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Pharmacology CSA236 > introduction to pharmacology > Flashcards

introduction to pharmacology Flashcards

1
Q

What are drugs?

A

A drug is a chemical substance of known structure
which, when administered to a living organism,
produces a biological effect.
- Chemicals obtained from plants or animals
- Synthetic chemicals
- Products of genetic engineering

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2
Q

What is Pharmacology?

A

The study of drugs, including their actions and

effects on living systems.

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3
Q

What is Pharmacodynamics?

A

What the drug does to the body

  • How does the drug work?
  • What effects does the drug have on the cell / tissue / body?
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4
Q

What is Pharmacokinetics?

A

What the body does to the drug

  • Absorption – how does the drug get into the body?
  • Distribution – where does the drug go and how does it get there?
  • Metabolism – is the drug broken down?
  • Excretion – how does the drug/metabolite leave the body?
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5
Q

What is Pharmacotherapeutics?

A

The use of drugs to prevent and treat diseases

  • What are the beneficial effects of the drug?
  • What are the adverse effects of the drug?
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6
Q

Why study pharmacology?

A 
As a paramedic... You will need to make recommendations and
decisions regarding:
---Treatment requirements/drug selection
---Dosage requirements
---Indications
---Effects
---Contraindications
---Drug interactions
---Adverse effects

———-Pharmacology provides the foundation for
therapeutic decision making
———-Pharmacology will underlie many clinical
decisions you make as a paramedic

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7
Q

Drug targets

A

Drugs bind to drug targets, mostly in/on cells:

—-Binding results in a biological response

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8
Q

What are most drug targets?

A

Protein molecules:

  • –Receptors
  • –Ion channels
  • –Transporters
  • –Enzymes
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9
Q

What do these proteins generally have?

A

These proteins generally (but not always) have corresponding endogenous ligands (compounds normally present in the body).

  • –e.g. Opioid receptors respond to endorphins (endogenous
    ligand) and morphine (drug).
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10
Q

Binding

A 
Drugs that bind to drug
targets are similar to the
endogenous ligands in:
----Size
---Shape
---Chemical binding (ionic
(positive/negative), H-bonding, polarity)
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11
Q

Receptors

A

Respond to chemical messengers such as neurotransmitters, hormones, and other
mediators (endogenous ligands).
—-Drugs can activate or block
these receptors.

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12
Q

What are agonists?

A

Activate receptors

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13
Q

What are antagonists?

A

Block receptors

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14
Q

What is a receptor?

A

In pharmacology, it describes protein molecules whose function is to recognize and respond to endogenous signals.

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15
Q

What are ion channels?

A 
Transmembrane proteins with a
central core.
---Allow the transfer of ions down
their electrochemical gradient.
---The open/closed state is
sensitive to chemicals
(neurotransmitters, drugs) or
changes in voltage across the cell membrane (e.g.
depolarisation).
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16
Q

What do agonists and antagonists do in regard to ion channels?

A

Agonists - open channels

Antagonist- block channels

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17
Q

What is an example of ion channeling?

A

Sodium channels:

  • —-The channels open when the cell membrane is partially depolarised.
  • —-Na+ flows into the cell, causing depolarisation.

In nerve cells:

  • Depolarisation ——-nerve conduction.
  • Lignocaine blocks Na+ channels —- loss of sensation (local anaesthetic).
  • Common mechanism of action for drugs used to treat neuropathic pain

In cardiac cells:

  • Depolarisation —cardiac rhythm.
  • Lignocaine blocks Na+ channels —– treats arrhythmias (anti-arrhythmic).
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18
Q

What are enzymes?

A

Proteins that catalyse biochemical reactions.

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19
Q

What does the enzyme drug molecule resemble?

A

Drug molecules may resemble the enzyme substrate and act as inhibitors.
—–Drug molecule may resemble the
enzyme-substrate and act as a false substrate:
—-The drug molecule undergoes a chemical transformation to an abnormal product that changes
the normal metabolic pathway

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20
Q

What is an example of an enzyme inhibitor?

A

Ramipril, an antihypertensive drug, inhibits angiotensin converting enzyme (ACE).

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21
Q

What is an example of a false substrate?

A

Fluorouracil, an anticancer drug, is an analogue of uracil and acts as a false substrate, thereby blocking DNA synthesis.

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22
Q

What are transporters?

