q

What is an antagonist?

A

Something that blocks/ decreased receptor action

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55
Q

Which factors does the potency of a drug depend on?

A
  1. Affinity –> how strong/easy does the drug bind to the target
  2. Efficacy –> how strong is the effect of the drug on the target
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56
Q

What is the Affinity of a Drug?

A

How strongly/easy the drug binds to its target

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57
Q

Descibe/draw a dose-response curve of a full agonist in comparison to a partial agonist

A
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58
Q

Describe /draw how a log- dose response curve of a full agonist with high efficacy, full agonist with low efficacy and partial agonist would look like

A
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59
Q

What is teh effecacy of a drug?

A

How strong the effect is on the target

(e.g. conformatin change in receptor)

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60
Q

What are the characteristics of a full agoinst?

A

It binds to and activate a receptor with the maximum response that an agonist can elicit at the receptor

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61
Q

Whar are the charcteristics of a partial agonist?

A

Bind to and activate the receptor but only have a partial efficacy in comparison to full agonist

–> can have antagonist property in presence of a full agonist

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62
Q

What is the selectivity of a drug?

A

How selective the drug is to its target (will be overlap, often resulting in side-effects)

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63
Q

How would a log dose response curve look like in presence of

  • agonist alone
  • with competitve agonist
  • with irreversible agonist
A
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64
Q

What does the structure-activity relationship descibe?

A

Small changes in structure can have major effects on results (because of lock-and key modell)

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67
Q

How efficiant are antagonist?

A

Not at all –> have affinity but no efficacy (don’t do anything)

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68
Q

What two types of Antagonists are there?

A
  1. Competitive
    • same binding site as substrate
    • Shifts Dose-response curve to the right
    • surmountable (überwindbar bei hohen Substratkonenztrationen)
  2. Irreversible
    • different binding site or binds tighly
    • –> incativate enzyme/receptor
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69
Q

What are the characteristivs of competitive antagonist binding?

A

Competitive

  • same binding site as substrate
  • Shifts Dose-response curve to the right
  • surmountable (überwindbar bei hohen Substratkonenztrationen)
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70
Q

What are the characteristics of irreversible antagonsit binding?

A

Irreversible

  • different binding site or binds tighly
  • –> incativate enzyme/receptor
  • insurmountable (unüberwindbar bei hohen Substratkonzentration)
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72
Q

Explain the concept of receptor blockage antagonism

A

Competitive binding or Irreversible binding

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73
Q

Through which mechanisms can a drug act as an antagonist?

A
  1. Receptor blockage
    • competitive
    • irreversible
  2. Physiological antagonism
    • opposite effect in same tissue
  3. Chemical antagonism
    • reduces concentration of agonist by forming chemical complexes
  4. Pharmacokinietic antagonism
    • reduce concentration by: decreasing absorbtio, increasing metabolism/excretion
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74
Q

Explain the conecegt of physiological antagonism

A

A drug has the opposite effect as the agonist in the same tissue

e.g. Noradrenaline is an antagonist of histamine in blood vessel (dilation vs. constriction)

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75
Q

Explain the conept of chemical antagonism

A

Antagonist reduces concentration by reducing formin chemical complex with agonist

e.g. Dimercaprol with heavy metals

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76
Q

Explain the concept of pharmacokinetic antagonism

A

decrease concentration of agonist at site of action by

  • decreasing absorbtion
  • increasing excretion
  • increasing metabolism
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77
Q

What is drug tolerance?

A

A gradual decrease to drug afer longer time of administration

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78
Q

Which concepts can lead to drug tolerance?

A
  1. Pharmacokinetic factors
    • adaptive increase in metabolism (e.g. enzymes)
  2. Receptor loss/increase
  3. Change in receptor (desensitisation)
  4. Exhaution of mediator store
  5. Physiological adaption (to side effects)
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79
Q

Explain the concept of pharmacokinetic in drug tolerance

A

Ther ecan be an adaptive increase in drug metabolites etc. e.g. enzmyes

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80
Q

Explain the concept of receptor loss/increase with drug tolerance

A

Receptors can be lossed by plasma endocytosis

less receptors —> less action

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81
Q

What happens at receptor desensitzation in drug tolerances?

A

Conformation change in receptor leading to desensitization

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82
Q

Explain the concept or exhaution of mediator site in the context of drug tolerance

A

E.g. Amphitamines cause release of amines

–> Amine storages get exhaused –> can’t be released

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83
Q

Explain the concept of physiological adaptation in the context of drug tolerance

A

it is a homeostatic response

often a tolerance to the drug side effects

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84
Q

What is pharmacokinetics?

A

The way of a drug through the body + what the body does to it

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85
Q

What is the significance of pharmacokinetics?

A

It determines the does of the drug that is available to the tissue

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86
Q

Which steps does a drug in the body undergo from Administration to removal?

A

A bsorbtion

D istribution

M etabolism

E xcretion

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87
Q

What are the different routes a drug can be administered?

A

…

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89
Q

Explain systemic and local administration

A

Systemic: entrire organism

Local: specific tissue of organism

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90
Q

What is enternal and parenternal administration of drugs?

A

Enternal: via GI tract

Parenternal: without GI tract

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91
Q

How do drugs move around in the body?

A
  1. Bulk flow transfer
    • bloodstream, lymph
  2. Diffustion transfer
    • molecule by moelcule over a short distance
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92
Q

Through which mechanisms do drugs cross cell membranes?

A
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93
Q

What kind of molecules can cross via the following routes? Which one is the least important?

A

Diffusion: Fat soluble molecules (or very small)

Diffusion through aqueous pores: small watersolube molecules —> barly any drug –> least important

Active transport: the rest

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94
Q

Why do drugs have to pass aqueous and lipid compartments?

A

Aqueous: to move around e.g. in bloodstream, lymph , extracellulra, intracellular fluid

Lipid: To reach their target (to cross membranes)

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95
Q

How does the Handerson Hasselbach equation look like to determine, how the ration between Ionised and unionised forms of bases/acids look like when pka and pH are known?

A
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98
Q

Which chemical feature do most drugs have in common? Why?

A

They are either weak acids or bases

–> can be ionised and unionised, depending on the environment (often therefore polar and non-polar)

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99
Q

How does capillary permeability influence drug distribution?

A
  • Fat soluble: can cross all membranes, into all tissues (even blood-brain barrier)
  • Water soluble: often rely on transport emchanisms /pores –> will me distributed more unevenly (and more in capillaries with large gaps)
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101
Q

Which factors influence drug distribution?

A
  • Regional blood flow
  • Extracellular binding (plasma protein)
  • Capillary permeability
  • Localisation in tissues
  • Solibility (e.g. general anestetics are very fat soluble –> large proportion will be in fat even though only very little blood flow to it)
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102
Q

How does regional blood flow influence distribution of drugs?

