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Year 2 LCRS > Pharmacology 2 > Flashcards

Pharmacology 2 Flashcards

1
Q

Explain how depolarisation of heart tissue leads to contraction

A
  1. Depolarisation of membrane causes Ca2+ channels to open (voltage-gated)
  2. Subsequent Ca2+ influx allows Ca2+ to bind to Ryanodine receptors on the sarcop;aspic reticulum
  3. Opening of RyR causes Ca2+ to be released from intracellular stores
  4. Ca2+ binds to troponin causing tropomyosin to move, exposing the mysoin-binding site on the actin filament
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2
Q

What are the currents that control heart depolarisation?

A

If - hyperpolerisation-activated cyclic nucleotide gated channels are the sodium channels that kick start the whole process, opening at the lowest mV
ICa(t or l) - facilitate Ca2+ induced Ca2+ release
Ik - potassium channels allow re-polerisation

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3
Q

How does activation of cardiac B1 receptors produce effects?

A

Stimulates production of cAMP which increases intracellular Ca2+ by increasing activity of Ica(l). It also stimulates Na-K ATPase, increasing If.

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4
Q

What effects does B1 activation have on cardiac myocytes?

A
  • Positive chronotropic
  • Positive ionotropic
  • Increased automacity
  • Repolarisation and restoration of function
  • Reduced cardiac efficiency (CO demand is increased)
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5
Q

What results from activation of muscarinic receptors on cardiac myocytes?

A
  • decreased production of ATP and increased iK current. Resulting in:
  • cardiac slowing and reduced automacity
  • inhibition of AV conduction
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6
Q

What factors determine cardiac work?

A
  • Heart Rate
  • Preload
  • Afterload
  • Contractility
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7
Q

What factors influence supply for cardiac oxygen?

A
  • Coronary blood flow

- Arterial O2 content

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8
Q

What is angina a result of?

A

An imbalance between cardiac oxygen supply and demand

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9
Q

How can beta blockers treat angina?

A

Reduce cardiac demand (work) by:

- decreasing If and Ica and therefore decreased heart rate and contractility

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10
Q

How do calcium channel blockers work?

A

Bind to and inhibit the opening of L-type calcium channels.

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11
Q

How can calcium channel blockers be used to treat angina?

A

Decreasing Ica current decreases contractility and heart rate, therefore reducing workload. It also causes vascular smooth muscle relaxation –> arterial vasodilation and thus increased supply of blood to heart.

Note: Verapamil also inhibits AV node conduction

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12
Q

What are the types of calcium channel blockers, and the families of drugs that fit the category?

A

Rate slowing (cardiac AND smooth muscle action):

  • Phenylalkylamines
  • Benzothiapines

Non-rate slowing (smooth muscle action only)
- Dihydropyridines

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13
Q

Why shouldn’t dihydropyridines be used to treat angina?

A

It is a non-rate slowing calcium channel blocker. Although will cause vasodilation, will also result in reflex tachycardia.

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14
Q

What family of calcium channel blockers do the following drugs belong to?

  • Nifedipine
  • Verapamil
  • Amlodipine
  • Nicardipine
  • Diltiazem
A
  • The ones ending in -ipine are dihydropiridines
  • VerapAMIL is a phenylalklyAMIne
  • DilTIAzem is a BenzoTHIAzepine
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15
Q

What are the side effects of calcium channel blockers?

A
  • Ankle oedema (due to venodilation)
  • Headache and Flushing
  • Palpitations
  • Reflex adrenergic activation
  • Verapamil also causes AV block and commonly constipation
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16
Q

How can organic nitrates be used to treat angina?

A

They are substrates for NO production. NO diffuses into vascular smooth muscle and causes vasodilation by activating guanalyl cyclase. This reduces venous return and this cardiac work. Also increases coronary blood flow.

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17
Q

How can potassium channel openers be used to treat angina?

A

(Nicorandil) opens potassium channels leading to hyperpolarisation and relaxation of smooth muscle. As well as decreasing afterload and preload, they also increase coronary blood flow.

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18
Q

When are the different anti-angina drugs used?

A
  • Beta-blockers and Ca2+ antagonists are the background anti-angina treatment
  • Nitrates are good to take with exercise as causes vasodilation
  • Potassium channel openers tend to be reserved if patient is intolerant to other drugs.
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19
Q

How many people in the UK are affected by cardiac rhythm abnormalities?

A

700,000

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20
Q

What is the aim of treatment against arrhythmia?

A
  • Prevent sudden death (due to ventricular fibrillation)
  • Prevent stroke
  • Alleviate symptoms
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21
Q

What are the general types of arrhythmias?

A

Can be tachyarrhythmias or bradyarrhythmias.

Also classed based on site of origin such as supraventricular or ventricular or complex arrhythmias

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22
Q

What drugs belong to the Vaughn-Williams classification of anti-arrhythmic drugs?

A

Type I: sodium channel blocker
Type II: beta adrenergic blocker
Type III: potassium channel BLOCKERS
Type IV: Calcium channel blocker

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23
Q

What are the main anti-arrythmics?

A
  • Adenosine
  • Digoxin
  • Verapamil
  • Amiodarone
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24
Q

How does adenosine treat arrhythmias?

A

It acts on A1 receptors to hyperpolarise cardiac tissue and slow reduction through AV node. Its mode of action is the receptor being negatively coupled with adenyl cyclase –> less Ca2+ and less Na+/K+ activity.

Adenosine is short lived and immediately terminates supraventricular tachyarrhythmias.

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25
Q

How does Verapamil treat arrhythmias?

A

It is a Phenylalkylamine (calcium channel blocker) that depresses AV node conduction and therefore used to treat paroxysmal supraventricular tacyarrhythmias

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26
Q

What are the side effects of potassium channel blockers?

A

Amiodarone has a number of important adverse effects:

  • photosensitive skin rashes
  • hypo/hyperthyroidism
  • pulmonary fibrosis
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27
Q

What are the effects of cardiac glycosides?

A

Digoxin inhibits the Na+/K+ pump. This results in:

  • reduced chronotropic effect and reduced rate of conduction through AV node (due to enhanced vagal stimulation)
  • positive chronotropic effect because increased intracellular Na+ is exchanged for Ca2+ by Na/Ca exchangers.
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28
Q

What are the uses of Digoxin?

A

The cardiac glycoside is used in:

  • treating supraventricular tachyarrhythmias due to reduce rate of conduction through AV node and vagal stimulation
  • treating heart failure due to positive ionotropic effect
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29
Q

Why is digoxin toxicity a problem?

A

Results in:

disarrhythmias and hypokalaemia

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30
Q

What are the cardiac ionitropes?

A
  • Digoxin (cardiac glycoside)

- Dobutamine (B1 adrenoreceptor agonist)

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31
Q

What are the effects of angiotensin II?

A
  • Thirst activation
  • Vasoconstriction
  • Salt and water retention
  • aldosterone release
  • vasopressin release
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32
Q

What causes renin release?

A
  • decreased renal perfusion pressure
  • increased sympathetic activity
  • decreased [Na} as detected by macula dense
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33
Q

Describe the production of angiotensin II

A

The liver makes angiotensinogen. Renin converts this to angiotensin I. Angiotensin Converting Enzyme converts this to angiotensin II.

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34
Q

Through what receptor does angiotensin II work?

A

AT1

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35
Q

What is the suffix that ACE inhibitors share?

A

-pril

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36
Q

Name two ACE inhibitors

A

Enalapril and Captopril

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37
Q

What is the function of ACE?

A
  • conversion of angiotensin I to angiotensin II

- breakdown of bradykinin

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38
Q

What are ACE inhibitors used to treat?

A
  • Hypertension
  • Heart failure
  • Post-MI
  • Diabeti nephropathy
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39
Q

How do ACE inhibitors treat hypertension?

A
  • decreased vasoconstriction

- reduced salt and water retention

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40
Q

How do ACE inhibitors treat heart failure and post-MI heart conditions?

A
  • decreased vasoconstriction –> decreased TPR –> reduction in after load –> heart pushes against less pressure, –> less work
  • decreased salt and volume retention –> reduction in blood volume –> reduced preload –> reduced contractility –> reduced work done by heart
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41
Q

How do ACE inhibitors treat diabetic nephropathy?

A

Normally Angiotensin II contracts efferent arteriole of the nephron to maintain GFR. Directing blood flow away from the nephron by decreasing GFR is useful as to reduce accumulation of toxic end products in diabetes.

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42
Q

How do Angiotensin receptor blockers work, and why are they used?

A

They act as non-competitive antagonists of At1 receptors. Widely used in hypertension and heart failure as an alternate to ACE inhibitors with fewer side effects.

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43
Q

Name an angiotensin receptor blocker

A

Lasartan

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44
Q

What are the side effects for ACE inhibitors and Angiotensin receptor blockers?

A
  • persistent dry cough [ACEI]
  • Hypotension [both]
  • Urticaria/Angioedema [ACEi]
  • Hyperkalaemia [ACEi]
  • Foetal injury [both]
  • Renal failure in patients with artery stenosis [both]
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45
Q

Why are dihydropyridines non-rate limiting?

A

They cannot access intracellular domain of the Ca2+ of the heart because it is not lipid soluble enough.

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46
Q

Why are beta blockers not used as first line treatments for hypotension?

A

They are not effective in affecting blood vessels.

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47
Q

What are the NICE treatment guidelines for treating hypertension:

A

Step 1: If younger than 55 then ACEi or ARB. If not (or black) then CCB or Thiazide-type diuretic

Step 2: [ACEi + CCB] or [ACEi + Thiazide]

Step 3: ACEi + CCB + Thiazide

Step 4: ACEi + CCB + Thiazide + alpha or beta blocker
+ maybe spironolactone

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48
Q

What cocktail of drugs do chronic heart failure patients typically receive?

