Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Block 32 GI and surgery > PPT (pharmacology) > Flashcards

PPT (pharmacology) Flashcards

1
Q

give examples of antacids and alginates?

A

Magnesium trisilicate
Aluminium/magnesium
mixtures (Maalox)
Alginates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

give an example of H2-receptor antagonists?

A

Ranitidine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

give examples of PPIs

A

Lansoprazole
Omeprazole
Pantoprazole

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What classes of drugs can be used in patients with dyspepsia?

A

antacids and alginates
H2 receptor antagonists
PPIs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what classes of drugs can be used in patients with GORD?

A

antacids and alginates
H2 receptor antagonists
PPIs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what classes of drugs can be used in peptic ulceration prophylaxis of NSAID associated peptic ulceration?

A

H2 receptor antagonists

PPIs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what class of drug (other than antibiotics) are used in H.pylori eradication therapy?

A

PPIs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

describe the pharmacodynamics of magnesium trisilicate?

A

increasing the pH of gastric juice via a neutralisation reaction. It also precipitates colloidal silica, which can coat gastrointestinal mucosa conferring further protection.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what is the mechanism of action of magnesium trisilicate?

A

increasing the pH of gastric juice via a neutralisation reaction. It also precipitates colloidal silica, which can coat gastrointestinal mucosa conferring further protection.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what are the indications of alginates?

A

Indicated for the management of gastric reflux, reflux oesophagitis, hiatus hernia, heartburn (including heartburn of pregnancy) and similar gastric distress

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what are the pharmacodynamics of alginate?

A

Alginic acid reduces reflux via its floating, foaming, and viscous properties. Alginic acid precipitates upon contact with gastric acid to create a mechanical barrier, or a “raft”, that displaces the postprandial acid pocket. The formation of a raft is thought to occur rapidly, often within a few seconds of dosing. In clinical trials, alginic acid was effective in reducing the symptoms of gastroesophageal reflux disease (GERD). In healthy volunteers, alginic acid in combination with an antacid was effective in decreasing postprandial reflux in the upright position. Alginic acid is able to bind to cations when ingested

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is the mechanism of action of alginates?

A

Once orally administered, alginic acid reacts with gastric acid to form a floating “raft” of alginic acid gel on the gastric acid pool. Alginate-based raft-forming formulations commonly contain sodium or bicarbonate; bicarbonate ions are converted to carbon dioxide in presence of gastric acid and get entrapped within the gel precipitate, converting it into a foam which floats on the surface of the gastric contents, much like a raft on water. The “raft” has a near neutral pH due to carbon dioxide and floats on the stomach contents and potentially functions as a barrier to impede gastroesophageal reflux 1,7. In severe cases, the raft itself may be refluxed into the oesophagus in preference to the stomach contents and exert a demulcent effect.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what are the indications for ranitidine?

A

Duodenal ulcer
-Treatment of active duodenal ulcer (short-term), maintenance therapy of duodenal ulcers after healing (reduced dose)

Pathological hypersecretion of gastric acid
Zollinger-Ellison syndrome, systemic mastocytosis, and other conditions causing gastric acid hypersecretion

Gastric ulcer
Short term treatment of active gastric ulcer (benign), maintenance of healing after gastric acid ulcer therapy (reduced dose)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what are the pharmacodynamics of ranitidine?

A

Ranitidine decreases the secretion of gastric acid stimulated by food and drugs. It also reduces the secretion of gastric acid in hypersecretory conditions such as Zollinger-Ellison syndrome.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is the mechanism of action of ranitidine?

A

After a meal, gastrin is produced by G cells and stimulates the release of histamine, which binds to H2 receptors, leading to the secretion of gastric acid.

reversible binding to H2 receptors, on gastric parietal cells leading to inhibition of histamine binding and reduction of gastric acid secretion.

symptom relief in 60 minutes after administration of a single dose, and effects last 4-10 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what is the mechanism of lansoprazole?

when should it be administered?

A

decreases gastric acid secretion by targeting H+,K+-ATPase (catalyzes final step in acid secretion in parietal cells.)
administered any time of day is able to inhibit daytime and nocturnal acid secretion so is effective at healing duodenal ulcers, reduces ulcer-related pain, and offers relief from symptoms of heartburn
reduces pepsin secretion, so is an option for hypersecretory conditions such as Zollinger-Ellison syndrome.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is the mechanism of action of PPIs?

A

As a PPI, lansoprazole is a prodrug and requires protonation via an acidic environment to become activated. Once protonated, lansoprazole is able to react with cysteine residues, specifically Cys813 and Cys321, on parietal H+,K+-ATPase resulting in stable disulfides. PPI’s in general are able to provide prolonged inhibition of acid secretion due to their ability to bind covalently to their targets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what parameters affect the speed of onset, intensity and duration of response of a drug?

A
  • rate and extent of uptake of the drug from its site of administration
  • rate and extent of distribution of the drug to different tissues and site of action
  • rate of elimination of the drug
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what are the 4 processes that pharmacokinetics can be divided into?

A 
absorption
distribution
metabolism
excretion
(ADME)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what is absorption?

A

the transfer of the drug from its site of administration to the general circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what is distribution?

A

the transfer of the drug from the general circulation into the different organs of the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what is metabolism of a drug?

A

the extent to which the drug molecule is chemically modified by the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what is excretion of a drug?