A

Highly metabolically active tissues have more blood flow + denser capillary networks (can change e.g. with exercise in skeletal muscle)

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103
Q

How does extrcellular binding of drugs influence their distribution (passage of membranes)

A

Extracellular binding to plasma proteins

  • determines availability e.g. if 95% is bound –> only 5% are able to cross membranes
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104
Q

What happens during phase one of drug metabolism?

Which reactions take place to let this happen?

A

Adding/unmasking a reactive group to the drug (increasing polarity)

  • most reactions are oxidations (ofter start with hydroxylation)
  • But also: redeuction, hydrolisis
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106
Q

Which characteristics can the metabolite have that is formed after Phase one of the drug metabolism?

A
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107
Q

How does localisation in tissues influence drug distribution?

A

Fat: 15% body weight, but 2% blood supply

Very fat soluble drugs – 75% partitioned in fat at equilibrium

–> disproportional high amounts of drugs in fat tissue (e.g. general anestetics)

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108
Q

What happens during phase 2 of drug metabolism?

What are common reactions?

A

Add a water soluble conjugate to the reactive group

there will be a conjugate and a conjugative agent

Recations involve

  • Glucoronidation (most common)
  • Sulfation
  • Glutathionine conjugation

Less common:

  • Acetylation
  • Methylation
  • Aminoacid conjugation
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109
Q

What is the most common reaction in phase 2 of drug metabolism?

What are its characteristics?

A

Glucoronidation

low affinity/high capacity – more likely to occur at high drug dosages

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110
Q

What is an example of a phase 2 drug high affinity low capacity metabolism?

A

Sulfation –> More likely to occur at low drug dosages

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111
Q

In which drug metabolism phase does glutathiodine conjugation take place? What does it require? What might be the problem with it?

A

Drug needs to be electrophilic to be conjugated or biotransformed to an electrophilic conjugate

–> But electropiles are extremely reactive

When overdosing –> no glutathiodine available –> electrophile might cause tissue damage

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112
Q

What is the aim of metabolism of a drug?

Why is that so?

A

To make the drug more water soluble for easier excretion

  1. no diffusion back into bloodstream once in kidney nephron
  2. more drug in bloodstream (less in tissue) hence more excretion
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113
Q

Why are most drugs rather fat soluble?

A

To get into tissues (be able to cross cell membranes)

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114
Q

How are drugs excreted in the kidney?

Which factor influence each step?

A
  1. Glumerular filtration
    • size dependant
  2. Active secretion
    • dependant on available transporters + transport mechanisms
  3. Passive reabsorbtion
    • urine pH (–> determines ionisation) + drug characteristics, state of metabolism (fat soluble drugs just diffuse back into systemic circulation)
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115
Q

What are the two phases in drug metabolism? What are their respective aims

A
  • Phase 1: introduce(add/unmask) a reactive group to the drug (to increase polarity)
  • Phae 2: add a water soluble conjugate to the reactive group
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116
Q

How does the Enterohepatic cycling influence drug excretion?

A

Recycling of drugs can significantly increase half life and concentration of drugs!

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118
Q

Which is the most common enzyme to oxidise drugs in phase 1 of drug metabolism?

What are its characteristics

A

Cytochrome P450

  • 57 enzymes (each do different drugs)
  • has low specifity
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120
Q

What is a prodrug?

A

A drug that is activated by Phase 1 of drug metabolism (not active at administration)

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125
Q

Why is drug metabolism important? (What are the overall aims - not on a chemical level)

A
  • The biological half-life of the chemical is decreased.
  • The duration of exposure is reduced.
  • Accumulation of the compound in the body is avoided.
  • Potency/duration of the biological activity of the chemical can be altered.
  • The pharmacology/ toxicology of the drug can be governed by its metabolism.
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126
Q

Through which main organ systems are drugs excreted?

A

Mainly via the

  • kidney
  • liver
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128
Q

How does drug excretion via the liver work?

A
  1. Diffusion from sinusoids into hepativ tissue (via discontinuous capillaries/ diffusion through cells)
  2. Active transport (or fat soluble –> diffusion) into bile
  3. Excretion via bile

–> Mint the Enterohepatic cycling! (reabsorbtion)

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130
Q

Other than the kidney and liver: Through which routes can drugs also be excreted?

A
  • lungs
  • skin
  • gastrointestinal secretions
  • saliva
  • sweat
  • milk
  • genital secretions
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131
Q

Define Bioavailability

A

Proportion of the administered drug that is available within the body to exert its pharmacological effect

(dependant on absorbtion + distribution???)

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132
Q

Define Apparent volume distribution

A

The volume in which a drug appears to be distributed

  • an indicator of the pattern of distribution
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133
Q

Define Biological half life

A

Time taken for the concentration of drug (in blood/plasma) to fall to half its original value

(linked to metabolism/excretion)

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134
Q

Define Clearance (pharmacokinetics)

A

Blood (plasma) clearance is the volume of blood (plasma) cleared of a drug (i.e. from which the drug is completely removed) in a unit time

(Related to volume of distribution and the rate at which the drug is eliminated. If clearance involves several processes, then total clearance is the sum of these processes)

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135
Q

Where are the Cytochrome P450 enzymes located?

A

Primarily in the Smooth ER (in liver but also in other tissues)

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136
Q

Which factors does Oxitation reaction in Phase 1 metabolism require?

A

Requires

  • NADPH (as co-enzyme)
  • often molecular oxygen
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137
Q

Glutathione is a tripeptide consisting of:

A
  • Glycin
  • Cystein (with thiol group)
  • Glutamic acid
138
Q

What is the enzyme and co-substrate needed for Sulphation reaction?

A

Sulphation

  • sulphotransferase
  • 3’phosphoadenosyl-5’-phosphosulphate (PAPS)
139
Q

Which enzyme and co-substrate are needed for Glucoronidation?

A

Glucoronidation

  • Enzyme: UDP-glucuronosyltransferase
  • Co-substrate: UDP-glucuronic acid (UDP-GA)
143
Q

Which Enzyme and Co-enzyme is needed for Glutathione conjugation reactions?

A

Glutathiodine conjugation

  • for electrophilic substraties (often produced by phase I oxidation)
  • Co-substrate: Glutathione
  • Enzyme needed: Glutathione-S-transferase
144
Q

Which Phase 2 Metabolism reactions does Paracetamol undergo?

A
  1. 40-60% sulfation
  2. 20-30% glucoronidation
  3. 10% Glutathione conjugation –> neutralisation of NAPQI
145
Q

How could you treat a Paracetamol overdose?