A
  • Diuretic
  • ACEi
  • B-blockers
  • Spironolactone
  • Digoxin
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49
Q

Describe the reward pathway of the brain

A

The pathway begins at the Ventral Tegmental Area of the midbrain –> Nucleus accumbens to release dopamine.

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50
Q

What are the routes of administration of drugs of abuse?

A
  • Intra-nasal (snorting): across mucous membrane of nasal sinus –> general circulation –> brain
  • Oral: drug is absorbed in GI tract –> portal circulation –> systemic circulation –> brain
  • Inhalation: drug diffuses across alveoli into pulmonary circulation –> systemic circulation at close proximity –> brain
  • Intravenously –> systemic –> brain
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51
Q

What is the relationship between the rate of absorption of a DoA and its addictive-ness?

A

The quicker the rate of absorption, the quicker the feeling of euphoria and the more addictive it is.

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52
Q

Sort the routes of administration of DoA by speed of absorption

A

oral

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53
Q

What is the classification for the drugs of abuse?

A

Class 1: Painkillers/Narcotics are opiate like drugs
Class 2: Depressants slow down the CNS
Class 3: Stimulants speed up the CNS
Miscellaneous category includes cannabis, ecstasy - MDMA, and hallucinogens such as LSD

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54
Q

What are narcotics?

A

A narcotic is a drug that reduces pain and induces drowsiness, stupor or insensibility

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55
Q

What are Class 2 Drugs of Abuse?

A

Alcohol, Benzodiazepines and Barbiturates

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56
Q

What are the Class 3 Drugs of Abuse?

A

Cocaine, Amphetamines, Caffeine and Methylamphetamines

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57
Q

What is the active ingredient in cannabis?

A

delta-9-tetrahydrocannibol

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58
Q

What is the dose of cannabis from one cigarette?

A

150mg

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59
Q

What percentage of inhaled and consumed cannabinoids enters the systemic circulation?

A
  • 30% of inhaled dose

- 10% of oral dose

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60
Q

What is the relevance of cannabis’ high lipid solubility?

A
  • can easily diffuse into various tissues e.g brain
  • especially diffuses into fat.
  • adipose tissue becomes a reserve, determining how much THC gets into the blood stream and how long it stays in the body (dynamic equilibrium)
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61
Q

Describe the distribution of cannabis to highly perfused tissues

A

High perfused tissues e,g brain have a quick build up of cannabis, but also leave these tissues very quickly.

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62
Q

How long can cannabis from a single cigarette remain in the body for?

A

In fat tissue for up to 30 days

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63
Q

Where is cannabis metabolised and excreted?

A

Cannabinoids are metabolised in the liver and GIT. Metabolism in GIT allows metabolites to be excreted into the bile which enters the enter-hepatic recycling system. Also excreted through urine and faeces.

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64
Q

Why is there a poor correlation between plasma cannabinoid concentration and degree of intoxication?

A

Enterohepatic circulation of active metabolites such as 11-hydroxy-THC can still work on cannabinoid receptors.

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65
Q

What is the tissue half-life of delta-9-THC?

A

7 days

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66
Q

Where are the cannabinoid receptors found?

A
  • CB1 are neuronal cannabinoids found in high concentrations in the hippocampus, cerebellum, cerebral cortex and basal ganglia.
  • CB2 are found in peripheral immune cells
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67
Q

How do the cannabinoid receptors work?

A

G-protein coupled receptors that are negatively coupled to adenyl cyclase, associated with a reduction in cellular activity

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68
Q

What are the endogenous agonist for cannabinoid receptors?

A

Anandamine

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69
Q

How do cannabinoids cause euphoria?

A

CB1 receptors are found in GABAergic neurones in the VTA. Reducing their firing rate, reduces the inhibitory effect on the dopaminergic neurones. Increases DA release into nucleus accumbens

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70
Q

List the psychological (central) effects of cannabis?

A
  • psychosis and schizophrenia
  • increase in appetite
  • short-term memory loss
  • altering of perception
  • decrease in cognitive performance
  • slows reactions
  • motor incoordination
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71
Q

How may cannabis precipitate schizophrenia?

A

CB1 receptors are present on neurones in the ANTERIOR CINGULATE CORTEX. This is usually involved in error detection, acting as a filter/amplifier to improve emotional processing.
Long-term inhibition of this may precipitate psychosis and predispose to schizophrenia.

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72
Q

How does cannabis increase appetite?

A

CB1 receptors in the hypothalamus allows a positive effect on orexigenic neurones in the lateral hypothalamus.

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73
Q

How does cannabis cause short-term memory loss?

A

CB1 receptors have depressant effect on hippocampus. This causes a decrease in Brain Derived Neurotrophic Factor production which is needed to lay down new neurones and memory within these neurones.

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74
Q

What are the peripheral effects of cannabis?

A
  • Immunosuppressant (CB2 binding suppresses immune cell function)
  • Tachycardia and widespread vasodilation (due to interaction with TRPV1 receptors)
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75
Q

When may cannabinoid receptors be unregulated?

A

In certain diseases such as MS and chronic pain.

Can also be pathologically unregulated in fertility, obesity and stroke

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76
Q

What drugs are developed form cannabinoids?

A
  • Dronabinol and Nabilone are delta-9-THC preparations used to increase appetite in AIDS and cancer cachexia patients
  • Sativex is a combination of cannabinoids to treat neuropathic pain, and pain relief for multiple sclerosis
  • Rimonabant is an antagonist used as an anti-obesity drug that may lead to depression
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77
Q

What type of DoA is Cocaine?

A

Stimulant

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78
Q

What are the different preparations of cocaine, and how are they administered?

A
  1. Paste is 80% cocaine
  2. Cocaine hydrochloride - when paste is dissolved in acid before extraction by recrystallisation.
    * * above taken IV, oral, and intranasal **
  • ** below taken by intranasal only ***
    3. Crack cocaine is when cocaine is precipitated out with an alkaline solution. It is easer and cheaper to prepare
    4. Freebase cocaine is purified crack dissolved in non-polar solvent
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79
Q

What is the pKa of cocaine, and how is this relevant?

A

pKa of 8.7

Oral cocaine is ionised in the acidic environment of the stomach, slowing absorption and prolonging action

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80
Q

How/where is cocaine metabolised?

A

Plasma and liver cholinesterase break down cocaine.
Liver metabolises 75-90% of cocaine to ecgonine methyl ester and benzoylcognine on first pass.
The blood metabolises 10-25% giving cocaine a shirt life..

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81
Q

What are the effects of cocaine (and how)?

A
  • Local anaesthetic (by blocking VSSC to preventing nerve conduction)
  • Euphoria: binds to monoamine transporter proteins on dopaminergic neurones in the mesolimbic pathway preventing uptake of dopamine from synapse. This leads to DA build up in the nucleus accumbens
  • Stimulant: general stimulatory effect on brain as it decrease conduction of the inhibitory pathways more than excitatory pathways.
  • Cardiovascular effects: increased endothelin 1 (vasoconstrictor) and decreases NO production. Increase platelet activation. Increased sympathetic stimulation (preventing NA reuptake) and causes tachycardia.
  • Cerebral effects: decrease in CBF due to vasoconstriction. Inflammation in walls of blood vessels. Hyperpyrexia.
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82
Q

How much nicotine is contained in:

  • nicotine spray
  • cigarettes
  • nicotine patches
  • nicotine gum
A
  • nicotine spray: 1mg
  • cigarettes: 2-4mg
  • nicotine patches: 9-17mg
  • nicotine gum: 15-22mg
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83
Q

Rank the routes of nicotine administration based on bioavailability

A
  1. Patches - 70% enters the bloodstream as good absorption through skin
  2. Nicotine gum - 50-70% through diffusion across buccal membranes
  3. Nicotine spray - 20-50%
  4. Cigarette - 20% - contained in tar droplets
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84
Q

Why may nicotine patches not provide a ‘good enough’ kick for smokers?

A

Cigarettes allow very rapid delivery of nicotine to the brain, providing a ‘spike’.
Even though patches contain more mg of nicotine, there is no spike.

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85
Q

Describe the metabolism and excretion of nicotine

A

Metabolism: in liver by hepatic cytochrome P2A6 to cotinine
Excretion: urine

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86
Q

How does nicotine interact with its receptors?

A

Nicotine acts on each receptors in the CNS. Binding causes the opening of Na+ channels and depolarisation. Causes more APs at all autonomic ganglia as well as adrenal medulla.

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87
Q

What are the effects of nicotine (and how)?

A
  • Euphoria: binding to nAch on cell bodies of VTA dopaminergic neurones.
  • Cardiovascular effects: lots (on another Q)
  • Metabolic effects: increase in metabolic rate and appetite suppressant
  • Endocrine: increased levels of ACTH and Cortisol
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88
Q

What are cardiovascular effects of nicotine?

A
  • increased sympathetic stimulation centrally and through adrenaline
  • increased blood coagulation and increased platelet aggregation
  • peripheral vasoconstriction but skeletal muscle vasodilation
  • increased lipolysis
  • ** increased risk of atherosclerosis, MI, and CVD due to reduced cardiac flow and greater risk of thrombus formation **
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89
Q

What are beneficial effects of nicotine on certain diseases?

A

Slows down progression of:

  • Parkinson’s disease: increasing level of brain cytochrome P450 which metabolises neurotoxins
  • Alzheimer’s disease: decreases beta-amyloid toxicity
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90
Q

How does caffein cause euphoria?

