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ESA5 > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What is the therapeutic window?

A

range of drug concentrations where a clinically useful effect is exerted, but not a exerting toxic effect

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2
Q

Give examples of drugs with a narrow therapeutic window

A
  • Warfarin
  • Aminophylline
  • Digoxin
  • Aminoglycosides
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3
Q

What pharmacokinetic drug interactions can occur in absorption?

A

changes in gut motility

  • slow down eg. morphine leads to enhanced absorption
  • speed up eg. metoclopramide impairs absorption

drugs can bind to other drugs and reduce their absorption

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4
Q

What pharmacokinetic drug interactions can occur in distribution?

A

compete for a common binding site

displacement of object drug by precipitant drug -> total plasma [object drug] increased transiently

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5
Q

Why is the rise in [object drug] only transient after displacement by a precipitant drug?

A

increased elimination of object drug due to increased conc

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6
Q

What pharmacokinetic drug interactions can occur in metabolism?

A

induction or inhibition of CYP450

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7
Q

What pharmacokinetic drug interactions can occur in excretion?

A

changes in protein binding
- increases/deceases conc free drug. unbound drugs can be excreted

inhibition tubular secretion
- results in increased plasma conc

changes to urine flow/pH

  • acidic urine = alkaline drugs eliminated at faster rate
  • alkaline urine = acidic drugs eliminated at faster rate
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8
Q

Which drug groups commonly contribute to drug-frug interactions?

A
  • Anticonvulsants
  • Anticoagulants
  • Antidepressants
  • Antibiotics
  • Antiarrhythmics
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9
Q

What effects does induction of CYP450 enzymes have?

A

accelerates drug metabolism
increases toxicity of drugs that have toxic metabolites
more rapid elimination

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10
Q

How does induction of CYP450 occur at a cellular level?

A

implemented by increased transcription, translation or slower degradation of CYP450

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11
Q

How long does it take for induction of CYP450 to happen?

A

1-2 weeks

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12
Q

Give examples of drugs that induce CYP450

A
  • Phenytoin
  • Carbamazepine
  • Barbiturates
  • Rifampicin
  • Alcohol (chronic)
  • Sulphonylureas and St John’s Wort
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13
Q

What effects does inhibition of CYP450 enzymes have?

A

slows drug metabolism

increases action of drugs

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14
Q

How long does it take for inhibition of CYP450 to happen?

A

few days

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15
Q

Give examples of drugs that inhibit CYP450

A
  • Omeprazole
  • Disulfiram
  • Erythromycin
  • Valproate
  • Isoniazid
  • Cimetidine and ciprofloxacin
  • Ethanol (acute)
  • Sulphonamides
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16
Q

How does cranberry affect CYP450?

A

inhibits CYP2C9
reduces clearance of warfarin
raises INR and increases risk of haemorrhage

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17
Q

How does grapefruit affect CYP450?

A

inhibits CYP450
reduces clearance
eg. simvastatin

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18
Q

How does renal disease cause disease-drug interactions?

A

falling GFR

reduced clearance of renally excreted drugs

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19
Q

How do NSAIDs and ACEi affect the kidney?

A

reduce GFR

due to decreased blood flow

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20
Q

How does hepatic disease cause disease-drug interactions?

A

reduced activity CYP450
reduced clearance of hepatically metabolised drugs
longer half lives

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21
Q

How does cardiac disease cause disease-drug interactions?

A

reduced cardiac output
reduced organ perfusion
reduced hepatic and renal blood flow
reduced blood clearance

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22
Q

How does hypoalbuminaemia cause disease-drug interactions?

A

higher free drug levels
increased free drug conc
increased clearance

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23
Q

What is an ADR?

A

an unwanted or harmful reaction
which occurs after administration of a drug or drugs
and is suspected or known to be due to the drug

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24
Q

What is an on-target ADR?

A

an ADR due to the exaggerated therapeutic effect of the drug
most likely due to increased dosing or due to factors affecting the PK or PD

includes effects on the same receptor type but found in other tissues.

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25
Q

What is an off-target ADR?

A

an ADR involving the drug interacting with other receptor subtypes secondarily to the one intended for the therapeutic effect.

also occurs with metabolites that can subsequently act as a toxin and Inappropriate immune responses

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26
Q

Under what circumstances are drug interactions more likely to occur?

A

• polypharmacy
• ignorant, inappropriate or reckless prescribing
• patients at the extremes of age
o renal and hepatic insufficiency
o comorbidities
• multiple medical problems
• use of drugs with a narrow therapeutic index
o greater risk of toxicity
• drugs used ear their minimum effective dose
o greater risk of treatment failure if metabolism increased

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27
Q

What can alter the absorption of a drug into the GI system?

A 
gastrointestinal motility
splanchnic blood flow
molecular size
pH levels
presence of active transport systems
first pass metabolism
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28
Q

What is first pass metabolism?

A

any metabolism that occurs before the drug enters the systemic circulation

occurs within gut lumen, gut wall and in the liver

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29
Q

How are drugs metabolised in the gut lumen?

A

gastric acid

proteolytic enzymes

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30
Q

How is drug absorption affected by the gut wall?

A

P-glycoprotein efflux pumps drugs out of enterocyte and back into the lumen

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31
Q

Define bioavailability

A

the amount of drug which reaches the systemic circulation in an unchanged form (once overcome all barriers to its absorption) relative to that if it was administered via IV.

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32
Q

what is bioavailability affected by?

A 
drug preparation 
intestinal motility, 
food (lipid-soluble or water-soluble), 
age, 
first-pass metabolism.

therefore it varies between patients

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33
Q

What factors affect the distribution of a drug through the body?

A

lipophilic/hydrophilic
protein binding

also:
disease states
regional blood flow
specific receptor sites in tissues

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34
Q

If a drug is lipophilic, how does this affect it’s distribution?

A

it will move out of the plasma into tissues with a higher lipid content
reaches all body compartments and accumulate in fat

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35
Q

If a drug is lipid-insoluble, how does this affect it’s distribution?

A

the drug is mainly confined to the plasma an interstitial fluid

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36
Q

If a drug is not lipid soluble or is highly plasma bound, what does this mean for it’s volume of distribution and plasma concentration?

A

low Vd

therefore plasma concentration remains high

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37
Q

If the drug can diffuse out of the plasma compartments and pass into other fluid compartments, what does this mean for it’s volume of distribution and plasma concentration?

A

high Vd

plasma conc falls

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38
Q

If a drug is highly bound by tissue proteins, what does this mean for it’s volume of distribution and plasma concentration?

A

Vd becomes very high

large proportion of drug removed from fluid compartments
low plasma conc

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39
Q

Why are acute increases in Vd seen in sepsis?

A

increased vascular permeability

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40
Q

Describe Phase 1 drug metabolism in the liver

A

dependent on CYP450
catabolic
produces products that are chemically active

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41
Q

Describe Phase 2 drug metabolism in the liver

A

anabolic
involve conjugation
less pharmacologically active and less lipid-soluble products

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42
Q

What factors determine the rate of renal excretion of drugs?

A

GFR
passive tubular secretion
active tubular secretion

renal blood flow
plasma protein binding
tubular urinary pH

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43
Q

Why would a drug need to be monitored?

A
  • Zero-order kinetics
  • Long half life
  • Narrow therapeutic window
  • High risk of drug-drug interactions
  • Known toxic effects
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44
Q

How can steady state (CpSS) be calculated?

A

CpSS = dose rate / clearance

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45
Q

How can a loading dose be calculated?

A

Loading Dose (DoseL) = Vd x CpSS

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46
Q

How are acidic drugs actively secreted in the proximal tubule?

A

OAT
transports in negatively charged anionic form
can transport against electrochemical gradient

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47
Q

How are basic drugs actively secreted in the proximal tubule?

A

OCT
in their protonated cationic form
only down a electrochemical gradient

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48
Q

State some of the actions of insulin

A
  • Activates GLUT4 to relocate to the cell membrane, to increase uptake of glucose into cells
  • Inhibits glycogen breakdown and enhances uptake by liver and adipose tissue
  • Stimulates fatty acid synthesis for transport as lipoproteins and inhibits lipolysis in adipocytes
  • Inhibits proteolysis to reduce amino acid levels in the blood
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49
Q

What is the difference between type 1 and type 2 diabetes?

A

Type 1 = absolute insulin deficiency from destruction of β-cells in the pancreas; = “insulin-dependent diabetes”

Type 2 diabetes is due to insulin resistance and progressive insulin deficiency

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50
Q

What lifestyle changes can act to control diabetes a first?

A 
limiting fat intake
increasing proportion of complex carbohydrates
reduction in alcohol
smoking cessation
increase exercise
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51
Q

Give the name of a biguanide drug

A

metformin

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52
Q

Describe the mechanism of action of metformin

A
  • increasing cells sensitivity to insulin
  • reduces hepatic gluconeogenesis – primary effect
  • increased glucose intake and utilisation in skeletal muscle
  • reduced carbohydrate absorption from the intestine
  • increased fa oxidation
  • reduced circulating LDLs and VLDLs
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53
Q

Describe the pharmacokinetics of metformin

A 
oral administration
half-life 2-3 hours
no binding to plasma proteins
no metabolism
renal elimination
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54
Q

Why is metformin the first line therapy for type 2 diabetes?

A

can reduce HbA1c by 2%
does not stimulate appetite
weight neutral

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55
Q

What are metformin’s ADRs?

A

Gi disturbances

interferes with absorption of vitamin B12 in long term

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56
Q

Why I smetformin contraindicated in patients with compromised HRH function or respiratory disease?

A

risk of lactic acidosis

reduced tissue perfusion

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57
Q

Give an example of a sulphonylurea

A

gliclazide

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58
Q

Describe the mechanism of action of sulphonylureas

A

bind to and antagonise β-cells’ K+-ATP channel activity,
increases K+ concentration within the cell
leads to depolarisation.

increases Ca2+ ion entry into the cell
increases insulin release from β-cells.