A

Oral/I.V. N-acetylcysteine

  • promote synthesis of GSH (Glutathione)
  • more capacity for metabolism of Paracetamol
  • needed for conjugation of NAPQI and for protection of protein thiols
146
Q

What kind of drug is Atropine?

A

It is a kompetitive Muscarinic receptor antagonist

147
Q

What does muscarine do?

A

Agonist of the Muscarinic receptor

–> Stimmulation (not broken down by Ach-esterase)

  • tears
  • saliva
  • miosis
  • sweating etc.
148
Q

Where are the M1 muscarenic achetylcholine receptors loacted?

Which secound messenger system do they activatie?

A

•M1:

  • Salivary glands
  • Stomach
  • CNS

Activate Gq-Protein: exitory

  • IP3 + DAG (–> increases Ca2+ influx)
149
Q

Where are the M2 muscarenic achetylcholine receptors loacted?

Which secound messenger system do they activatie?

A

•M2: Heart

  • are inhibitory

Activate Gi-protein

  • downregulation of cAMP
150
Q

Where are the M3 muscarenic achetylcholine receptors loacted?

Which secound messenger system do they activatie?

A

M3:

  • Salivary glands
  • Bronchial/visceral SM
  • Sweat glands
  • Eye

Are exitory: Activate Gq protein

  • increase in IP3 and DAG
151
Q

What are the structural features of the Muscarinic receptor?

A

Has 7 transmembrane regions

connencted to loop + G-protein in the inside

153
Q

What are the effects of muscarinic exitation in the eye?

A

Contraction of the ciliary muscle: accommodation for near vision

Contraction of the sphincter pupillae (circular muscle of the iris): Constricts pupil (miosis) and improves drainage of intraocular fluid

Lacrimation (tears)

154
Q

What is the effect of contraction of the spincter puppilare?

How can this be used in glaucoma treatment?

A

Contraction of sphincter pupillae opens pathway for aqueous humour, allowing drainage

–> reducing intra-ocular pressure

–> in some form of glaucoma, iris is deformed, blocking fluid drainage and hence increasing intraoccular pressure

155
Q

What are the effects of muscarinic stimmulation on the heart?

A
156
Q

Explain the structure of a nicotinic receptor

A
  • Ionotropic receptor
  • Has 5 subunites (alpha-epsylon)
  • Binding property is determines by the combination of Subunits
  • •Effects of ACh relatively weak
160
Q

Which effect does Ach has on the vasculature?

A

No direct PNS innervation but has M3 receptors:

  • stimmulation causing endothelial NO release
  • SM relaxation
161
Q

Which effect does parasympathetic innervation has on the non-vascular smooth muscle?

A

–> Constriction:

  • Lung: Bronchoconstriction
  • Gut: Increased peristalsis (motility)
  • Bladder: Increased bladder emptying
162
Q

Which effect does stimmulation of muscarinic Ach receptor have on excretions?

A

Exitory:

  • Salivation
  • •Increased bronchial secretions
  • •Increased gastro-intestinal secretions (including gastric HCl production)
  • •Increased sweating (SNS-mediated)
163
Q

What directly acting cholinomimetic drugs are there?

A
  1. Alkaloids (Pilocarpine)
  2. Choline esters (Bethanechol)
164
Q

What are the characteristics of Pilocarpine?

What kind of drug is it?

A

It is a non-selective muscarenic agonist

–> good lipid solubility

–> half life around 3-4h

165
Q

What is the clinical use of pilocarpine?

A

Mostly used for local treatment of glaucoma

(non-selective muscarenic agonist)

166
Q

What are possible side effects of pilocarpine? Why?

A
  • Blurred vision (–> PNS stimmulation of eye)
  • sweating (SNS stimmulation)
  • gastro-intestinal disturbance and pain
  • hypotension
  • respiratory distress

–> all others: PNS stimmulation

167
Q

What kind of drug is Bethanechol?

What are its characteristics?

A

M3 Acetylcholinereceptor selective agonist

  • no degradation
  • orally active (can be orally given)
  • half life: 3-4h
168
Q

What is the clinical use of Bethanechol?

A

To assist bladder emptying and enhance gastric motility

169
Q

What are the side effects of Bethanechol administration?

A
  • Sweating
  • imparied vision
  • bradycardia
  • hypotension
  • respiratory distress
170
Q

What is the function of Acetylcholinesterase?

Where is it found?

A

Break down ACh to acetate and choline

  • found in all cholinergic synapses
  • very fast and highly selective
171
Q

What is the function of Butyrylcholinesterase?

Where is it found?

What are its characteristics?

A
  • Break down ACH
  • found in plasma and most tissues, not in synapse –> reason for low ACh plasma levels
  • •Broad substrate specificity - hydrolyses other esters e.g. suxamethonium
  • Genetic variation
172
Q

What happens at a low, medium and high dose of cholinesterase inhibitors?

A

Low dose

  • Enhanced muscarinic activity (see above)

Moderate dose

  • Further enhancement of muscarinic activity
  • Increased transmission at ALL autonomic ganglia (nAChRs)

High dose (toxic)

  • Depolarising block at autonomic ganglia & NMJ (see PT9 NMJ lecture) –> too much fiering –> receptors shout down –> paralysis
173
Q

Which drug is a reversibel Anticholinesterase drug?

Why is it reversible?

A

Physostigmine and Neostigmine

  • competitive inhibitor –> binds to active side
  • Donates Carbamyl group that blocks the receptor
  • Carbamyl group removed by slow hydrolysis (mins rather than msecs)
174
Q

What is physiostigme?

What are its characteristics?

A

A reversibele indirectly cholinomimetic drug

  • reversibly blocks Cholinesterase (get freed again after minutes)
  • Primarily acts on postganglionic parasympathetic synapse
  • Half life about 30m
175
Q

What is the clinical use of physiosigme?

A

Clinical use:

  • Glaucoma treatment
  • To treat atropine poisoning (particularly in children)
176
Q

What kind of drugs are irreversibel Anticholinesterase Drugs?

How do they act?

A
  1. ecothiopate (only one with clinical use)
  2. dyflos, parathion and sarin used as pestisides or chemical weapons

React with enzyme active side

  • Make a stable block, resistant to hydrolysis
  • –> recovery may require production of new enzymes
177
Q

What is Ecothiopate?

A

Potent inhibitor of acetylcholinesterase

–> Slow reactivation of the enzyme by hydrolysis takes several days

178
Q

What is the clinical use of Ecothiopate?

A

Irreversible anticholinesterase inhibitor

Used in treatment of glaucoma

  • prolonged effect in fluid drainage
179
Q

What are the side effect of Ecothiopate?

A
  • Sweating
  • blurred vision
  • GI pain
  • bradycardia
  • hypotension
  • Respiratory problems

–> PNS stimmulation

180
Q

What are the effect of Anicholinestases in the CNS?