A 
Carrier proteins (transporters)
----Transport ions across cell membranes against their concentration gradient.

—–Transport and small organic
molecules across cell membranes because the
molecules may be too water soluble to penetrate lipid membranes on their own.

—Drugs may act to inhibit the transporter or may sufficiently resemble the endogenous substrate to use the transporter

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23
Q

What is an example of a carrier protein? (transporter)

A

Thiazide diuretics inhibit the Na+/Cl- co-transporter in the kidneys, causing increased excretion of Na+ and Cl- ions.

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24
Q

How does a drug elicit a tissue response?

A

It must bind to the drug target and activate the drug target.

Binding is governed by affinity and activation is governed by efficacy

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25
Q

What is affinity?

A

The tendency of a drug to bind to a drug target.
Governed by intermolecular forces.
Drug molecule should fit binding site.
Poorer fit—- lower affinity.

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26
Q

What is efficacy?

A

The tendency for a drug to activate a drug target upon binding.

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27
Q

What do level of efficacy do agonist, antagonist, and partial agonist elicit?

A

Agonists elicit the full response (100% efficacy). eg morphine

Antagonists elicit no response (zero efficacy). (can be reversible or irreversible)

Partial agonists elicit a partial response (intermediate efficacy). Partial agonists have submaximal (1-99%) efficacy. eg buprenorphine

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28
Q

What is potency?

A

The concentration of a drug required
to produce a specific response.
Lower concentration = higher potency

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29
Q

What is potency determined by?

A

Affinity and efficacy

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30
Q

What is the difference between reversible and irreversible antagonists?

A

Reversible —-raising the concentration of an
agonist will overcome the block

Irreversible—- raising the concentration of an
agonist will not overcome the block

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31
Q

What can we derive from Log concentration-response curves?

A

The maximal response that the
drug can produce (Emax)
—–Emax determines efficacy

The concentration required to
produce 50% of maximal response (EC50).
—–EC50 is a common measure of
potency

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32
Q

Why is the response different for partial

and full agonists?

A

Some drugs (full agonists) can produce a maximal response (the largest response that the tissue is capable of giving), whereas others (partial agonists) can produce only a submaximal response.

Because partial agonists occupy receptors, they compete with the action of a full agonist while producing a small effect of their own.

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33
Q

What have experiments shown regarding the different responses of partial and full agonists?

A

Partial agonists don’t bind to fewer receptors

  • —Even when 100% of receptors are occupied, the response for the partial agonist is smaller than the response for a full agonist.
  • —-they have lower efficacy.
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34
Q

What are antagonists?

A

An antagonist drug binds selectively to a particular type of receptor without activating it, but in such a way as to prevent the binding of the agonist.

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35
Q

What are reversible antagonists?

A

A reversible (competitive) antagonist dissociates from the drug target.

Because the receptor can only bind one drug molecule at a time, the antagonist and agonist molecules compete with each other during rapid association and dissociation with the receptor.

The effect of the antagonist can be overcome by raising the concentration of the agonist and vice versa.

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36
Q

What is an example of a reversible antagonist?

A

atropine reversibly inhibits muscarinic ACh receptors.
—-This causes antimuscarinic effects in the body: dry mouth, dilated pupils, increased heart rate etc.

—This can be overcome by increasing the concentration of ACh at muscarinic receptors (usually with a drug that inhibits the breakdown of
ACh).

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37
Q

Reversible antagonism - graph

A

As the concentration of antagonist increases, the
concentration of agonist required to maintain the receptor occupied with agonist increases.
“Competitive binding”

The shape of the curve, and the maximum occupancy stays the same (curve shifts to right ie. now need higher concentration of agonist to
achieve same effect).

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38
Q

What are Irreversible antagonists?

A

An irreversible antagonist dissociates very slowly, or not at all, from the drug target (the binding is irreversible).

Due to the strong antagonist binding, an agonist cannot compete for binding.

Raising the concentration of the agonist will not reverse the effect of the antagonist.

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39
Q

What is an example of an irreversible antagonist?

A

aspirin irreversibly inhibits the enzyme cyclo-oxygenase in platelets.

  • —-This leads to decreased platelet aggregation (‘blood thinning’).
  • —-Recovery requires synthesis of new platelets (7-10 days).
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40
Q

Irreversible antagonists - graph

A

In the presence of an irreversible antagonist, the agonist occupancy can no longer be reached.