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59
Q

Describe the pharmacokinetics of sulphonylureas

A

oral
bind to albumin - 99% affinity
metabolised in liver
excreted by kidneys

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60
Q

Why are sulphonylureas contraindicated in pregnancy?

A

can cross placenta and enter breast milk

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61
Q

Describe the ADRs of sulphonyureas

A

hypoglycaemia
stimulate appetite
weight gain

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62
Q

Give the names of two thiazolidinediones

A

Rosiglatazone

pioglatizone

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63
Q

Describe the mechanism of action of thiazolidinediones

A

agonistically bind to nuclear hormone receptor site the peroxisome proliferator-activated receptor-γ or PPAR- γ (mainly found in adipose tissue, but also in muscle and liver)
Activation of PPARγ regulates the transcription of several insulin responsive genes
results in increased insulin sensitivity in adipose tissue, liver, and skeletal muscle

There is differentiation of adipocytes, increased lipogenesis and increased uptake of fatty acids and glucose. It also promotes amiloride sensitive sodium ion reabsorption, which leads to fluid retention.

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64
Q

Describe the pharmacokinetics of thiazolidinediones

A 
oral
rapidly absorbed
99% albumin affinity
metabolised by CYP450
pioglatizone eliminated in bile
rosiglatoazobe renal elimination
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65
Q

Describe the ADRs of thiazolidinediones

A

liver toxicity
weight gain - increase in subcutaneous fat
fluid retention
osteopenia and increased fracture risk

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66
Q

State the mechanism of action of acarbose

A

reversibly Inhibits intestinal α glucosidase.
delays carbohydrate absorption from gut
reducing increase in blood glucose after a meal.

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67
Q

Describe the pharmacokinetics of acarbose

A

oral
poorly absorbed
metabolised by intestinal bacteria
some of the metabolites are absorbed and excreted into the urine

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68
Q

Describe the ADRs of acarbose

A

flatulence, loose stools and diarrhoea, abdominal pain and bloating

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69
Q

Describe the mechanism of action of Glucagon-like Peptide 1 (GLP1) Analogues

A

lowers blood glucose after a meal by:
increasing insulin secretion, -> increases peripheral glucose uptake
supressing glucagon secretion -> reduced hepatic glucose output
slowing gastric emptying.

So:
They reduce food intake and are associated with weight loss. They reduce hepatic fat accumulation.

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70
Q

Describe the pharmacokinetics of Glucagon-like Peptide 1 (GLP1) Analogues

A

SC twice daily

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71
Q

Describe the ADRs of Glucagon-like Peptide 1 (GLP1) Analogues

A

hypoglycaemia

gastrointestinal effects

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72
Q

Describe the mechanism of action of Dipeptyl-peptidase 4 (DPP4) Inhibitors

A

competitively inhibit DPP-4 - normally responsible for breakinf down GLP-1
increases endogenous GLP-1 concentration after eating.
GLP-1 stimulates insulin secretion

weight neutral

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73
Q

Describe the pharmacokinetics of Dipeptyl-peptidase 4 (DPP4) Inhibitors

A

oral
well absorbed
Saxagliptin metabolised by CYP450 to active metabolite
renal excretion

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74
Q

Describe the ADRs of Dipeptyl-peptidase 4 (DPP4) Inhibitors

A

nasopharyngitis
headache
Although infrequent, pancreatitis

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75
Q

How is gradation of glycaemic control achieved using exogenous insulins?

A

variation in pharmaceutical preparation

single amino acid substitutions

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76
Q

Describe a ‘pre-mixed’ insulin regime

A

injected twice a day, with morning and evening meals

mixture of short and long acting insulin

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77
Q

Describe a Basal Bolus insulin Regimen

A

intermediate/long lasting insulin to provide a basal level that extends overnight.
supplemented with short acting insulin injected with meals to provide acute response,

This involves injecting around 5 times a day yet does provide good flexibility and better control

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78
Q

Describe the action of short-acting insulin

A

onsets around 30min after injected
peak around 2-5h after injections
can be given just before a meal.

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79
Q

Describe the action of intermediate-acting insulin

A

onsets around 2h after injected
peak around 4-10h after injection
can be given as basal control

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80
Q

Describe the action of long-acting insulin

A

onsets around 5h after injected
peak around 8-30h after injection
can be given as basal control

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81
Q

Describe the treatment steps in type 2 diabetes

A

lifestyle
metformin
HbA1c >7% = sulphonylureas
HbA1c >7.5% = TZDs/insulin

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82
Q

What needs to be monitored during diabetes treatment?

A 
glycaemic levels
dietary habit
HbA1c
renal function
hepatic function
neurological function
cardiovascular function
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83
Q

State an anti-obesity lipase inhibitor drug

A

Orlistat

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84
Q

Describe the mechanism of action of orlistat

A

inhibits gastric and pancreatic lipase
decreases the breakdown of dietary fat
decreases fat absorption by about 30%. T

The loss of calories from decreased absorption of fat is the main cause of weight loss.

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85
Q

Describe the pharmacokinetics of orlistat

A

oral
minimal systemic absorption
mainly excreted in the faeces

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86
Q

Describe the ADRs of orlistat

A 
oily spotting,
 flatulence with discharge, 
fecal urgency,
increased defecation
Pancreatitis
liver injury 
interferes with the absorption of fat-soluble vitamins and β-carotene, as well as some drugs
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87
Q

State the names of some short-acting insulin drugs

A

Actrapid,
Humulin S,
Novorapid

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88
Q

State the names of some intermediate-acting and long-acting insulin drugs

A

Insulin Glargine,

Isophane insulin

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89
Q

What is the method of administration of insulin?

A

Subcutaneous injection

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90
Q

What levels should cholesterol, LDLs and HDLs be at?

A

Total cholesterol 5.0mmol/L or below
Fasting LDL 3mmol/L or below
HDL 1.2mmol/L or above

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91
Q

Give two examples of a statins

A

Simvastatin

Atorvastain

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92
Q

What is the mechanism of action of statins?

A

Inhibit HMG-CoA reductase in hepatocytes
Decreases hepatic cholesterol synthesis
Up regulates LDL receptor synthesis
Increases LDL clearance from plasma into hepatocytes

Reduce LDL

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93
Q

Give an example of a cholesterol lipase inhibitor

A

Ezetimibe

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94
Q

Describe the mechanism of action of ezetimibe

A

Blocks cholesterol transport protein NPC1L1 in brush border of intestine
Inhibits intestinal cholesterol uptake
Reduces dietary cholesterol reaching liver
Up regulates LDL transporter expression

Reduces circulating Cholesterol levels

NB does not affect absorption of fat soluble vitamins, TAGs or bile acids

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95
Q

Describe the pharmacokinetics of cholesterol lipase inhibitors

A

Metabolised in brush border to active metabolite
Repeated enterohepatic circulation
Slowly eliminated

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96
Q

Describe ADRs of cholesterol lipase inhibitors

A

Abdominal pain
Diarrhoea
Head aches

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97
Q

Give an example of a fibrate

A

Bezafibrate

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98
Q

Describe the mechanism of action of fibrates

A

Stimulate PPAR-alpha (Peroxisome proliferator-activated receptor-alpha)
Increases production of lipoprotein lipase
Increases hepatic LDL uptake

Lowers TAGs
Slightly Lowers LDL and raises HDL

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99
Q

Give examples of the ADRs of fibrates

A

Rhabdomyolysis resulting in AKI
GI upsets
Rash
Pruritis

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100
Q

What is the mechanism of action of nicotinic acid?

A

Inhibits hepatic VLDL secretion
Reduces circulating triglyceride and LDL
Raises HDL

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101
Q

What are the ADRs of nicotinic acid?

A

Flushing
Palpitations
GI disturbance

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102
Q

What levels should cholesterol, LDLs and HDLs be at?

A

Total cholesterol 5.0mmol/L or below
Fasting LDL 3mmol/L or below
HDL 1.2mmol/L or above

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103
Q

Give two examples of a statins

A

Simvastatin

Atorvastain

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104
Q

What is the mechanism of action of statins?

A

Inhibit HMG-CoA reductase in hepatocytes
Decreases hepatic cholesterol synthesis
Up regulates LDL receptor synthesis
Increases LDL clearance from plasma into hepatocytes

Reduce LDL

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105
Q

Give an example of a cholesterol lipase inhibitor

A

Ezetimibe

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106
Q

Describe the mechanism of action of ezetimibe

A

Blocks cholesterol transport protein NPC1L1 in brush border of intestine
Inhibits intestinal cholesterol uptake
Reduces dietary cholesterol reaching liver
Up regulates LDL transporter expression

Reduces circulating Cholesterol levels

NB does not affect absorption of fat soluble vitamins, TAGs or bile acids

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107
Q

Describe the pharmacokinetics of cholesterol lipase inhibitors

A

Metabolised in brush border to active metabolite
Repeated enterohepatic circulation
Slowly eliminated

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108
Q

Describe ADRs of cholesterol lipase inhibitors

A

Abdominal pain
Diarrhoea
Head aches

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109
Q

Give an example of a fibrate

A

Bezafibrate

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110
Q

Describe the mechanism of action of fibrates

A

Stimulate PPAR-alpha (Peroxisome proliferator-activated receptor-alpha)
Increases production of lipoprotein lipase
Increases hepatic LDL uptake

Lowers TAGs
Slightly Lowers LDL and raises HDL

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111
Q

Give examples of the ADRs of fibrates

A

Rhabdomyolysis resulting in AKI
GI upsets
Rash
Pruritis

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112
Q

What is the mechanism of action of nicotinic acid?