A

Non-polar Anticholinesterases can cross BBB

Low doses

  • exitation with possibility of convulsions (Krämpfe)

High dose:

Unconsciousness, respiratory depression, death

181
Q

What are possible treatments for Organophosphate Poisonings?

A

Organophsphate = irreversible anticholinesterase

Can be treated via

  • Atropine (Muscarenic antagonist)
  • Parlidoxime within first hours –> displaces the bound organophsphate from enzyme
182
Q

What is pharmacology?

A

It it the science of chemicals that potentially could benefit patietns

183
Q

What is the difference between a drug and a medicine?

A

A drug is the chemical which should have its effect

A medicine is a dosage form of the drug but also contains excipients (zusätze)

184
Q

What is the functio of exipents in a medicine?

A
  • to improve its chemical and biological stability
  • to increase its acceptability to the patient by improving its flavour, fragrance or appearance
  • To make it able to grab e.g. the pill (increase size)
  • to increase its bioavilibility
185
Q

What involves the process called formulation?

A

The process of making a medicine (with excipients) containing a drug

186
Q

What are the advantages and disadvantages of oral administration of a medicine?

A

Advantage

  • It permits self-medication
  • It does not require rigorously sterile preparations
  • The incidence of anaphylactic shock is lower (than intravenous)
  • There is the capacity to prevent complete absorption (vomiting, lavage).

Disadvantage

It is inappropriate for drugs which:

  • are labile in acid pH of stomach or otherwise degraded
  • or undergo extensive ‘first-pass’ metabolism,

It requires patient compliance.

187
Q

What are the advantages and disadvantages of IV administration of drugs?

A

Advantage

  • rapid onset of action
  • avoids poor absorption from, and destruction within, the g.i. tract permits careful control of blood levels

Disadvantages

  • slow injection necessary (to avoid toxic bolus) higher incidence of anaphylactic shock
  • trained personnel required
  • complications possible; embolism, phlebitis, pai
188
Q

What are the advantages and disadvantages of inhalation/ administration of a drug via the lungs?

A

Advantages

  • ideal for small molecules, particles, gases, volatile liquids, aerosols
  • enormous surface area presented by alveolar membranes
  • simple diffusion, also phagocytic cells clear particles

Disadvantages

  • possible localised effect within lung (unless this is desired)
189
Q

What are the advantages and disadvanatages of IM administration of a drug?

A

Advantages

  • relatively high blood flow, increased during exercise enables DEPOT THERAPY (prolonged absorption from pellet, microcrystalline suspension or solution in oily vehicle).

Disadvantages

  • possible infection and nerve damage (especially in gluteal region)
190
Q

What are the advantages and disadvantages of a subcutaneous administratio of a drug?

A

Advantages

  • Local administration, dissemination can be minimised for local effect
  • enables DEPOT THERAPY (as for intramuscular above)

Disadvantages

  • pain, abscess, tissue necrosis
191
Q

What are the advantages and disadvantages of percutaneous (across the skin) administration of a drug?

A

Advantages

  • local application and action
  • lipid soluble compounds diffuse rapidly (may be assisted by vehicles)

Disadvantages

  • local irritation and skin reactions
  • alteration of skin structure (e.g. steroids – subcutaneous adipose tissue)
192
Q

What is bioavailibility?

A

The amount of a drug contained in a medicine that enters the systemic circulation in an unchanged form after administration of the product

193
Q

How do each of the following influene bioavailibitly of a drug?

  1. the physicochemical characteristics of the drug (ionisation in gut)
  2. gastrointestinal pH
  3. whether or not the drug is passively or actively transported
  4. gastrointestinal motility
  5. particle size of the drug
  6. physicochemical interaction between drug and gut contents (e.g. chemical interaction between calcium and tetracycline antibiotics)
A
  • the physicochemical characteristics of the drug (ionisation in gut)
  • gastrointestinal pH

–> diffusion of ver membrane

  • whether or not the drug is passively or actively transported

–> might rely on transport mechanisms (can be genetically different)

  • gastrointestinal motility
  • particle size of the drug

–> Smaller Particle, higher motility= more/faster absorbtion

physicochemical interaction between drug and gut contents (e.g. chemical interaction between calcium and tetracycline antibiotics)

194
Q

Does the measurement of bioavailability always reflect the effectiveness of a drug?

A

No, some durgs can be effective without having a high bioavailability

Also, some drugs have to be metabolised to be effective –> would potentially have low bioavilibilty (because of its definition)

195
Q

What is the therapeutic index/therapeutic window?

A

The range of mount of drug that can be administered between

  • Lower end: its usefullness
  • Upper end: its toxicity
196
Q

Name examples of how a drug can be altered in the presystemic metabolism/ first pass metabolism)

A
  • the microbes within the gut lumen
  • enzymes present in the gut wall
  • enzymes in the liver
197
Q

Under what circumstances could a drug, which undergoes 100% first pass metabolism, be therapeutically useful?

A

Either

  • target side is berfore first pass site (e.g. Intestinal target after oral use)
  • administration without going to liver (e.g. iv, sublingual)
  • Metabolism required to make drug usefull
198
Q

What is bioequivalence?

A

evidence that the new ‘generic’ product behaves sufficiently similar to the existing one to be substituted for it without causing clinical problems

–> otherwie coule be different e.g. because of excipients

199
Q

What are Nicotinic receptor antagonists also called?

A

Ganglion blocking drugs

–> Block transmission of whole autonomic devision at ganglion

200
Q

Explain the mechanism of action, effect and use of Hexamethonium

A

Nicotinic receptor antagonist, first ever antihypertensive drug!

–> Ion channel block

  • creates a use-dependant block

Effect:

  • loss of function of the dominant autonomic NS
  • e.g. at rest : increased HR, bronchodilation, hypotension –> vasodilation + less retention in Kidney

Also:

  • pupil dilation (light sensitivity)
  • constipation
  • no bladder emptiying
  • –> too unspecific, no clinical use anymore
201
Q

What is a use-dependant block?

A

The more a channel/recptor etc, is used, the stronger its blocke

–> At high usage–> high blocking

e.g. at Ion channel blockers, where Ion channels need to be open (working) for blocking to go into channel and create effect

202
Q

Explain the mechanism of action, effect and use of Trimetaphon

A

Trimetaphon: Nicotinic receptor antagonist

  • receptor blocking antagonist
  • half life of around 30 min
  • effects same as Hexamethonium (dominant autonomic System functions are lost)

Used in controll of BP during surgery (as single dose shot)

203
Q

Name two Nicotinic receptor antagonists (including their mechanism of action and effect

A

Hexamethonium

  • ion channel blocker
  • 1st ever hypertensive drug (no clinical use anymore)

Trimetaphon

  • receptor blocker
  • t1/2= 30min
  • used in controll of BP during surgery

Effect:

  • loss of function of dominant Autonomic system
  • at high dosage: blocking of NMJ –> paralysis (many poisons)
204
Q

What is the clinical use of Nicotinic receptor antagonists?