Raising the concentration of the agonist has no effect on the occupancy because the receptors are irreversibly blocked by the antagonist (“non-competitive binding”)

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41
Q

What is absorption?

A

The passage of a drug from its site of administration into the plasma.

  • —-Absorption is important for all routes of administration, except for iv injection.
  • —–In most cases, the drug must enter plasma before reaching its site of action (except when the drug is administered for local effect).
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42
Q

What are the barriers to oral absorption?

A

Disintegration, Dissolution
Instability
Lipid solubility, Metabolism
Metabolism

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43
Q

Water soluble drugs are…?

A

Hydrophilic
Ionised
Polar (charged)

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44
Q

What are lipid soluble drugs?

A

Hydrophobic

  • –Lipophilic
  • –Unionised
  • –Non-polar (neutral)
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45
Q

What is Lipophilicity?

A

Most important property that determines permeation:

  • –Ability of drug to dissolve in lipids
  • –Drugs with good lipophilicity can diffuse passively through cell membranes!
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46
Q

What is oral administration?

A

Absorption occurs through the gastrointestinal tract (GIT).

  • —Via the stomach (very little absorption due to low surface area):
  • —Protective mucous barrier slows absorption.
  • —Acidic pH (hydrolysis of acid labile drugs, favours absorption of weak acids).

Via the small intestine (mainly):

  • –Large surface area (villi and microvilli).
  • –Vascular
  • –pH ~ 6.
  • —Fastest GI site of absorption for all drugs (even when ionisation is unfavourable).

Via large intestine:
—Mucous layer and lack of villi – slower absorption.

GI absorption is affected by:
—GI motility, blood flow, particle size, solubility, pH, pharmaceutical formulation.

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47
Q

What is first past metabolism?

A

Depending on whether the drug is metabolised or not, a variable amount of drug may be extracted by the liver before the drug ever reaches the systemic
circulation and its site of action. Also occurs to lesser extent in wall of small intestines.

If a drug undergoes substantial metabolism on the first pass through the liver, only a small fraction of the dose is available for systemic distribution and to produce a pharmacological effect.

The oral drug dose must be calculated to compensate for this first-pass effect.

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48
Q

What is bioavailiability?

A

Extent of bioavailability is the fraction of the dose that is absorbed into the systemic circulation, escaping degradation in the GIT and first-pass metabolism.

Bioavailability is 100% following an intravenous injection, but less following oral administration.

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49
Q

Bioavailibility varies with what?

A
  • –Routes of administration (e.g. oral vs. intravenous).
  • –Preparations and batches (e.g. tablets vs. capsules, batch-to-batch differences in the same formulation).
  • –Individuals (e.g. differences in enzyme activity, GI motility, food intake, gastric pH etc.)
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50
Q

What is distribution?

A

Distribution around the body occurs when the drug reaches the circulation.
—-Drugs are distributed throughout various body compartments, including plasma, adipose tissue, the CNS and other organs.

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51
Q

The distribution pattern between various body compartments depends on:

A
  • —Permeability across tissue barriers
  • —Binding within compartments
  • —Physicochemical properties of drugs
  • —Regional blood flow
  • —Cardiac output
  • —Capillary permeability (except in the CNS protected by the blood brain barrier)
  • —Plasma protein binding
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52
Q

What is the blood brain barrier?

A

Brain capillaries are much less permeable than most other body capillaries.

Tight junctions seal together the endothelial cells of brain capillaries, which are also surrounded by a continuous basement membrane.

The brain is consequently inaccessible to many drugs, unless they are highly lipid soluble.

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53
Q

What is plasma protein binding?

A

In the circulation, drug molecules bind to proteins to form drug-protein complexes
—-An equilibrium establishes between free and bound drug
—-Only free (unbound) drug is able to move to its site of action and exert a
pharmacological effect.

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54
Q

What factors affect protein binding?

A

Two drugs can compete for one binding sites on proteins.

  • —Changes the amount of plasma protein (e.g. low levels due to liver damage).
  • –Reduced protein binding increases the amount of unbound drug which can lead to toxic effects (but effects have been over-stated in the past).
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55
Q

What happens when a free drug is eliminated?

A

When free drug is eliminated the drug-protein complex dissociates to re-establish
the equilibrium.
—-The equilibrium dictates a certain fraction/percentage to be protein-bound
—-e.g. warfarin (an anticoagulant) is normally 99% bound

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56
Q

What is the volume of distribution?