A

the removal of the parent drug and any metabolites from the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what is elimination of a drug?

A

the process of metabolism and excretion together

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

pharmacodynamics or pharmacokinetics?

  1. specific to drug or drug class
  2. non specific, general processes
A
  1. pharmacodynamics

2. pharmacokinetic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what pharmacodynamic factors determine the response of an individual to a drug?

A
  • interaction with cellular component
  • effects at site of action
  • concentration-effect relationship
  • reduction in symptoms
  • modification of disease progression
  • unwanted effects
  • drug interaction
  • inter and intraindividual differences
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what pharmacokinetic factors determine the response of an individual to a drug?

A
  • absorption from the site of administration
  • delivery to the site of action
  • elimination from the body
  • time to onset of effect
  • duration of effect
  • accumulation on repeat dosage
  • drug interations
  • inter and intraindividual differences
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

what is the definition of pharmacodynamics?

A

Pharmacodynamics is the study of the biochemical and physiologic effects of drugs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

what is the definition of pharmacokinetics?

A

Pharmacokinetics, sometimes described as what the body does to a drug, refers to the movement of drug into, through, and out of the body—the time course of its absorption, bioavailability, distribution, metabolism, and excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what is the definition of volume of distribution?

A

Volume of distribution (VD, also known as apparent volume of distribution) is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

how can apparent volume of distribution be calculated?

A

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

the calculated Vd is the hypothetical volume you would need to place the drug dose in for all of the concentration to be free drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

what will the Vd of polar water soluble drugs be, give an example and why is the Vd this?

A

polar drugs such as penicillins will have a small Vd

water soluble/polar drugs remain free in the ‘central compartment’ aka the blood plasma as they cannot bind to plasma proteins and do not move across the membrane.

for example if you inject 10mg of a drug into the blood which is 5L, then 10mg may remain free in the plasma so when you calculate Vd
10mg / (10mg/5L) = 5L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

what will the Vd of lipid soluble drugs be, give an example and why is the Vd this?

A

lipid soluble drugs such as tricyclic antidepressants will have a high Vd as they are highly distributed in the body

lipid soluble drugs can bind to plasma proteins and easily cross membrane barriers to distribute.

for example, if you inject 10mg of a drug into the blood compartment of 5L, most of this will bind to proteins or move into other compartments and therefore maybe only 1mg will remain free in the plasma so when you calculate Vd
10mg/ (1mg/ 5L) = 50L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

going from drugs with a low Vd to drugs with a high Vd describe how they would be distributed in the body?

A

Low Vd = drug concentrated in blood stream
drug in blood and extracellular space
drug equally distributed in blood and tissues
drug moderately concentrated in tissues
high Vd=drug highly concentrated in tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

what implications does the Volume of distribution of a drug have on its loading dose?

A

small Vd need a high initial loading dose

large Vd may not require a high loading dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

if the Vd is equal to the water volume in the body what does this suggest about the drug?

A

it is water soluble

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

describe the compartment model in pharmacokinetics?

A

Pharmacokinetic two-compartment model divided the body into central and peripheral compartment. The central compartment (compartment 1) consists of the plasma and tissues where the distribution of the drug is practically instantaneous. The peripheral compartment (compartment 2) consists of tissues where the distribution of the drug is slower

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

what is the importance of half life when considering an oral drug?

A

oral drugs require 5 half lives to reach a steady state when no loading dose is given

it will also indicate is accumulation of drug will occur under a multiple dosage regimen

also need to decide appropriate dosing interval

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

what affect does half life of a drug have on its dosing interval?

A

longer the half life the longer the dosing interval

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

what affect does Vd have on half life of a drug?

A

larger the Vd means a longer half life because the drug travels to different compartments and is temporarily ‘locked in place’

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

how is drug half life calculated?

A

Drug half-life is calculated from a plasma concentration (Cp) versus time curve.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

what variables is half life dependent on?

A

Volume of distribution and clearance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

what effect does half life have on the therapeutic effect of a drug?

A

the larger the half life the greater the minimum toxic concentration
the lower the half life the lower the minimum effective concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

what is oral availability?

A

Oral availability (F) is the fraction of drug that reaches the systemic circulation after oral ingestion. It is determined by ‘absorption’ and ‘first-pass’ metabolism.

Oral availability is usually defined by comparing the fraction (F) of drug that gets into the body after oral (po) versus IV administration.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

what is first pass metabolism?

A

First-pass metabolism describes pre-systemic drug elimination and can occur in the gut wall, portal vein or liver. The liver is usually the most important contributor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

what is P-glycoprotein?

A

P-glycoprotein (P-gp) is an active transporter that protects the body from some harmful substances (including some drugs) by transporting the substance out of the body or out of sensitive organs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

give examples in the body of the importance of p-glycoprotein?

A

1) It transports drugs back out of the gut wall into the gut lumen, thus reducing absorption!
2) It helps keep some drugs out of the brain.
3) It transports drugs out of the kidney into the urine. Some drugs inhibit P-glycoprotein, allowing more of the first drug to be absorbed and less to be excreted, and allowing more of the drug to reach organs such as the brain.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

what are the important efflux pumps in the small intestine?

A

ATP-binding cassette (ABC) transporter family membersP-glycoprotein(P-gp)

breast cancer resistance protein(BCRP)

multidrug resistance protein 2(MRP2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

where are the important efflux pumps in the small intestine localised and what is their purpose?