A

Inhibits hepatic VLDL secretion
Reduces circulating triglyceride and LDL
Raises HDL

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113
Q

What are the ADRs of nicotinic acid?

A

Flushing
Palpitations
GI disturbance

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114
Q

What serum levels need to be checked when taking statins and why?

A

transaminase - risk of liver failure

creatine kinase - risk of Myopathy and rhabdomyolysis

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115
Q

Describe the effects of drug interactions between statins and CYP inducers

A

decrease the plasma levels of statin

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116
Q

Describe the effects of drug interactions between statins and CYP inhibitors

A

increase the risk of myopathy and other side effects

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117
Q

How are statin used in primary prevention?

A

primary prevention of arterial disease in patients who are at high risk because of elevated serum cholesterol.

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118
Q

How are statin used in secondary prevention?

A

secondary prevention of MI and stroke in those who already have symptomatic atherosclerosis.

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119
Q

Describe the transport of oestrogens in the blood

A

most bound to albumin or sex-hormone binding globulin

2% travels as free hormone

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120
Q

How does oestrogen bind ot oestrogen receptors?

A

travels across cell membranes

binds to nuclear receptors - ERα and ERβ

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121
Q

What effect does oestrogen binding to its receptor cause?

A

the oestrogen receptors form dimers once oestrogen binds
activated steroid-receptor complex interacts with nuclear chromatin
initiates hormone-specific RNA synthesis.
results in the synthesis of specific proteins that mediate physiologic functions.

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122
Q

what effect does oestrogen have on progesterone?

A

Oestrogens induce PR expression in endometrial cells, so act to condition the endometrium

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123
Q

Describe the ligand-receptor interactions of progesterone

A

Progesterone binds to the dimeric progesterone receptor, PR,

induces secretory changes the endometrium

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124
Q

What are the effects of progesterone in females?

A

promotes the development of a secretory endometrium
high levels of progesterone inhibit the production of gonadotropin and, therefore, prevent further ovulation.
If conception takes place, progesterone continues to be secreted, maintaining the endometrium and reducing uterine contractions.
increases bone density
fluid retention

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125
Q

What are the side effects of progesterone?

A
  • Weight gain
  • Fluid retention
  • Acne
  • Nausea and vomiting
  • Irritability
  • Lack of concentration
    headache
    depression
    increased risk breast cancer
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126
Q

What are the systemic effects of oestrogen in females?

A
  • Mild anabolic
  • Sodium and water retention
  • Raise HDL, lower LDL
  • Decrease bone reabsorption
  • Improve blood coagulability
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127
Q

What are the side effects of oestrogen?

A
  • Nausea and vomiting
  • Water retention and peripheral oedema
  • Risk of thromboembolism and MI
  • Impaired glucose tolerance
  • Endometrial hyperplasia and cancer
    breast tenderness
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128
Q

Describe the pharmacokinetics of oestrogen

A

low oral bioavailability due to first pass metabolism
hydroxylated in liver by CYP450 , then subsequently glucuronidated or sulfated.
excreted into bile and then reabsorbed through the enterohepatic circulation
Inactive products are excreted in urine

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129
Q

Describe the pharmacokinetics of progesterone

A

rapid absorption orally
metabolised in liver by CYP450 - glucaronidation
short half life
excreted primarily by the kidney

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130
Q

What is the COCP?

A

oestrogens in combination with progesterone

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131
Q

Describe the mechanism of action of the COCP

A

Oestrogen inhibits secretion of FSH by –ve feedback at the anterior pituitary.
This supresses follicular development in the ovary.

Progesterone inhibits secretion of LH and therefore prevents ovulation.

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132
Q

What is the difference between monophasic and triphasic COCP?

A

mono = dose of oestrogen and progesterone is constant in the active tablets

tri = attempt to mimic the natural female cycle and most contain a constant dose of estrogen with increasing doses of progestin given over three successive 7-day periods

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133
Q

How should COCP be taken?

A

The combined pill is usually taken for 21 days followed by 7 placebo pill days. This causes a withdrawal bleed.

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134
Q

What is the POP?

A

progesterone only pill

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135
Q

what is the mechanism of action of POP?

A

cause cervical mucus thickening

preventing sperm movement into uterus

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136
Q

In which patients is POP commonly used?

A

offered to women for whom the COCP is contraindicated

e.g. risk factors for venous thromboemboli, smokers, or hypertensive.

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137
Q

How is POP taken?

A

at the same time each day, every day

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138
Q

What are the problems with POP?

A

less effective than COCP

may produce irregular menstrual cycles and spotting more frequently

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139
Q

What are the ADRs of COCP?

A 
increased risk of DVT
raising blood pressure
increased risk of gall stones, 
decrease glucose tolerance, 
nausea, 
weight gain (due to anabolic state or fluid retention)
increased risk of breast cancer
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140
Q

Describe the Drug interactions of COCP

A

CYP450 inducers (increase plasma clearance) and inhibitors (decrease plasma clearance)

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141
Q

Name some CYP450 inducers

A 
PCBRAS 
Phenytoin, 
Carbamazapine, 
Barbiturates, 
Rifampicin/rifabutin, 
Alcohol, 
Sulphonylureas/St John’s Wort
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142
Q

why is the dose of oestrogen kept to a minimum?

A

avoid excess risk of thromboembolism

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143
Q

How do broad-spectrum antibiotics affect plasma concentration of the COCP?

A

reduce efficacy of COCP
the effect they have on intestinal flora will reduce their re-uptake into the circulation (by lowering enterohepatic recycling)

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144
Q

What is the menopause?

A

cessation of menstrual periods

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145
Q

What is the perimenopause?

A

time shortly before the occurrence of the menopause

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146
Q

Why are sex steroids given in menopause?

A

to reduce the symptoms of the menopause

and to prevent osteoporosis

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147
Q

What is ERT?

A

just oestrogen given in menopause

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148
Q

what is HRT?

Why could this be better than ERT?

A

oestrogen + progesterone.

Reduces risk of endometrial carcinoma

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149
Q

Why is history of a hysterectomy important when prescribing HRT?

A

For women who have an intact uterus, a progestogen is always included with the estrogen therapy, because the combination reduces the risk of endometrial carcinoma associated with unopposed estrogen.

For women who have undergone a hysterectomy, unopposed estrogen therapy is recommended because progestins may unfavourably alter the beneficial effects of estrogen on lipid parameters

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150
Q

Describe the side-effects of HRT

A

increased risk of stroke
increases HDLs
increased risk venous thromboembolism
decreased resorption of bone

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151
Q

What is the difference between bacteriostatic and bacteriacidal drugs?

A

Bacteriostatic drugs arrest the growth and replication of bacteria, limiting the spread of infection

Bactericidal drugs kill bacteria

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152
Q

What is an MIC?

A

Minimum inhibitory concentration

lowest concentration of antibiotic that inhibits bacterial growth

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153
Q

What is MBC?

A

Minimum bactericidal concentration
lowest concentration of antimicrobial agent that results in a 99.9 percent decline in colony count after overnight broth dilution incubations

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154
Q

Which antibiotics affect DNA synthesis?

A

quinolones

folic acid antagonists

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155
Q

Which antibiotics affect protein synthesis?

A

aminoglycosides
macrolides
tetracyclines

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156
Q

Which antibiotics affect cell wall synthesis?

A

beta-lactams - (penicillins and cephalosporins)

glycopeptides

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157
Q

Give some examples of penicillins

A

Penicillin,
Amoxicillin,
Flucloxacillin,
Co-amoxiclav

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158
Q

Describe the mechanism of action of penicillins

A

bind to penicillin binding proteins in peptidoglycan cell wall
inhibit transpeptidation enzyme that cross-links peptidoglycan chains

inactivates inhibitor of autolytic enzymes
cell lysis occurs

bacteriacidal

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159
Q

Describe the antibacterial spectrum of penicillins

A

gram positive microorganisms have cell walls that are easily traversed by penicillins so are susceptible

Gram-negative microorganisms have an outer LPS envelope surrounding the cell wall that acts as a barrier to the water-soluble penicillins.

BUT gram-negative bacteria have proteins inserted in the lipopolysaccharide layer that act as water-filled channels (called porins) to permit transmembrane entry

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160
Q

How is the GI absorption of penicillins affected by food?

A

most incompletely absorebed
BUT amoxicillin almost completely absorbed

absorption decreased by food in the stomach, because gastric emptying time is lengthened, and the drugs are destroyed in the acidic environment

administered 30 to 60 minutes before meals or 2 to 3 hours postprandial.

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161
Q

How are penicillins excreted?

A 
organic acid (tubular) secretory system 
glomerular filtration.
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162
Q

State the ADRs of penicillins

A

hypersensitivity
diarrhoea
nephritis
neurotoxicity

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163
Q

Name some cephalosporins

A

Cefaclor,
Cefotaxime,
Aztreonam

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164
Q

Describe the mechanism of action of cephalosporins

A

bind to penicillin binding proteins in peptidoglycan cell wall
inhibit transpeptidation enzyme that cross-links peptidoglycan chains

inactivates inhibitor of autolytic enzymes
cell lysis occurs

bacteriacidal

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165
Q

How are cephalosporins administered?

A

most IV or IM

poor oral absorption

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166
Q

Which cephalosporins are readily able to cross the BBB?

A

ceftriaxone
cefotaxime

therefore used in meningitis

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167
Q

How are cephalosporins excreted?

A

tubular secretion and/or glomerular filtration

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168
Q

Describe the ADRs of cephalosporins

A

hypersensitivity reactions.
Nephrotoxicity
Diarrhoea common, leading to C. diff.