A

Vd = Total amount of drug in the body (dose with I.V.)/Plasma drug concentration

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57
Q

What does it mean to have a small Vd?

A

Drugs with a small Vd may be confined to the plasma due to plasma protein binding (little
free drug available) or be very hydrophilic
—-These tend not to accumulate in the body
—-Safer to use in pregnancy and breastfeeding and have fewer CNS effects

58
Q

What does it mean to have a large Vd?

A

Drugs with a large Vd may have accumulated in adipose tissue.
—They also tend to accumulate in the body with repeated dosing, cross the the placenta and into
breast milk, cross the blood-brain barrier and require loading doses.

59
Q

What is drug metabolism?

A

Biotransformation of a drug by enzymes.

60
Q

What is one important effect of drug metabolism?

A

The drug is made more polar (hydrophilic) – this hastens excretion by the kidneys, because the polar metabolite is not readily reabsorbed in the renal tubules.

  • –The metabolites are usually less active than the parent drug but may have equivalent or higher activity.
  • –Prodrugs are inactive until they are metabolised in the body to the active drug.
  • –Occasionally, the metabolite may be toxic (undesirable
61
Q

What is the second effect of drug metabolism?

A

The liver is the primary site of drug metabolism, but other tissues may be involved in the process to a limited extent (e.g. kidneys, lungs and intestinal
mucosa.
—By cytochrome P450 enzymes and other enzymes.
—-Rate of metabolism is not constant as enzymes can become saturated, or be
inhibited or induced.

62
Q

What is excretion?

A

Excretion is the irreversible removal of drug from the body in urine, bile, expired air, sweat, saliva, breast milk or faeces.

63
Q

What are the three fundamental processes

account for renal drug excretion?

A
  • –Glomerular filtration
  • –Tubular reabsorption
  • –Tubular secretion
64
Q

Renal function varies with…

A
  • –Age
  • –Health
  • –Drugs
65
Q

What is the glomerular filtrate rate of a healthy adult?

A

In a healthy adult the
Glomerular filtration rate
(GFR) is ~ 120 mL/minute.

66
Q

What is involved in tubular reabsorption?

A

If the tubule is freely permeable to drug molecules, a significant proportion (as much as 99%) of the filtered drug will be reabsorbed actively and passively.

Lipid-soluble drugs are therefore excreted poorly, whereas water
soluble drugs remain in the lumen and are excreted

67
Q

What happens when weak bases are ionized?

A

Weak bases are unionised in basic urine, and therefore readily reabsorbed.
—-Weak bases are ionised, trapped and highly excreted from acidic urine

68
Q

What happens when weak acids are ionised?

A

Weak acids are unionised in acidic urine, and therefore readily reabsorbed.
—Weak acids are ionised, trapped and highly excreted from basic urine

69
Q

What can donate H+ ions and what can accept?

A

Acids can donate H+ whilst bases can accept H+

70
Q

What is the relevance of ion trapping?

A

Many drugs are weak acids or bases,
which means their charge (or lack thereof) depends on pH
—pH is important to understand how compounds move around the body.
—Ionised compounds are water soluble.
—Neutral compounds are lipid
soluble.

71
Q

What occurs in ion trapping?

A

Ionised drugs are water soluble and cannot cross

lipid cell membranes. They are trapped.

72
Q

What environment are weak acids ionised?

A

alkaline environments

73
Q

What environment are weak bases ionised.

A

Acidic environments

74
Q

What occurs in tubular secretion?

A

Up to 20% of renal plasma flow is filtered through the glomerulus, leaving about 80% to pass on to the peritubular capillaries

75
Q

Drug molecules can be secreted int what and by what?

A

Drug molecules may be secreted into the tubular lumen by the organic acid transporter or the organic base transporter

76
Q

How is tubular secretion different from glomerular filtration?

A

Unlike glomerular filtration, tubular secretion can achieve maximal drug clearance even when most of the drug is bound to plasma protein.

77
Q

What is half-life?

A

Half life (t1/2) is the time take for the concentration of drug in the plasma to fall by half its original value.

Half-life can be used to guide dosing frequency, but other factors must be taken into consideration, such as formulation (e.g. sustained release), therapeutic index, likely adherence rates etc.

78
Q

Why is it best to keep the plasma drug concentrations steady?

