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Bateman - Phase 2a COPY > Pharmocology > Flashcards

Pharmocology Flashcards

1
Q

What is absorption?

A

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

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2
Q

What are some routes of administration of drugs?

A 
Oral		
Intra venous
Intra arterial
Intramuscular
Subcutaneous
Inhalational
Topical
Sublingual
Rectal
Intrathecal
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3
Q

How many membranes must most drugs cross? What is the exception to this?

A

One.

IV and IA.

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4
Q

How can transfer through a membrane occur?

A

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

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5
Q

What do drugs need to be to pass directly through the cell membrane?

A

Lipid soluble.

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6
Q

What is the rate of diffusion proportional to?

A

Rate of diffusion proportional to concentration gradient, the area & permeability of the membrane and inversely proportional to thickness.

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7
Q

How does movement through channels occur and why?

A

Down concentration gradient.

Restricted to small water soluble molecules.

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8
Q

What are the family of carriers in carrier mediated transport called?

A

ATP- Binding Cassette (ABC).

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9
Q

How many ABCs do humans have?

A

49.

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10
Q

What is P-gp known as and what does it do?

A

Multi Drug Resistance (MDR1).

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

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11
Q

What does Verapamil do?

A

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

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12
Q

What is an example of a solute carrier? What blocks this and what does it lead to?

A

One example is OAT1 ( organic anion transporter) which is found in kidney and secretes Penicillin & uric acid. Probenicid blocks it, leading to uric acid being excreted.

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13
Q

What is pinocytosis?

A

A form of carrier mediated entry into the cytoplasm

Usually involved in uptake of endogenous macro molecules, can be involved in uptake of recombinant therapeutic proteins.

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14
Q

What drugs can be taken up by pinocytosis?

A

Drugs such as Amphotericin can be taken up into liposome for pinocytosis

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15
Q

What is drug ionisation?

A

Basic property of weak acids or weak bases.

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16
Q

Why are ionisable groups important for drugs?

A

The ionic forces are part of the ligand receptor interaction.

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17
Q

What is the PKa of a drug?

A

pH of which half the substance is ionised and half not.

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18
Q

Where are weak acids absorbed?

A

Stomach.

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19
Q

Where are weak bases absorbed?

A

Intestine.

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20
Q

What gives rapid absorption of oral drugs?

A

Large surface area and high blood flow.

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21
Q

What are four factors that determine the rate of oral absorption of a drug?

A

Drug Structure.
Drug formulation.
Gastric emptying.
First pass metabolism.

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22
Q

What is important about drug structure in relation to absorption?

A

Drug needs to be lipid soluble to be absorbed from the gut.
Highly polarised drugs tend to be only partially absorbed with much passed into the faeces.
Some drugs are unstable at low pH or in the presence of digestive enzymes.

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23
Q

What is important about drug formulation?

A

The capsule or tablet must disintegrate & dissolve to be absorbed.
Most do so rapidly.
Some having coating e.g. Enteric.

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24
Q

What is first pass metabolism?

A 
Drugs taken orally have to pass four major metabolic barriers to reach circulation;
Intestinal lumen
Intestinal wall
Liver
Lungs
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25
Q

What is contained within the intestinal lumen which limits absorption?

A

Contains digestive enzymes that can split peptide ,ester & glycosidic bonds.
Peptide drugs broken down by proteases (Insulin).
Colonic bacteria hydrolysis & reduction of drugs.

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26
Q

What is contained within the intestinal wall which limits absorption?

A

Walls of upper intestine rich in cellular enzymes e.g. Mono amine oxidases (MAO)
Luminal membrane of enterocytes contains efflux transporters such as P-gp which may limit absorption by transporting drug back into the gut lumen
Extensive bowel surgery “short gut syndrome” – poor oral absorption as little surface left and rapid transit time.

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27
Q

How is the liver a metabolic barrier? How can you avoid this barrier?

A

Blood form gut delivered by splanchnic circulation directly to liver.
Liver is major site of drug metabolism
Avoid hepatic first pass metabolism by giving drug to region of gut not drained by splanchnic e.g mouth or rectum ( GTN )

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28
Q

What is transcutaneous?

A

Human epidermis effective barrier to water soluble compounds. Limited rate & extent of absorption of lipid soluble drugs. Need potent, non irritant drugs.
Slow and continued absorption useful with transdermal patches

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29
Q

What layer does Intradermal and subcutaneous miss? What is it limited by and what is it used for?