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169
Q

Name some tetracyclines

A

Tetracycline,
Doxycycline,
Oxytetracycline

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170
Q

Describe the mechanism of action of tetracyclines

A

enter into organisms by passive diffusion or energy dependant transport
organism accumulates drug
binds to 30S subunit of bacterial ribosome, blocking accses of amino-acyl tRNA
prevents translation
protein synthesis inhibited

bacteriostatic

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171
Q

Describe the antibacterial spectrum of tetracyclines

A

broad spectrum

gram +ve
gram -ve
Mycoplasma
Chlamydia

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172
Q

Describe the pharmacokinetics of tetracyclines

A 
oral
well absorbed (especially doxycycline)
cross placental barrier
metabolised in liver
excreted in bile
enterohepatic circulation
enter urine by glomerular filtration
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173
Q

What affects the absorption of tetracyclines in the gut?

A 
form complexes with metal ions, 
so absorption decreased in presence of:
dairy products
iron preparations
antacids
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174
Q

Can tetracyclines be given to pregnant or breast feeding women?

A

no
cross placenta and enter breast milk
deposited in fetal bone and teeth

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175
Q

Describe the ADRs of tetracyclines

A 
irritation gastric mucosa
depostioni n frug and bones
liver failure
phototoxicity - increased risk of burning in sunlight
vertigo
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176
Q

Name some aminoglycosides

A

gentamicin

neomycin

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177
Q

Describe the mechanism of action of aminoglycosides

A

orgs allow drug to enter cell
binds to 30S subunit before ribosome formation
interferes with assembly of functional ribosome
protein synthesis cannot be initiated

bactericidal

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178
Q

Describe the antibacterial spectrum of aminoglycosides

A

broad spectrum

some gram +ve
aerobic gram –ve

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179
Q

Describe the pharmacokinetics of aminoglycosides

A

IV or intrathecally
high conc in renal cortec and endolymph and perilymph of inner ear
no metabolism in host
excreted in urine by glomerular filtration

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180
Q

Describe the ADRs of aminoglycosides

A

ototoxicity
nephrotoxicity
paralysis

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181
Q

Can aminoglycosides be given to pregnant women?

A

no
crosses placenta
accumulates in fetal plasma and amniotic fluid

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182
Q

What needs to be monitored when taking aminoglycosides?

A

plasma concentration

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183
Q

Name some macrolides

A

Erythromycin,

Clarithromycin

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184
Q

Describe the mechanism of action of macrolides

A

irreversibly bind to 50s subunit
inhibiting translocation in protein synthesis

bacteriostatic

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185
Q

Describe the antibacterial spectrum of macrolides

A

erythromycin = similar to penicillins (gram +ve and gram -ve)

clarithromycin = similar to erythromycin, but also H influenae, Chlamydia and H pylori

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186
Q

Describe the pharmacokinetics of macrolides

A

oral or IV
good GI absorption

erythromycin = excreted in active form in bile and partial enterohepatic circulation. inactive form by kidneys
clarithromycin eliminated by kidneys

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187
Q

Describe the drug interactions of macrolides

A

inhibit CYP450

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188
Q

Describe the ADRs of macrolides

A

GI disturbance
jaundice
ototoxicity

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189
Q

Describe the mechanism of action of vancomycin

A

inhibits synthesis bacterial cell wall phospholipids and peptidoglycan polymerisation

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190
Q

Describe the antibacterial spectrum of vancomycin

A

gram +ve orgs
MRSA
Enterococci

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191
Q

Describe the pharmacokinetics of vancomycin

A

IV infusion
(oral in C. diff)
eliminated by glomerular filtration

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192
Q

Describe the ADRs of vancomycin

A 
fever
rashes
chills
phlebitis
ototoxicity 
nephrotoxicity
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193
Q

What determines bacterial killing?

A

time

concentration above the MIC

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194
Q

What is time-dependant killing?

A

major killing affect of an antibiotic depends on how long the drug is bound to the receptor

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195
Q

What is concentration-dependant killing?

A

major killing affect of an antibiotic depends on their concentration

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196
Q

Describe the steps of Influenza virus replication?

A
  • Binding and adsorption, facilitated by haemagglutinin glycoprotein surface molecule
  • endocytosis into the cell. ATP-driven entry into the endosome. Protons gain entry into the virus via an M2-ion channel. The fall in pH within the virus allows for the viral coat of the nucleocapsid to breakdown.
  • The viral RNA is synthesised and replicated to form viral proteins. The virus is then assembled within the cell
  • virus is released from the cell via budding. Neuraminidase is a glycoprotein antigen found in the viral membrane and enables the virus to leave the host cell.
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197
Q

What is the role of the Influenza protein haemagglutinin?

A

facilitates adhesion of virus to host cell

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198
Q

What is the role of the Influenza protein Neuraminidase?

A

Neuraminidase is a transmembrane viral protein which enables newly formed virions to escape from their host cell.

As the newly formed virus egresses from its host cell many re-attach to the sialic acid membrane glycoprotein residues on the cell membrane.
To get released and infect other host cells they need to break this bond. This is carried out by the viral neuraminidase.

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199
Q

What is the role of the Influenza M2 ion channel??

A

allows H+ ions to enter the endosome, causing the viral coat of the nucleocapsid to break down

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200
Q

Describe the differences between the Influenza virus classes

A

A - multiple host species, greatest severity, undergoes antigenic drift and shift

B - no animal host, low severity

C - common cold like

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201
Q

Name some M2 ion channel blockers

A

amantadine

rimantadine

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202
Q

Describe the mechanism of action of M2 channel blockers

A

blocking the M2 channels
prevents entry of H+ into endosome
inhibits viral uncoating,
inhibits of viral replication

203
Q

Which classes of influenza are M2 channel blockers effective in treating?

204
Q

Describe the ADRs of M2 channel blockers

A

dizziness,
GI disturbances
hypotension,

more serious complications include confusion, insomnia and dizziness

Rimantadine causes less CNS side effects as it does not cross BBB

205
Q

Name some neuraminidase inhibitors

A

zanamivir

ostelamivir

206
Q

Describe the mechanism of action of neuraminidase inhibitors

A

Neuraminidase inhibitors bind to neuraminidase and prevent newly formed virions detaching from the host cell.

207
Q

Which classes of influenza are neuraminidase inhibitors effective in treating?

208
Q

Can neuraminidase inhibitors be used for prophylaxis?

A

Zanamivir is given as an aerosol and has low bioavailability and can only be used for treatment of an already infected patient.

Oseltamivir is a prodrug and by contrast is well absorbed, with 80% bioavailability This enables it to be given orally for both treatment and prophylaxis.

209
Q

Describe the ADRs of neuraminidase inhibitors

A

GI disturbance (not zanamivir as administered orally)
headaches
nose bleed
irritation of airways - zanamivir

210
Q

what is inflamed in RA?

211
Q

what causes the inflammation in RA?

A

TH1 cells release rheumatic factor
stimulates macrophages to release I:-1 and TNFalpha
stimulates fibroblasts and osteoblasts to damage cartilage and bone by releasing metalloproteinases

212
Q

What is the purpose of DMARDs?

A

to halt and reverse the underlying processes of RA

213
Q

What is the mechanism of action of methotrexate in RA?

A

folic acid antagonist
inhibition of enzymes involved in purine metabolism
accumulation of adenosine within the cell.
Adenosine is released following cell injury
acts on GPCRs of inflammatory and immune cells
reduced activity of T-cells

214
Q

how is methotrexate administered?

A

oral, IV or IM

215
Q

describe the pharmacokinetics of methotrexate

A

50% protein bound
hepatic metabolism
renal excretion

216
Q

Describe the ADRs of methotrexate

A
  • Mucositis - pain and inflammation of the body’s mucous membrane.
  • bone marrow suppression,
  • hepatitis,
  • cirrhosis,
  • increased infection risk
  • acts as teratogenic and abortifactant
217
Q

Describe the mechanism of action of sulfasalazine

A

combination of 5-aminosalicylate acid (5-ASA) and sulfapyridine
The 5-ASA is the active component in treating IBD. The sulfapyridine allows the 5-ASA to reach the intended area

inhibits T cell proliferation
inhibits IL2 productions
reduces chemotaxis and degranulation of neutrophils

218
Q

how is sulfasalazine administered?

219
Q

Describe the ADRs of sulfasalazine

A
  • nausea,
  • fatigue,
  • headaches.
  • myelosuppression,
  • hepatitis
  • allergic rash
220
Q

What is the mechanism of action of rituximab?

A

anti-lymphocyte monoclonal antibodies that cause lysis of B lymphocytes
prevents stimulation of T lymphocytes by B lymphocytes

221
Q

What is the mechanism of action of infliximab?

A

antibody that binds to human TNF-α, and inhibits binding with its receptors
prevents stimulation of synovial cells to proliferate and synthesize collagenase

222
Q

What is the mechanism of action of adalimumab?

A

monoclonal antibody that binds to TNF-α, blocking its binding to the surface receptors

223
Q

How are biological DMARDs administered?

A

IV

adalimumab = SC

224
Q

What are the ADRs of biological DMARDs?

A

hypersensitivity
infections
injection site reactions

225
Q

How do corticosteroids affect the immune system?

A

IMMUNOSUPRESSION
redistribution of leukocytes to other body compartments
increase in the concentration of neutrophils
decrease in the concentration of lymphocytes (T and B cells), basophils, eosinophils, and monocytes;
inhibition of the ability of leukocytes and macrophages to respond to antigens
decreased production of prostaglandins and leukotrienes

226
Q

Describe the pharmacokinetics of corticosteroids

A

90% protein bound
metabolised in liver
excreted by kidney

227
Q

Describe the ADRs of corticosteroids

A
  • glucose intolerance
  • hypercholesterolemia,
  • cataracts,
  • osteoporosis
  • hypertension with prolonged use
  • infection risk
228
Q

Describe the mechanism of action of azathioprine

A

prodrug which is metabolised to 6-mercaptopurine (6-MP) which inhibits purine synthesis
reduces DNA and RNA synthesis
lymphocytes affected as high mitotic rate

229
Q

What are the ADRs of azathioprine?

A
  • bone marrow suppression,
  • increased risk of infection,
  • emergence of malignant cell lines.
  • Nausea and vomiting
230
Q

describe the mechanism of action of Mycophenolate mofetil

A

potent, reversible, uncompetitive inhibitor of inosine monophosphate dehydrogenase,
blocks formation of guanosine phosphate.
deprives the rapidly proliferating T and B cells of a key component of nucleic acids

231
Q

What is the mechanism of action of cyclophosphamide?

A

prodrug
metabolised by CYP450 to active form
prevents DNA replication
acts on cells with high mitotic rates

232
Q

What are the ADRs of cyclophosphamide?

A
  • Alopecia
  • Nausea, vomiting and diarrhoea
  • increased risk of bladder cancer (due to toxic metabolite to bladder epithelium produced),
  • lymphoma
  • leukaemia,
  • infertility
  • teratogenesis
233
Q

Name some IV anaesthetic agents

A

Propofol

Ketamine

234
Q

Name some inhalational anaesthetic agents

A

Nitrous oxide
Isoflurane
Sevoflurane

235
Q

What are the effects of anaesthesia?

A 
Sedation
Reduction in anxiety
Lack of awareness
Amnesia
Skeletal muscle relaxation
Suppression reflexes
Analgesia
236
Q

Describe the agents used and the effects of general anaesthesia

A

Affect whole body
Uses IV and inhalational with adjuvants

Act reversibly
Inhibits sensory, motor and sympathetic transmission

Unconsciousness
Absence of sensation

237
Q

Describe the process of and effects of regional anaesthesia

A

Stops sensation in specific regions of the body

Transmission block between body part and spinal cord

Patient it conscious

Spinal and epidural anaesthesia

238
Q

Describe the effects of local anaesthesia

A

Defined peripheral nerve block

Injection of anaesthetic

239
Q

Describe dissociative anaesthesia

A

Inhibition of transmission of nerve impulses between higher and lower centres of brain

240
Q

Which area of the Brain is involved in mediating unconsciousness in anaesthesia?

241
Q

How is anaesthetic potency predicted?

A

Lipid solubility - abide it to dissolve and enter cell membranes

242
Q

Define potency

A

Concentration of drug needed to give 50% maximal therapeutic effect

243
Q

How do anaesthetics mediate their effects?

A

Affect post synaptic transmission at ligand gated ion channels

244
Q

Describe the effect of anaesthetics at GABAA LGICs

A

Increase sensitivity to GABA
increases chloride currents
Hyperpolarises cell
Decreases excitability

245
Q

Which channel does propofol act at?

A

GABAA

increases chloride current

246
Q

Describe the action of anaesthetics at glycine LGIC

A

Increases sensitivity to glycine
Increases chloride current
Hyper polarisation
Decreases excitability

247
Q

Describe the action of anaesthetics at neuronal nicotinic ACh LGIC

A

Reduces Na+ currents

Contributes to analgesia and amnesia

248
Q

Describe the effect of anaesthetics at NMDA receptors

A

Reduces Ca2+ currents

Altered modulation of synaptic responses

249
Q

Which anaesthetics Mediate their response at NMDA receptors?

A

Nitrous oxide

Ketamine

250
Q

How are inhalational anaesthetics administered?

A

Volatile liquids at room temp
Mixed with oxygen or nitrous oxide carrier
Fed to respiratory system via mask

251
Q

What is the minimal alveolar concentration?

A

End tidal conc needed to eliminate movement in 50% of patients challenged by standardised skin incision

Expressed as percentage of gas in a mixture required to achieve the effect

252
Q

What does a low MAC value show about an anaesthetic’s potency?

A

Low MAC = high potency

253
Q

What is the blood:gas coefficient?

A

Volume of gas in litres that can dissolve in one litre if blood

Measure degree of absorption across the alveoli into the blood

254
Q

What does a high blood:gas coefficient mean?

A

High b:g c means that the gas will more readily enter the blood

255
Q

What does the distribution of anaesthetic around the body depend on?

A

Relative blood supply to each tissue

Specific tissue uptake capacity

256
Q

What is a tissue:blood coefficient?

A

Shows How readily the anaesthetic will move from blood to a specific tissue type

257
Q

Describe the elimination of anaesthetics

A

Anaesthetic moves out of cells into blood stream as conc anaesthetic in blood drops
Well perfume tissues first - kidney, brain, liver
Then muscle
Then fat

Can leave body via alveoli or redistribute

258
Q

What affects the duration of recovery from anaesthesia?

A

length if procedure

Degree of fat and muscle loading

259
Q

What would be included in a pre-surgical review?

A 
Age
BMI
Medical and surgical history
Medication
History of drug abuse
Fasting time
Airway assessment
260
Q

What pp need to be monitored during surgery?

A

Oxygen
Flurane
Nitrous oxide
Nitrogen

261
Q

What physiological monitoring is carried out during surgery?

A 
ECG
BP
pulse oximetry
Expired CO2 - assess ventilation rate 
Core temp
262
Q

Describe the induction phase of anaesthesia

A

Beginning of inhalational agent delivery

IV adjuvants also given

263
Q

Describe the maintenance phase of anaesthesia

A

Maintain adequate anaesthetic depth using adjuvants

Regular adjustments made

264
Q

Describe the recovery of anaesthesia

A

Agents withdrawn

Physiological function monitored

265
Q

State the names of the stages of anaesthesia

A

Stage I analgesia
Stage II excitement
Stage III surgical anaesthesia
Stage IV Medullary paralysis

266
Q

Describe stage I of anaesthesia

A

Loss of pain sensation
Progression from conscious and conversational to drowsy
Amnesia

267
Q

Describe stage II of anaesthesia

A

Delirium
Combative behaviour
Rise and irregularity in blood pressure and resp rate
Moderate eye movements

268
Q

Describe stage III of anaesthesia

A

Gradual loss tone and reflexes
Regular resp
Muscles relax - loss of spontaneous movement
Ideal state for surgery

Careful monitoring to check do not enter stage IV

269
Q

Describe stage IV of anaesthesia

A

Severe depression resp and vasomotor centres

Death unless resp and circulation controlled

270
Q

Name the endogenous groups of opioids

A

Enkephalins
Endorphins
Dynorphins

271
Q

Name opioids uses in clinical practice

A

Morphine
Diamorphine
Codeine
Tramadol

272
Q

Name the types of Opioid receptor

273
Q

Describe the MOP receptors location

A

Found supraspinally

274
Q

Describe KOP receptors location

A

Found spinally

275
Q

Describe DOP receptors location

A

Wide distribution

276
Q

What happens when opioids bind to an opioid receptor?

A

GPCR
Increase outward efflux of K+
Decrease influx Ca2+
Reduce cAMP synthesis -> reduces influx Ca2+

Fall in [Ca2+]i
Decreased release neurotransmitter at synapse

277
Q

Describe the ADRs of opioids

A 
Respiratory depression 
Constipation
Drowsiness
Miosis
Nausea and vomiting
Dysphoria
278
Q

How is an opiate overdose treated?

279
Q

Name some class 1a anti-arrhythmic drugs

A

Quinolone

Procainamide

280
Q

Describe the mechanism of action of class 1a anti arrhythmics

A

Blocks Na channels that are open or inactivated
Slows phase 0 depolarisation in myocytes
Increases AP duration
Slow conduction velocity

281
Q

What are the ADRs of class 1a anti arrhythmics?

A

Prolonged QT interval
Hypotension
SA and AV block

282
Q

Name some class 1b anti arrhythmics

283
Q

Describe the mechanism of action of class 1b AA

A

Blocks open or inactivated sodium channels
Shortens phase 3 repolarisation
Decreases duration AP
Shortens QT

284
Q

What are the ADRs of class 1b AA?

A

Drowsiness
Slurred speech
Agitation
Short QT interval

285
Q

Name a class 1c AA

A

Flecainide

286
Q

Describe the mechanism of action of class 1c AA

A

Blocks open or inactivated sodium channels
Slows phase 0 depolarisation greatly
No effect on AP duration

287
Q

Describe the effect if the different class 1 AA’s on the AP duration

A

1a - prolongs
1b - shortens
1c - no effect

288
Q

Describe the effect of the class 1 AAs on phase 0 of the ventricular AP

A

1a - slows
1b - no effect
1c - slows greatly

289
Q

When are class 1 AA used?

A

1a - AF, re entrant loops, ventricular tachycardia
1b - ventricular arrhythmia after MI
1c - arrhythmia

290
Q

Name some class II AA

A

Propanolol

Sotalol

291
Q

Describe the mechanism of action of class II AA

A

Slows phase 4 depolarisation at SA and AV nodes

Slows heart rate

292
Q

What are class II AA used to treat?

A

Protect ventricles in AF

293
Q

Name some class III AA

A

Amiodarone

Sotalol

294
Q

Describe the mechanism of action of class III AA

A

Blocks K channels
Prolongs phase 3 repolarisation
Prolongs effective refractory period

295
Q

When are class III AA used in treatment?

296
Q

Describe the ADRs of class III AA

A 
Interstitial pulmonary fibrosis
GI tract intolerance 
Corneal micro deposits 
Thyroid probs 
Peripheral neuropathy 
Hepatotoxic 
Hypokalaemia
297
Q

Name some class IV AA

A

Diltiazem

Verapamil

298
Q

Describe the mechanism of action of class IV AA

A 
Use dependant!  
Block ca2+ channels
Slow phase 4 spontaneous depolarisation 
Slow conduction in AV node
Prolongs effective refractory period in AV node
299
Q

When are class IV AA used?

A

Re entrant tachycardia

AF

300
Q

What are the ADRs of class IV AA

A

Worsen heart failure
Hypotension
Sympathetic nervous system activation

301
Q

What is tumour compartmentation?

A

A way of dividing the cells of a tumour by whether they are involved in active proliferation or not

302
Q

Describe the activity of cells in tumour compartment A

A

Dividing

Receiving adequate nutrient and vascular supply

303
Q

Describe the activity of cells in tumour compartment B

A

Resting
Remind in G0
Able to join compartment A if there are changes in cell signally or the local environment
Situated in middle of tumour

304
Q

Describe the activity of cells in tumour compartment C

A

No longer able to divide

Contribute to bulk of tumour

305
Q

Which tumour compartment is most susceptible to chemo?

A

Compartment A - only 5-20% of tumour cells

306
Q

Are cells in compartment B affected by chemo?

A

Maybe
Some RNA and protein synthesis may be happening.
BUT
Cells in G0 are not available for attack
Low effective kill ratio

307
Q

What is a log kill ratio?

A

Chemo agents kill a constant fraction of cells - first order kinetics

308
Q

What does the kill rate for cancer cells need to be balanced against in chemotherapy?

A

Kill rate for healthy cells

Need to secure that the kill rate does not lead to mortality
Ensure that the rate of regrowth in healthy tissues is sufficiently faster than in tumour cells

309
Q

Name an alkylating agent

310
Q

What is the mechanism of action of alkylating agents?

A

Allow covalent bonds to form between DNA strands - interstrand or intrastrand
Prevents DNA replication
Prevents tumour growth

311
Q

Name some antimetabolite chemo drugs

A

6-mercaptopurine
5-fluorouracil
Methotrexate

312
Q

Describe the mechanism of action of methotrexate in chemo

A

Inhibits dihydrofolate reductase
Prevents formation purines
Cells unable to form DNA

313
Q

Describe the mechanism of action of 5-fluorouracil

A

Activated into 5-FdUMP
Inhibits action thymidylate synthase
Prevents formation pyramidines
Reduces DNA synthesis

314
Q

What is the overall action of antimetabolites?

A

Prevent formation DNA

Prevent cell replication

315
Q

Name some spindle poison chemo drugs

A

Vincristine
Vinblastine
Paclitaxel

316
Q

State the mechanism of action of spindle poison chemo drugs

A

Affects spindle fibre formation during metaphase
Damages the spindle fibres
Causes cell death
Prevents excessive growth

317
Q

Why are most chemo drugs not given orally?

A

Toxicity would damage GI tract

Patient will vomit - limits practicality

318
Q

How are most chemo drugs given?

Why?

A

IV

Allows fine control
Infusion can be stopped immediately in an emergency

319
Q

How do cells become resistant to chemotherapy?

A

Decreased entry of agent or increased exit
Inactivation of agents within cell
Enhanced repair of DNA lesion produced by alkylation

320
Q

Why does acquired chemotherapy resistance happen?

A

Suboptimal repeat doses given

Gives cells time to manifest response to agent

321
Q

How can chemo resistance be prevented?

A

High dose
Short term Intermittent repeat
Optimal combination for tumour type

322
Q

Why do chemo drugs cause so many ADRs

A

Targeted at rapidly dividing cells

Most of GI tract, hair follicles

323
Q

What are the common chemo ADRs

A 
Nausea, vomiting, diarrhoea
Mucositis 
Alopecia
Myelosupression
Impaired wound healing
Skin toxicity
324
Q

Which ADR limits chemo dose?

A

Haematological toxicity

Most common cause of death in chemo

325
Q

Why does acute renal failure occur during chemo?

A

Rapid tumour lysis releases purines into circulation
Metabolism creates urates
causes hyperuricaemia
Precipitation of urate crystals in renal tubules

326
Q

Which chemo drugs is neuropathy seen as an ADR with?

A

Cisplatin

Mitotic spindle inhibitors

327
Q

What is monitored during chemo?

A

Response of the cancer
Pharmacokinetics - measuring of drug in body
Organ function deficit - heart, lungs, liver, kidney, nerves

328
Q

What is neoadjuvant chemo?

A

Given before surgery

Decrease primary tumour size

329
Q

What is adjuvant chemo?

A

After surgery

Minimises risk of relapse due to metastasis

330
Q

What is palliative chemo?

A

Treat symptoms without curative intent

331
Q

How is acid formed by the parietal cells in the stomach?

A

Water split to form OH- and H+
H+ enters lumen of canaliculi using H+K+ATPase
Chloride and potassium ions enter canaliculi through channels

OH- combines with CO2 to form HCO3-
HCO3- and Cl- antiporter in basolateral membrane
Creates alkaline tide

332
Q

What stimulates the parietal cell to release more acid

A

Gastric distension -> Parasympathetic nervous system -> ACh

Gastrin

Histamine from enterochromaffin cells

333
Q

What does parietal cell stimulation result in at a molecular level?

A

Increased intracellular calcium

Histamine activates adenylyl Cyclase, increasing cAMP

334
Q

Describe the effect somatostatin has on parietal cells

A

Released from D cells in response to low pH
Bind to enterochromaffin cells
Inhibit histamine release
Decrease acid secretion from parietal cells

335
Q

Name some H2 receptor antagonists

A

Ranitidine

336
Q

Describe the mechanism of action of H2 antagonists

A

Block H2 histamine receptor on parietal cell

Inhibits stimulation acid secretion

337
Q

Describe the pharmacokinetics of H2 antagonists

A

Oral

Excreted in urine

338
Q

Describe the ADRs of H2 antagonists

A

Headache
Dizziness.
Diarrhoea
Muscular pain

339
Q

Name some PPIs

A

Omeprazole
Lansoprazole
Esomeprazole

340
Q

What is the mechanism of action of PPIs

A

Bind to H+K+ATPase of parietal cell
Irreversible inactivation
Suppress H+ secretion

341
Q

What are the ADRs of PPI s

A

Vitamin B12 deficiency- acid is required for absorption

Increased risk bone fractures - bad calcium absorption

342
Q

What effect do PPI have on CYP450

A

Inhibition

343
Q

describe the neural control of the gut motility

A

stimulation of post-ganglionic cholinergic enteric nerves leads to increased force of contraction
stimulation noradrenergic inhibitory nerves inhibits contractions

344
Q

What si the enteric nervous system?

A

autonomic nerves within the gut wall

345
Q

What is the intestino-intestinal inhibitory reflex?

A

distention of one intestinal segment causes complete intestinal inhibition

346
Q

What is the anointestinal inhibitory reflex

A

distention of the anus causes itestinal inhibition

347
Q

What is the effect of the gastrocolic and duodenocolic reflexes?

A

material enters stomach or duodenum

stimulates motility

348
Q

Describe the process of vomiting

A

pyloric sphincter closes
cardia and oesophagus relax
abdominal wall and diaphragm contract to propel gastric contents
glottis closes and soft palate elevate to prevent entry of vomitus into trachea and nasopharynx

349
Q

What causes vomiting?

A 
pregnancy
medications
pain
toxins
smell/touch
RICP
rotational movement
stretching of stomach
350
Q

What neurotransmitters act to stimulate the vomiting centre in the medullla?

A

ACh
histamine -H1
dopamine - acts at postrema on floor fourth ventricle

351
Q

Name some D2 receptor antagonists

A

Metoclopramide,

Domperidone

352
Q

Describe the mechanism of action of the D2 receptor antagonists

A

inhibition at postrema

353
Q

Name a 5-HT3 antagonist

A

ondansetron

354
Q

Describe the mechanism of action of 5-HT3 antagonists

A

5-HT released into the ut would normally ause vagal stimulation and therefore increased gut motilty
blockade decreases gut motility

355
Q

What kind of drug is Hyoscine

A

ACh antagonist

anti-emetic used in travel sickness

356
Q

Name an H1 antagonist

357
Q

How can constipation be treated non-pharmacologically?

A

treating underlying cause
increasing fluid intake
high fibre diet
exercise

358
Q

Describe eh mechanism of action of bulk laxatives, such as fybogel

A

insoluble and non-absorbable substance
causes gut fisetion
stimulates stretch receptors
re-establish normal peristalsis

359
Q

What is isphagula husk?

A

fybogel!

bulk laxative

360
Q

Describe the mechanism of action of senna

A 
stimulant laxative
irritates mucosa
excites sensory nerve endings
decreases water and electrolyte absorption
leads to peristalsis
361
Q

What are the ADRs of senna?

A

colonic atony

hypokalaemia

362
Q

Name osmotically active laxatives

A

Lactulose

Macrogols - Movicol

363
Q

Describe the mechanism of action of osmotically active laxatives

A

increase the amount of water in the large bowel,

either by drawing fluid from the body into the bowel or by retaining the fluid they were administered with.

364
Q

Describe the mechanism of action of lactulose

A

cannot be hydrolysed by digestive enzymes
fementation by colonic bacteria leads to acetic and lactic acid
this decreases water reabsorption

365
Q

Name some faecal softeners

A

Glycerol Supps,

Phosphate enemas

366
Q

State the mechanism of action of glycerol suppositories

A

rectal stimulant

mildly irritant

367
Q

What type of laxative should be given if the faeces are soft?

368
Q

What type of laxative should be given if the faeces are hard?

A

osmotic laxatives

bulk forming laxatives

369
Q

Why does treatment of constipation with laxatives lead to hypokalaemia

A 
laxatives cause enteral loss of K+
loss Of H20 and Na+ causes increased aldosterone release
increases renal loss K+
hypokalaemia causes bowel inertia
constipation
more laxatives given

IT’S A CYCLE!

370
Q

What drugs can cause constipation?

A 
anti-cholinergics
antidepressants
AEDs
antipsychotics
antispasmodics
calcium supplements
diuretics
opiods
verpamil
371
Q

Name an antimotility drug

A

Loperamide

372
Q

State the mechanism of action of loperimide

A

binds to opiate receptors in bowel
reduces bowel motility = more time for fluid absorption
increases anal tone
reduces sensory defecation reflex

activate presynaptic opioid receptors in the enteric nervous system to inhibit acetylcholine release and decrease peristalsis.