A

They are localized in the luminal membrane of enterocytes and useATPas an energy source, allowing them to transport substrates against a concentration gradient. Their partially overlapping substrate spectrum, coupled with their cellular colocalization, suggests a concerted function of these three efflux pumps that would comprise a significant barrier to the intestinal absorption of xenobiotics.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

how does the level of drug absorption affect oral availability

A

the greater the drug absorption the better the oral availabiity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

how does first pass metabolism affect oral availability?

A

the greater the first pass metabolism, the lower the oral availability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

where does first pass metabolism occur

A

the gut wall, portal vein (uncommon) and in the liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

what affect does high levels of gut wall and hepatic metabolism have on oral availability?

A

decreases oral availability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

what is defined by the area under the concentration-time curve (AUC).

A

The total amount of drug in the systemic circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

how do you calculate oral availability (F)?

A

F = AUC (po) / AUC (iv)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

what affect does acidic conditions have on equilibrium of drugs?

A

Acidic conditions (low pH, high H+ concentrations) push the equilibrium of acidic drugs towards their un-ionised (protonated) form, and basic drugs towards their ionised form. Basic conditions (high pH) have the opposite effect.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

what physiochemical factors affect drug absorption?

A

The same drug produced in different formulations can have different oral bioavailability.

Slow/modified release preparations
May need to be prescribed non-generically (using trade name
For example:
Lithium modified release preparations
Diltiazem slow release preparations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

what affect does cirrhosis have on the bioavailability of drugs?

A

Oral bioavailability is substantially increased in cirrhosis for drugs with a moderate to high hepatic extraction ratio.

eg metoprolol is 50% available in normal liver where as in patient with cirrhosis it is 84% available (with a fold increase of 1.7)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

how do you calculate concentration steady state?

A

Css = [D x F] / [t x CL]

Css=conc. steady state
D=dose
F=oral bioavailability
t=time
CL=clearance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

what is the benefit of giving a loading dose?

A

A loading dose also allows earlier achievement of effective concentrations.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

why is there often a need for dose reduction of drugs metabolised by the liver in patients with liver disease?

A

The need for dose reduction arises primarily from an increase in bioavailability and a decrease in systemic clearance, both of which increase the average steady-state plasma concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

what is the role of cytochrome p450 in drug metabolism?

A

Cytochrome P450 enzymeschemically oxidize or reduce drugs (for example through hydroxylation). These are also known asPhase I reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

what is the role of conjugation enzymes in drug metabolism?

A

Conjugation enzymeslink one chemical to another. For example, glucuronyl transferases link a glucuronide group to zidovudine (AZT, Retrovir®), which makes it more water soluble and allows elimination in the urine. Acetylases link an acetyl group to isoniazid (INH), which is its major route of clearance. These are also known asPhase II reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

describe how a healthy liver is able to metabolise drugs?

A

fenestrations in the endothelium, allowing ready access to extracellular fluid
rapid diffusion across the space of Disse
brush border on hepatocytes, allowing rapid uptake
high intracellular enzyme activity for both phase 1 and phase 2 metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

describe how a liver with cirrhosis is less able to metabolise drugs?

A

fenestrations in the endothelium are lost
diffusion across the space of Disse may be reduced in fibrosis/cirrhosis
the brush border on hepatocytes is lost
intracellular enzyme activity is reduced
intrahepatic vascular shunts may reduce the perfusion of hepatocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

what affect will drugs with a high fraction unbound in plasma have in patients with

  1. renal impairment
  2. liver impairment
A
  1. renal impairment will decrease the clearance

2. liver impairment will not affect clearance of these drugs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

what affect will drugs with a low fraction unbound in plasma have in patients with

  1. renal impairment
  2. liver impairment
A
  1. renal impairment will not affect clearance

2. liver impairment will affect clearance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

describe how the liver and kidneys eliminate drugs?

A

Drugs are eliminated by excretion unchanged through the kidneys, or by metabolism to an inactive product usually in the liver.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

using fraction excreted unchanged (fu) define

  1. renal elimination
  2. metabolic elimination
A
  1. renal elimination =fu

2. metabolic elimination = 1-fu

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

describe first order kinetics?

A

The amount of drug is eliminated per unit time is proportional to the drug concentration – so a constant % of the drug is eliminated per unit time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

describe zero order kinetics?

A

The amount of drug eliminated is constant per unit time and not related to the concentration
This is saturation kinetics

alcohol is a zero order drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

in what situation can drugs move from a first order to a zero order drug?

A

when the enzyme metabolising them becomes saturated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

on a dose-plasma concentration graph what results in the line no longer being linear?

A

When metabolism becomes saturated the relationship between dose and plasma concentration is no longer linear.
ie dose is still increasing yet the body can not metabolise the drug in these quantities

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

give examples of drugs with a narrow therapeutic index?

A

lithium
gentamycin
digoxin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

what is the potential issue with making dose changes to a zero order drug?

A

a small dose change in zero order drug has a big effect on therapeutic levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

in patients with renal impairment what may cause them to show an abnormal drug response?

A
  1. failure to excrete the drug or its metabolites may produce toxicity
  2. there may be increased sensitivity, even if elimination is unaltered
  3. many unwanted effects are poorly tolerated
  4. some drugs cease to be effective
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

what type of drugs do the kidneys provide elimination for?