A

Barely any clinical use:

  • drugs are too messy, too many side effects because all autonimic functions are blocked + interference with NMJ

Ony use

Trimetaphon to controll BP during surgery

205
Q

What are the side effects of Nicotinic antagonist drugs?

A

Too messy: interfer with many systems

E.g. somatic (NMJ) –> used in animal poisons (alpha-bungarotoxin) leading to parlaysis

But also:

  • hypotension
  • light senstitivity
  • constipation
  • no bladder emptying
  • etc.
206
Q

What are the effects of Atropine and Hyoscine on the CNS?

Why?

A

Atropine;

  • Normal dose – Little effect
  • Toxic dose - Mild restlessness –>Agitation (normal effect of M-antagonists)
  • (Less M1 selective)

Hyoscine;

  • Normal dose – Sedation, amnesia
  • Toxic dose – CNS depression or paradoxical CNS excitation (associated with pain)
  • (Greater permeation into CNS. Influence at therapeutic dose)

–> Difference not yet fully understood, probably because Hyoscine more lipophilic –> BBB maybe more M1 selective

207
Q

What is the mechanism of action and use of Tropicamide

A

Tropicamide

Muscarenic receptor antagonist

Causing pupil dilation (relaxation of Spincter Pupillae) –> Mydriasis and blurred vision (paralysis of ciliary muscle of eye)

  • Used for examination of the retina
208
Q

Explain the clinical use of Muscarenic receptor antagonists in Anestehetic premedication

A

Hyoscine

Causes sedation

  • blocks bronchioconstrition –> dilation (good for e.g. inhaled anesthetics)
  • blocks glandular secretions (good e.g. to prevent aspiration of saliva)
  • Blocks HR reduction (good because anesthetics generally decrease HR –> prevention of bradycardia)
209
Q

Explain the clinical use of Hyoscine

A

Used as hyoscine patch in motion sickness

Normally: Auditory signals + visual sicknes are combined and when missmatch: transport to vomiting centre

When blocked: Pathway to vomiting centre blocked –> prevention of motion sickness

210
Q

Explain the use of Muscarenic antagonists in Parkinsons disese

A

Problem in Parkinsons is: too little Dopamine

this can’t be changed but amount of dopamine receptor can be increased –> less dopamine needed for same effect

  • Dopamine receptor is downregulated by M4 activity
  • When blocking M4 –> less downregulation –> More Dopamine receptors
213
Q

What are the side effects of Muscarenic Receptor Antagonists?

A
  • Heat intolerance –> no thermoregulation via sweating
  • Dry –> decreased secretions
  • Blind –> Cyclopegia (cillary muscle paralysis)
  • Mad –> CNS disturbance
214
Q

Which drug would be used to treat Atropine poisoning?

A

Preferably: Physiostime –> reversible Anti-cholinesterase drug

Atropine: Blocks Muscarenic receptors (kompetitevely)

Physiostigme –> increases dose of available ACh

215
Q

Explain the effect of Botolinum Toxin on the body

A

Extremely dangerous (only low dose required)

Blocks release of ACh out of vesicles

–> (by interfering with SNARE complex)

–> Paralysis of everythingn

217
Q

Explain the clinical use of muscarenic antatgonists in respiratory disease

Which drug is commonly used to achive this?

A

Blocking of Bronchioconstriction –> Bronchiodilation

  • e.g. Ipratropium Bromide
  • Atropine
218
Q

Explain the clinical use of a Muscarenic antagonist in GI conditions such as Irritatable bowl syndrome

A

IBS: movement of GI tract causes pain

(Usually M3 selective antagonists)

With antagonist:

  • Slows GI tract down
    • motility and tone
    • secretions
  • –> reduction of symptoms of IBS
222
Q

What are the clinical uses of Muscareninc antagonists?

A
  • Preanesthesia medication
  • Motion sickness
  • Astmah/Airway disease
  • GI disturbances
  • Prakinsons
  • Ophtalmology
223
Q

Where are a1 adrenoreceptors located?

What is their second messenger mechanism and prinicpal effect?

A

Alpha 1 receptors:

  • Eye (contraction of iris dilator muscle)
  • vasoconstriction (SM constriction)
  • excretion of nose
  • contraction of ureter–> holding urine

–> Exitory via

PLC into IP3 and DAG

224
Q

Where are alpha 2 adrenorecpetors commonly found?

What is their secound messenger system and principal effect?

A

Usually inhibitory –> decerease of cAMP

  • regulation in CNS
  • reduction of aqueous humor production in ciliary body
226
Q

Where are ß2 adrenoreceptors located?

What is their 2nd messenger system

A

Bronchios/Airway

Vessels –> causing vasodilation

uterine smooth muscle

increase in cAMP

227
Q

How would you medically treat an anaphylactic shock?

What are the (desired) effects?

A

Adrenaline (non-selective adrenoreceptor agonist) e.g. in Epipen

It counteracts the problems associated with too much histamine release:

  • ß2–> Bronchiodilation
  • ß1 –> tachycardia
  • a1 –> vasoconstriction
  • Might bind to ß receptors on mast cells and supresses the release of mediator cells

–> to increase BP and maintain breathing

228
Q

What do you use adrenaline for? (as drug)

A
  1. Anaphylactic shock
  2. Emergency Astmah + acute bronchspasm (ß2)
  3. Cardiogenic shock (ß1)
  4. Maintaining BP during spinal anestehsia (a1)
  5. Prolonging effect during local anesthesia (a1)
230
Q

Where are ß1 receptors located?

What is their secound messenger system?

A

Heart –> icrease heart rate + force of contraction

Kideny–> increase renin –> increase reabsorbtion

Messenger System: increase in cAMP

231
Q

Which drug is a a1 selective agonist?

A

More or less selective:

Phenylephrine

235
Q

What are the side effects of Adrenaline use?

When might this be problematic?

A
  • Reduces and thickened secretions
  • Tremor (skeletal muslce)
  • CVS effects
    • tachycardia, palpitation, arrythmias
    • vasoconstriction (cold extremities)+ high BP
    • at overdose: cerebral haemorrhage and pulmonary oedema
  • (Minimal CNS and GI effects)

Overall: not too severe, only in elderly patients of with underyling condition (e.g. heart problems)

236
Q

What are COMT and MAO?