373
Q

Name some anti-spasmodics

A

Hyoscine,

Mebeverine

374
Q

State the mehanism of action of antispasmodics

A

relieves spasm of intestinal muscle

375
Q

What is Virchow’s triad?

A

Hypercoaguability
Endothelial damage
Stasis

Situations that make haemostasis more likely

376
Q

State the general mechanism of thrombus formation

A 
Rupture endothelial wall
Adhesion, activation and aggregation of platelets
Secretion of mediators
Further aggregation of platelets
Coagulation cascade
Thrombus formation
377
Q

Describe the mechanism of action of warfarin

A

Prevents production of vit K dependant clotting factors - prothrombin, VII, IX and X
Competitive antagonism reduction of oxidised vit K required for clotting factor formation

378
Q

How long does it take for warfarin to have a therapeutic effect? Why?

A

Days
Non-functional clotting factors are synthesised
Takes time for functional clotting factors to be broken down

379
Q

Where in the clotting cascade does warfarin act?

A

Extrinsic and intrinsic pathways

380
Q

Describe the pharmacokinetics of warfarin

A 
Oral
Slow onset and offset
Heavily protein bound 
Metabolism by CYP450
Crosses placenta 
Excreted in urine and faeces
381
Q

Why are patients given heparin cover initially when prescribed warfarin?

A

Takes a few days for warfarin to become effective - clotting factor turnover

382
Q

What effects does warfarin have when it crossed the placenta?

A

First trimester - teratogenic

Third trimester - fetal brain haemorrhage

383
Q

How is the effect of warfarin measured?

A

Checking extrinsic pathway
Prothrombin time = Time taken for blood to clot after tissue factor and calcium added
Converted to INR

384
Q

What is the INR?

A

International normalised ratio
Time taken for blood to clot compared to average for age and gender
High INR means poor blood clotting

385
Q

What is the target INRs in warfarin use?

A

2-3 in DVT, PE, AF

2.5-4.5 in prosthetic valves, recurrent thrombosis on warfarin of inherited thrombophilia

386
Q

Why drugs potentiate the effects of warfarin by inhibiting hepatic metabolism?

A

Drugs that inhibit CYP450

387
Q

How does aspirin affect the action of warfarin?

A

Inhibits platelet function

Potentiates warfarin action

388
Q

How do cephalosporins affect the action of warfarin?

A

Reduce vit K uptake from gut bacteria

Increases effects of warfarin

389
Q

What are the ADRs of warfarin?

A

GI haemorrhage
Epistaxis
Intracranial haemorrhage
Excessive bruising

390
Q

How is reversal of warfarin therapy achieved?

A

Minor bleeding - withdrawal of warfarin and oral Vit K

Severe bleeding - IV vit K, blood products

391
Q

Describe the mechanism of action of heparin

A

Activates anti-thrombin III which inhibits thrombin and factor Xa

392
Q

What is the difference in action of unfractionated and LMWH?

A

Unfractionated binds to ATIII and inhibits thrombin and Xa

LMWH binds to ATIII and inhibits factor Xa only
Due to being too short polysaccharide sequence to bind to both ATIII and thrombin

393
Q

What are LMWH used in the treatment of?

A 
VTE prophylaxis 
DVT
PE
MI
CHD
during surgery - quick offset if haemmorhage occurs
394
Q

How is heparin administered?

A

IV (unfractionated)

SC (LMWH)

395
Q

Why does unfractionated heparin have unpredictable pharmacokinetics?

A

Binds to proteins in blood that neutralise its activity

396
Q

Can heparin cross the placenta?

397
Q

How is heparin activity monitored?

A

Measures intrinsic pathway

APTT - activated partial thromboplastin time

398
Q

How is APTT measured?

A

Time taken for blood to clot after addition Ca2+, partial thromboplastin and activator

399
Q

What are the ADRs of heparin?

A

Haemorrhage- intracranial, at injection sites, GI, epistaxis
Thrombocytopenia - autoimmune.
Osteoporosis in long term use

400
Q

Why does heparin induce thrombocytopenia?

A

Heparin bind to PF4 on platelet surface

Stimulates autoimmune response

401
Q

How is heparin treatment reversed?

A

Protamine sulphate
Dissociates heparin from ATIII
Binds to heparin irreversibly

402
Q

Why are anti platelet medications used?

A

Prophylaxis for problems with clotting

403
Q

Describe the mechanism of action of aspirin

A

Inhibits COX-1
Prevents thromboxane A2 production
Prevents platelet aggregation

404
Q

Describe the mechanism of action of dipyridamole

A

Inhibits cyclic nucleotide phosphodiesterase enzymes
Decreased thromboxane A2 production
Prevention platelet aggregation

405
Q

Describe the mechanism of action of clopidogrel

A

Inhibits binding of ADP to ADP receptor on platelets
Inhibits GL IIb/IIa receptors needed for fibrinogen to bind together
Inhibits ADP dependant platelet aggregation

406
Q

Describe the formation of prostaglandins

A

Phospholipase A2 catalyses change of phospholipids to arachidonic acid
COX1 and CLX2 catalyse change of arachidonic acid to prostaglandins (PGH2)

407
Q

What is the difference in function between cox1 and cox2?

A

COX1 - physiologic production prostaglandins

COX2 - elevated production prostaglandins in sites of chronic disease and inflammation

408
Q

Where and when are COX1 and COX2 expressed?

A

COX1 - constitutive. Ensures local perfusion. Constant synthesis

COX2 - always in brain, kidney and bone. Increased in chronic inflammation due to TNFalpha and IL-1

409
Q

Describe the difference in binding sites in the COX enzymes

A

COX1 - narrow substrate binding site

COX2 - larger more flexible substrate channel. Large space for inhibitors to bind to

410
Q

How do prostaglandins mediate their effects?

A

Bind to GPCRs - EP1, EP2 and EP3

411
Q

What is the effect of PGE2 at EP1?

How is this experienced by the patient?

A 
Bind to Gq GPCR in C fibres (unmyelinated pain fibres) 
Inhibit K+ channels, 
increase Na+ channel expression
Increases sensitivity to bradykinin
Increased C-fibre activity

Allodynia and hyperalgesia

412
Q

What is Allodynia?

A

Pain caused by something that wouldn’t normally cause pain

413
Q

What is hyperalgesia?

A

Increased sensitivity to pain

414
Q

What is the effect of PGE2 at EP2 receptors

A 
Found in dorsal horn spinal cord
Gs GPCR 
increased cAMP, activation PKA
Reduced glycine receptor binding affinity
Increased pain reception
415
Q

What does PGE2 binding to EP3 receptors cause?

A 
Receptors on neurones regulating temp
Gi GPCR
Fall in cAMP
Increase in intracellular Ca2+ 
Increased heat production
Reduced heat loss
416
Q

How can the actions of PGE2 at prostaglandin receptors be summarised?

A

EP1 - peripheral sensetisation
EP2 - central sensetisation
EL3 - pyrexia

417
Q

Name some NSAIDs

A

Ibuprofen
Naproxen
Diclofenac
Celecoxib

418
Q

What is the mechanism of action of NSAIDs

A

Inhibition COX2
Decreased production prostaglandins

Analgesia, anti-inflammation, anti-pyrexia

419
Q

Describe the time frame of COX1 and COX2 inhibition

A

COX 1 - rapid and competitive

COX 2 - slower and irreversible

420
Q

How do NSAIDs cause analgesia?

A

Reduction prostaglandins
Decreased sensitisation of nociceptors
Decreased central sensitisation

421
Q

How do NSAIDs lead to anti-inflammation

A

Reduction in prostaglandins

Effect proportionate to PG involvement (there are other inflammatory mediators!)

422
Q

How do NSAIDs decrease pyrexia?

A

Bacterial endotoxins trigger macrophages to release IL1 which stimulates hypothalamus to release PGE

NSAIDs inhibit PGE synthesis

423
Q

Describe the pharmacokinetics of NSAIDs

A

Oral or topical
Heavily protein bound
First order elimination

424
Q

What is the cause of most of the ADRs of NSAIDs?

A

Inhibition of COX1 - reduction in constitutive prostaglandin expression

425
Q

State the ADRs of NSAIDs

A

GI ulceration, haemorrhage and perforation
Reduced GFR
Increased brushing
Increased risk of haemorrhage
Hypersensitivity - rashes and bronchospasm

426
Q

Why do NSAIDs cause GI problems?

A

Prostaglandins would normally stimulate mucus production and inhibit acid production
Decreased prostaglandins increases mucosal permeability and decreased mucosal blood flow and protection

427
Q

Why do NSAIDs cause kidney problems?

A

Prostaglandins normally maintain adequate blood flow to kidney

428
Q

Why do NSAIDs increase the risk of bleeding?

A

NSAIDs inhibit thromboxane A2 synthesis by COX1

Reduces platelet aggregation

429
Q

Which drugs are commonly displaced from protein biding sites by NSAIDs?

A

Sulphonylureas
Warfarin
Methotrexate

430
Q

Describe the metabolism of paracetemol

A

90% directly enters phase 2 metabolism - glucaronidation and sulphation
10% enters phase 1 to produce NAPQI

Both have linear PKs

431
Q

What happens to the toxic metabolite NAPQI?

A

Detoxified using phase 2 conjugation with glutathione

Limited by glutathione availability

432
Q

What happens to the PK of paracetemol metabolism at high doses?

A

Turn form linear to non-linear PKs

Both phase 1 and 2

433
Q

How is paracetemol metabolised at high doses?

A

Phase II becomes saturated
Increase in phase I production NAPQI
Depletes glutathione
Increased unconjugated NAPQI

434
Q

What is the result of NAPQI’s toxicity

A

Highly nucelophilic
Binds with cellular macromolecules or mitochondria
Loss hepatic cell function and cell death
Renal failure

435
Q

Why are the elderly and young even more at risk of NAPQI toxicity?

A

Have less glutathione

436
Q

What are the signs and symptoms of paracetamol toxicity?

A 
Nausea and vomiting in first 24hrs
RUQ pain and tenderness - hepatic necrosis 
Encephalopathy 
Haemorrhage 
Hypoglycaemia
Cerebral oedema
Death
437
Q

What is the treatment for paracetamol overdose?

A

0-4 hours after overdose = oral activated charcoal. Reduced uptake
0-36 hours after overdose = IV N-acetylcysteine. Increases glutathione levels. Protects liver. Most effective if given within 8 hours

438
Q

What classes of drugs are used as AEDs

A

Voltage gated sodium channel blockers

Enhancers of GABA mediated inhibition

439
Q

Name some voltage gated sodium channel blockers used in epilepsy

A

Carbemezepine
Lamotrigine
Phenytoin

440
Q

State the mechanism of action on VGSC blockers used in epilepsy

A

Bind to internal face inactivated sodium channel
Act at neurones with high frequency discharge
Prevent return of channel to resting state
Reduce number of functional channels

441
Q

What types of seizures are the VGSC blockers used to treat?

A

Carbamezepine - tonic clonic, partial
Lamotrigine - tonic clonic, partial, absence
Phenytoin - tonic clonic, partial

442
Q

What affect does carbamezepine have on CYP450?

443
Q

What are the ADRs of carbamezepine

A 
Drowsiness
Dizziness
Ataxia
Paraesthesia
Anaesthesia 
Bone marrow suppression
Neutropenia
444
Q

What affect do oral contraceptives have on lamtorigine?

A

Reduce plasma levels

445
Q

What effect does phenytoin have on CYP450

446
Q

What ADRs are seen with phenytoin?

A

Ataxia
Nystagmus
Gingival hyperplasia
Hypersensitivity - Stevens-Johnson

447
Q

Which VGSC blockers competitively bind with sodium valproate?

A

Phenytoin

Lamotrigine

448
Q

What effect does phenytoin have on the OCP?

A

Decreased plasma concentrations

449
Q

Name some drugs that enhance GABA mediated inhibition in epilepsy

A

Sodium valproate
Diazepam
Lorazepam

450
Q

State the mechanism of action of sodium valproate

A

STimualtes GABA synthesising enzymes

Inhibits GABA inactivating enzymes

451
Q

What is sodium valproate used for?

A

Adjunct therapy in partial and generalised seizures

452
Q

What are the ADRs of sodium valproate

A

Ataxia
Tremor
Increases transaminase levels in blood
Teratogenic

453
Q

What interactions occur with antidepressants, antipsychotics and sodium valproate?

A

Antidepressant and antipsychotic antagonise sodium valproate

454
Q

State the mechanism of action of benzodiazepines

A

Bind to BZD binding site on GABAA
Enhances GABA binding
Increases Cl- into neurone
Increases threshold for AP

455
Q

What are benzodiazepines used to treat?

A

Status epilepticus

456
Q

What are the ADRs of benzodiazepines

A 
Sedation
Confusion 
Impaired coordination
Aggression
Tolerance and dependance
Resp and CNS depression
457
Q

What is the first line therapy for primary generalised seizures?

A

Sodium valproate

458
Q

What is the first line therapy for partial seizures?

A

Carbamezepine

459
Q

What AED drug is used in women of child bearing age?

A

Lamotrigine

460
Q

What are the diagnostic symptoms of depression?

A

Two out of three of:
Low mood
Anhedonia
Decreased energy

Other symptoms are loss of concentration, decreased appetite, sleep disturbance, irritability

461
Q

What are the theories behind the development of depression?

A

Monoamine hypothesis - deficient monoamine neurotransmitter

Neurotransmitter receptor hypothesis - abnormality in receptors for monoamines

Monoamine hypothesis of gene expression

462
Q

Name some SSRIs

A

Citalopram
Fluoxetine
Sertraline

463
Q

State the mechanism of action of SSRIs

A

Prevent reuptake of serotonin at ore synaptic membrane

Increases concentration in the synaptic cleft

464
Q

Describe the pharmacokinetics of SSRIs

A

Oral
Long half life
Metabolised by CYP450

465
Q

State the ADRs of SSRIs

A 
Nausea
Diarrhoea
Anorexia
Mania
Extrapyramidal syndromes

Citalopram can prolong QTc

466
Q

Name some tricyclic antidepressants

A

Imipramine

Lofepramine

467
Q

State the mechanism of action of TCAs

A

Inhibition reuptake of serotonin and noradrenaline at pre synaptic membrane, increasing concentration

Block serotonin, alpha adrenergic, histamine and muscarinic receptors - responsible for side-effects

468
Q

Describe the pharmacokinetics of TCAs

A

Oral
Lipid soluble
Long half life

469
Q

State the ADRs of TCAs

A 
Sedation
Impaired psychomotor function
Reduced glandular secretion 
Tachycardia
Postural hypertension
Sudden cardiac death 
Constipation
470
Q

What are the effects of overdose of antidepressants?

A

SSRIs - very safe

TCAs - dangerous. Short term prescriptions given

471
Q

Name an SNRI

A

Venlafaxine

472
Q

Describe the mechanism of action of SNRIs

A

Inhibition reuptake serotonin and noradrenaline

473
Q

State the ADRs of SNRIs

A 
Nausea
Diarrhoea 
Sleep disturbance 
Increased BP
dry mouth
Hyponatremia
474
Q

State the order of antidepressant treatment

A

SSRIs first line
SNRIs
TCAs

475
Q

What is psychosis?

A

Loss of contact with reality

476
Q

State the positive symptoms of schizophrenia

A

Hallucination
Disturbances in thinking
Delusions
Behavioural change

477
Q

What is a hallucination?

A

Perception in the absence of an external stimulus

478
Q

What is a delusion?

A

Fixed false belief despite clear and obvious evidence it isn’t true

479
Q

What are the negative symptoms of schizophrenia

A

Social withdrawal

Unusual speech and thought - jumbled. Difficult to understand. New words, pressure of speech

480
Q

What are the cognitive symptoms of schizophrenia

A

Selective attention
Poor memory
Reduced abstract thought
Lack of insight

481
Q

State the main dopamine pathways in the CNS and their importance

A 
Meso-limbic = emotional response and behaviour 
Meso-cortical = arousal and mood 
Nigrostriatal = control of movement
Tubero-hypophyseal = pituitary and hypothalamus function
482
Q

What is the main treatment of schizophrenia

A

Block dopaminergic pathways

Thought to be due to increased dopamine

483
Q

State the effects of blocking the dopamine pathways in schizophrenia

A 
Meso-limbic = therapeutic action on positive symptoms 
Meso-cortical = enhancement of negative and cognitive symptoms 
Nigrostriatal = extra pyramidal side effects and tardive dyskinesia 
Tubero-hypophyseal = hyperprolactiniaemia
484
Q

What other neurotransmitters are affected inn schizophrenia

A

Serotonin - increased

Glutamate - decreased in cortex

485
Q

What are the effects of anti-psychotics?

A 
Sedation 
Tranquilisation 
Antipsychotic effects
Activation of negative symptoms 
Extra pyramidal side effects
486
Q

Name some typical anti-psychotics

A

Haloperidol

Chlorpromazine

487
Q

Describe the mechanism of action of typical anti-psychotics

A

Competitive D2-antagonists

488
Q

What are the ADRs of typical anti-psychotics

A

Extra-pyramidal effects
CNS depression
Cardiac toxicity - lengthens QT
Studen death

489
Q

Name some atypical antipsychotics

A

Olanzapine
Risperidone
Quetiapine
Clozapine

490
Q

What is the difference between typical and atypical anti-psychotics?

A

Atypical cause less extrapyramidal effects
More acceptable to patient

But higher risk of metabolic side effects

491
Q

State the ADRs of atypical antipsychotics

A

Excessive weight gain
Increased prolactin secretion
Sedation
(Uncommon extrapyramidal)

492
Q

What is the mechanism of action of atypical antipsychotics

A

Blockade of serotonin and dopamine

493
Q

What is the first line treatment for schizophrenia?

A

Atypical antipsychotics

494
Q

Why are benzodiazepines rarely prescribed as a treatment for anxiety?

A

Tolerance
Dependance - withdrawal
Severe side effects

495
Q

What are the ADRs of benzodiazepines

A

Drowsiness
Dissidents
Psychomotor impairment

496
Q

What effect do benzodiazepines have in pregnancy?

A

Cleft lip and palate
Respiratory depression in fetus
Feeding difficulties in baby

497
Q

What are the symptoms of mania in bipolar disorder

A 
Feeling unusually happy, optimistic or excited
Over activity
Poor concentration 
Poor sleep
Rapid speech
Poor judgement
Increased interest in sex
Psychotic symptoms
498
Q

What is bipolar disorder?

A

Episodes of both mania and depression

499
Q

What drugs are used to treat bipolar disorder?

A

Lithium
AEDs
Antipsychotics

500
Q

Describe the effect of lithium in bipolar disorder

A

Mood stabiliser

501
Q

Describe the pharmacokinetics of lithium

A

Not metabolised

Excreted renally - nephrotoxic

502
Q

What are the ADRs of lithium

A 
Nephrotoxicity
Hypothyroidism
Memory problems
Thirst
Polyuria 
Tremor
Drowsiness
Weight gain
503
Q

What are the symptoms of lithium toxicity

A 
Vomiting 
Diarrhoea
Coarse tremor
Dysarthria 
Cognitive impairment
Restlessness
Agitation

ESA5 (2 decks)

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