Week 1 Flashcards
1
Q
Pathophysiology
A
The study of how the function of cells, tissues and organs are altered in disease, illness or injury.
Represents a breakdown of homeostasis.
2
Q
Aetiology
Idiopathic
Iatrogenic
A
The study of the cause(s) of a disease. May be one factor or multifactor.
Idiopathic - cause of disease is unknown.
Iatrogenic - disease unintentionally caused by a medical treatment, diagnostic procedure or an error.
3
Q
Pathogenesis
Acute disease
Chronic disease
A
The development of a disease. Mechanisms by which a disease becomes established and progresses.
Acute disease - develops quickly
Chronic disease - develops gradually and lasts for a longer time
4
Q
Risk factors
A
places a person at greater risk for developing a particular disease
5
Q
modifiable risk factor
A
can be changed (e.g smoking, diet)
6
Q
non-modifiable risk factor
A
cannot be altered (e.g age, race)
7
Q
clinical manifestations
signs
symptoms
A
changes in function caused by a disease
signs - objective measurement / recording of a disease e.g heart rate, temperature, blood pressure
symptoms - subjective feelings e.g pain and nausea
8
Q
diagnosis
A
identification of a specific disease through the evaluation of signs, symptoms, laboratory tests and / or other tools
9
Q
management
A
aims to minimise the effects of a disease through illness-specific management, education, and patient support
10
Q
epidemiology
A
the study of how disease is distributed within populations and identification of factors that influence distribution of disease
11
Q
incidence
A
number of new cases of a disease diagnosed within a defined period
12
Q
prevalence
A
total number of cases of a disease at a particular time
13
Q
morbidity
A
proportion of a population with a disease
13
Q
mortality
A
number of deaths
14
Q
cell adaptation
reversible
irreversible
A
- response to persistent or intense stimuli
- cell can adapt to new conditions by changing size (atrophy and hypertrophy), number (hyperplasia) and type (metaplasia)
- if cells cannot adapt, they can become injured
reversible - affected cells recover after removal of stimulus
irreversible - results in cell death
14
Q
atrophy
A
a decrease in cell size due to a lower than normal demand being placed on a cell
15
Q
hypertrophy
A
an increase in cell size due to a greater than normal demand being placed on a cell
16
Q
hyperplasia
A
an increase in cell number in response to increase demand
- due to an increased rate of cellular division
- usually, increase is a combination of hyperplasia and hypertrophy
17
Q
metaplasia
A
cells change from one cell type to another cell type
- if stimulus is removed, cells may revert to original type
18
Q
dysplasia
A
abnormal differentiation or maturation of tissue
- variation in cell size, shape and organisation which leads to breakdown of tissue
- often a precursor to cancer
- may be benign or malignant
- may be reversed if stimulus is discontinued / removed
19
Q
reversible cell injury: hydropic swelling
A
- regulates flow of sodium (Na) and potassium (K) across membrane
- Na+/K+ ATPase pump requires energy produced by mitochondria
20
Q
reversible cell injury: intracellular accumulation
A
- substances that can accumulate: normal nutrients, pigments and inorganic particles
- accumulate due to excessive levels and / or metabolic dysfunction
21
Q
irreversible cell injury
A
- energy production in the mitochondria below essential minimal requirement and unable to be restored
- disruption of nuclear function: without a viable nucleus the cell cannot survive
- loss of cell integrity, cell membrane ruptures
- results in cell death - necrosis and apoptosis
22
Q
necrosis
A
cell injury leads to unplanned cell death and autolysis
23
fat necrosis
- occurs in adipose tissue
- damaged fat cell membranes release triglycerides into the tissue
- formation of free fatty acids
- calcium ions bind to free fatty acids > calcium soaps
- affected tissue becomes chalky and white
24
necrotic process
- intracellular enzymes move into extracellular fluid
- eventually diffuse into the bloodstream
- presence indicates necrotic cell death and can be used for clinical diagnosis
- release of chemical mediators triggers inflammatory reaction to remove debris and start the healing process
-types - coagulative, liquefactive, caseous, fat
24
coagulative necrosis
- most common form of necrosis
- characterised by protein denaturation e.g cooking an egg
- tissues retain original shape and consistency before breaking down
- often caused by ischaemic injury
24
gangrene
- necrosis of a large amount of tissue due to ischaemia
- often seen in toes and lower extremities, usually caused by peripheral vascular disease
- gangrene of toes and / or foot is common in diabetic patients
25
liquefactive necrosis
- characterised by dissolution of tissues - cell liquefies
- lysosomal digestive enzymes released in large amounts during cell death
- autolysis - tissue transforms into liquid and pus
- most often occurs in the brain due to irreversible ischaemic brain injury
26
caseous necrosis
- combination of coagulative and liquefactive processes
- tissue framework is not completely broken down
- consistency is "cottage cheese"
- typically seen in tuberculosis
27
wet gangrene
liquefactive necrosis of internal organs
28
dry gangrene