A

Avoids barrier of stratum corneum
Mainly limited by blood flow
Small volume can be given
Use for local effect (e.g. local anaesthetic) or to deliberately limit rate of absorption (e.g. long term contraceptive implants)

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30
Q

What does an intramuscular injection depend on? What can you make the drug into?

A

Depends on blood flow and water solubility
Increase in either enhances removal of drug from injection site
Can make a Depot injection by incorporating drug into lipophilic formulation which releases drug over days or weeks.

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31
Q

What is contained with intranasal drugs?

A

Low level of proteases and drug metabolising enzymes. Good surface area.

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32
Q

What are the properties of giving a drug inhaltionaly?

A

Large surface area & blood flow BUT limited by risks of toxicity to alveoli and delivery of non volatile drugs
Largely restricted to volatiles such as general anaesthetics and locally acting drugs such as bronchodilators in asthma
Asthma drugs non volatile so given as aerosol or dry powder

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33
Q

What is 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.
Occurs by passive diffusion.

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34
Q

What can some drugs bind to? And what do these act as?

A

Plasma proteins.

Act as a depot as they release the drug when the blood concentration becomes lower giving a slow release.

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35
Q

What is elimination?

A

The removal of a drugs activity from the body.

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36
Q

What is metabolism?

A

The transformation of the drug molecule into a different molecule.

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37
Q

What is excretion?

A

The molecule is expelled in liquid, solid or gaseous “waste”.

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38
Q

What happens in metabolism?

A

Lipid soluble drugs are converted into water soluble ones. Two phases.

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39
Q

What is involved in phase 1 of metabolism?

A

These reactions 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)
Oxidations are the commonest reactions catalysed by important enzymes called Cytochrome P450.

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40
Q

What is Cytochrome P450 found?

A

Smooth endoplasmic reticulum. Largely in liver tissue.

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41
Q

What increases and decreases P450 metabolism?

A

Smoking and alcohol increase.

Grapefruit and Cimetidine decrease.

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42
Q

Where are some other drugs metabolised?

A

Plasma, lungs gut.

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43
Q

What happens in a phase 2 reaction?

A 
Phase 2 (conjugation)involves the 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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44
Q

What molecular weight is in each excretion route?

A

Low for urine.

High for faeces.

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45
Q

What does total excretion equal?

A

Total excretion = glomerular filtration+ tubular secretion-reabsorption.

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46
Q

What is first order kinetics?

A

An exponential fall in the plasma drug concentration.

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47
Q

What is zero order kinetics?

A

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

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48
Q

What happens when you plot the log of the concentration in first order kinetics?

A

Gives a straight line with -k gradient and gives you the concentration at time 0.

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49
Q

What is the half life?

A

Time taken for a concentration to reduce by half.

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50
Q

What is bioavailability?

A

This is the fraction of the administered drug that reaches the systemic circulation unaltered. (F)

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51
Q

Why is bioavailability important?

A

If an oral drug has a score of 0.1 it will need to be 10x the IV dose to be as effective.

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52
Q

Why can’t you measure oral and iv bioavailability at a single point in time?

A

Different concentration/time profiles.

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53
Q

What is distribution?

A

Rate & extent of movement of a drug into (and out)of tissues from blood.

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54
Q

What does water soluble drugs rate depend on?

A

Water soluble drugs rate of distribution depends on rate of passage across membranes.

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55
Q

What does lipid soluble drugs rate depend on?

A

Lipid soluble drugs rate of distribution depends on blood flow to tissues that accumulate drug.

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56
Q

What does Vd stand for?

A

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

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57
Q

What does a low or high apperent volume show?

A

Low confined to circulatory volume.

High distributed in total body water.

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58
Q

What is clearance?

A

Clearance ( CL ) is the volume of blood or plasma cleared of drug per unit time.

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59
Q

If a drug has a high Vd what is the rate proportional to?

A

Rate of elimination is inversely proportional to Vd.

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60
Q

What is k equal to?

A

k =0.693/t1/2.

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61
Q

What is the AUC?

A

Area under the plasma drug concentration versus time curve; a measure of drug exposure.

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62
Q

How is clearance determined?

A

Clearance is usually determined using the AUC after an iv dose.
CL= Dose/AUC for iv drug
CL= Dose x F/AUC for oral drug with bioavailabilty of less than 1.

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63
Q

What is meant by steady state?

A

The rate of elimination is the same as drug input.

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64
Q

What does the rate of elimination equal?

A

Clearance x steady state.

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65
Q

What is the peripheral nervous system divided into?