A

Is best to keep the plasma drug concentration as steady as possible, and to prevent the plasma drug concentration to fall to zero between doses.

With repeated dosing, the plasma drug concentration starts to accumulate, until it
reaches a steady-state, Css.

It takes 3-5 half-lives to reach Css

79
Q

What can variability be a serious problem?

A

Lack of efficacy

unexpected side effects

80
Q

What are the types of variability?

A

Pharmacokinetic (what the body does to the drug)

Pharmacodynamic (what the drug does to the body)

81
Q

What are some causes of variability?

A 
Genetic factors
Ethnicity
Age
Disease
Pregnancy
Diet
Behavior
Pharmacodynamic sensitivity
82
Q

What is pharmacokinetic variability regarding absorption?

A

The passage of a drug from its site of administration into the plasma

Is the drug absorption significantly affected by GI motility?

83
Q

What is the pharmacokinetic variability of distribution?

A

How the drug is distributed in the body.

IS the drug highly bound to plasma proteins? Interaction with other plasma bound drugs?

Is the drug lipophilic? More adipose tissue in obese patient.

84
Q

What is the pharmacokinetic variability of metabolism?

A

Metabolic conversion of drugs via the liver.

–Is the drug metablised by the liver?

—Are there known genetic/ethnic problems with metabolic pathway?

85
Q

What is the pharmacokinetic variability of excretion?

A

Elimination of drugs from the body (via bile, enterohepatic circulation, kidneys).

–What is the age of the patient? Is the GFR normal?

86
Q

How do genetic polymorphisms contribute to pharmacokinetic variability?

A

Polymorphisms in the genes encoding cytochrome P450 enzymes

Polymorphisms is the genes encoding drug targets such as receptors and enzymes.

87
Q

What is an example of variations in metabolism due to ethnicity?

A

Asian people are more sensitive to the cardiovascular effects of beta-blockers than Anglo-Saxon people.

Additionally, 50% of Asian people cannot metablose alcohol.

88
Q

How does age affect pharmacokinetic variations?

A
  • Increased co-morbidities
  • Decreased liver metabolism
  • decreased cardiovascular reflexes
  • Decreased renal function
  • Decreased cognitive function
  • altered receptor sensitivities
  • increased proportion of body fat?
89
Q

What age-related variations in renal excretion?

A

GFR of a newborn is only 20% of adult valve

GFR increases to a maximum of twice the adult value at 6 months of age

Premature babies have a significantly lower GFR.

GFR declines slowly from about 20years, falling by 25% at age 50 and by 50% at 75 years

90
Q

What are other age-related factors affecting drug variability? (pharmacodynamic)

A

Midazolam produces more confusion and less sedation in the elderly than in young subjects.

91
Q

What are other age-related factors affecting drug variability? (physiological factors)

A

Reduced cardiovascular reflexes in the elderly cause increased postural hypotension with antihypertensives.

92
Q

What are other age-related factors affecting drug variability? (Poly-drug therapy)

A

Elderly people usually consume more drugs than younger adults —- potential for drug interactions and reduced medication adherence.

93
Q

Pathological factors relating to polypharmacy in the elderly

A

Impaired renal or hepatic function

  • –decreased drug clearnace
  • –increased effects and risk of toxity.

Gastric stasis (ie migraine)

  • decreased drug absorption following oral administration
  • decreased effects

Oedema (eg congestive heart failure)

  • decreased drug absorption following oral administration
  • decreased effects
93
Q

Pathological factors relating to polypharmacy in the elderly

A
94
Q

What physiological changes in pregnancy influence drug disposition in mother and fetus.

A

Maternal plasma albumin concentration is reduced, influencing drug-protein binding:

  • – less drug is bound to albumin in the plasma
  • – increased unbound drug available to work at the site of action.
95
Q

Things to consider with foetal exposure?

A

Is the drug safe in pregnancy?
—lipophilic molecules rapidly cross the placental barrier, increasing foetal drug exposure, whereas transfer of hydrophilic drugs is slow, limiting foetal drug exposure

—Drugs that are transferred to the foetus are slowly eliminated:
fetal liver is much less than that of an adults
the foetal kidney is not an efficient route of elimination as the excreted drug enters the amniotic fluid which is then swallowed by the foetus.