A

Adenosine binding on A1 receptors on dopaminergic neurones in the VTA usually dampen down dopamine release.

Caffeine inhibits the adenosine receptors, increasing the amount of Da in the NAcc

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91
Q

What is Alcohol By Volume (ABV)?

A

It is a measure of how much alcohol is contained in a given volume (expressed as a volume percentage)

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92
Q

How can you calculate g alcohol/100 ml?

A

%ABV x 0.78

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93
Q

How much alcohol is in 1 unit?

A

10ml/8g

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94
Q

How many units makes the maximum for men and women in a week?

A

Men: 21
Women: 14

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95
Q

Describe the absorption of alcohol

A

Ethanol is uncharged therefore rapidly absorbed from the mucous membranes of the stomach and gut (slowed by food). 20% absorbed in the stomach, 80% in gut.

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96
Q

Why is alcohol absorbed faster on an empty stomach?

A

20% absorbed in the stomach, 80% in gut.

On an empty stomach, it passes straight down to the ileum, where a large dose is more absorbed.

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97
Q

What percentage of ingested alcohol is metabolised, and what percentage is excreted?

A

90% metabolised, 10% excreted through urine and breath unchanged.

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98
Q

Where is alcohol metabolised?

A

85% in the liver

15% in the gut

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99
Q

How is alcohol metabolised in the liver?

A

75% by alcohol dehydrogenase, converting ethanol to acetaldehyde.
25% metabolised by mixed function oxidase (a CYP450 enzyme)

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100
Q

Describe the pharmacokinetic tolerance of alcohol

A

Liver enzymes, (in particular MFO) can be up-regulated by regular drinking. This means more alcohol needs to be consumed for the same effect.

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101
Q

How is rate of consumption important in alcohol toxicity?

A

Because there is first-pass metabolism before ethanol reaches systemic circulation. If liver enzymes are saturated due to high consumption, a large proportion of the dose will reach the systemic circulation, leading to a greater level of ethanol in the blood.

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102
Q

How is alcohol metabolised in the gut?

A

Alcohol absorbed from the stomach (20% of dose) is simultaneously metabolised by alcohol dehydrogenase present on the lining of the stomach.

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103
Q

Why do women get intoxicated (from alcohol) more easily than men?

A
  • Women have 50% less alcohol dehydrogenase in the stomach, and so more ethanol is absorbed into the bloodstream.
  • Women have a smaller volume of body water. As alcohol is distributed within body water, the ethanol is more concentrated in women.
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104
Q

How is Disulfiram used in alcohol aversion therapy?

A

Acetaldehyde is a toxic metabolic of alcohol. It is metabolised to acetic acid (inert) by aldehyde dehydrogenase.

Disulfiram is a drug that inhibits aldehyde dehydrogenase, allowing build-up of acetaldehyde

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105
Q

Describe the potency of alcohol

A

Alcohol has a low pharmacological potency. This is because of its simple chemical structure meaning it is not very selective of its targets.

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106
Q

List the CNS effects of alcohol

A
  • depressant
  • euphoria
  • sensory and motor impairment
  • disconnection between logic and impulsive feelings
  • increases appetite, emotions and decreases pain sensation
  • impaired consciousness
  • loss of memory
  • lack of psychomotor function
  • loss of time perception.
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107
Q

What areas of the brain must be affected by alcohol to produce the following effects:

  • disconnection between logic and impulsive feelings
  • increases appetite, emotions and decreases pain sensation
  • impaired consciousness
  • loss of memory
  • lack of psychomotor function
  • loss of time perception.
A
  • corpus callosum
  • hypothalamus
  • reticular activating system
  • hippocampus
  • cerebellum
  • basal ganglia
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108
Q

What are the three main targets for alcohol in the brain to produce depressant effects?

A
  1. GABA receptors - has a positive effect on GABA function. Also increases allopregnenolone which activates release of GABA
  2. NMDA receptors - alcohol has a negative effect on NMDA function by binding to the receptor and decreasing its effect by allosteric modulation.
  3. Calcium channels - negative effect on Ca2+ channels and this neurotransmitter release.
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109
Q

What systems/organs (apart from CNS) does alcohol effect?

A
  • Cardiovascular system
  • GI tract
  • Endocrine system
  • Liver
  • Foetal development
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110
Q

What are the cardiovascular effects of alcohol?

A
  • *short term**
  • cutaneous vasodilation due to decreased calcium entry and increased vasodilatory prostaglandins into the pre-capillary sphincters.
  • tachycardia and vasodilation due to depressant effect on arterial baroreceptors, slowing firing rate –> reduction in parasympathetic activity to heart and increase in sympathetic activity.

long term
beneficial effects in small daily amounts due to:
- increased levels of HDLs
- increased tissue plasminogen activator and so reduction in thrombus formation
- polyphenols found in wine has a protective effect from CVD.

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111
Q

What are the GI effects of alcohol?

A
  • increase in salivary and gastric acid secretions
  • irritant effects and stimulation of sensory nerve endings
  • chronic intake is linked to damage to the gastric mucosa due to acetaldehyde build-up
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112
Q

What are the endocrine effects of alcohol?

A
  • causes polyuria due to increased volume and inhibition of vasopressin release.
  • *chronic**
  • increased ACTH secretion leading to cushing’s-like syndrome
  • impaired testosterone synthesis leading to feminisation is male chronic alcoholics
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113
Q

What are the chronic CNS effects of alcohol?

A
  • dementia due to cortical atrophy and decreased white mater
  • ataxia due to cerebellar cortex degradation
  • Wernicke-Korsakoff syndrome due to reduced dietary thiamine (as chronic alcoholics get calories from their beverages). This is Wernicke’s encephalopathy where 3rd ventricle and aqueduct enlargement causes reduced eye movement, balance problems and ataxia. This leads to Korsakoff psychosis which is the dorsomedial loss of the thalamus and hippocampus –> irreversible interference with memory.
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114
Q

What are the effects on the liver of alcohol consumption?

A
  • Alcohol metabolism in the liver uses up all the NAD+ stores and oxygen. This affects glycolysis, kreb’s cycle and lipolysis at the most minimum.
  • Cell function diminishes as they have a poor ability to generate ATP
  • Fatty liver occurs due to reduced lipolysis and this increased storing of fats as triglycerides
  • Hepatitis occurs as toxic acetaldehyde and ROS stimulate inflammation
  • Cirrhosis occurs due to chronic inflammation triggering fibroblasts to lay down connective tissue –> loss of hepatic regeneration and active liver tissue is replaced by connective tissue
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115
Q

What are the foetal development effects of alcohol?

A

Inhibition of cell division and migration leads to foetal alcohol syndrome, abnormal facial development and growth + mental retardation.

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116
Q

When do hangover symptoms peak in relation to blood alcohol percentage?

A

Peak as alcohol concentration reaches 0

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117
Q

How can hangover symptoms be explained?

A
  • headache due to vasodilation
  • nausea as high doses of alcohol can irritate stomach through acetaldayhe - signalling vomiting centre.
  • fatigue due to sleep deprivation
  • poor sleep quality due to rebound CNS excitatory effect
  • restlessness and muscle tremors due to rebound CNS excitation
  • polyuria and polydipsia due to decreased vasopressin secretion.
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118
Q

What are plasma clotting factors?

A

They are the procoauglants and anticoagulants in the plasma

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119
Q

Differentiate between haemostasis and thrombostasis

A

Haemostasis is an essential physiological process where blood coagulation prevents excessive blood loss. Thrombosis is a pathophysiolocal process where blood coagulates within blood vessels obstructing blood flow.

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120
Q

Differentiate between the pathophysiology of venous and arterial thrombosis

A
  • venous thrombosis (red thrombi) occur as blood is slower in veins. Most common disorder is a DVT, which can become life-threatening if it dislodges and embolises.
  • arterial thrombosis (white thrombi) are usually due to atherosclerotic plaque rupture.
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121
Q

Differentiate between the clots of venous and arterial thrombosis

A
  • venous produce red thrombi. mainly composed of fibrin which traps erythrocytes
  • arterial are white thrombi because of high platelet component and leukocyte infiltration.
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122
Q

What is Virchow’s triad?

A

Describes why thrombi form:

  1. Rate of blood flow (slow flow reduced replenishment of anticoagulants)
  2. Consistency of blood (a natural imbalance from anticoagulants)
  3. Blood vessel integrity (damaged endothelia means blood is exposed to pro-coagulation factors)
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123
Q

Briefly describe the cell-based theory of blood coagulation

A
  1. Initiation - small scale production of thrombin mediated by and localised to tissue factor bearing cells
  2. Amplification - large scale thrombin production on the surface of platelets
  3. Propagation - large scale production of fibrin strands on the surface of platelets.
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124
Q

What type of drugs combat each stage of the cell-based theory of blood coagulation?

A
  1. Initiation - combatted by anticoagulants
  2. Amplification - combatted by antiplatelets
  3. Propagation - combatted by thrombolytics
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125
Q

Explain the process of haemostasis initiation

A

Tissue factor bearing cells activate factor X which when combined with factor V produce prothrombinase complex. Prothrombinase complex activates factor II (prothrombin) creating factor IIa (thrombin). This activates FVIII and FV ultimately leading to more production of itself.

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126
Q

What inactivates Factor Xa and Factor IIa

A

Antithrombin

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127
Q

List the anticoagulant drugs and how they work.

A
  • Rivaroxaban inhibits factor Xa
  • Dabigatran inhibits factor IIa (directly)
  • Heparin activates antithrombin, reducing levels of factor IIa and Xa. LMWHs such as Dalteparin only activate part of antithrombin that targets factor Xa.
  • Warfarin is a vitamin K agonist, preventing gamma carboxylation of factors II, VII, IX, X
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128
Q

What are the indications of anticoagulant drugs?