coagulative necrosis that dries out and becomes black and mummified
29
apoptosis
- programmed cell death that occurs normally in developing and adult tissues
- normal process of tissue maintenance and development
- physiologic: formation of our head, face, gastrointestinal tract and other body parts in utero
- pathologic: certain cancers, parkinson's disease, alzheimers disease
- occurs in response to a specific stimulus that the cell is no longer required or is redundant
- cell size decreases and nucleus condenses > cell membrane 'blebs' > cell fragments > apoptotic bodies form > engulfed by nearby phagocytes
- no inflammatory response
30
hypoxia and ischaemia
hypoxia: a state of low oxygen
ischaemia: inadequate blood flow to an organ or tissue
- ischaemia leads to hypoxia
- hypoxia can occur without ischaemia
31
ischaemic injury
1. compromised oxygen supply to cells
2. ATP production decreases
3. anaerobic metabolism used
4. low ATP production and increased lactic acid
5. failure of the membrane pumps
6. sodium ions accumulate inside cell
7. water moves into cell
8. cells swell and become damaged
9. calcium released impairing mitochondria
10. cellular waste accumulates leading to cell injury
32
pharmacology
the study of drugs, including their actions and effects on the body
- a drug is any substance or product that is used, or is intended to be used, to modify or explore physiological systems or pathological states for the benefit of the recipient
32
pharmakos
medicine or drug
33
logos
study
34
pharmacokinetics
the physiological processes that influence drug levels within the body: Absorption, Distribution, Metabolism and Elimination (ADME)
- the action of the body on the drug
- kinetic = movement > the movement of drugs into, through and out of the body
35
pharmacodynamics
the mechanism by which drugs exert their effects on the body
- the action of the drug on the body
- D = do > what the drugs do to the body for a response to occur
36
pharmacotherapy
the use of drugs for treating or preventing disease
37
therapeutic effects
intended effects
38
adverse drug reactions
undesirable effects that occur with the administration of medicines at normal doses
39
side effects
very common and are the unintended effects that are not related to the desired drug effects
- due to a lack of specificity of action
40
idiosyncratic reactions
abnormal reactivity to a medication
- unpredictable, likely genetic factor
41
allergic reactions
harmful effects at normal doses
- immune system has an inappropriate response
- can range from mild to severe
- also known as drug allergies
42
medication toxicity
predictable adverse drug effect related to the dose of the medication administered
- no such thing as a safe drug
- therapeutic index: difference between therapeutic dose and toxic dose
43
drug interactions
interaction with another drug causing variation in its metabolism or pharmacological response
- interaction may lead to an increase or decrease in drug effectiveness
44
drug intolerance
a lower threshold to the normal pharmacological action of the drug
45
drug tolerance
decreased response to the same amount of drug after repeated administration
46
drug teratogenicity
medications that cause congenital defect in an infant whose mother took the medication while pregnant
47
over-the-counter preparations
- also includes complementary, alternative and traditional medicines
- available to the general public at pharmacies, health food stores, supermarkets (dependent on restrictions) etc
- available without a prescription, restriction or supervision
- needs to be taken into consideration with a patients prescribed medications due to interactions and adverse effects
48
chemical name
extremely cumbersome and almost never used in the clinical setting
49
generic name
the shortened, simplified version of the chemical name
- active ingredient
- always stays the same regardless of which company makes the drug
- usually appears below the brand name in a smaller / lighter print with no capital letters
50
brand name
registered trademark used by the pharmaceutical company for commercial distribution
- several different brand names for the same generic drug
- usually in larger, bolder print and written as a proper noun and has capitals
51
Generic vs brand name
- one ingredient
- brand name is in larger, bolder print
- generic name appears beside the brand name in a smaller and lighter print
- more than one ingredient
- different generic medications are combined under 1 brand
52
bioequivalence
different brands of the same generic drug are considered to have the same response and could be interchangeable
- differences in bioequivalence can exist between different brands
53
drug classification
- can be grouped into drug classes according to shared characteristics
- therapeutic use - based on conditions being treated
- mode of action - based on how the drug exerts its effects
- structure - based on similarities to other drugs
- certain drug classes have generic names with common suffixes
54
Common routes of administration
- tablets
- enteric coated preparations
- capsules
- sustained-release and controlled-release preparations
- oral liquid preparations
- topical preparations
sublingual and buccal administration
- intranasal administration
- transdermal administration
- rectal administration