96
Q

Other causes Pharmacodynamic variability (Tolerance and tachyphylaxis)

A

Tolerance and tachyphylaxis

  • – a decrease in responsiveness to a drug
  • –Tolerance occurs gradually and tachyphylaxis occurs rapidly

Often involves drug target down-regulation — cells become less responsive to a drug

97
Q

Other Pharmacodynamic variability (super-sensitivity)

A

Super-sensitivity

  • – An increased responsiveness to a drug
  • –Often involves drug target up-regulation - cells become hypersensitive to a drug
98
Q

Behavioral causes of variability

A

Medication adherence

  • –The degree to which a patient correctly takes their medication
  • –Nonadherence is a very common cause of therapeutic failures, such as
  • excessive adverse effects
  • ineffective therapy
99
Q

How is the intensity of a drug’s pharmacological effect increased or decreased?

A

By the elimination of another drug.

— May result in loss of efficacy (diminished effect) or the development of toxicity (enhanced effect)

100
Q

What type of drugs interacts with other drugs?

A

Grapefruit juice and herbal remedies

101
Q

Classification of drug interactions.

A

The administration of drug (A) can alter the action of another drug (B) by one of two general mechanisms.

102
Q

What are the first general mechanisms of drug administration?

A

Pharmacokinetic interaction

    • Drug A alters the pharmacokinetic of drug B
  • -Pharmacokinetics is what the body does the drug - so dug A alters the absorption, distribution, metabolism or excretion of drug B.
  • -This results in alteration of the concentration of drug B that reaches the site of action.
103
Q

What are the second general mechanisms of drug interactions?

A

Pharmacodynamic interaction

    • Drug A alters the pharmacodynamics of drug B
  • Pharmacodynamic is what the drug does to the body- so drug A alters the pharmacological effects of drug B
  • -This results in alteration of the pharmacological effect of drug B without altering its concentration at the site of action.
104
Q

Absorption pharmacokinetic drug interactions

A
  • -Formation of insoluble complexes within GI fluid
  • -Altered gastric motility
  • -Altered GI blood flow
105
Q

Distribution Pharmacokinetic drug interactions examples

A

Displacement of protein binding

106
Q

Metabolism examples pharmacokinetic drug interactions

A
  • -inhibition of liver enzyme

- -induction of liver enzymes

107
Q

Explain pharmacokinetic interaction: excretion

A
  • –Altered urine flow
    • Altered urine pH (ion trapping)
  • – Inhibition of tubular secretion.
  • -Altered protein binding, and hence filtration.
108
Q

Explain enzyme inhibition in pharmacokinetic interaction: metabolism

A
  • may be competitive or non-competitive inhibition

- - usually results in increased effects of drug B and risk of toxicity

109
Q

Explain enzyme induction in pharmacokinetic interaction: metabolism

A
    • may occur by increased enzyme synthesis and/or reduced enzyme breakdown
  • usually results in decreased effects of drug B

ie rifamppicin induces the metabolism of warfarin– levels of warfarin fall–decreased warfarin effects (risk of thromboembolism)

110
Q

What does drug A do to drug B?

A

Drug A modifies of the pharmacodynamics of Drug B, without altering drug B’s concentration in the tissue

111
Q

Examples of addictive effects of drug interactions

A
  • –warfarin and aspirin increase risk of bleeding

- –Benzodiazepines and alcohol the risk of drowsiness.

112
Q

What are the opposing effects of pharmacodynamic drug interactions?

A

– Beta-receptor agonists cause bronchodilation and muscarinic agonist cause bronchoconstriction

113
Q

What are the altered effects at the drug target level with drug interactions?

A
  • –Digoxin competes with K+ for its binding site on the drug target. Many diuretics lower plasma K+ predisposing to digoxin toxicity.
  • -Beta-receptor antagonists diminish effectiveness of beta-receptor agonist
114
Q

When are drug interactions clinically significant?

A

Especially significant when the therapeutic index of drug B to be narrow
– ie small reduction in effect of Drug B will lead to loss of efficacy and small increase in effect of drug B will lead to toxicty.

115
Q

When are drug interactions clinically significant?

A

Some drug interactions are only theoretical in nature… while other can cause major problems

116
Q

What is toxicology?

A

The study of adverse effects of drugs and chemicals on biological systems

117
Q

What does ADE stand for?

A

Adverse Drug Effects

118
Q

What does ADR mean?