A

Sympathetic and Parasympathetic

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66
Q

What information does the autonomic nervous system convey?

A

All CNS information except for muscles.

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67
Q

What happens in the somatic nervous system?

A

One neurone comes from the CNS to innervate one muscle.

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68
Q

What happens in the autonomic nervous system?

A

Two nerves, pre and post ganglionic fibres.

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69
Q

How long is each parasympathetic and sympathetic fibre?

A

Parasympathetic long pre ganglionic with short post ganglionic.
Sympathetic short pre ganglionic with long post ganglionic.

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70
Q

What nerves are parasympathetic?

A

Some cranial nerves and sacral nerves.

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71
Q

What neurotransmitter do post ganglionic fibres release and what receptors do they act on in the parasympathetic system?

A

Acetylcholine on muscarinic receptors.

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72
Q

What neurotransmitter do post ganglionic fibres release and what receptors do they act on in the sympathetic system?

A

They release noradrenaline which activates adrenergic receptors, of which there are two main types (alpha/beta) with subtypes.

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73
Q

What parts of the body are only sympathetic control?

A

Sweat glands and blood vessels.

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74
Q

What parts of the body are only parasympathetic control?

A

eye and bronchial smooth muscle.

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75
Q

What is the pre ganglionic neurotransmitter for both autonomic systems and what receptor do they act on?

A

Acetylcholine and nicotinic receptor.

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76
Q

What is released at sweat glands from the sympathetic system?

A

Acetylcholine on muscarinic receptors.

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77
Q

What are some NANC neurotransmitters?

A

NO and vasoactive intestinal polypeptide parasympathetic.

ATP and neuropeptide Y.

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78
Q

What effect does nicotine have on receptors?

A

It activates both sympathetic and parasympathetic systems.

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79
Q

What effect does muscarine have on receptors?

A

Activates the muscarinic receptors on the parasympathetic system.

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80
Q

What are two types of muscarinic receptors?

A

M1-5, GPCRs.

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81
Q 
Where are each of these receptors found?
M1.
M2.
M3.
M4/M5.
A

M1: mainly in the brain.
M2: mainly in the heart. Their activation slows the heart, so we can block these (atropine for life- threatening bradycardias and cardiac arrest)
M3: glandular and smooth muscle. Cause bronchoconstriction, sweating, salivary gland secretion.
M4/5: mainly in the CNS.

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82
Q

What effects does the muscarnic agonist pilocarpine have on the body?

A

stimulates salivation. Activating the sympathetic nervous system.
Contracts iris smooth muscle (parasympathetic nervous system).
Side effects would be to slow the heart.

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83
Q

What are some examples of muscarinic antagonists?

A

Atropine.

Hyoscine.

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84
Q

What can Hyoscine be used for?

A

Antagonise sympathetic driven secretions.

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85
Q

What drugs can you use to treat bronchoconstriction?

A

Short-acting: ipratropium bromide (atrovent)

Long-acting: LAMAs such as tiotropium, glycopyrrhonium

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86
Q

What else is ACh involved in?

A

Memory.

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87
Q

What side effects do anti-cholinergic drugs have?

A

In the brain, anticholinergics worsen memory and may cause confusion
Peripherally, may get constipation, drying of the mouth, blurring of the vision, worsening of glaucoma
Tricyclic antidepressants, some early antihistamines, some anti-emetics (prochlorperazine).

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88
Q

What side effects do cholinergic drugs have?

A

Organophosphate insecticides and nerve gases causing poisoning are irreversible acetylcholinesterase inhibitors, and cause muscle paralysis and twitching, salivation, confusion.

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89
Q

What are the catecholamines?

A

Noradrenaline: released from sympathetic nerve fibre ends, beloved in the management of shock in the intensive care unit.
Adrenaline: released from the adrenal glands (fight and flight, management of anaphylaxis).
Dopamine (the precursor of adrenaline and noradrenaline).

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90
Q 
What do each of these receptors do? 
Alpha 1
Alpha 2
Beta 1
Beta 2
Beta 3
A

Alpha 1 - NAd>Ad
Increases intracellular Contracts smooth
calcium, Gq signalling muscle (pupil, blood
vessels)

Alpha 2 - NAd=Ad
Gi signalling, inhibition of cAMP generation
Mixed effects on smooth muscle

Beta 1 - NAd=Ad
Chronotropic and Gs, raises cAMP inotropic effects on
heart

Beta 2 - Ad»NAd
Gs, raises cAMP
Relaxes smooth muscle (premature labour, asthma)

Beta 3 - NAd>Ad
Gs, raises cAMP
Enhances lipolysis, relaxes bladder detrusor

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91
Q

What does alpha 2 receptor do?