- vaginal administration
- parenteral medicine administration
- nebuliser and inhaler administration
55
tablets
a disc containing one or more drugs, prepared by compressing a granulated powder
- small drug quantities, so other materials (inert filler) added for bulk
- lubricating agent: prevents ingredients sticking to manufacturing agent
- binding agent: keeps tablet whole
- starch: helps tablet disintegrate in gastrointestinal tract
- sugar-coated, film-coated, chewable, flavoured
56
enteric coated (EC) preparations
- coated with a material that does not disintegrate due to stomach acidity
- break down in alkaline conditions of intestine
- must not be crushed
57
capsules
- hard gelatin: solid medications, can be opened and contents mixed with food
- soft gelatin: liquid or semi-liquid form, medicines not easily dissolved in water
58
sustained-release (SR)
- medicine with a short half-life
- released slowly into the gastrointestinal tract
- increase patient adherence
- various ways to create slow release, but varied break-down of medication
59
controlled-release (CR)
- hole created by laser in membrane surrounding active drug
- water flows in the holes, forcing contents out
- more constant release
60
oral liquid preparations
for people who find it difficult to swallow tablets
- linctus: a syrup specifically formulated for coughs
- elixirs: drug insufficiently soluble in water, so prepared in alcoholic solution
- tinctures: like elixirs but more concentrated
- suspension: insoluble solid particles in a liquid
- emulsion: mixture of two liquids
- desiccated powders: water is added to the powder before use
61
topical preparations
application to an area of the body for direct treatment
- eye drops: aqueous or oily solutions or suspensions
- nose drops: cannot be oily
- ear drops: oily solutions
- creams: most common topical preparations, aqueous bases
- ointments: most common topical preparations, lipid base
- pastes: high powder content that protects skin from moisture
- gels and lotions: for hairy areas of the body. Gels are semisolid and liquids are lotion like
62
sublingual and buccal
effective absorption through mucosa of mouth into bloodstream
63
intranasal
- topical use for relief of nasal congestion
- drops, sprays and metered sprays
64
transdermal
- administration via skin of medicines that are very lipophilic and active in small amounts
- administered as sticky discs called "transdermal patches"
65
rectal (suppositories)
- usually inserted into the rectum pointed end first
- advantages: if patients is unconscious, has nausea or vomiting, difficulty swallowing, injections, etc.
- disadvantages: anal or rectal irritation, privacy and modesty, perforation of rectum, etc.
66
rectal (enemas)
- liquid preparation
- topical or systematic treatment; or cause a bowel motion
67
vaginal
- suppository shaped medicines are termed 'pessaries'
- used for topical treatment
- inserted as high in the vagina as possible to coat all of the mucosa
68
parenteral medicine
avoids the gastrointestinal tract
- term normally reserved for invasive procedures
69
intradermal (parenteral medicine)
injected into the dermis using a fine needle
70
subcutaneous injections (parenteral medicine)
slow absorption
71
intramuscular injections (parenteral medicine)
- lipid-soluble drugs absorbed rapidly into capillaries
- lipophilic drugs absorbed slowly into lymphatic system
72
intravenous injections (parenteral medicine)
bypasses absorption process very fast acting
73
other modes of injection (parenteral medicine)
- intra-arterial
- intrathecal
- epidural
- intra-articular
74
nebuliser and inhalers
administers medicines into lower respiratory passages
75
inhalers
- metered dose inhalers (MDI): require hand-breath coordination
- spacers: use with MDI for people who lack hand-breath coordination
- dry powder inhalers: dry powder activated by breath
76
nebuliser
produces an aerosol via air compressor or jet to deliver large doses of medication over a long period
77
Pharmacokinetics - ADME
Absorption
movement of the drug into bloodstream from site of administration
78
Pharmacokinetics - ADME
Distribution
movement of the drug to its site of action
79
Pharmacokinetics - ADME
Metabolism
how the drug is broken down
80
Pharmacokinetics - ADME
Excretion
how the drug is removed from the body
81
Absorption
- process of the drug moving from the site of administration into interior compartments e.g. bloodstream
- a drug must be dissolved before it can work
- most absorption occurs in the small intestine due to large surface area and oral administration
- exception : intravenous route - medication directly administered into systemic circulation
82
factors affecting absorption
1. drug formulation - liquids absorbed faster than tablets / capsules
2. route of administration - intravenous - directly enters the bloodstream
- buccal and sublingual - absorbed quickly into the bloodstream
- parenteral injections - subcutaneous injection slower than intramuscular
- transdermal patches
3. chemical nature of drug - majority of drugs: simple diffusion of small molecules
- affected by administration routes; e.g. enteric coated
4. gastric acidity (pH) - influences the proportion of drug that can be absorbed
- different at different times of the day, age of patient, etc.