A

water soluble drugs and metabolites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

in what ways can renal impairment affect handling of drugs?

A
  1. liver metabolism (reduction, acetylation and ester hydrolysis) affected by patients with uraemia
  2. metabolic functions of the kidneys (1-alpha hydroxylation of vit D, degradation of insulin) impaired
  3. drug distribution affected by fluid balance changes due to renal failure
  4. tissue binding of digoxin is reduced in renal failure so lower dose needed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

when is lowering drug dosage considered in renal failure?

A

GFR <50mLmin-1
if high proportion of drug metabolised in kidneys
compound has a low therapeutic index

dependent on drug
ampicillin dose reduced in stage 5 renal failure
cisplatin avoided in stage 2 renal failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

what are the 6 main problems with prescribing drugs for patients with liver failure?

A
  • impaired drug metabolism
  • hypoproteinaemia
  • reduced blood coagulation
  • hepatic encephalopathy
  • fluid overload
  • hepatotoxic drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

give examples of drugs that may have an enhanced affect on patients with liver failure?

A
  • morphine, chlorpromazine (sensitivity to neuronal tissue cause encephalopathy)
  • benzodiazepines
  • drugs causing constipation may cause encephalopathy
  • diuretics producing hypokalaemia can also cause encephalopathy
  • sensitive to anticoagulants
  • hepatotoxic drugs such as paracetamol, opioids, NSAIDs
82
Q

what is population pharmacokinetics?

A

Population pharmacokinetics (popPK) is the study of variability in drug concentrations within a patient population receiving clinically relevant doses of a drug of interest

83
Q

what are the 4 principal targets for drug action?

A

receptors
ion channels
carriers
enzymes

84
Q

what is a receptor?

A

a protein molecule in the body that acts as a recognition site for the body’s natural mediators or ligands. a ligand will specifically bind to the receptor, which then transmits a signal and elicits a biological effect. a ligand can switch this response on or off. drugs acting on receptors often resemble the ligand structurally and bind to the receptor

85
Q

describe ion channels as targets of drug action?

A

proteins in the membrane that form a pore or channel through which ions can pass. they only allow specific ions to pass through them and only when activated. drugs can bind to these ion channels and alter function
local anaesthetics block sodium ion channels

86
Q

describe carriers as targets of drug action?

A

they are membrane bound proteins that transport specific molecules across the plasma membrane of a cell. the molecules bind to specific recognition sites on the carrier which induces a change so the molecule is transferred to the other side of the membrane

87
Q

describe enzymes as targets of drug action?

A

biological catalysts that speed up chemical reactions without being changed themselves. an enzyme binds to the substrate and induces chemical reactions
aspirin works by inhibiting enzymes

88
Q

what are the 3 main pharmacological cellular mechanisms of action?

A

excitation
contraction
secretion

89
Q

define therapeutic index?

A

The therapeutic index (TI; also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity. The related terms therapeutic window or safety window refer to a range of doses which optimise between efficacy and toxicity, achieving the greatest therapeutic benefit without resulting in unacceptable side-effects or toxicity.

90
Q

define efficacy?

A

The word efficacy is used in pharmacology and medicine to refer both to the maximum response achievable from a pharmaceutical drug in research settings, and to the capacity for sufficient therapeutic effect or beneficial change in clinical settings

91
Q

define drug potency?

A

potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a given response at low concentrations, while a drug of lower potency evokes the same response only at higher concentrations.

92
Q

define desensitisation to a drug?

A

Desensitization refers to the common situation where the biological response to a drug diminishes when it is given continuously or repeatedly. It may be possible to restore the response by increasing the dose (or concentration) of the drug but, in some cases, the tissues may become completely refractory to its effect.

93
Q

define tolerance to a drug?

A

Drug tolerance is a pharmacological concept describing subjects’ reduced reaction to a drug following its repeated use. Increasing its dosage may re-amplify the drug’s effects; however, this may accelerate tolerance, further reducing the drug’s effects.

94
Q

what is an agonist?

A

An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response.

95
Q

what is an antagonist?

A

A substance that acts against and blocks an action. Antagonist is the opposite of agonist.

96
Q

what is a partial agonist?

A

partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist

97
Q

what is the definition of chemotherapy?

A

the therapeutic use ofchemicalagents to treat disease. especially:the administration of one or morecytotoxicdrugs to destroy or inhibit the growth and division ofmalignantcells in the treatment of cancer

98
Q

what are the side effects of chemotherapy?

A
  • GI-diarrhoea, sore mouth, nausea, vomiting
  • myelosuppresion can cause anaemia, neutropenia and thrombocytopenia
  • hair loss
  • reproductivity
  • tumour lysis syndrome
99
Q

what is tumour lisis syndrome

A

Rapid breakdown of malignant cells can cause hyperuricaemia, hyperkalaemia, hypophosphatemia, hypocalcaemia with consequent renal damage / arrhythmias

100
Q

what class of drug is capecitabine?

A

base analogue anti metabolite (for chemotherapy)

101
Q

give examples of base analogue anti-metabolites?

A

capecitabine
Cytarabine
Mercaptopurine (purine antagonist)
Flurouracil

102
Q

what is the mechanism of action of capecitabine?