Where are they situated

A

Both enzymes that break down Adrenaline/Noradrenaline

Catechol-O-Methyltransferase –> More peripheral

MAO –>Monoaminooxidase = More in CNS

238
Q

What is the mechanism of action and the clinical use of Phenylephrine?

A

It is a (more or less) a1 selective adreno agonist

It is more resistant than Adrenlaine to COMT –> longer there than Adrealine itself

  • vasoconstriction
  • Mydriasis
  • Nasal decongestant (abschwellendes Mittel)
    • vasoconstriction –> less fluid production
239
Q

Which drug is used as a a2 adrenergic agonist?

A

Clonidine

–> a2 receptors are inhibitory!

  • Glaucoma (decrease of humous production due to stimmulation of a2 receptor)
  • Treatment in hypertension and migrane
  • Reduction of sympathetic tone (by reducing sympathetic outflow via binding to a2 receptors in brainstem that then reduce signaling –< presynaptic inhibition of Noradrenline release)
240
Q

What are the clinical uses for Clonidine?

A

More or less selective a2 adrenoreceptor agonist

a2 receptors are inhibitory!

  • Treatment of Glaucoma (decrease of humous production due to stimmulation of a2 receptor)
  • Treatment in hypertension and migrane
  • Reduction of sympathetic tone (by reducing sympathetic outflow via binding to a2 receptors in brainstem that then reduce signaling –< presynaptic inhibition of Noradrenline release)
241
Q

What is the clinicl use of Salbutamol?

Explain the mechanism of action and unwanted effects

A

Salbutamol –> increase in cAMP –> increase in PKA

  • Main use in astmah
  • side effects
    • Cardiac–> increase in BP, tachycardia, arrythmias
    • hyperglycaemia
    • tremor, restlessness
242
Q

Which adrenorecepors controll vascular tone in the brain?

A

ß2 receptors–> would not want vasoconstriction to the brain

243
Q

What is an example of a adrenergic ß receptor selective drug?

A

Isoprenaline

  • more resistant to break down by MAO (central effects) and uptake 1 than Adrenaline
244
Q

When would you use Isoprenaline as medication?

What is the problem with the use of isoprnaline?

A

It is a adrenergic ß receptor selective agonsit (ß1=ß2)

Used in:

  • Cardiogenic shock
  • Acute heart failure
  • MI

Can be problematic: (especially in e.g. Astmah medication when patients would always get refelx tachycardia)

  • stimmulation of ß2 receptors causes vasodilation
  • –> drop in BP
  • Causing reflex tachycardia (via Baroreceptors)
245
Q

What is a adrenergic ß1 receptor selective drug?

A

Dobutamine

246
Q

What is the clinical use and characteristics of Dobutamine?

A

Used in

  • cardiogenic shock
  • (because of short half life of 2 min)

–> but does not have refelx tachycardia (like isoprenaline

247
Q

Name a adrenergic ß2 receptor selective drug?

A

Salbutamol

248
Q

What is the clinicl use of Salbutamol?

Explain the mechanism of action and unwanted effects

A

Salbutamol –> increase in cAMP –> increase in PKA

  • Main use in astmah
  • side effects
    • Cardiac–> increase in BP, tachycardia, arrythmias
    • hyperglycaemia
    • tremor, restlessness
249
Q

How are eye infections normally treated?

A

Allergy+ conditions that cause inflammation: corticosterids (antiinflammatory drugs)

Actue infections: dependant on cause: antibacterials, antifungals, antivirals

In severe cases: systemic treatment

250
Q

What is constriction and what is dilation of the pupil?

A

Constriction: Miosis

Dilation:Mydriasis

251
Q

Which drug types are used to induce mydriasis?

Name an example

A

Normally antimuscarenic agents are used

e.g. atropine, tropicamide

252
Q

How would you medically induce miosis?

What is the drug type and name examples

A

Obtained with muscarenic agonists (e.g. pilocarpine)

253
Q

What are the effects of tropicamide on

  • pupil diameter
  • accomodation
A

Tropicamide is a Muscarenic receptor antagonist

  • It dilates the pupil –> relaxation of the constrictor pupillae
  • Inpaires near vision (accomondation) –> relaxation of the ciliary muscle) (poit of focus is further away)
254
Q

What is the clinical use of tropicamide?

A

Muscarenic receptor antagonist–>

Use in diagnostics of the retina+ lens because of pupil dilation

255
Q

Explain the effects of pilocarpine on accomodation and pupil diameter

A

Pilocarpine is a muscarenic receptor agonist causes

  • constriction of the ciliary muscle –> very near accomodation
  • constriction of the constrictor pupillae –> small pupil diameter
256
Q

What is the clinical use of pilocarpine?

A

It increasing aqueous outflow –> used in glaucoma treatment

257
Q

How does the sympathetic NS influence occular function?

A
  • Dilation pupillae
  • aqueous humor production via
    • stimmulation of ß2 –> stimmulates production
    • also a1 in cillary muscle (vasoconstriction) –> inhibiton of production
    • a2 –> inhibiton of production
  • Vasoconstrictoon of blood to retina??
258
Q

How can a sympathomimetic drug be used in the tratment of glaucoma?

A

If it is alpha selective: reduces blood flow (a1) and inhibits formation of aqueous humor (a2)

259
Q

How can a ß-blocker be used in the treatment of glaucoma?

A

Antagonises the ß2-adrenoreceptors in the eye

–> decrease of aqueous humor production

260
Q

Explain the administration of drugs to the eye in terms of local and systemic effects

A

It is not easy to get drugs into the eye (local administration) but once they are in, they easily get into body (because of high vasculisation)

261
Q

Explain the mechanism by which opioids induce miosis

A

Heroin in stimulating the nerve (CNIII –> normally inhibited by GABA –> heroin is switching off GABA (physiologically done by endorphins)) and therefore causes stimmulation of the PNS –> miosis

262
Q

Explain the mechanism of action of the prostaglandin analogue Latanoprost in the treatment of glaucoma

A

Increases drainiage via clearing of the venous drainage channels (no function via the pupil)

263
Q

Explain the use of Carbonic anhydase inhibitors like Acetazolamide in the treatment of glaucoma

A

It directly stops ß receptor from producing aqueous humor (by blockign enzyme that produces aqueous humor)

264
Q

Explain the role of alopha 2 adrenoreceptors in Noradrenaline release

A

As soon as Noradrenaline is released into the synapse it binds to alpha 1+2 receptors

  1. Alpha 1: effect of Noradrenaline (vasoconstriction)
  2. Alpha 2: negative feedback on Noradrenaline release in presynaptic neuron to ensure short acting action of Noradrenaline
266
Q

Explain the effects and mechanisms of action in the clinical use of ß-Blockers

A

ß Blockers

  • Reduce blood volume (ß1 on kidney Via less Renin–> Aldosterone production)
  • Reduce TPR (less Renin –> less Vasocontriction as AGTII response)
  • Reduce CO (ß1 on heart: reduced cAMP leading to redcued HR+ Force of Contraction)
  • Minor effect: blockage of presynaptic ß receptors leading to a reduced NA release
267
Q

What is Propanolol?