A

Adverse Drug Reaction

119
Q

Type A (augmented) ADRs are characterized by…

A
  • —Relationship to dose
  • —Common occurrence (about 80%)
  • –High morbidity and low mortality
  • –Predictability from the known pharmacology of the drug
120
Q

What are some factors predisposing Type A reactions?

A
  • –Dose
  • -Pharmaceutical variation in drug formulation
  • –Pharmacokinetic variation
  • –Pharmacodynamic variation
  • –Drug interactions
121
Q

What are some examples of type A ADRs?

A
  • –Sedation with the use of antihistamines
  • –Bleeding with anticoagulants
  • –Hypoglycemia from the use of insulin
122
Q

What are type 2 (Bizarre) ADRs characterized by?

A
  • –unpredictability
  • –no relationship to dose
  • –an uncommon occurrence
  • –increased severity
  • –high morbidity and high mortality
123
Q

What are some factors predisposing to Type 2 ADRs?

A
  • –Drug allergies
  • –Abnormal drug metabolism
  • –biological deficiency (enzyme deficiencies)
  • –Receptor abnormalities
  • –Pharmaceutical variation in drug formulation
124
Q

What are some examples of Type 2 ADRs?

A
  • –Nephritis with the use of NSAIDs

- –anaphylaxis ith the use of penicillin

125
Q

What are some risk factors of ADRs for the patient?

A
  • –Age (elderly and neonates higher incidence rates)
  • –Gender (women more susceptible)
  • –comorbidities
  • –Genetic factors
  • –History of prior drug reactions
126
Q

What are the risk factors of ADRs specific to the drug?

A
  • –Chemical characteristics
  • –Route of drug administration
  • –dose
  • –Duration and frequency
127
Q

What is the therapeutic drug index?

A

is the ratio between the average minimum effective dose and the average maximum tolerated dose in a group of subjects.

128
Q

The TI indicates the margin of safety. What does a wide TI indicate?

A

A wide TI ratio indicates a safe dose range. The maximum non-toxic dose is much higher than the minimum effective dose.

A narrow TI ratio means the maximum non-toxic dose in not that higher than the minimum effective dose resulting in a smaller margin of safety.

129
Q

What is an example of a wide and narrow TI?

A

Wide - warfarin

Narrow - penicillin

130
Q

Over the past decade, what is the most likely reason for drug overdoses?

A

Drug-induced deaths were more likely o be due to prescription drugs than illegal drugs.

131
Q

What are some examples of reducing toxic effects?

A
  • Decrease the systemic absorption of the toxin—-activated charcoal in paracetamol overdose
  • Bind the toxin o that it cannot interact with its drug target—Obidoxime organphosphateposining
  • increase urinary excretion of the toxin—sodium bicarbonate in aspirin overdose
  • oppose pharmacological action of the toxin —Naxlone n opioid overdose, atropine in organophosphate posing
  • treat the symptoms — manage the airway, perfusion etc
132
Q

What is the treatment of overdoses and poisonings?

A
  • – stabilization of the patient
  • –clinical evaluation and risk assessment
  • –prevention of further toxin absorption
  • –enhancement of toxin elimination
  • –administration of an antidote
  • – supportive care and follow up
133
Q

What are the potential drug effects during pregnancy?

A

first trimester - congenital malformations

second and third trimester – fetal growth and functional development

close to term - affect labour or the neonate

134
Q

What does category A of drug use in pregnancy mean?

A

Drugs have been taken y a large number of pregnant women with no increase in malformations r harmful effects of the fetus.

135
Q

What does category B of drug use in pregnancy mean?

A

The drug has been taken by a limited number of pregnant women without an increase in malformations or harmful effects on the fetus

136
Q

What does category C of drug use in pregnancy mean?

A

Drugs, owing to their pharmacological effects, have caused or may have been suspected of causing an increase in malformation and harmful effects on the fetus. But these effects are reversible.

137
Q

What does category D of drug use in pregnancy mean?

A

Drugs that have caused, are suspective of causing or may be expected to cause an increased incidence of fetal malformation or irreversible damage.

138
Q

What does category X of drug use in pregnancy mean?

A

Drugs that have a high risk of using permanent damage o the fetus hat should not be used in pregnancy or when there is a possibility of pregnancy.

139
Q

What happens to drugs during breastfeeding?

A

Any drug consumed and absorbed may reach the infant by the maternal circulation.

Pharmacology CSA236 (3 decks)

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