A

Interferes with DNA synthesis - Stops cells making and repairing DNA
It is a pro-drug of Fluorouracil and thus a pyrimidine antagonist.

103
Q

how is capecitabine administered?

A

oral tablet, usually twice daily for 14 days

104
Q

what is the class and mechanism of oxaliplatin?

A

platinum compound
inhibits DNA synthesis
oxaliplatin exerts its cytotoxic effect mostly throughdnadamage. Apoptosis of cancer cells can be caused by formation ofdnalesions, arrest ofdnasynthesis, inhibition ofrnasynthesis, and triggering of immunologic reactions. Oxaliplatin also exhibits synergism with other cytotoxic drugs

105
Q

what are platinum compounds used for?

A

cisplatin and carboplatin- ovarian and lung tumours

solid malignancies

106
Q

give examples of platinum compounds?

A

Oxiplatinin, cisplatin, carboplatin.

107
Q

what are the side effects of platinum compounds?

A 
Severe nausea and vomiting
Nephrotoxicity (hydration is essential)
Ototoxicity
Peripheral neuropathy
Myelosupression
108
Q

what is extravasation?

A

Extravasation is the leakage of intravenously (IV) infused, and potentially damaging, medications into the extravascular tissue around the site of infusion.

109
Q

how can extravasation be prevented?

A
  • flushing cannula
  • observe cannula
  • cannula in appropriate place (avoid previously radiotherapy areas, joints, damaged skin etc, insert cannula proximal to previous cannulation attempts, keep cannula visible at all times)
110
Q

what is anastrozole and describe its mechanism of action?

A

aromatase inhibitor
competitive inhibition blocks the conversion of androgens to estrogens
used in breast cancer treatment

111
Q

what group of women are aromatase inhibitors not used in?

A

not given to premenopausal women because
their ovaries still produce oestrogen. aromatase inhibitors will not
stop the ovaries from making the oestrogen that
feeds the tumour.

112
Q

what are the potential adverse effects from anastrazole?

A 
Hot flushes 
Vaginal dryness 
Vaginal bleeding 
Hair thinning 
Anorexia 
Nausea &amp; Vomiting
Diarrhoea 
Headache
Arthralgia 
Arthritis
Bone fractures, 
Bone pain, 
Rash (including Stevens-Johnson syndrome), 
Cutaneous vasculitis; asthenia
Drowsiness—may initially affect ability to drive or operate machinery
113
Q

what is Stevens Johnson syndrome?

A

severe skin reaction, frequently involving the mucus membranes
blisters, fever, flu like symptoms
if untreated can progress to sepsis, multi organ failure and death

114
Q

what is tamoxifen?

A

selective oestrogen receptor modulator
affective in pre and post menopausal women
nonsteroidal triphenylethylene derivative that binds to the estrogen receptor
strongly antiestrogenic on mammary epithelium, hence its use in both the prevention and treatment of breast cancer
Inhibits the transcription of oestrogen-receptive genes

115
Q

what are the drug interactions of tamoxifen?

A

SSRIs can inhibit tamoxifen metabolism

warfarin-tamoxifen inhibits CYP3A4 so increases the risk of bleeding

116
Q

what is the duration of treatment of tamoxifen?

A

20mg OD for 5 years

117
Q

what are the differentials for a child presenting with unexplained bruising?

A 
child abuse
acute lymphoblastic leukaemia 
idiopathic thrombocytopenia purpura 
genetic clotting disorder eg haemophilia
vitamin k deficiency
118
Q

what are the stages of chemotherapy treatment?

A

induction
consolidation
maintenance

119
Q

what is induction of chemotherapy treatment?

A

intensive treatment aimed at destroying as many leukaemia cells as possible and achieving remission (no leukaemia cells on bone marrow biopsy). Lasts 4-6 weeks

120
Q

what is consolidation in chemotherapy treatment ?

A

aimed at remission and preventing spread. Often involves intra-spinal injections and then tablets.

121
Q

what is maintenance of chemotherapy treatment?

A

lasts 2 years (girls) or 3 years (boys) from the start of interim treatment. Involves regular tablets and possible injections.

122
Q

what is cyclophosphamide?

A

alkylating agents
They include a side chain which undergoes metabolic activation and binds to DNA, preventing DNA synthesis
Alternatively, it binds to proteins which blocks DNA repair processes.
Forms DNA crosslinks within and between DNA strands leading to cell apoptosis

123
Q

what are the side effects of cyclophosphamide?

A

-Impaired fertility in the future
-Bone marrow suppression and neutropenia
-Can develop other malignancies,
e.g. Acute Myeloid leukaemia,
Bladder cancer (reduced risk by given mesna (mercaptoethane sulphonic acid) prior to treatment)

124
Q

what is vincristine?

A

vinca alkaloid
Miotic inhibitors
Binds to tubulin molecules and prevent the formation of microtubules, preventing chromosome separation
Eventually leads to cell death

125
Q

what is doxarubicin?

A

“Cytotoxic antibiotic”
Anthracycline
Multiple mechanisms of action including prevention of the DNA double helix from being resealed

126
Q

what are the side effects of doxarubicin?

A

dilated cardiomyopathy

127
Q

what is methotrexate?