A

It is a non-selective ß antagonist (equal afinity for ß1+2 receptors)

268
Q

What is Atenolol?

A

It is a ß1 “selective” antagonist

269
Q

What is Carvedilol?

A

Mixed b and a blockers

•a1 blockade gives additional vasodilator properties

270
Q

Which different ß Blocker classes are there?

Name examples for each class

A
  1. Non selective (ß1+2)
    • Propanolol
  2. Cardio-selective
    • Atenolol
  3. Mixed ß-a- blockers
    • Cervedilol
  4. Other
    • Nebivolol: also potentiates NO
    • Sotalol: also inhibits K+ channels
271
Q

Which drug class of SNS antagonists is commonly used in the chronical treatment of hypertension?

A

ß-Blockers

276
Q

What are the side effects of Beta-blockers

A

1+2 are the major concerns

  1. Bronchoconstriction (no pure slectivity for ß1)–> might not be tolerated by astmathics (ß2 activity)
  2. Hypoglycaemia –> might not be toleareated by Diabetics
    • masking of hypoglycaemic symptoms
    • Inhibits glycogen break down in liver (ß2)
  3. Cardiac failure (some SNS activity required for heart)
  4. Cold extremitis (no cutaneous ß2 mediated vasodilation)
  5. Fatigue (reduced CO+ reduced muscle blood flow (ß2 antagonism))
  6. Bad dreams
277
Q

Which group of patients might not tolerate ß-blockers?

A
  1. Astmatics (inhibitionof ß2-mediated bronchiodilation)
  2. Diabetics (risk of hypoglycaemia –> inhibition ß-2 mediated glycogen break down and release)
  3. Cardiac failure –> loss of SNS innervation to the heart which keeps the heart running
278
Q

What is the clinical use for alpha blockers?

A

Limited use in treament of hypertension

279
Q

Name 2 alpha-blockers and explain their mechanism of action, effect and use

A
  1. Phenotolamine
    • used in reduceing phaeochomocytoma-induced hypertension
    • alpha-non selective antagonist
  2. Prazosin
    • limited BP lowering effect
    • only used in combination with other hypertensive drugs
280
Q

What is Phenotolamine?

When is it used?

A

It is a non-selective adrenergic alpha antagonist

Used in management of phaechromycytoma-induced hypertension

281
Q

What is prazosin?

What is its clinical use?

A

It is a alpha1 selective adrenergic antagonist

  • used in hypertension treatment (in combination with other hpyertensive drugs due to limited effects)
282
Q

What are the side-effects of alpha-blocker?

A

Side effect mainly GI tracts

  • reduces SNS innervation to gut –> leading to increased gut activity
  • diarreah etc.
283
Q

Explain the mechnism of action of Methyldopa

A

It is a false substrate for DOPA-methyltransferase that gets converted into alpha-methylnoradrenaline

Alpha-methylnoradrenaline is a false transmitter resulting in

  • Increased selectivity for alpha2 receptors
  • Decreased sensitivity for alpha1+ß receptors
  • Decreased break down by MAO

​–> Higher concentration of alpha-methylnoradrenaline in synapse with high A2 affinity

–> Decreased SNS activtity–> hypotension

284
Q

Which drug can be used as a false transmitter in the treatment of hypertensoion?

A

Methyldopa

  • Mmimics DOPA
  • Gets transfered to the false transmitter alpha-methylnoradrenaline
285
Q

Explain the use of SNS antagonists in the treatment of Glaucoma

A

Target: ß1 receptors on cliary body –> reduction in production of aqueous humor (ß-blockers)

286
Q

What is the clinical use of Methyldopa?

A

Used to treat Hypertension

  • linked to Kidney disease
  • linked to CNS + cerebrovascular disease
287
Q

What are the (main) side effects of the use of Methyldopa?

A

Many side effects because it interferes with almost whole SNS

–> Mainly

  • Hypotension: Very potent anti-hypertensive drug
  • Dry mouth
288
Q

Ich which clinical conditions could you use SNS antagonists as a treatment?

A
  1. In Hypertension
  2. In Arrythmias
  3. In Angina
  4. In Glaucoma
289
Q

Explain the use of SNS antagonists in the treatment of Arrythmias

A

Mainly Propanolol

  • blocks the ß1 receptors in heart
  • –> slows heart rate –> giving heart more time to fill
290
Q

Explain the use of SNS antagonists in Angina Pectoris

A

There are two ways of treating Angina:

  1. Increasing the Oxygen availibility to the Myocardium
  2. Decreasing the Oxygen demand of the Myocardium –> ß Blockers (less work for heart muscles)
291
Q

What kind of drug groups can be differentated within the neuromuscular blocking drugs?

What are the drugs for each?

A
  1. Non-depolarising (competittive antagonist)
  2. Or depolarising (agnoist) Suxaemethonium = succinylcholine
292
Q

What is succinylcholine?

A

The same drug as suxamethonium

–> action at the Motor end plate AP initiasation

293
Q

What is the mechanism of action of suxamethonium?

A

It is a muscular ACh receptor agonist

It causes an

  • overstimmulation causing
    • extended depolerisation –> fasciculations
    • Leading to shut down of receptors –> depolerisation block (phase 1)
294
Q

What is the mechanims of action of Tubocurarine?

How much of is is needed to get an effect (on molecular level)

A

Is a competittive nictinic AChR antagoist

–> 70-80% must be blocked to achieve flaccid paralisis

295
Q

What is flaccid paralsisi?

A

Paralysis due to reduced muscle tone

296
Q

What are FASCICULATIONS?

A

Twitching of muscles due to overstimmulation and hence generation of AP

297
Q

What is the effect of suxamethonium?

A

Extended depolerisation on the muscular end plate –> (ACh agonist)

Causes overstimmulation

  • fasciculations

Shut down of receptors

  • causes flaccid paralysis

No interference with conciousness and no analgesic effect

298
Q

What is the effect of Tubocuranine?

A

Flaccid paralysis in following order

  1. of the extrinsic eye muscles causing double vision
  2. Small muscles of face, limbs, larynx
  3. Respiratory muscles

(Also recoverers in reverse order)

No analgesic or nor interference with conciousness

300
Q

What is the clinical use of Tubocurarine?

What do you always have to provide when administering tubocurarine?

A
  1. Relaxation of skeletal muscle during surgical operations–> reduces dose of required anesthetic (reduces risk)
  2. Permits artificial ventilation

Always assist ventilation!