A

Prophylaxis of DVT, thrombi during surgery, and for patients with aFib

129
Q

Explain the process of haemostasis amplification

A

Platelet aggregation and activation occurs because thrombin activates platelets. Thrombin binds to protease activated receptor (PAR), which causes a rise in intracellular Ca2+. This causes exocytosis of ADP from dense granules.

ADP activates P2Y12 receptors in platelets leading to further activation, and this aggregation.

PAR also liberates arachidonic acid, which is used by COX enzymes to generate thromboxane A2.

Thromboxane A2 allows for the expression of GPIIb/IIIa integrin receptor on platelet surface, which allows aggregation.

130
Q

List the antiplatelet drugs and how they work.

A
  • Clopridogrel is a P2Y12 receptor antagonist, preventing platelet activation
  • Aspirin is an irreversible COX-1 inhibitor that inhibit thromboxane A2 production
  • Abciximab is a gpIIb/IIIa inhibitor preventing platelet aggregation.
131
Q

What are the indications of antiplatelet drugs?

A

Used to treat acute coronary syndromes (such as MI) and aFib for the prophylaxis of stroke.

132
Q

Explain the process of haemostasis propagation

A

This occurs through the generation of fibrin strands. Activated platelets produce thrombin at a large scale. Thrombin binds to fibrinogen, converting it to fibrin strands.

133
Q

List the thrombolytic drugs and how they work

A

They remove clots unlike anticoags or antiplatelets.
- Plasmin is a protease that degrades fibrin. Alteplase is a recombinant type plasminogen activator. First line treatment for stroke and used to treat ST-elevated MI.

134
Q

What type of anti-haemostatic drugs would you use to treat clots in the brain?

A
  • Anti-platelets and Thrombolytics to treat stroke
135
Q

What type of anti-haemostatic drugs would you use to treat clots in the heart?

A
  • Non-ST elevated MI (partially occluded) treat with antiplatelets
  • ST-elevated MI (fully occurred) treat with antiplatelets and thrombolytics
136
Q

What type of anti-haemostatic drugs would you use to treat Atrial fibrillation?

A

antiplatelets and anticoagulants

137
Q

What type of anti-haemostatic drugs would you use to treat arterial diseases?

A

Aortic aneurysms and Peripheral artery disease treated with antiplatelets.

138
Q

What type of anti-haemostatic drugs would you use to treat venous derived clots?

A

DVT treated with anticoagulants.

Subsequent pulmonary emoji treated with anticoagulants and thrombolytics

139
Q

What percentage of cholesterol is made in the liver?

A

80%

140
Q

Define the exogenous pathway of lipid metabolism

A

It is the pathway involved in the transport and utilisation of dietary fats

141
Q

Describe the exogenous pathway of lipid metabolism up to lipid transport into the blood.

A
  • dietary fat broken down in GI tract to cholesterol, fatty acids, monoglycerides and diglycerides
  • together with bile acids they form water soluble micelles that carry the lips to the duodenum where most triglycerides and half of the cholesterol is absorbed
  • chylomicrons are formed in the enterocytes that enter the bloodstream via intestinal lymphatics and the thoracic duct
142
Q

Describe the exogenous pathway of lipid metabolism, after chylomicrons are in the blood

A
  • chylomicrons are hydrolysed by LIPOPROTEIN LIPASE, releasing the triglyceride core, free fatty acids, and mono/di glycerides for energy production or storage
  • residual chylomicron remnants are taken up by various tissues such as hepatocytes, or can enter atheroma
143
Q

Describe the endogenous pathway of lipid metabolism

A

VLDLs transports triglycerides, cholesterol and cholesterol esters from the liver to the rest of the body. LIPOPROTEIN LIPASE converts VLDLs to IDLs (which are atherogenic) to LDLs (which are the most atherogenic) to HDLs .

Cholesterol is transported to the liver via HDLs to be excreted.

144
Q

Describe the pathogenesis of an atherosclerotic plaque

A
  1. Endothelial damage allows LDLs to move into the sub-endothelial space in the vessel wall
  2. Protective response results in production of cellular adhesion molecules
  3. Monocytes and T-lymphocytes attach to the sticky surface of the endothelial cells before migration through the arterial wall into the sub-endothelial space.
  4. Macrophage uptake of oxidised LDL-cholesterol
  5. Formation of lipid-rich foam cells
  6. Foam cells accumulate and smooth muscle cells proliferate resulting in a fatty streak and subsequently a plaque.
145
Q

What are the sequelae of atherosclerosis at:

  • coronary blood vessels
  • cerebral vessels
  • peripheral arteries?
A
  • coronary heart disease –> angina pectorals, myocardial infarction
  • transient ischaemic attack or stroke
  • peripheral artery disease –> intermittent claudication and gangrene
146
Q

What endothelial changes prelude plaque formation?

A
  • greater permeability
  • up-regulation of leukocyte and endothelial adhesion molecules
  • migration of leukocytes and into the artery wall
  • migration of LDLs into sub-endothelial space
147
Q

What are the first recognisable signs of atherosclerosis?

A

Fatty streaks, caused by the aggregation of foam cells within the tunica intima.

148
Q

How does a atherosclerotic plaque form from a fatty streak?

A

The rupture of lipid-rich foam cells, releasing their contents to form a necrotic core. This leads to the formation of a protective cap, separating the highly thrombogenic core from circulating platelets and other coagulation factors.

149
Q

What is the difference between stable and unstable atherosclerotic plaques?

A
  • stable plaques have a thick fibrous cap; lumen is usually very compressed though. still better to have a stable plaque
  • unstable plaques have a thin fibrous cap; lumen is not very reduced, making it difficult to detect
150
Q

What increase in CHD risk results from a 10% increase in LDL levels?

A

20% increase in CHD risk

151
Q

How are HDL levels lowered?

A
  • smoking
  • physical inactivity
  • obesity
152
Q

What are the first-line treatments of dyslipidaemias?

A

Statins

153
Q

How do statins treat dyslipidaemias?

A

Inhibit HMG-CoA-reductase, which is the enzyme of the rate-limiting step in the formation of cholesterol in hepatocytes. As a result, hepatocytes up regulate the number of LDL receptors, increasing binding a removal of LDL cholesterol and resulting in an increasing of HDL cholesterol.

Sidenote: also increases plaque stability

154
Q

By how much can statins reduce CVD risk?

A

30%

155
Q

What are the side-effects of statins?

A

Reduced platelet aggregation, thrombogenesis, vascular inflammation, SMC hypertrophy and proliferation, endothelial dysfunction and vasoconstriction.

156
Q

What classes of drugs can treat dyslipidaemias?

A
  • statins
  • bile acid sequestrants
  • nicotinic acid
  • fibrates
  • ezetimibe
  • CETP inhibitors
157
Q

How do bile acid sequestrants treat dyslipidaemias?

A

They bind to bile acids, preventing absorption of cholesterol.

158
Q

What are the side effects of bile acid sequestrants?

A

Bloating, nausea and constipation

159
Q

How does nicotinic acid treat dyslipidaemias?

A

It is a beta-complex vitamin used in therapy, increasing HDL, lowering LDLs, triglycerides and clotting.

160
Q

Why isn’t nicotinic acid used to treat dyslipidaemias?

A

very low tolerability. ADRs include flushing, skin problems, GI disease, liver toxicity, hyperglycaemia and hyperuricaemia

161
Q

How do fibrates treat dyslipidaemias?

A

They activate PPAR(alpha) receptors. They modulate carbohydrate and fat metabolism. Activation induces transcription of genes that facilitate lipid metabolism. They reduce FFAs, triglycerides and increase HDLs.

They also reduce thrombosis, cell recruitment, migration and activation (to foam cells). They also increase plaque stability

162
Q

How does ezetimibe treat dyslipidaemias?

A

Inhibits cholesterol absorption from intestine. –> increased LDL receptors and thus uptake into liver. Also promotes secretion of glucoronide into bile, blocking cholesterol uptake. Reduction in LDL not effective as statins, so often combined.

163
Q

How do CETP inhibitors treat dyslipidaemias?

A

Cholesterol Ester Transfer Protein facilitates transport of cholesterol esters and triglycerides between lipoproteins. However this is mainly from HDLs to LDLs. Blocking this reduced LDL and increases HDL levels.

164
Q

What are the uses for NSAIDs?

A
  • Analgesic for relief of mild to moderate pain e.g muscoloskelatal pain, headache, toothache etc
  • Anti-pyretic to reduce fever, such as in the case of influenza
  • Anti-inflammatory for chronic control of inflammatory diseases such as RA, osteoarthritis, soft tissue injuries or gout
  • Aspirin can be used as a anti-platelet
165
Q

What is the main cause of deaths by high doses of NSAIDs?

A

GI ulceration

166
Q

What is the mechanism of action of NSAIDs?

A

Preventing production of prostanoids by inhibiting COX (cyclo-oxygenase enzyme) as it is the rate limiting step in converting Arachidonic Acid to Prostaglandin H2.

167
Q

What are the main subgroups of prostanoids?

A
  • Prostaglandins
  • Prostacyclins
  • Thromboxanes
168
Q

Are prostanoids synthesised when needed, or synthesised all the time and stored?

A

synthesised when needed

169
Q

What are the 10 prostanoid receptors?

A 
DP1, DP2
EP1, EP2, EP3, EP4
FP
IP1, IP2
TP
170
Q

What type of receptors are prostanoid receptors?