A

folic acid antagonist
Immunosuppresant
DMARD used in rheumatoid arthritis, psoriasis etc
Other uses include abortion and molar pregnancy
Excreted renally, nephrotoxic, hepatotoxic and bone marrow toxic. Requires regular monitoring.

128
Q

what blood results would suggest acute blood loss?

A

low haemoglobin but normal MCV, MCD and MCHC

129
Q

what causes urea to be raised?

A

blood has been digested

130
Q

what blood results would cause you to consider blood loss?

A

high urea with normal creatinine

131
Q

what is the management stages for peptic/duodenal ulcer or oesophagitis in hypovolaemic shock?

A
  • ABCDE
  • Cannula (maybe X2)
  • 0.9% NaCl 500ml over <15 mins / compound sodium lactose 500ml 15min X2
  • Upper GI endoscopy
  • Stop bleed-inject adrenaline (vasoconstrict) or cautorise
  • Withhold Blood pressure medications due to hypovolaemic shock and low blood pressure
132
Q

what is the mechanism of PPI?

A

inhibit gastric acid secretion by blocking hydrogen potassium adenosine triphosphate enzyme system of gastric parietal cell

133
Q

how does COX1 affect the GI tract?

A

removes GI mucosa

134
Q

what are the ways of testing for H.pylori?

A

urease breath test
CLO test
wait for ulcer to heal before eradication therapy, high dose PPI and 2 antibiotics

135
Q

what interacts with azathiprine due to xanthine oxidase?

A

allopurinol

136
Q

what important drug interacts with clarithromycin?

A

simvastatin

137
Q

what classes of drugs can be used to treat constipation?

A

bulk forming laxatives
osmotic laxatives
irritant and stimulant laxatives
faecal softeners

138
Q

which laxatives appear to be safe in pregnancy?

A

senna
magnesium salts
docusate

139
Q

which laxatives are suitable for the elderly or for the terminally ill with opioid induced constipation?

A

bisacodyl
co-danthramer
co-danthrusate

140
Q

what drug can be used for opioid induced constipation when other laxatives are ineffective?

A

methylnatrexone (peripheral opioid receptor antagonist)

141
Q

what laxative should be used for patients who have neurological disease affecting bowel motility as the cause of constipation?

A

faecal softener with regular enemas or rectal washouts

142
Q

what drugs can be used to treat diarrhoea?

A

codeine phosphate
diphenoxylate
loperamide

143
Q

what drugs can be used in the treatment of irritable bowel syndrome?

A 
antimuscarinic drugs (dicycloverine, propantheline)
other antispasmadic agents (mebeverine, peppermint oil)
144
Q

what classes of drugs can be used in the treatment of ulcerative colitis?

A 
aminosalicylates 
corticosteroids
cytokine modulators 
immunosuppresants 
antibiotics
145
Q

give examples of aminosalicylates?

A

mesalazine
olsalazine
sulfasalazine

146
Q

give examples of corticosteroids

A

hydrocortisone
prednisolone
budenoside

147
Q

give examples of cytokine modulators

A

adalimumab

infliximab

148
Q

give examples of immunosuppresants?

A

azathioprine

methotrexate

149
Q

what monitoring is required for patients on corticosteroids/

A

assess for osteoporosis
assess for cushingoid features
assess for hyperglycaemia, cataracts or glaucoma

150
Q

what are the significant side effects from corticosteroids?

A 
systemic infectios
gastritis 
diabetes
heart failure
psychiatric effect
sleep disturbance
osteoporosis 
growth suppresion in children
151
Q

what monitoring is required for patients on aminosalicylates/

A

mesalazine
U&E annually
sulfasalazine-FBC, LFT every 3 months

152
Q

what are the significant side effects of aminosalicylates?

A

headache

153
Q

what monitoring is required for patients on immunosuppresants?

A

once stable-FBC &LFT every 3 months

U&E every 6 months

154
Q

what are the significant side effects from immunosuppresants?

A

increased susceptibility to sunburn
increased risk of cervical abnormalities
increased susceptibility to infectins
increased risk of lymphoma

155
Q

what monitoring is required for patients on biologic agents?

A

FBC, CRP, U&E, LFT every 6 months

lipid profile and hepaitis B statis checkes

156
Q

what are the significant side effects of biologic agents?

A

injection site skin reactions

increased susceptibillty to infectons such as TB

157
Q

what is the primary care management of ulcerative colitis flare up of proctitis?

A

mesalazine salofalk suppository, pentasa suppository

158
Q

what is the primary care management of ulcerative colitis flare up of left sided disease?

A

mesalazine foamenema, pentasa liquid enema or salofalk liquid enema
budesonide budenofalk foam enema or predinsolone redsol liquid enema
-add 5ASA if still asymptomatic

159
Q

what is the primary care management of ulcerative colitis flare up of pancolitis/extensive disease?

A
  • maximise 5-ASA

- add topical therapy

160
Q

what is the primary care management of ulcerative colitis flare up if previous treatment fails?

A

oral prednisolone

161
Q

what is azathioprine?

A

Azathioprineis a prodrug that is quickly converted to 6-mercaptopurine via a nonenzymatic nucleophilic attack by sulfhydryl-containing compounds, such as glutathione, present in red blood cells and other tissues. 6-MP is then metabolized in the liver and gut by one of three enzymes.

162
Q

what are the 2 serious drug interactions with azathioprine?