5. surface area of absorptive site - most common: small intestine
- affected by other foods / drugs due to delayed transit time and dissolution by gastric acids
6. blood flow - high flow facilitates, low flow impedes
- affected by hot and cold packs, massage, etc.
- transdermal patches
7. lipid solubility of drug - most membranes are comprised of lipid materials
- lipophilic ('fat-liking') or lipid-soluble substances
8. degree of ionisation - influenced by surrounding pH, e.g. aspirin
83
distribution
movement of a drug from site of absorption to site of action
84
factors affecting distribution
1. blood supply to tissues - rapid distribution to well perfused organs (i.e. heart, brain, kidneys)
- slow distribution to skin, bone and adipose tissue
2. physical properties of the drug - fat-soluble (lipophilic) crosses cell membranes more easily than water-soluble (hydrophilic) drugs
3. barriers - prevents drugs from entering some body compartments for example: blood brain barrier, placental barrier
4. protein binding: drug reservoir that can prolong presence
-transported attached to blood proteins: albumin usually binds acidic drugs, globulin usually binds basic drugs
- is usually reversible
- drugs in the plasma can be free or protein bound
- protein bound: pharmacologically inactive
- free form: pharmacologically active
- stronger the protein binding, the lower the free form
5. other drug reservoirs:
-adipose tissue: lipid soluble drugs have a high affinity for adipose tissue
- slow release into the circulation over time
- can delay effects of the drug and elimination
-e.g. THC - once use can still be detectable in the blood weeks later
- hydrophilic drugs: dissolve in water and tend to stay in the interstitial space
- may require transport mechanisms to move in and out of cells
- volume of distribution: the extent to which a drug is distributed to the tissues
- the higher the amount in tissue, the higher the distribution
85
metabolism
- the process of converting a drug to a form that is more easily removed from the body
- can be metabolised in most body cells, but principal site is the liver
- liver cells have 'microsomes', which contain enzymes suitable for metabolism - breaks down the bonds and groupings
- two phases of metabolism
- phase 1: enzymes modify the drug altering solubility and activity of the drug (becomes hydrophilic). Cytochrome P450 enzyme family is important
- phase 2: a drug or phase 1 metabolite is joined with a polar molecule to make it soluble for excretion
86
Hepatic first-pass effects
- all oral drugs must pass through the liver before entering the systemic circulation
- drugs may be extensively metabolised before entering the circulation
- example: glyceryl trinitrate - 96% destroyed by the liver resulting in a high hepatic first pass if given orally
87
excretion
- the process that removes the drug or its metabolites
- routes of excretion: - primary: kidneys (urine) and gastrointestinal tract (bile and faeces)
- respiratory (breath exhalation), saliva, sweat and breast milk
88
drug clearance
drug elimination from the body - includes both metabolism and excretion
- sum of clearance through each body site
special considerations: patients with liver and kidney problems often need reduced dosages
- hepatic disorders may reduce rate of drug metabolism
89
drug bioavailability
- the amount of a drug that is available to the body to produce a therapeutic effect
- determined by absorption and hepatic first-pass
- drugs given intravenous (IV), sublingual, buccal, rectum or inhalation bypass the liver
- 1000% bioavailability as all of it reaches the circulation
- morphine example:
- IV dose = 100% bioavailability
- oral dose = 30% bioavailability
- to get a similar dose: IV dose = 10mg, oral dose = 30mg
90
drug half life
- the amount of time taken for the drug to be reduced by half (elimination) - blood concentration = 100mg/L
- four hours later = 50mg/L
- drugs half-life is four hours
- usually takes 4 to 5 half-lives for a drug to be considered eliminated
- in accidental or deliberate overdosing, longer time periods may be necessary
- useful for calculating timing for repeat doses
- want to attain drug steady-state concentration which is after 5 half-lives in image
- long half lives = more days to achieve steady-state e.g. half-life is 48 hours > about 10 days (antidepressants)
- short half lives [ need less time to achieve steady-state e.g. half life is 2 hours > less than a day