A

Type 2: Metabotropic

171
Q

What reaction do the COX enzymes catalyse?

A

Arachidonic Acid —-> Prostaglandin H2

172
Q

Describe the differences between the two main isoforms of Cyclo-oxygenase

A

COX-1:

  • Constitutive (made all the time)
  • Ubiquitous
  • Physiological (regulation of homeostatic function)

COX-2:

  • Inducible
  • Also ubiquitous
  • Physiological and pro-inflammatory roles
173
Q

What receptors can Prostaglandin E2 bind to?

A

EP1, EP2, EP3, EP4

174
Q

What are the unwanted actions of prostaglandin E2 that are thus reduced by NSAIDs?

A
  • Increased pain perception: stimulation of PG receptors on nerve endings SENSITISES (lowers activation threshold) nociceptors so they fire off at a lower level of stimuli
  • Pyrogenic: PGE2 stimulates hypothalamic neurones to imitate a rise in body temperature.
  • Acute inflammatory response: EP3 receptors causes mast cell degranulation
  • Immune responses: EP3 receptors causes Th1 and Th17 expansion. Th1 produced IFN-y contributing to inflammation. Th17 produces IL-17 contributing to autoimmunity
  • Anti-apoptotic actions
175
Q

What are the side effects of NSAIDs?

A
  • Gastric ulceration
  • Renal toxicity
  • Bronchoconstriction
  • Cardiovascular effects
176
Q

What are the desirable actions of prostainoids (that thus precipitate as NSAID side-effects)?

A
  • Gastric Cytoprotection: PGE2 downregulates Hal secretion in the stomach and stimulates mucus and bicarbonate secretion - producing a physiological barrier
  • Renal blood flow: PGE2 increases renal blood flow
  • Bronchodilation
  • Vasoregulation
177
Q

What are the non-selective NSAIDs?

A

Ibuprofen and Indomethacin

They have anti-inflammatory, anti-pyretic and analgesic actions

178
Q

What is the COX-2 selective NSAID, and its effects?

A

Celecoxib.

Reduces risk of gastric ulcers. However increasing evidence shows that COX-2 inhibitors pose higher risk of CVD that conventional COX inhibitors (nobody knows y)

179
Q

What are the strategies (other than selective COX-2) for limiting NSAID’s GI effects?

A
  • Topical administration
  • Minimise NSAID use in patients with a history of GI ulcers
  • Treat H.Pylori if present
  • If NSAID essential, administer with omeprazole or other PPI
  • Minimise NSAID use in patients with other risk factors
180
Q

Why is Aspirin a unique NSAID?

A

Binds to COX-1 selectively and IRREVERSIBLY. Also is an anti-platelet drug as prevents Thromboxane A2 production.

181
Q

How is water reabsorbed in the PCT

A
  • Na/H+ exchange in the apical membrane.
  • Carbonic anhydrase on apical membrane as well as intracellular to recycle H+. H+ excreted due to exchange is combined with bicarbonate to form H20 and CO2. Intracellular bicarbonate converts this back to H+ which is excreted again. Bicarb ion is CO-TRANSPORTED into interstitium with more Na+.
  • Na+ channel also in apical membrane.

When Na+ in PCT cell. It moves into interstitium through Na+/K+ ATPase. (and Na+/Bicarb co-transporter).

Water follows Na+.
Oncotic pressure of the blood also draws blood in.

182
Q

How is the fluid tubule made hypoosmolar by the ascending limb of the loop of Henle?

A
  • Ascending limb is not permeable to water
  • Apical membrane has Na+/K+/2Cl- symporter
  • N+/K+ ATPase on basal membrane
  • K+/Cl- co-transpprter removes sodium and potassium ions from cell

The sodium and chloride ions create a concentration gradient, which drives the apical co-transporter.

The active reabsorption of NaCl unaccompanied by water reduces osmolarity of tubular fluid and makes the interstitial fluid of the medulla hypertonic.

183
Q

Describe the countercurrent multiplier effect

A

As sodium is being moved into the interstitium when it reaches the ascending limb, the osmolarity of the tubular fluid decreases.
The longer the loop of Henle, the more concentrated the interstitium becomes as you travel down the medulla.

184
Q

What does the distal collecting tubule do?

A

Na+/Cl- cotransporters on the apical membrane further dilutes the tubular fluid. Transport is driven by Na+/K+ ATPase in the basolateral.

185
Q

What are the effects of aldosterone on collecting duct cells?

A
  • Insert sodium and potassium channels in the apical membrane
  • Increase function, and addition of basal Na+/K+ ATPase
186
Q

What are the classes of diuretics:

A
  1. Osmotic diuretics
  2. Carbonic anhydrase inhibitors
  3. Loop diuretics
  4. Thiazides
  5. Potassium sparing diuretics
187
Q

What are the most important groups of diuretics?

A
  • Loop diuretics (most powerful)
  • Thiazides
  • Potassium-sparing diuretic
188
Q

Explain how osmotic diuretics alter the ionic composition, volume and osmolarity of the urine.

A

They are pharmacologically inert compounds such as Mannitol - that is filtered by the glomerulus, but not reabsorbed. This increases the osmolarity of the tubular fluid (and thus of urine).

Therefore increasing volume of urine as less water is reabsorbed at the PCT, Descending loop of Henle and Collecting duct.

189
Q

Give examples of osmotic diuretics

A

Mannitol

190
Q

What are the uses of osmotic diuretics?

A

Not generally used for kidney-related issues. Instead used to increase osmolarity of the plasma to treat:

  • oedema
  • high intra-cranial and intra-occular pressure
191
Q

Explain how carbonic anhydrase inhibitors alter the ionic composition, volume and osmolarity of the urine

A

They are only weak diuretics. By blocking carbonic anhydrase, you decrease the amount of protons available to drive the Na/H exchanger in the PCT –> reducing water reabsorption.
Increased bicarbonate delivery to the DCT causes increased K+ loss.

Ultimately this increases tubular osmolarity and thus decreases H2O reabsorption.

192
Q

What are the uses of carbonic anhydrase inhibitors?

A
  • treat metabolic alkalosis (due to loss of bicarbonate ions)
  • renal stone prophylaxis (promotes excretion of uric acid)
  • reduce IOP (treat glaucoma)
193
Q

What are the unwanted effects of carbonic anhydrase inhibitors

A
  • hypokalaemia

- metabolic acidosis

194
Q

Give an example of a carbonic anhydrase inhibitor

A

Acetazolamide

195
Q

Explain how loop diuretics alter the ionic composition, volume and osmolarity of the urine

A

They act on the ascending limb, blocking the Na+/K+/2Cl- co-transporter. This leads to less Na+ and Cl- reabsorption in ascending limb.

The loss of K+ recycling means there is a positive lumen potential in the tubule lumen, increasing excretion of Ca2+ and Mg2+.

Increased delivery of Na+ to distal tubule causes K+ loss.

Most powerful diuretic (produces most urine volume) as disrupts countercurrent multiplier effect.

196
Q

Give an example of a Loop Diuretic, and it’s clinical uses.

A

Frusemide is used to treat:

  • Pulmonary, renal, hepatic or cerebral Oedema due to heart failure.
  • Moderate hypertension
  • Hypercalcaemia
  • Hyperkalaemia
197
Q

What are the unwanted effects of loop diuretics?

A
  • Hypovolaemia and this hypertension
  • Hypokalaemia
  • Metabolic acidosis
198
Q

Explain how thiazides alter the ionic composition, volume and osmolarity of the urine

A

Mainly work on distal tubule thus cannot have a large impact on fluid retention.

They bind to the Na+/Cl- co-transporter decreasing Na+ reabsorption and thus H20.

Again increases delivery of Na+ to DCT thus causing K+ loss.

Thiazides also increase Mg2+ loss and Ca2+ REABSORPTION

199
Q

Give an example of a Thiazide, and it’s clinical uses.

A

Bendroflumethiazide. Used to treat:

  • Cardiac failure
  • Hypertension (also causes vasodilation)
  • Idiopathic hypercalciuria
  • Nephrogenic diabetes insipidus (paradoxical I know)
200
Q

What are the unwanted effects of thiazides?

A
  • hypokalaemia
  • metabolic alkalosis
  • diabetes mellitus as inhibits insulin secretion
201
Q

What are the potassium sparing diuretics?

A
  • Spironolactone is a Aldosterone receptor antagonist

- Amiloride is an inhibitor of aldosterone-sensitive Na+ channels

202
Q

Explain how potassium sparing diuretics alter the ionic composition, volume and osmolarity of the urine

A
  • inhibit Na+ reabsorption (and concomitant K+ secretion) in late DCT
  • Increase in tubular fluid osmolarity and thus decrease in H2O reab
  • does NOT increase K+ excretion
203
Q

What are the uses of potassium sparing diuretics?

A
  • Administered with K+ losing diuretics
  • Hypertension/ Heart failure
  • Hyperadosteronism
204
Q

What are the unwanted effects of potassium sparing diuretics?

A
  • hyperkalaemia and thus metabolic acidosis

- spironolactone can cause gynaecomastia, menstrual disorders and testicular atrophy

205
Q

What are the two major forms of IBD?

A

Ulcerative colitis and Chron’s disease

206
Q

What are the similarities between Ulcerative Colitis and Chron’s disease?

A
  • They are both autoimmune disorders believe to be triggered by an abnormal response to bacterial lipopolysaccharide by the mucosal immune system.
  • This leads to uncontrolled inflammation causing physical damage to the epithelium and leakiness of right junctions.
207
Q

Which of the inflammatory bowel diseases has the greatest genetic input?

A

Chron’s disease more than Ulcerative Colitis.