A

Lower blood pressure.

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92
Q

What are some alpha blockers?

A

Doxazosin and tamsulosin.

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93
Q

Are there any alpha 2 blockers?

A

No.

94
Q

What will beta 1 activation do?

A

Increase heart rate and chronotropic effects.

95
Q

What do beta 2 agonists induce?

A

Muscle relaxation: beta 2 activation is life saving in asthma, and can delay onset of premature labour

But beta agonists will cause tachycardia and affect glucose metabolism in the liver: beta 1/3 affect carbohydrate and lipid metabolism

96
Q

What can beta 3 agonists do?

A

Reduce over-active bladder.

97
Q

Give examples of some beta blockers?

A

Propanolol and atenolol.

98
Q

What does propranolol do?

A

Blocks beta 1 and beta 2. Will slow heart rate, reduce tremor, but may cause wheeze.

99
Q

What does atenolol do?

A

Beta 1 selective, main effects on heart.

100
Q

What is Methyldopa useful for?

A

Useful in preeclampsia and clampsia.

101
Q

What is an 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.

102
Q

What are the different severities of adverse drug reactions?

A

Can be mild eg nausea, drowsiness, itching rash

Can be severe eg respiratory depression, neutropenia, catastrophic haemorrhage, anaphylaxis.

103
Q

What is an example of an adverse drug effect? e.g. Beta blockers

A

Bradycardia and heart block are primary adverse effects

Bronchospasm is a secondary pharmacological adverse effect.

104
Q

What is the Rawlins Thompson classification? Different types?

A 
Type A (Augmented pharmacological)– predictable, dose dependent, common (morphine and constipation, hypotension and antihypertensive)
Type B (Bizarre or idiosyncratic)– not predictable and not dose dependent (anaphylaxis and penicillin)
Type C (Chronic) – osteoporosis and steroids
Type D (Delayed) – malignancies after immunosuppression
Type E – (End of treatment) – occur after abrupt drug withdrawal.
105
Q

What are some causes of adverse drug reactions?

A 
Pharmaceutical variation.
Receptor abnormality.
Abnormal biological system unmasked by drug.
Abnormalities in drug metabolism.
Immunological.
Drug-drug interactions.
Multifactorial.
106
Q

What are the effects of type A adverse drug reactions (augmented)?

A 
Extension of primary effect (bradycardia and propranolol, hypoglycaemia and insulin, haemorrhage due to anticoagulants).
Secondary effect (bronchospasm with propranolol B2 blocking effect).
107
Q

What are the properties of type B adverse drug reactions?

A 
Not predictable
Not dose dependant
Cant be readily reversed
Less common but often serious
Life threatening
Can be idiosyncrasy
Can be allergy or hypersensitivity
108
Q

What is idiosyncrasy?

A

Inherent abnormal response to a drug
Genetic abnormality, enzyme deficiency
May be due to abnormal receptor activity
Rare but serious

109
Q

What is an example of enzyme abnormality?

A

Haemolysis with primaquine
Glucose 6 phosphate dehydrogenase (G6PD) enzyme deficiency + primaquine
Haemolysis and haemolytic anaemia

110
Q

What is an example of receptor abnormality?

A

Malignant hyperpyrexia with general anaesthetics
Sudden huge rise in calcium concentration
Increase in muscle contraction
Increase in metabolic activity
Rise in body temperature

111
Q

What is allergy/hypersensitivity?

A

Antigen/antibody reaction
First dose acts as antigen
Antibody produced
Second dose causes antibody-antigen reaction

112
Q

What are the different types of allergic reaction?

A

Type 1 immediate anaphylactic IgE eg penicillin allergy
Type 2 cytotoxic antibody IgG, IgM eg methyl dopa and haemolytic anaemia
Type 3 eg procainamide induced lupus
Type 4 delayed hypersensitivity T cell eg contact dermatitis

113
Q

What are examples of type C adverse reactions?

A

Steroids and osteoporosis
Analgesic nephropathy
Steroids and iatrogenic Cushing’s syndrome
Colonic dysfunction due to laxatives

114
Q

What are examples of type D adverse reactions?

A

Teratogenesis – drugs taken in the first trimester e.g. thalidomide.
Carcinogenesis eg cyclophosphamide and bladder cancer.

115
Q

What are some examples of type E adverse reactions?

A

Glucocorticoid abruptly withdrawn leads to adrenocortical insufficiency.
Withdrawal seizures when anti-convulsants are stopped.

116
Q

What are the patient risks for adverse drug reactions?

A 
Gender
Elderly
Neonates
Polypharmacy
Genetic predisposition
Hypersensitivity/allergies
Hepatic/renal impairment
Adherence problems
117
Q

What are the drug risks for adverse drug reactions?

A

Steep dose-response curve.
Low therapeutic index.
Commonly causes ADR’s.

118
Q

When should we suspect an adverse drug reaction?

A

Symptoms soon after a new drug is started.
Symptoms after a dosage increase.
Symptoms disappear when the drug is stopped.
Symptoms reappear when the drug is restarted.

119
Q

What are the most common drugs to have an adverse drug reaction?

A 
Antibiotics
Anti-neoplastics
Cardiovascular drugs
Hypoglycaemics
NSAIDS
CNS drugs
120
Q

What are the most common places to have an adverse reaction?

A 
GI 
Renal
Haemorrhagic
Metabolic
Endocrine
Dermatologic
121
Q

What are the most common adverse drug reactions?

A 
Confusion
Nausea
Balance problems
Diarrhea
Constipation
Hypotension
122
Q

Who is responsible for approving medicine and devices for use?

A

Medicines and Healthcare products Regulatory Agency (MHRA).

123
Q

What is the yellow card scheme?

A

The Yellow Card Scheme was introduced in 1964.
The world’s first ADR reporting scheme.
Collects spontaneous reports.
Collects suspected adverse drug reactions.
Is a voluntary reporting scheme.

124
Q

Where are the yellow cards?

A

Back of the BNF.

125
Q

What are the advantages of yellow cards?

A

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

126
Q

What are the weaknesses of yellow cards?

A

Cannot provide estimates of risk as
true number of cases is underestimated
total number of patients exposed is unknown
Relies on ADR being recognised
Not all ADRs are reported.
Only 10% serious reactions reported
May be stimulated by promotion and publicity
Reporting high for newly marketed drugs and falls off over time

127
Q

What must be included in a yellow card report?

A 
Suspected drug(s).
Suspect reaction(s).
Patient details.
Reporter details.
Additional useful information.
128
Q

What does a black triangle mean?

A

Additional monitoring on the drug is being done.

129
Q

What are the different types of drug interactions?

A

Synergy.
Antagonism.
Other.

130
Q

What are the risks for drug interactions for the patient?

A 
Polypharmacy
Old age
Genetics
Hepatic disease
Renal Disease
131
Q

What are the risks for drug interactions for the drug?

A

Narrow therapeutic index
Steep Dose/Response Curve
Saturable Metabolism

132
Q

What are the mechanisms of pharmacokinetics?

A

Absorption.
Distribution.
Metabolism.
Excretion.

133
Q

What are the mechanisms of pharmacodynamics?

A

Receptor based.
Signal transduction.
Physiological systems.

134
Q

What affects absorption of a drug?

A 
Motility
Acidity
Solubility
Complex formation
Direct action on enterocytes
135
Q

What affects distribution of a drug?

A

Protein binding.

136
Q

What affects metabolism of a drug?

A

CYP450
Inhibition
Induction

137
Q

What is CYP450?

A

Haemoprotein,.

138
Q

How does inhibition work?

A

Drug A blocks metabolism of Drug B, leaving more free Drug B in the plasma -> increased effects.

139
Q

How does induction work?

A

Drug C induces CYP540 isoenzyme, leading to increased metabolism of Drug D -> decreased therapeutic effects.

140
Q

What are the excretion exits for drugs?

A

Renal.

Biliary.

141
Q

What is renal excretion dependent on?

A

pH.

142
Q

How do weak acids and bases differ in urine excretion?

A

Weak bases - cleared faster if urine acidic

Weak acids - cleared faster if urine alkali

143
Q

What are the types of pharmacodynamics mechanisms?

A

Receptor based
Signal transduction
Physiological systems

144
Q

What are the properties of receptor based mechanism?

A 
Agonists
Partial Agonists
Antagonists
Competitive
Non-competitive
145
Q

What are the properties of physiological systems?

A

Different drugs that effect different receptors, but in the same physiological system.
Ca Channel antagonist + B-Blocker.
ACE-I + NSAID.

146
Q

What does a allergic reaction to a drug involve?

A

Interaction of drug/metabolite with patient and disease.

Subsequent re-exposure.

147
Q

What are the different types of hypersensitivity?

A

Type 1 – IgE mediated drug hypersensitivity.
Type 2 – IgG mediated cytotoxicity.
Type 3 – Immune complex deposition.
Type 4 – T cell mediated.

148
Q

What is involved in type 1 hypersensitivity reactions? Acute Anaphylaxis?

A

Prior exposure to the antigen/drug.
IgE antibodies formed after exposure to molecule.
IgE becomes attached to mast cells or leucocytes, expressed as cell surface receptors.
Re-exposure causes mast cell degranulation and release of pharmacologically active sustances.

149
Q

What is involved with acute anaphylaxis?

A 
Occurs within minutes and lasts 1-2 hours.
Vasodilation.
Increased vascular permeability.
Bronchoconstriction.
Urticaria.
Angio-oedema.
150
Q

What is involved with type 2 hypersensitivity reactions?

A

Drug or metabolite combines with a protein.
Body treats it as foreign protein and forms antibodies (IgG, IgM).
Antibodies combine with the antigen and complement activation damages the cells e.g. methyl-dopa-induced haemolytic anaemia.

151
Q

What is involved with type 3 hypersensitivity reactions?

A

Antigen and antibody form large complexes and activate complement.
Small blood vessels are damaged or blocked.
Leucocytes attracted to the site of reaction release pharmacologically active substances leading to an inflammatory process.
Includes glomerulonephritis, vasculitis.

152
Q

What is involved with type 4 hypersensitivity reactions?

A

Antigen specific receptors develop on T-lymphocytes
Subsequent administration leads to local or tissue allergic reaction.
E.g. contact dermatitis.

153
Q

What is non immune anaphylaxis?

A 
Due to direct mast cell degranulation. 
Previously called Anaphylactoid reactions
Some drugs recognised to cause this
No prior exposure
Clinically identical
154
Q

What are the main features of anaphylaxis?

A 
Exposure to drug, immediate rapid onset
Rash
Swelling of lips, face, oedema, central cyanosis
Wheeze / SOB
Hypotension (Anaphylactic shock)
Cardiac Arrest.
155
Q

What is the management of anaphylaxis?

A

Commence basic life support. ABC

Stop the drug if infusion
Adrenaline IM 500micrograms(300mcg epi-pen)
High flow oxygen
IV fluids
IV Anti histamine (Chlorphenamine 10mg)
IV Hydrocortisone (100 to 200mg)
If anaphylactic shock may need IV adrenaline with close monitoring

156
Q

What effect does adrenaline have to help anaphylaxis?

A

Vasoconstriction - increase in peripheral vascular resistance, increased BP and coronary perfusion via alpha1-adrenoceptors
Stimulation of Beta1-adrenoceptors positive ionotropic and chronotropic effects on the heart
Reduces oedema and bronchodilates via beta2-adrenoceptors
Attenuates further release of mediators from mast cells and basophils by increasing intracellular c-AMP and so reducing the release of inflammatory mediators

157
Q

What are some risk factors for hypersensitivity?

A

Medicine factors:
Protein or polysacharide based macro molecules

Host factors:
Females > Males
Immunosuppression

Genetic factors:
Certain HLA groups

158
Q

What happens if morphine is taken orally?

A

First pass metabolism by the liver
50% of oral (enteral) morphine is metabolised by first pass metabolism Halve the dose if giving it s/c, IM, IV (parenterally) etc.

159
Q

What does opium contain?

A

morphine and codeine.

160
Q

What is heroin?

A

Diamorphine

161
Q

How do opioids work?

A 
Review of pain pathways - opioid drugs simply use the existing pain  modulation system
Natural endorphins (endogenous morphine) and enkephalins  G protein coupled receptors - act via second messengers
Inhibit the release of pain transmitters at spinal cord and midbrain - and  modulate pain perception in higher centres - euphoria - changes the  emotional perception of pain.
162
Q

What is the problem with inhibiting the pain pathway like opioid do?

A

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

163
Q

What are some examples of opioid receptors?

A

mew, delta and kappa.

nociceptin opioid-like receptor

164
Q

What happens if you activate the kappa receptor?

A

Depression.

165
Q

What does potency mean?

A

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

166
Q

What is the efficiency of a drug?

A

Is it possible to get a maximal response with the drug or not?
Or even if all the receptor sites are occupied do you get a ceiling response?
The concept of full or partial agonists.

167
Q

Which opioid has the most potency?

A

Diamorphine.

168
Q

What does tolerance mean?

A

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

169
Q

What does craving mean?

A

Psychological - craving, euphoria

Physical.

170
Q

How long does opioid withdrawal last?

A

Starts within 24 hours, lasts about 72 hours.

171
Q

What are the side effects of opioids?

A 
Respiratory Depression.
Sedation.
Nausea and Vomiting.
Constipation.
Itching.
Immune Suppression. 
Endocrine Effects.
172
Q

What is the response to opioid induced respiratory depression?

A

Call for help
ABC
Naloxone
IV is fastest route
Titrate to effect - don’t have to give it all once - once you’ve injected a drug you can’t get it back!
Short half-life of naloxone - beware drug addict overdoses in A&E

173
Q

What is codeine? and what does this mean?

A

A prodrug. It needs to be metabolised by cytochrome CYP2D6 to work.

174
Q

How is morphine metabolised and into what?

A

Morphine is metabolised to morphine 6 glucuronide which is more potent than morphine and is renally excreted. With normal renal function this is cleared quickly.

175
Q

What is pharmacodynamics?

A

How the drug affects the body.

176
Q

What is pharmacokinetics?

A

describes the disposition of acompoundwithin anorganism.
ADME (absorption,distribution,metabolism andexcretion.

177
Q

What does draggability mean?

A

The ability of a protein target to bind small molecules with high affinity.

178
Q

What are some drug targets?

A

receptors.
enzymes.
transporters.
ion channels.

179
Q

What is a receptor?

A

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

180
Q

What are the different types of receptors? Example of each?

A

ligand-gated ion channels
nicotinic ACh receptor

G protein coupled receptors
beta-adrenoceptors

kinase-linked receptors
receptors for growth factors

cytosolic/nuclear receptors
steroid receptors

181
Q

What are some ligands on G coupled receptors?

A

Ligands include light energy, peptides, lipids, sugars, and proteins.

182
Q

What do the majority of G coupled receptors interact with?

A

The majority of GPCRs interact with PLC or adenylyl cyclase.

183
Q

How do kinase-linked receptors work?

A

Signal dimer binds.
Kinase activity stimulated.
tyrosine are phosphorylated.
intracellular proteins bind to phosphorus-tyrosine doing sites.

184
Q

What do nuclear receptors do?

A

Modify transcription.

185
Q

What do zinc fingers do?

A

Bind DNA.

186
Q

What are some imbalances in chemicals which lead to disease?

A

Chemicals
allergy; increased histamine
Parkinson’s; reduced dopamine

187
Q

What are some imbalances in receptors which lead to disease?

A

myasthenia gravis; loss of ACh receptors

mastocytosis; increased c-kit receptor

188
Q

What is an agonist?

A

a compound that binds to a receptor and activates it.

189
Q

What is an antagonist?

A

a compound that reduces the effect of an agonist.

190
Q

What does an agonist response curve look like?

A

Steep rise with little increase in concentration.

191
Q

What does a log concentration response curve look like?

A

Sigmoidal.

192
Q

What is EC50?

A

Concentration that gives half the maximal response.

193
Q

What is a partial agonist?

A

Agonist which never gives the full maximal response.

194
Q

What is Efficacy?

A

The maximum response achievable from a dose.

195
Q

What does intrinsic activity mean?

A

Intrinsic activity(IA) orefficacyrefers to the ability of a drug-receptor complex to produce a maximum functional response.

196
Q

What are the different types of antagonism?

A

Competitive and non-competitive.

197
Q

What are some examples of cholinergic receptor subtypes?

A

muscarine atropine mAChR

nicotine curare nAChR

198
Q

What happens when the H2 receptor is activated and antagonised?

A

Histamine (agonist)
contraction of ileum
acid secretion from parietal cells

Mepyramine (antagonist)
reversed contraction of ileum
no effect on acid secretion.

199
Q

What are the different Histamine receptors?

A

H1 - Allergic reactions.
H2 - Gastric acid secretion.
H3 - Mostly CNS disorders.
H4 - Immune system and inflammatory disorders.

200
Q

What is affinity?

A

Describes how well a ligand binds to the receptor.

Affinity is a property shown by both agonists and antagonists.

201
Q

What is efficacy?

A

Describes how well a ligand activates the receptor.

202
Q

What is the receptor reserve about?

A

Holds for a full agonist in a given tissue

reserve can be large or small; depends on tissue.

203
Q

What does signal amplification do?

A

Starts at a small response but amplified to give a bigger response.

204
Q

What is an allosteric modulation?

A

Other site on receptor for a different ligand to bind.

205
Q

What is an inverse agonist?

A

Gives less activation the more if binds.

206
Q

What is tolerance?

A

reduction in drug* effect over time

continuously, repeatedly, high concentrations.

207
Q

What is desensitisation?

A

uncoupled.
internalized.
degraded.

208
Q

What is an enzyme inhibitor?

A

An enzyme inhibitoris a molecule that binds to anenzymeand decreases (normally) itsactivity.

209
Q

What are the two types of enzyme inhibitor?

A

Irreversible inhibitors usually react with the enzyme and change it chemically (e.g. viacovalent bondformation).
Reversible inhibitors bindnon-covalentlyand different types of inhibition are produced depending on whether these inhibitors bind to theenzyme, the enzyme-substrate complex, or both.

210
Q

How do statins work?

A

Block the rate limiting step in the Cholesterol pathway

A class oflipid-lowering medications that reduces the levels of “bad cholesterol”

Reducecardiovascular disease(CVD) and mortality in those who are at high risk.

Huge cost to health care but being reduced by generics.

211
Q

How does the renin-angiotensin-aldosterone system work?

A

Renin-angiotensin-aldosterone system is a major blood pressure regulating mechanism. The system increases blood pressure by increasing the amount of salt and water the body retains.

212
Q

What does inhibiting ACE do?

A

Inhibiting ACE reduces ATII production and therefore causes a reduction in blood pressure.

213
Q

How is L-DOPA made?

A

produced from the amino acid L-Tyrosine as a precursor for neurotransmitter biosynthesis.

214
Q

What is Carbidopa?

A

Peripheral DDC Inhibitor. Blocks DDC in the periphery generating more for the CNS pathway.

215
Q

What is COMT?

A

Peripheral COMT Inhibitorprevents breakdown of L-DOPA generating more for the CNS pathway.

216
Q

What does mono amine oxidase B inhibitor do?

A

Mono Amine Oxidase B InhibitorPrevents Dopamine breakdown and increases availability.

217
Q

What do Central Dopamine Receptor Agonists do?

A

Antagonise dopamine receptors (not enzyme inhibitors).

218
Q

What are the three main proteins ports in a cell?

A

Uniporters: use energy from ATP to pull molecules in.

Symporters: use the movement in of one molecule to pull in another molecule against a concentration gradient.

Antiporters: one substance moves against its gradient, using energy from the second substance (mostly Na+, K+ or H+) moving down its gradient.

219
Q

What is an example of a supporter?

A

NKCC.

220
Q

What are some examples of ion channels.

A

Epithelial (Sodium) – heart failure
Voltage-gated (Calcium, Sodium) – nerve, arrhythmia
Metabolic (Potassium) – diabetes
Receptor Activated (Chloride) - epilepsy

221
Q

Where are voltage gated calcium channels?

A

In nerves, activated upon sodium flooding into the axon.

222
Q

What is Amlodipine?

A

Amlodipine is an angioselective (Why is that important?) Ca channel blocker that inhibits the movement of Ca ions into vascular smooth muscle cells and cardiac muscle cells.

223
Q

What do voltage gated sodium channels do?

A

In excitable cells Voltage-gated Na+channels have three main conformational states: closed, open and inactivated..

224
Q

What blocks voltage gated sodium channels?

A

Lidocane.

225
Q

What is an example of voltage gated potassium channels?

A

Regulate insulin in Pancreas:  Islets of Langerhans
Increased glucose leads to block of ATP dependent K+ channels.
Repetitive firing of action potentials increases Ca+ influx and triggers insulin secretion.

226
Q

What blocks voltage gated potassium channels?

A

Repaglinide, nateglinide and sulfonylureal.

227
Q

What does the GABA-A receptor do?

A

Endogenous ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the CNS.
GABA A receptor is post-synaptic, opens Cl- channel - induces hyperpolarisation.

228
Q

What increases the permeability of the GABA channel?

A

Barbiturates.

229
Q

What inhibits the sodium potassium pump?

A

Digoxin.

230
Q

What does digoxin do?

A

This inhibition causes an increase in intracellular Na, resulting in decreased activity of the Na-Ca exchanger and increases intracellular Ca.
This lengthens the cardiac action potential, which leads to a decrease in heart rate.

231
Q

What is the hydrogen potassium ATPase of the stomach?

A

The gastric hydrogen potassium ATPase or

H+/K+ ATPase is the proton pump of the stomach.

232
Q

What is an inhibitor of the hydrogen potassium ATPase?

A

Omeprazole.

Bateman - Phase 2a COPY (15 decks)

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