301
Q

What is the clinical use of suxamehtonium?

What do always need to provide when administering it?

A
  • To allow endotracheal intubation
  • Relaxation for Electroconvulsive therapy (ECT)
    • used in very severe deppression
    • provide electric impulses over brain

Always assist ventilation

302
Q

Explain the pharmacokinetic administration and properties of Suxamethonium

A
  • IV administration (highly charged)
  • short action (about 5 min)
  • Metabolised by pseudo-cholinesterases (cholinesterase is too selevtiv efor ACh) in plasma and liver
303
Q

Explain the pharmacokinetic properties and route of administration of Tubocurarine

A
  • IV adminstration (highly charged)
  • long paralytic action (1-2h)
  • does not cross BBB or placenta
  • not metabolised
    • excretion 70% via kidney, 30% via bile (important in renal/ hepatic disfunction)
304
Q

How could you treat an overdosation of Tubocurarine?

A

because it is a competitive antagonist–> effects can be reversed by increased ACh

  1. Neostigme (Anticholinesterases)
  2. (In combination with Atropine to not cause overstimmulation of muscarenic receptors)
305
Q

What are the side effects of Tubocurarine?

A

It is a muscular nicotinicAChR antagonist–> only limited selectivity for muscular nicotinic R

Occuring side effects are because of Ganglion bloockage and histamine release (because of basic properties of Tubocurarine)

  1. Hypotension
  2. Tachycardia (may trigger arrythmias)
    • Reflex
    • inhibition of vagal ganglia (less PNS to heart)
  3. Bronchospasm + excessive bonchiosecretion (histamine release)
  4. Apnoe –> always assist respiration
306
Q

What are the side effects of suxamehtonium?

A
  • Post-opperative muscle pains
  • Bradycardia (direct muscarenic action on heart –> for prevention Atropine is normally given as pre-medication)
  • Hyperkalaemia
    • Expecially in patients with soft-tissue injury or burns –> nerve damage–> no innervation to these tissues –> receptor upregulation
    • When receptors are stimmulated–> More NA+ inflow + K+ outlow
    • Migh trigger arrythmias, cardiac arrest
  • increase in Intra-occular pressure
    • avoid in eye injuries and glaucoma
307
Q

What is atrarium?

What is its mechanism of action, use, side effects?

A

It is just like Tubocurarine a competitive NMJ antagoinst

–> Use: just like Tubocurarine atratium has just a different duration of action

308
Q

What kind of drug groups can be differentated within the neuromuscular blocking drugs?

What are the drugs for each?

A
  1. Non-depolarising (competittive antagonist)
  2. Or depolarising (agnoist) Suxaemethonium = succinylcholine
309
Q

What is succinylcholine?

A

The same drug as suxamethonium

–> action at the Motor end plate AP initiasation

310
Q

What is the mechanism of action of suxamethonium?

A

It is a muscular ACh receptor agonist

It causes an

  • overstimmulation causing
    • extended depolerisation –> fasciculations
    • Leading to shut down of receptors –> depolerisation block (phase 1)
311
Q

What is the mechanims of action of Tubocurarine?

How much of is is needed to get an effect (on molecular level)

A

Is a competittive nictinic AChR antagoist

–> 70-80% must be blocked to achieve flaccid paralisis

312
Q

What is flaccid paralsisi?

A

Paralysis due to reduced muscle tone

313
Q

What are FASCICULATIONS?

A

Twitching of muscles due to overstimmulation and hence generation of AP

314
Q

What is the effect of suxamethonium?

A

Extended depolerisation on the muscular end plate –> (ACh agonist)

Causes overstimmulation

  • fasciculations

Shut down of receptors

  • causes flaccid paralysis

No interference with conciousness and no analgesic effect

315
Q

What is the effect of Tubocuranine?

A

Flaccid paralysis in following order

  1. of the extrinsic eye muscles causing double vision
  2. Small muscles of face, limbs, larynx
  3. Respiratory muscles

(Also recoverers in reverse order)

No analgesic or nor interference with conciousness

317
Q

What is the clinical use of Tubocurarine?

What do you always have to provide when administering tubocurarine?

A
  1. Relaxation of skeletal muscle during surgical operations–> reduces dose of required anesthetic (reduces risk)
  2. Permits artificial ventilation

Always assist ventilation!

318
Q

What is the clinical use of suxamehtonium?

What do always need to provide when administering it?

A
  • To allow endotracheal intubation
  • Relaxation for Electroconvulsive therapy (ECT)
    • used in very severe deppression
    • provide electric impulses over brain

Always assist ventilation

319
Q

Explain the pharmacokinetic administration and properties of Suxamethonium

A
  • IV administration (highly charged)
  • short action (about 5 min)
  • Metabolised by pseudo-cholinesterases (cholinesterase is too selevtiv efor ACh) in plasma and liver
320
Q

Explain the pharmacokinetic properties and route of administration of Tubocurarine

A
  • IV adminstration (highly charged)
  • long paralytic action (1-2h)
  • does not cross BBB or placenta
  • not metabolised
    • excretion 70% via kidney, 30% via bile (important in renal/ hepatic disfunction)
321
Q

How could you treat an overdosation of Tubocurarine?

A

because it is a competitive antagonist–> effects can be reversed by increased ACh

  1. Neostigme (Anticholinesterases)
  2. (In combination with Atropine to not cause overstimmulation of muscarenic receptors)
322
Q

What are the side effects of Tubocurarine?

A

It is a muscular nicotinicAChR antagonist–> only limited selectivity for muscular nicotinic R

Occuring side effects are because of Ganglion bloockage and histamine release (because of basic properties of Tubocurarine)

  1. Hypotension
  2. Tachycardia (may trigger arrythmias)
    • Reflex
    • inhibition of vagal ganglia (less PNS to heart)
  3. Bronchospasm + excessive bonchiosecretion (histamine release)
  4. Apnoe –> always assist respiration
323
Q

What are the side effects of suxamehtonium?

A
  • Post-opperative muscle pains
  • Bradycardia (direct muscarenic action on heart –> for prevention Atropine is normally given as pre-medication)
  • Hyperkalaemia
    • Expecially in patients with soft-tissue injury or burns –> nerve damage–> no innervation to these tissues –> receptor upregulation
    • When receptors are stimmulated–> More NA+ inflow + K+ outlow
    • Migh trigger arrythmias, cardiac arrest
  • increase in Intra-occular pressure
    • avoid in eye injuries and glaucoma
324
Q

What is atrarium?

What is its mechanism of action, use, side effects?

A

It is just like Tubocurarine a competitive NMJ antagoinst

–> Use: just like Tubocurarine atratium has just a different duration of action

Year 2 LCRS Pharmacology (38 decks)

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