A

allopurinolandfebuxostat, which slow the elimination of 6-MP by inhibiting xanthine oxidase.

163
Q

what is infliximab?

A

chimeric monoclonal antibody comprised of 75 percent human and 25 percent murine sequences, which has a high specificity for and affinity to tumor necrosis factor (TNF)-alpha. Infliximab neutralizes the biologic activity of TNF-alpha by inhibiting binding to its receptors. Infliximab can also stimulate apoptosis of activated lymphocytes in the gut mucosa.

164
Q

what is adalimumab?

A

recombinant fully human monoclonal antibody that binds to TNF-alpha, thereby interfering with binding to TNF-alpha receptor sites and subsequent cytokine-driven inflammatory processes

165
Q

what are the risks of empiric antibiotic therapy in treating acute infective diarrhoea?

A

potential side effects, promotion of bacterial resistance, eradication of normal flora (and increased risk ofC. difficileinfection), and cost.

166
Q

when is empiric antibiotic therapy appropriate for patients with acute diarrhoea?

A
  • Severe disease (fever, more than six stools per day, volume depletion warranting hospitalization).
  • Features suggestive of invasive bacterial infection, such as bloody or mucoid stools (except in cases of non-severe disease when fever is low or absent).
  • Host factors that increase the risk for complications, including age >70 years old and comorbidities such as cardiac disease and immunocompromised patients.
167
Q

what is fidaxomicin?

A

relatively new drug which was originally discovered in actinomycetes. It inhibits bacterial RNA polymerase. It is not used to treat systemic infections as it is poorly absorbed from the gut, but has a role in treatingC. difficileinfections

168
Q

what is vancomycin?

A

glycopeptide antibiotic similar to teicoplanin – also used to treat MRSA.

169
Q

what is the mechanism of perioperative pain?

A

results from inflammation caused by tissue trauma (i.e., surgical incision, dissection, burns) or direct nerve injury (i.e., nerve transection, stretching, or compression)

170
Q

describe transmission of pain impulses?

A

Tissue injury leads to release of inflammatory mediators with subsequent nociceptor stimulation.
Pain impulses are then transmitted to the dorsal horn of the spinal cord, where they make contact with second-order neurons that cross to the opposite side of the cord and ascend via the spinothalamic tract to the reticular activating system (RAS) and thalamus.

171
Q

at what level does the localisation and meaning of pain occur at?

A

somatosensory cortex

172
Q

what can cause hyperalgesia and allodynia?

A
  • tissue trauma releasing local inflammatory mediators
  • sensitization of the peripheral pain receptors (primary hyperalgesia) and increased excitability of central nervous system neurons (secondary hyperalgesia).
173
Q

what is the classical model for central pain sensation in surgical trauma?

A

The transmission of incoming nociceptive impulses is modulated by dorsal horn circuitry that receives input from peripheral touch receptors and from descending pathways that involve the limbic cortical systems (orbital frontal cortex, amygdala, and hypothalamus), periaqueductal endogenous analgesic center in the midbrain, pontine noradrenergic neurons, and the nucleus raphe magnus (NRM) in the medulla.

174
Q

what modulates the transmission of incoming nociceptive impulses?

A

dorsal horn circuitry that receives input from peripheral touch receptors and from descending pathways involving limbic cortical system

175
Q

how do anaesthetists traditionally reduce peri operative pain?

A

Traditionally, acute perioperative pain management has relied solely on opioid medications to target central mechanisms involved in the perception of pain

176
Q

why are numerous anaesthetic agents given?

A

For anesthesia 3 different agents are used as lower dosages can be used and therefore there will be fewer side effects

177
Q

what are the most widely used treatment of postoperative pain?

A

Opioids are the most widely used treatment of postoperative pain. Morphine is the prototype opioid and the drug with which other analgesics are compared.

178
Q

what are the side effects of opioids?

A

These include somnolence, depression of brainstem control of respiratory drive, hypotension (more common in hypovolaemic patients and following rapid injection), urinary retention, and nausea and vomiting due to direct stimulation of the chemoreceptor trigger zone.
Histamine release often follows morphine administration and may produce flushing, tachycardia, hypotension, pruritus, and bronchospasm.
Gastrointestinal transit slows with prolonged administration, resulting in constipation and ileus in many patients; this effect is thought to reflect binding to local opioid receptors in the gut.

179
Q

what is a competitive agonist?

A

Competitive antagonists are drugs that bind to the receptor in a reversible way without activating the effector system for that receptor. In the presence of a competitive antagonist, the log dose-response curve is shifted to higher doses (ie, horizontally to the right on the dose axis) but the same maximal effect is reached.

180
Q

what is an irreversible antagonist?

A

an irreversible antagonist causes a downward shift of the maximum, with no shift of the curve on the dose axis unless spare receptors are present (Figure 2-5B). The effects of competitive antagonists can be overcome by adding more agonist. Irreversible antagonists cannot be overcome by adding more agonist. Competitive antagonists increase the ED50; irreversible antagonists do not (unless spare receptors are present).

181
Q

what is multimodal analgesia?

A

uses several agents, each acting at different sites of the pain pathway, and is known as multimodal analgesia. This approach lessens the dependence on a single medication and mechanism.

182
Q

how can pain receptor activity be blocked directly and indirectly?