91
types of drug interactions
outside of the body
- storage conditions: drugs can deteriorate or become inactive if subjected to sunlight, bright light, extreme temperatures, oxygen, moisture, shelf life, expiry date and type of container
- drug incompatibilities; mixing drugs in the same syringe for injection, e.g. rapid and slow and acting insulin become primarily slow insulin
92
types of drug interactions
in the gastrointestinal tract
- drug formulation affects absorption e.g. slow-release tablets designed to prolong duration of action but may decrease bioavailability
- foods can react with medicines e.g. calcium can reduce the therapeutic activity of medications such as bisphosphonates
- medicines may prevent absorption of some fat-soluble vitamins
- broad-spectrum antibiotics may kill off some natural flora of the intestines
- some foods may significantly increase bioavailability > more drug is available than expected, e.g. felodipine and grapefruit juice
93
types of drug interactions
after absorption
- usually when two or more medicines are administered together
- interactions between medicines and compounds absorbed from food - vitamin K can interfere with warfarin activity
94
types of drug interactions
pharmacokinetic interactions
- length of time a drug remains active can be altered by: - interactions between drugs and enzymes in the liver
- interference with the excretion of other drugs
95
types of drug interactions
pharmacodynamic interactions
- when the action of one drug interferes with another drug
- can cause significant reduction or increase in the effects of one or both drugs
- enhancing these interactions can be beneficial
- summation: the two drugs produce an additive effect
- potential: the two drugs produce an effect that is more than additive, i.e. 1+1=3
96
types of drug interactions
enzyme activity
- enzyme induction: when a drug is present for prolonged periods, enzyme levels can increase to speed up drug metabolism
- enzyme inhibition: drugs that are enzyme inhibitors can moderate enzyme activity and slow down body processes
- can lead to an accumulation of drugs and possible toxicity
97
drugs and enzymes
enzymes
biological catalysts that carry out many reactions in the body
- remains unchanged at the end of the reaction
- relatively specific for a certain substrate: pepsin: breaks down protein peptide bonds
- completely specific for a certain substrate
- glucose dehydrogenase: only acts on glucose
- like a lock and key mechanism
- only one substrate will fit into the binding site of an enzyme
98
drugs and enzymes
competitive inhibition
- medicine is competing with the natural substance for access to the binding site of the enzyme
- excessive levels of the inhibitor significantly slows down the normal reaction
99
drugs and enzymes
non-competitive inhibition
- inhibitor binds to a part of the enzyme's structure other than the binding site causing the enzyme to change structure making it inactive
100
drugs and enzymes
enzymes as drugs
- replacing a deficiency in a natural enzyme, pancreatin: pancreatic enzymes
- used to speed up the absorption of injected medicines, absorbed faster and with less discomfort
- used to destroy unwanted materials in the body
101
drugs and receptors
- many processes controlled by chemicals
- chemicals bind to receptors, cells surface, in the cytoplasm or in the nucleus
- receptors bound to a chemical state > alters cell activity
- receptors = lock; specific chemical = key
- substances that stimulate receptors are first messengers; ion channels, G-protein-coupled receptors, tyrosine kinase receptors, cytoplasmic receptors (action within the nucleus)
102
agonist
when a drug acts on a receptor to create a response
103
antagonist
when a drug acts on a receptor to block the response
104
affinity
how good the fit is of the drug into the receptor
105
specificity
the degree of selectivity
106
inverse agonists
some drugs stimulate the receptor so that the opposite effect to the normal agonistic effect is seen
106
receptor modulators
can work either as an antagonist or as an agonist depending on the receptor subtype involved
106
potency
the relative amount of the drug that has to be present to produce a desired effect
106
partial agonists
- some drugs do not fit exactly on the receptor site, but binds enough to initiate some form of response
- drugs with a lower affinity create an action that is less than normal