208
Q

Which of the inflammatory bowel diseases in more common in Europe?

A

There is a higher incidence of Ulcerative Colitis than Chron’s disease

209
Q

What are the differences in the immunology between Ulcerative Colitis and Chron’s disease?

A
  • Chron’s disease is Th1 mediated. Therefore characterised by release of INF-y, TNF-a, IL-17 and IL-23. Also associated with florid T-cell expansion with defective apoptosis
  • Ulcerative Colitis is Th2 mediated. Therefore characterised by IL-15 and IL-13 release. Associated with n limited clonal expansion with normal T-cell apoptosis.
210
Q

What are the clinical differences between Ulcerative Colitis and Chron’s disease?

A

Chrons:

  • affects any part of the GI
  • patchy inflamed areas
  • surgery not always curative

UC:

  • affects mainly rectum, spreading proximally
  • continuous inflamed areas
  • surgery curative
211
Q

What are the clinical features and symptoms of IBD?

A
  • Diarrhoea
  • Blood and/or mucous in stools
  • Skin rash
  • Right iliac fossa mass/pain
  • Primary sclerosing cholangitis
  • Mouth ulcers
  • Anaemia
  • Uveitis
  • Fever and sweats
  • Jaundice
  • Abdominal pain
  • Weight loss
  • Arthritis arthralgia
212
Q

What are the two parts of managing IBD?

A
  • Treatment of active disease

- Maintenance of remission

213
Q

What are the three types of therapies in treating IBD?

A
  • Supportive therapies
  • Therapies to reduce inflammation and maintain remission
  • Biological therapies
214
Q

When are supportive therapies for IBD used, and what do they involve?

A

Used as ACUTE medical treatment during an attack of CD/UC. It involves:

  • Fluid/electrolyte replacement
  • Blood transfusion/oral iron
  • Parenteral nutritional support
  • Antibiotics as infection is common
215
Q

What supportive therapies in IBD are used to maintain remission?

A

Enteric nutrition (although weak evidence)

216
Q

List the three major classes of drug used to treat the symptoms of inflammatory bowel disease and name one example of each.

A
  1. Aminosalicylates such as mesalazine
  2. Glucocorticoids such as prednisolone
  3. Immunosuppresives such as azathioprine
217
Q

What is the use of aminosalicylates in the treatment of IBD?

A

They are the first line treatment for UC (treatment of flares and remission). Not effective in CD, but may help in surgically-induce maintaince of remission.

218
Q

What is the mechanism by which aminosalicylates treat IBD?

A

5-Aminosalicyclic acid (mesalazine) is the active part of the aminosalicylates (Olsalazine has two).

Mesalazine is absorbed in the small bowel and colon (but works throughout GI tract).

Mechanism of anti-inflammatory action:

  • Inhibition of Th2, TNF-a, and PAF
  • Decreased Ab secretion
  • Non-speific cytokine inhibition
  • Reduced cell migration
  • Localised inhibition of immune response
219
Q

What are the uses of glucocorticoids in the treatment of IBD?

A

Decline in use for UC as aminosalicyclates are more effective.
Drug of choice for inducing remission in Chron’s Disease patients.

220
Q

What are the mechanisms by which glucocorticoids maintain remission in CD patients?

A

Anti-inflammatory and immunosuppressive actions:

  • intracellular GC receptor migrates to the nucleus acting as a positive transcription factor to increase expression of anti-inflammatory genes, and negative transcription factor to decrease expression of pro-inflammatory genes
  • reduce activation and influx of pro-inflammatory cells
  • reduce production of mediators which cause vasodilation, fluid exudation, further inflammatory cell recruitment and tissue degradation
  • reduce in antigen presentation, cell proliferation and clonal expansion.
221
Q

What are the side-effects of glucocorticoids in the treatment of Chron’s disease?

A
  • osteoporosis
  • increased risk of gastric ulceration
  • suppression of HPA axis
  • type II diabetes
  • hypertension
  • susceptibility to infection
  • skin thinning and bruising
  • slow wound healing
  • muscle wasting and buffalo hump
222
Q

What are the strategies in reducing the side-effects of glucocorticoids in the treatment of Chron’s disease?

A
  • topical administration through fluid or foam enemas or suppositories
  • use a low dose in combination with another drug
  • use of tapered dose
  • use drugs with better therapeutic induces (like fluticasone)
  • administer drugs that are degraded locally, preventing access to systemic circulation
223
Q

What is the mechanism by which Azathioprine is used to treat IBD?

A

A prodrug activated by gut flora to 6-mercaptopurine which is a purine anaglonge, interfering prune biosynthesis, DNA synthesis and cell replication (dampening down inflammatory response). It therefore impairs:

  • cell and anti-body mediated response
  • lymphocyte proliferation
  • mononuclear cell infiltration
  • synthesis of antibodies
  • enhanced T-cell apoptosis
224
Q

Nearly 10% of patients need to stop treatment of Azathiproine in the treatment of IBD. What side effects does it cause?

A
  • Pancreatitis
  • Bone marrow suppression
  • hepatotoxicity
  • increased risk (x4) of lymphoma and skin cancer
  • as it is metabolised by xanthine oxidase do not administered with gout treatment (allopurinol) which would cause build-up of 6-mercaptopurine –> blood disorders
225
Q

How can biologic therapies treat IBD?

A

Infliximab is an anti-TNF-a antibody. Potentially curative in Chron’s Disease! Safety profile is also good, although some patients develop serious side effects.

Some effectiveness in treatment of UC

226
Q

What are the adverse effects associated with infliximab in the treatment of IBD?

A
  • 4-5x increase in incidence of TB and other infections
  • increased risk of septicaemia
  • worsening of heart failure
  • increased risk of demyelinating disease
  • increased risk of malignancy
227
Q

What is an opiate, and an opioid

A

An opiate is an alkaloid derived from the poppy. An opioid is a compound that acts like morphine, but which does not resemble morphine chemically.

228
Q

List the opiates

A

Morphine, codeine and phenathene

229
Q

What are the types of opioids?

A
  • endorphins
  • enkephalins
  • dynorphins
  • synthetic opiates
230
Q

What key structure is present in opiates?

A

The tertiary nitrogen (as it is important in affinity of the molecule to the receptor)

231
Q

How is the structure of morphine different from the structure of heroin?

A

Heroin has two acetyl groups instead of two hydroxyl groups at positions 3 and 6

232
Q

Why is heroin more potent than morphine?

A

It is much more lipophilic allowing it to penetrate the brain more effectively and rapidly for immediate effects. [ even though nearly all heroin is converted to morphine]

233
Q

How is the structure of codeine different from morphine?

A

Codeine is also called 3-methylmorphine. It has a methyl group instead of a hydroxyl group in position 3.1

234
Q

Describe the pharmacokinetics of morphine

A
  • Oral administration with rapid onset of action (peak at 30 mins)
  • Only 40-50% is absorbed.
  • Has a poor lipid solubility and is highly plasma protein bound
  • Ionised at physiological pH reducing its ability to cross membranes
  • rapidly conjugated and metabolised in the liver to morphine-6-glucoronide
  • excreted in urine
235
Q

Rank the opioids in terms of their lipid solubility

A

Methadone/fentanyl&raquo_space; heroin > morphine

236
Q

Why is codeine less potent than morphine?

A

It is a prodrug. Only 5-10% of codeine is converted to morphine by enzyme CYP2D6 (o-dealkylation). However, this enzyme is slower than CYP3A4 which deactivates codeine. Hence it is metabolised faster than it is activated.

237
Q

What are the endogenous opioid peptides?

A

Endorphins, Enkephalins, dynoprhins/neoendorphins

238
Q

Where are Mu, Detla and Kappa Opiate receptors found? What are their main functions?

A

Mu - pituitary, hypothalamus, thalamus, brainstem, 20+ locations; Analgesia, stress response, euphoria
Delta - Nucleus Acc, cerebral cortex and amygdala; Unknown function
Kappa - Limbic and diencephalic structures; Appetite control and temperature regulation

239
Q

What endogenous opioids act on the different opioid receptors?

A
  • Endorphins act on Mu (mainly, also delta)
  • Enkephalins act on Delta (mainly)
  • Dynorphins act on Kappa
240
Q

What is the mechanism by which opioid receptors work?

A

G-protein coupled receptors that have three effects:

  1. Reduced activity of Adenyl Cyclase (decreased cAMP)
  2. Increased K+ influx resulting in cell hyper polarisation
  3. Decreasing entry of Ca2+ ions thus decreasing neurotransmitter release
241
Q

What are the main pharmacological effects of opioids?

A
  1. Analgesia
  2. Euphoria
  3. Anti-tussive
242
Q

What are the main side-effects of opioids?

A
  1. Respiratory (medulla) depression
  2. Stimulation of chemoreceptor trigger zone (nausea/vomiting)
  3. Pupillary constriction
  4. G.I. disturbance
  5. Histamine release
243
Q

Outline the ways opioids cause analgesia

A
  1. Decrease pain perception
  2. Increase pain tolerance
  3. Affect central pain perception
244
Q

Describe the ascending pathway of pain

A

Nociceptors synapse with spinothalamic neurones in the dorsal horns. This carries the impulse to the thalamus. The thalamus acts as the central integrating centre. It relays painful information to the cortex (as well PAG area)

245
Q

Explain the role of the PeriAqueductal Grey area of the brain in central pain tolerance

A

[In the midbrain]

  • Receives excitatory input from thalamus. Receives inhibitory and excitatory input from cortex and hypothalamus.
  • Output to excite the NRM which dampens pain perception.
246
Q

Explain the role of the Nucleus Raphe Magnus of the brain in central pain tolerance

A
  • Receives excitatory input from PAG area and NRPG
  • Inhibitory output to the dorsal horn by:
    1) Projecting directly onto synapse between nociceptor and spinothalamic neurone to inhibit post-synaptic potentials
    2) Synapse with short interneurones in the substantia gelatinosa in the dorsal horn. This processes the information and determines the levels of inhibition that needs to be projection onto the sensory neurones
247
Q

Describe the immediate auto-regulatory circuit of pain perception

A

Spinothalamic neurones also synapse with the Nucleus Reticularis Para Gigantocellularis before it reaches the thalamus.
This sends excitatory neurones to the NRM which dampens pain perception.

248
Q

How is pain perception dampened when the flight/fight response is activated?

A

The Locus Correleous nucleus uses NA to down regulate the pain response by directly acting on spinal chord neurones.

249
Q

How do opioids reduce pain perception, and increase pain tolerance?

A

Reduce pain perception:

  • huge concentration of mu and kappa opioid receptors within spinal chord as opioids are depressants, they decrease ability of information to be passed to the spinothalamic neurones.
  • decrease activation of the nociceptors themselves

Increase tolerance:
- normally GABAergic interneurones inhibit PAG and NRPG to switch off descending inhibition. Opioid receptors on the GABAergic neurones inhibit these neurones –> decreased GABA release –> decrease inhibition of PAG and NRPG –> increase descending inhibition.

250
Q

How do opioids cause euphoria?

A

Mu receptors on GABA interneurones that project to mesolimbic dopaminergic neurones. Inhibiting them, disinhibits the dopaminergic neurones, causing greater release of dopamine into the Nucleus Accumbens.

251
Q

How are opioids antitussives?

A

Sensory receptors (Ach/NK C-fibres) relate irritant information to the CNS via the vagus nerve. This is processed in the cough centre in the dorsal raphe nucleus (DRN), where there is a high concentration of serotonin receptors (5HT1aR).

Serratonin is an anti-tussive. Opioids inhibit the 5HT1-aR, increasing the amount of serotonin available.

Opioids also reduce the firing rate of sensory neurones by inhibiting the release of ACh and neurokinin.

252
Q

How do opioids cause respiratory depression?

A
  • Central chemoreceptors sample the blood for PcCO2 levels relaying this information to the medullary control centre to alter breathing rate
  • Opioids act on mu2 receptors to suppress the central chemoreceptors –> reduction in signals to the medullary control centre and decreasing breathing rate
  • Opiates have an inhibitory effect on the intrinsic medullary rhythm
253
Q

How do opioids cause nausea and vomiting?

A
  • Opioids act centrally on the Chemoreceptor Trigger Zone via mu receptors to suppress GABA neurones which normally inhibit the CTZ.
  • CTZ relays this to the medullary vomiting centre to stimulate the vomiting reflex
  • Opioids can interfere with the vestibular apparatus, causing mismatch between the information between the vestibular apparatus and other sensory information –> nausea
254
Q

How do opioids cause pin-prick pupils?

A

Large number of mu receptors on the Edinger-Westphal nucleus, which projects parasympathetic neurones to the eye, stimulating pupil constriction.

255
Q

How do opioids cause reduced GI motility?

A
  • Opioid receptors in the enteric nervous stem reduce gastric motility, gastric emptying and impairs water reabsorption.
256
Q

How do opioids cause histamine release?

A

Mediated through protein kinase A. Causes skin mast-cells to release histamine.

257
Q

How do opioids cause tolerance and dependence issues when withdrawn?

A
  • Tolerance is due to receptor desensitisation to opiates. Normal levels don’t have intended effects
  • Dependence: opioid withdrawal is associated with psychological craving and physical withdrawal symptoms (compensatory up-regulation of adenyl cyclase –> overactive cellular activity without opioids)
258
Q

How can an opioid overdose be treated?

A

I.V Naloxone (opioid receptor antagonist). It has similar structure to morphine but has a 3 carbon side chain on its tertiary amine.

259
Q

What percentage of people develop serious ADRs?

A

6.7%

260
Q

What are the three ways ADRs are classified?

A
  1. Onset
  2. Severity
  3. Type
261
Q

How can the onset of an ADR be described?

A
  • Acute is defined within an hour
  • Subacute is defined between 1-24 hours
  • Latent is defined as greater than 2 days
262
Q

How can the severity of an ADR be described?

A
  • mild requires no change in therapy
  • moderate requires change in therapy, additional treatment and/or hospitalisation
  • severe is disabling or life-threatening
263
Q

How can the type of ADR be described?

A
  • Type A: extension of pharmacological effect
  • Type B: iodosynchratic or immunologic reactions (includes allergy and psudoallergy)
  • Type C: associated with long-term use involving dose accumulation
  • Type D: delated, sometimes dose dependent (such as cancer or teratogenicity)
  • Type E: withdrawal reactions (opioids), rebound reactions (clonidine removal), adaptive reactions
264
Q

What drugs cause different types of hypersensitivity reactions?

A
  • Peniciliins often cause type-1 - anaphylactic shock
  • methyldopa can cause haemolytic anaemia (type 2)
  • procainamide can cause SLE (type 3)
265
Q

Give examples of psuedoallergic reactions

A
  • Apirins/NSAIDs can cause bronchospasm by blocking COX enzymes in the bronchial smooth muscle, diverting arachidonic t make leukotrienes
  • ACE inhibitors can cause cough and angioedema, due to accumulation of bradykinin
266
Q

What is the DoTS classification of ADRs?

A
  • Dosage
  • Timing
  • Susceptibility
267
Q

How can ADRs be detected?

A
  • subjective methods such as patient complaints
  • objective methods such as direct observation, abnormal findings in physical examinations, lab results or other diagnostic procedures.
268
Q

Describe the use of the Yellow Card Scheme

A

The Yellow Card Scheme was introduced after the thalidomide disaster to detect ADRs. For established drugs, only serious ADRs should be reported. For ‘black triangle’ (newly licensed) drugs, any suspected ADRs should be reported.

269
Q

What are the types of drug-drug interactions?

A
  1. Pharmacodynamic e.g receptor site occupancy
  2. Pharmacokinetic (ADME effects)
  3. Pharmaceutical (outside body)
270
Q

What type of pharmacodynamic interactions can drugs have?

A
  • Additive - similar effects by different mechanisms
  • Synergistic - produce a greater response together
  • Antagonistic - two drugs that counteract eachother
271
Q

How can drug-drug interactions have effects on drug absorption?

A

Drugs can interact to form chelates. For example tetracyclines, quinolone antibiotics etc.

272
Q

How can drug-drug interactions have effects on drug distribution?

A
  • competition for protein or tissue binding sites. A drug bound to albumin could be displaced by another drug, increasing its bioactivity.
  • Warfarin is 99.9% bound, anything that displaces warfarin makes a huge difference
273
Q

How can drug-drug interactions have effects on drug metabolism?

A
  • CYP450 inhibitors and inducers
  • inhibition is very rapid
  • inducers are slow as it requires transcription of new drugs.
274
Q

Differentiate between Nausea and Vomiting

A

Nausea is the subjective, unpleasant sensation in the throat and stomach, often preceding vomiting.
Vomiting is the forceful propulsion of stomach contents out of the mouth.

275
Q

What symptoms can often precede nausea and vomiting?

A

Salivation, sweating and increased heart rate

276
Q

Describe the process of vomiting

A
  • stomach, oesophagus and associated sphincters are RELAXED; tension in gastric and oesophageal muscles trigger afferent nerve impulses
  • contraction of upper small intestine, pyloric spinster and pyloric region of the stomach moves the contents of the DUODENUM and upper JEJUNUM into the body of the fundus of stomach
  • lower and upper oesophageal sphincters RELAX
  • vomiting may/may not occur
277
Q

What are the consequences of severe vomiting?

A
  • dehydration
  • loss of gastric hydrogen –> hypochloraemic metabolic alkalosis
  • hypokalaemia (as kidneys secrete potassium to obtain more protons)
278
Q

Where is the vomiting centre located?

A

Medulla

279
Q

Outline the four pathways in nausea/vomiting

A
  1. Stimuli from peripheral organs activates CTZ as well as Vomiting centre directly.
  2. Stimuli from motion activates CTZ as well as vomiting centre directly
  3. Endogenous toxins and Drugs stimulate the Chemoreceptor Trigger Zone which stimulates Vomiting Centre. Alternately can stimulate visceral afferents (Pathway 1)
  4. Cognitive centres can activate the vomiting centre
280
Q

Using what receptors and transmitters does stimuli from peripheral organs activate the Vomiting Centre?

A

Stimuli such as GI mucosal injury causes the release of 5-HT (a serotonin precursor).

  • Visceral afferent pathway: visceral afferent nerves such as vagus nerve detect 5-HT by 5-HT(3) receptors, transmitting the signal to the nucleus solitarius. The nucleus solitarius then transmits the signal to the Vomiting Centre via mACh and H1 receptors.
  • Chemoreceptor Trigger Zone also has 5-HT(3) receptors and will send impulses to the vomiting centre via mAChR and H1 receptors.
281
Q

Using what receptors and transmitters does stimuli from motion activate the Vomiting Centre?

A
  • Labyrinth sends impulses to the brain via the vestibular nuclei (mAChR and H1 receptors). Vestibular nucleus then sends impulses to the CTZ and to the Vomiting Centre
282
Q

Using what receptors and transmitters does stimuli from endogenous toxins and drugs activate the Vomiting Centre?

A

They cause the release of EMETOGENIC AGENTS such as 5-HT, prostanoids, free radicals etc into the blood. This will either activate:

  • CTZ directly via DA2R (dopamine2 receptors) or 5-HT(3)R which relays the information to the Vomiting Centre
  • Visceral afferent pathways to Vomiting Centre via mAChR and H1R
283
Q

Using what receptors and transmitters does stimuli from cognitive centres activate the Vomiting Centre?

A

Pain, repulsive sights/smells, emotions etc activate the vomiting centre via H1 or mAChR.

284
Q

Name 4 main anti-emetic drug and their specificities

A
  1. Promethazine is a mixed antagonist with potency to H1>M>D2 receptors
  2. Metoclopramide and Domperidone are dopamine receptor antagonists (although have a slight affinity to H1&raquo_space; mAChR)
  3. Hyoscine is an mAChR antagonist
  4. Ondansetrone is a 5-HT(3) receptor antagonist
285
Q

How does Promethazine act as an anti-emetic?

What is it indicated for?

A

Promethazine is a mixed antagonist with potency to H1>M>D2 receptors.
- It acts centrally in the vestibular nucleus, NTS, higher centres and Vomiting centre to block transmission.

Therefore used in:

  • motion sickness (prophylactically)
  • hyperemesis gravidarium (preggers humans)
  • pre and post-operatively as has sedative properties as well as anti-muscarinic to dry secretions. Anaesthetia can also cause nausea
  • night sedation for insomnia, anaphylactic emergency, relief of allergy
286
Q

What are the unwanted effects of promethazine?

A
  • dizziness
  • tinnitus
  • fatigue
  • sedation
  • convulsions
  • anti-muscarinic (dry as bone etc)
287
Q

How do Metoclopramide and Domperidone act as an anti-emetics?
What are they indicated for?

A

Metoclopramide and Domperidone are dopamine receptor antagonists (although have a slight affinity to H1&raquo_space; mAChR)

  • they act on the CTZ
  • also has pro kinetic effects on GI tract, decreasing chances of vomiting

Indicated for:

  • Uraemia
  • Radiation sickness and chemotherapy
  • GI Disorders
  • Reducing nausea from Parkinson’s treatment
288
Q

What are the unwanted effects of Metoclopramide and Domperidone?

A
  • Only metoclopramide has CNS side-effects as domperidone doesn’t cross the BBB. Causes drowsiness, dizziness and anxiety. Also has extrapyramidal reactions which are parkinson-like symptoms (common in children)
  • Both can cause hyperprolacintaemia –> galactorrhea and hypogonadism
289
Q

How does Hyoscine act as an anti-emetic?

What is it indicated for?

A 
Muscarinic receptor antagonist.
It acts on the vestibular nucleus and CTZ --> very effective anti-emetic as blocks activation of vomiting centre. 
Used to:
- prevent motion sickness
- operative premedication
290
Q

What are the side-effects of Hyoscine?

A
  • Hot: decreased sweating and thermoregulation
  • Dry: decreased secretions
  • Blind: mydriasis and cycloplegia
  • Mad: drowsiness, CNS effects
291
Q

How does Ondansetron act as an anti-emetic?

What is it indicated for?

A

5-HT3 receptor antagonist
- acts to block transmission from visceral afferents as well as CTZ

Indicated in treating:

  • chemotherapy and radiation sickness
  • post-operative nausea and vomiting
292
Q

What are the side-effects of Ondansetron?

A

Headache, sensation of flushing/warmth and constipation

293
Q

What are the protective and potentially damaging factors secreted into the GI tract?

A

Protective:

  • mucous production from gastric mucosa creating a GI mucosal barrier
  • bicarbonate ion production, as the HCO3- ions get trapped in the mucus increasing the pH to 6-7 near the mucosal surface.

Damaging:

  • HCl secretion by parietal cells
  • Pepsinogen secretion from chief cells
294
Q

What causes mucous and bicarbonate ion production from the GI tract?

A

Prostoglandins

295
Q

What is the underlying pathophysiology in the formation of peptic ulcers?

A
  • IMBALANCE of protective and damaging factors –> DAMAGE to the inner lining of the GI tract.
296
Q

What is the difference in presentation between a gastric and duodenal ulcer?

A
  • gastric causes pain at mealtimes (when gastric acid is secreted)
  • duodenal ulcer pain is relieved by meal time as the pyloric sphincter is closed preventing HCl leaking
297
Q

What is the more common type of peptic ulcer?

A

Gastric (4:1)

298
Q

What are the factors that contribute to damaging the GI barrier?

A
  • Helicobacter pylori infection
  • Loss of prostaglandin synthesis therefore causing:
  • Increased gastric acid secretion and/or reduced bicarbonate production
  • decreased thickness of mucus layer
  • increase in pepsin type 1
  • decreased mucosal blood flow
299
Q

What leads to a loss of prostaglandin synthesis?

A
  • genetic predisposition
  • alcohol
  • diet
  • smoking
  • aspirin?
300
Q

What are the four types of drug treatments used to treat peptic ulcers?

A
  1. Antibiotics
  2. Gastric Acid Inhibitors
  3. Cytoprotective drugs
  4. Antacids
301
Q

What percentage of the world is infected with H.pylori? What is the significance of this?

A

50-80%
10% go on to produce peptic ulcers or neoplasia

100% of patients with duodenal ulcers are infected
80-90% of patients with gastric ulcers are infected.

302
Q

Describe the formation and release of gastric acid

A
  • Carbonic anhydrase converts CO2+H2O –> HCO3- and H+
  • HCO3- is exchanged for a Cl- ion from the BASAL membrane
  • Potassium and chloride diffuse out from the apical membrane freely
  • H+/K+ ATPase exchanges external potassium to pump out H+ against steep concentration gradient.
303
Q

What are the ultrastructural features of gastric parietal cells?

A
  • Vesicles storing H+/K+ ATPase

- Canaliculi

304
Q

What three stimuli lead to the fusion of vesicles containing H+/K+ ATPase to the apical membrane of the gastric parietal cells?

A
  1. Histamine (through H2 receptors) - most important
  2. Acetylcholine - PNS activity
  3. Gastrin - least important
305
Q

How does the vagus nerve and local enteric neurones stimulate the production of gastric acid?

A

They secrete ACh to act on parietal AND enterochromaffin cells. In response:

  • Parietal cells see an increase in [Ca2+] –> protein kinase pathway –> phosphorylation of vesicle –> insertion of K+/H+ ATPase pumps on apical surface of parietal cells
  • enterochromaffin cells see an increase in [Ca2+] –> release of histamine. This histamine acts on H2R on parietal cells, activating adenyl cyclase to increase [cAMP], which leads to phosphorylation of vesicles containing H+/K+ ATPase pumps.
306
Q

What types of drugs prevent gastric acid secretion? Give examples of specific drugs

A
  • Proton pump inhibitors such as Omeprazole
  • Histamine type 2 antagonists such as Cimetidine and Ranitidine
  • Antimuscarnic drugs - have little use as anti-ulcer drugs as has a wide variety of side-effects
307
Q

How does Omeprazole treat peptic ulcers?

A
  • Inhibits BASAL and stimulated gastric acid secretion by 90%
  • PPIs are irreversible, by binding covalently to the H+/K+ pump
  • Only active in stomach as it requires protonation, minimising side-effects
308
Q

How do Histamine type 2 antagonists treat peptic ulcers?

A
  • reduce Gastric Acid secretion by 60% as blocks pathway resulting in release of proton pumps to the apical membrane of the parietal cell
  • however, less effective than PPI as ACh and gastrin pathways can still stimulate release.
309
Q

Why is Ranitidine preferable than Cimetidine as a histamine antagonist?

A

It is longer acting

310
Q

What cytoprotective drugs can be used to treat peptic ulcers?

A
  • Sulcrafate is a polymer containing aluminium hydroxide and sucrose octal sulphate
  • Bismuth Chelate (similar to sulcrafate)
  • Misoprostol is a prostaglandin analogue
311
Q

How does sulcrafate treat peptic ulcers?

A
  • Sulcrafate is a polymer containing aluminium hydroxide and sucrose octal sulphate
  • It acquires a strong negative charge in the stomach, binding to charged groups such as proteins and glycoproteins to form a gel-like complex.
  • protects ulcer, limiting H+ diffusion to the damaged tissue to PROMOTE HEALING
  • increases local PROSTAGLANDIN PRODUCTION –> improved mucus and bicarb secretion
312
Q

How does Misoprostol treat peptic ulcers? What are the side-effects?

A

It is a prostaglandin analogue. It therefore increases mucous secretion and reduces gastric acid secretion.

Side effects include:

  • diarrhoea
  • abdominal cramps
  • uterine contractions (DONT USE IN PREGGERS HUMANS)
313
Q

How do antacids treat peptic ulcers?

A

They are mainly salts of Na+, Al3+, and Mg2+. They undergo neutralisation reactions to raise pH and reduce pepsin activity.

314
Q

When are antacids indicated?

A
  • non-ulcer dyspepsia
  • heart-burn
  • GORD
315
Q

What is triple therapy in the treatment of peptic ulcers?

A

The use of:

  1. (two) antibiotics
  2. Gastric acid inhibitors
  3. Cytoprotective drugs

together

316
Q

What are the problems associated with triple therapy?

A
  1. Compliance
  2. Development of resistance
  3. Adverse response to alcohol
317
Q

What is GORD?

A

Gastro-Oesophageal Reflex Disease results from reflux of stomach acid and duodenal contents into oesophagus, resulting in inflammation (oesophagitis)

318
Q

How is GORD treated?

A
  • mainly PPIs

- combined with drugs that increase GI motility and emptying of stomach

Year 2 LCRS (5 decks)

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