A

Pain receptor activity can be directly blocked, e.g. lidocaine, , or anti-inflammatory agents, e.g. NSAIDs, can be used to diminish the local hormonal response to injury, thus indirectly decreasing pain receptor activation.

183
Q

what do local anaesthetics such as bupivacaine do?

A

Local anaesthetics disrupt ion channel function within the neurone cell membrane preventing the transmission of the neuronal action potential. This is thought to occur via specific binding of the local anaesthetic molecules (in their ionised form) to sodium channels, holding them in an inactive state so that no further depolarisation can occur.

184
Q

describe the action of epidural opiates?

A

direct action on opioid receptors - Opioids have actions at two sites, the presynaptic nerve terminal and the postsynaptic neuron. The postsynaptic actions of opioids are usually inhibitory. The presynaptic action of opioids is to inhibit neurotransmitter release, and this is considered to be their major effect in the nervous system. However, the final effect of an opioid in the brain is the result, not only of its action at multiple presynaptic sites on both inhibitory and excitatory neurons, but also of its postsynaptic effects. For example, presynaptic inhibition of neurotransmitter release may result in excitatory effects in a target neuron if the neurotransmitter normally produces an inhibitory effect. However, if the opioid also has a postsynaptic inhibitory effect on the target neuron, the excitatory effects may not occur. Thus, the location and density of opioid receptors on a neuron determines the overall effect of opioids on the neuron. Morphine, by an action on m receptors, inhibits release of several different neurotransmitters including noradrenaline, acetylcholine and the neuropeptide, substance P. The opioid drugs produce analgesia by actions at several levels of the nervous system, in particular, inhibition of neurotransmitter release from the primary afferent terminals in the spinal cord and activation of descending inhibitory controls in the midbrain.

185
Q

how is postoperative pain usually managed especially following abdominal and thoracic surgical procedures?

A

A combination of a local anesthetic and opioid is commonly administered by infusion via an epidural catheter for postoperative pain, especially for abdominal and thoracic surgical procedures. This combination reduces the dose required and the frequency of side effects.

186
Q

what drugs are commonly used for multimodal analgesia in acute pain?

A

opioids, nonopioids, and a variety of adjuvant analgesics. Combinations of analgesics are chosen based on a mechanistic approach that targets the pain pathway in both the peripheral and central nervous system

187
Q

what is paracetamol also known as?

A

acetaminophren

188
Q

what medication could be added during the operation if there is a concern of breakthrough pain?

A

IV opioid

a regular NSAID and oral opiate tailing off from strong to moderate

189
Q

what is nausea and vomiting controlled by?

A

vomiting centre in brainstem
efferent impulses from medullary centres influence related brainstem nuclei to initiate vomiting reflex
afferent stimuli arrive from chemoreceptors and pressure receptors in the gut and CNS as well as peripheral pain receptors, other sites on input in the CNS include cerebral cortex (pain, fear, anxiety), vestibular and cerebellar nuclei and in CTZ

190
Q

what drugs can be used for propylaxis or rescue therapy for nausea and vomiting?

A

serotonin-receptor antagonists, corticosteroids, anticholinergic agents, and neurokinin-receptor antagonists.

191
Q

what is the most commonly used pharmacological agent used for PONV, why and how do they work?

A

Selective serotonic receptor (5-HT3) antagonists
they do not have sedative side effects and intravenous preparations are available. They can be used prophylactically or for rescue treatment of PONV. Serotonin receptor-antagonists suppress the initiation of nausea and vomiting by blocking serotonin peripherally at vagal afferents and centrally in the chemoreceptor trigger zone.

192
Q

what drug is usually given for nausea and vomiting if the cause is unknown?

A

ondansetron as it works on many aspects of the brain

193
Q

give an example of a serotonin receptor antagonist, its mode of action, ECG changes it may cause and other effects?

A

ondansetron
5-HT3 antagonism Both peripherally And CTZ
causes QT prolongation
non-sedating

194
Q

give an example of a glucocorticoid, its mode of action, and other effects?

A

dexamethasone
unknown mode of action
no significant increase in periop hyperglycaemia or wound infections

195
Q

give an example of an anticholinergic, its mode of action, ECG changes it may cause and other effects?

A

scopolamine
unknown, possibly blocking communication to vomiting centre
sedating, don’t use in patient with narrow angle glaucoma

196
Q

give an example of a neurokinin-receptor antagonist, its mode of action, ECG changes it may cause and other effects?

A

aprepitant
blocks neurokinins effect (pro-emetic agent) at receptor site
expensive

197
Q

what adverse effect can metoclopramide cause especially in young people?

A

metoclopramide

198
Q

what can be used as effective emergency treatment for acute drug induced dystonic reactions?

A

procyclidine hydrochloride given parenterally
Response is often dramatic and generally occurs in 5-20mins
if symptoms persist after 15-30mins a second dose can be given.
if symptoms persist and are not improving after second dose consider the possibility of an alternative diagnosis.

199
Q

give examples of IV fluid therapy?

A

0.9% sodium chloride
Hartmann’s solution (isotonic)
glucose saline

200
Q

what is the composition of sodium chloride 0.9%?

A

sodium
chloride
pH 4.5-7

201
Q

what is the composition of Hartmann’s solution?

A 
sodium
chloride
potassium
bicarbonate 
calcium
pH 5-7

Block 32 GI and surgery (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions